The American Chamber of Commerce in Japan. ACCJ EBC Health Policy White Paper Lengthening Healthy Lifespans to Boost Economic Growth

Transcription

1 The American Chamber of Commerce in Japan ACCJ EBC Health Policy White Paper 2017 Lengthening Healthy Lifespans to Boost Economic Growth

2 Lengthening Healthy Lifespans to Boost Economic Growth 1

3 Welcome Message The American Chamber of Commerce in Japan (ACCJ) was established in 1948 by representatives of 40 American companies and has grown into one of the most influential business organizations in Japan. Committed to strengthening the U.S. Japan commercial relationship, the ACCJ currently has approximately 3,500 members representing over 1,000 companies with offices in Tokyo, Nagoya and Osaka. The European Business Council in Japan (EBC) is the trade policy arm of 16 European National Chambers of Commerce and Business Associations in Japan and has been operating to improve the trade and investment environment for European companies in Japan since The EBC currently works through 26 committees for around 2,500 local European corporate and individual members with some 350 companies participating directly. Working closely with the government of Japan, business organizations and others, the ACCJ and EBC strive to promote activities that help develop opportunities and commerce while promoting the interests of their companies and members, and improving the international business environment in Japan. The information and analysis in this white paper were jointly developed based on the work of representatives of a wide variety of ACCJ and EBC corporate members who provided information and analysis, as well as invested substantial amounts of time and other resources. To the extent possible, we sought to include all views, so that the final product would reflect a balanced, consensus-based set of recommendations. The common bond among the members of our respective associations is the importance of Japan to our members global businesses and our desire to contribute to the strengthening of the healthcare system in Japan and to the wellbeing of the Japanese people. Sincerely, Christopher J. LaFleur, ACCJ President Danny Risberg, EBC Chairman Published September 2017 by: The American Chamber of Commerce in Japan Masonic 39 MT Bldg. 10F Azabudai Minato-ku, Tokyo Japan Tel: Fax: info@accj.or.jp The American Chamber of Commerce in Japan The European Business Council in Japan Sanbancho POULA Bldg. 2F 6-7 Sanbancho Chiyoda-ku, Tokyo Japan Tel: Fax: ebc@gol.com Cover Design and Layout: Custom Media KK 2 Lengthening Healthy Lifespans to Boost Economic Growth

4 Background: Linking Health to Economic Competitiveness The high productivity level of the Japanese labor force is a primary source of international competitiveness for the Japanese manufacturing and services sectors, and a key reason that many foreign companies choose to invest in Japan. Faced with an aging population, more and more attention is shifting to the question of how to invest in health in a way that increases labor productivity and economic competitiveness. It is now more important than ever for the government, healthcare practitioners and private corporations in Japan to focus on promoting wellness and the prevention and early detection of chronic and infectious disease. The policy recommendations outlined in the joint ACCJ EBC Health Policy White Paper 2017 were compiled and based on the belief that investing in the health of the Japanese people would not only result in a higher quality of life, but could also boost economic competitiveness by reducing worker absenteeism and disability while increasing labor productivity. Further, we believe these policies could boost the efficiency of healthcare spending and prevent excessive increases in healthcare costs. Healthcare is a strategic investment in the single most vital resource of the nation its people helping them live longer, healthier, and more productive lives. Healthcare providers, governments and company executives around the world are increasingly aware of the potential benefits of wellness and prevention for improving patients quality of life, for increasing workforce productivity, and for achieving cost efficiency gains. The policy recommendations in the 41 Topic Sections of this white paper are not meant to represent a comprehensive overview, but rather meant as examples of the kinds of policies likely to yield significant positive potential impact. We wish to express our deep appreciation to everyone who contributed to the development of this white paper. Sincerely, John Carlson Chair ACCJ Healthcare Committee Danny Risberg Chair EBC Medical Equipment Committee Hiroko Sugiyama 2017 ACCJ-EBC Healthcare White Paper Project Leader ACCJ Healthcare Committee Lengthening Healthy Lifespans to Boost Economic Growth 3

5 A Special Thank You to Our Sponsors No project of this scope could be accomplished without the combined efforts of many dedicated people. More than 200 people, representing several dozen companies, are registered as members of the ACCJ Healthcare and EBC Medical Equipment committees. We would like to thank everyone who contributed time and expertise to the development of these policy recommendations. In particular, we would like to extend a special thank you to our sponsors who provided funding for the translation and printing, and our in-kind sponsors who provided valuable expertise and time to edit, design, and publicize this white paper. Platinum Gold Silver Bronze In-Kind Sponsor 4 Lengthening Healthy Lifespans to Boost Economic Growth

6 Introduction Japan faces a very modern problem: its success in delivering universal health coverage and fostering longer life expectancy has led to demographic and social changes that give rise to a new set of inter-connected healthcare challenges. As the Japanese government moves to reform its healthcare system to address these challenges, we encourage Japan to develop new policy approaches that promote innovation in all areas of the healthcare system so that Japan can continue to make advances in healthy life expectancy, improve productivity and move to the next phase of economic growth, while maintaining Japanese patients access to the most cutting edge medicines, technologies and treatments and the security and stability of Japanese health and social care provision. At the root of these challenges is the dramatic aging of Japanese society and its low birth rate. A quarter of Japanese people are aged 65 and over, and that percentage is expected to rise to 45% by Aging populations create pressing needs in nursing care and chronic disease care in areas including diabetes, dementia, heart disease and cancer. As the population ages, health is increasingly in the financial spotlight: public expenditure on healthcare hit a record high in 2015 for the 13th consecutive year. As the Japanese government has recognized, adapting to this situation requires a variety of policy approaches, including improving the fiscal sustainability of the social security system and fostering a more dynamic society with higher productivity and more women and seniors in the workforce. Against this backdrop, it is clear that health should be viewed as an investment: improving the health of Japanese people will be critical to reducing cost, lowering the incidence of preventable diseases and ensuring that more people can lead active, productive lives well into their senior years. More than most nations, Japan is well-placed to meet these challenges: healthy life expectancy in Japan the period when people can live without sustained medical or nursing care assistance is about 71 years on average for men and 74 for women. With the right policies and approach to healthcare, Japan can continue to improve the health of its citizens and create a blueprint that aging societies across the world can follow. The aim of this white paper is to introduce evidence-based global best practices that can assist the Japanese government in the development and implementation of relevant policies. Addressing Fiscal Sustainability Japan s healthcare system is respected around the world for quality of care and its contribution to the long life expectancy of Japanese people. However, the aging society and low birth rate together with the need for fiscal discipline are causing strain on a system that was designed mainly for controlling infectious and acute diseases within a different population structure. Japan s national debt is more than double the size of its economy, the highest ratio among developed countries, and social security expenditure now accounts for approximately 33% of the national budget. 1 As fiscal pressure grows, out of pocket expenses are increasing and individuals have to take more responsibility for healthcare risk. An important part of the solution to this challenge comes from investing in preventive healthcare and earlier and aggressive treatment of chronic diseases to boost healthy life expectancy and lower the incidence of non-communicable diseases and other preventable conditions. When compared to the OECD average, health spending in Japan as percentage of GDP remains low, especially Lengthening Healthy Lifespans to Boost Economic Growth 5

7 compared with individual countries aging population ratios. On the other hand, improving the overall financial health of the system will also be critical as the population ages. This could require steps such as raising the consumption tax rate, raising employer and employee contributions or increasing individual co-payments to healthcare costs, or providing incentives to purchase private-sector medical and nursing care insurance products. A long-term solution will likely require a combination of all of the above. As the government enters a critical period in terms of preparing the economy for the accelerated aging of Japanese society, now is the time to have an open, holistic and constructive debate among all stakeholders about long-term social security reform to create a blueprint that other aging societies can adapt to their own needs. Investing in Prevention, Early Detection and Treatment The rising incidence of non-communicable diseases is a cause of increased economic burden and lower productivity across the world. According to the World Health Organization, a 10% rise in cancer, diabetes, Alzheimer s, cardiovascular and other chronic, non-infectious diseases is associated with a 0.5% lower rate of annual global growth. 2 Reducing the incidence of these diseases should increase economic growth. In Japan, the government s ability to promote healthy aging is critical for sustaining economic output and consumption, as well as for keeping healthcare costs under control; nearly 80% of all medical expenses come in the last years of a person s life. Healthy workers will take fewer sick days or shorter periods of time off, and be less of a burden on family members who provide care, improving productivity. The government estimates that approximately 100,000 people leave their jobs each year to provide nursing care for a family member. 3 The positive economic impact of investing in prevention, early detection and treatment can be significant: keeping people healthier for longer means being productive for longer including staying in the workforce contributing to increased quality of life and spurring increased economic activity and tax contributions that further the overall sustainability of the social security system. While the Japanese government currently has in place a variety of initiatives for immunization, early detection and awareness, and early-stage treatments for non-communicable chronic diseases, more could be done to drive gains in quality of life, workforce productivity, and cost efficiency while minimizing relatively expensive healthcare spending in later stages of treatment. The government should broaden its focus from containment of health expenditures, which when used alone could result in reduced access to cost-effective advanced health technology, to include initiatives that prevent patients from getting serious illnesses or having recurrences, and promote preventive care based on a mid- and long-term perspective. To achieve this vision, it is important to create incentives, both financial and otherwise, to motivate more people to undergo health risk assessments and to adopt healthier lifestyles and behaviors long before the onset of illness or at least in the earlier stages of disease progression, when the risk of disease and its progression can be more easily reduced. The use of information technology (IT) will be at the core of this change, including the more widespread adoption of electronic health records and other data to provide improved and innovative new products and services that 6 Lengthening Healthy Lifespans to Boost Economic Growth

8 allow healthcare practitioners and individuals to monitor health indicators. In parallel, it is important to shift the health insurance reimbursement model to one in which healthcare practitioners earn more through outcomes based on keeping patients healthy. One way to accomplish this is to provide general practitioners with meaningful incentives to maintain patients healthier outcomes by promoting prevention and early detection in their clinics. Women s Health Of particular relevance to Japan is the issue of women s health amid efforts to foster greater female participation in the economy. To date, the Japanese government s main focus has been on reforms to support working mothers and to increase the number of women in managerial positions. While these are important areas for reform, Japan lags behind other developed countries in the prevention and treatment of female-specific health risks. Ensuring that Japanese women are aware of such risks and have access to screening and treatment is essential to the ability to stay healthy throughout their lives. Healthcare-related measures are, therefore, critical to the attainment of the government s gender-equality goals and should go hand-in-hand with structural and social reforms. Improving the prevention and treatment of female-specific health conditions will deliver benefits not only to individual women, but also to families and society as a whole. According to a 2016 Cabinet Office survey, lack of confidence in one s own health is one of the primary reasons given by women for not entering the workforce. Meanwhile, the cost of gynecological conditions such as menstrual symptoms, breast cancer and cervical cancer to the Japanese economy in terms of medical expenses and lost productivity is estimated to be at least 6.37 trillion JPY per year. 4 Mental Health Addressing mental health challenges is another area of focus in Japan to ensure that people can remain productive and lead fulfilling lives well into their senior years. In a 2016 study, the World Health Organization (WHO) estimated that the cost to the global economy of anxiety and depression is around 1 trillion USD per year. The WHO also estimated that every 1 USD invested in treatment for depression and anxiety leads to a return of 4 USD in better health and productivity. At present, the total number of people in Japan with some kind of mental illness is estimated to be nearly four million. In addition to those struggling with anxiety and depression, which are among the most prevalent conditions, approximately 300,000 people in Japan receive in-patient care for serious mental illness, most notably schizophrenia. This white paper presents recommendations for improving the quality of care for mental health in Japan, including supporting the ability of municipal governments to provide effective community-based care. Incentivizing Innovation As Japanese policymakers consider reform of the healthcare system, it is imperative that they continue to put a high priority on policies that encourage innovation. Innovative healthcare products and services have the potential to drastically change clinical outcomes to the benefit of Japanese patients. Examples include penicillin, vaccines, H2 blockers, and HMG-CoA inhibitors, which have significantly improved healthcare conditions and quality of life. Recent breakthroughs have cured HCV-induced chronic hepatitis, brought certain types of cancer under control and downgraded HIV/AIDS from Lengthening Healthy Lifespans to Boost Economic Growth 7

9 a terminal illness to a chronic disease. These innovations also can lead to considerable savings to the healthcare system. Typically, the full nature and scale of such changes are known only once innovative products and services are implemented into real world medical practices. This paper highlights potential outcomes from adopting evidence-based best practices across a wide range of healthcare products and services. Billions of dollars of research funding and thousands of research professionals around the globe continue to focus on developing innovative medical solutions to unmet medical needs. All advances in therapy should be recognized and rewarded appropriately. Appropriate pricing is critical to secure access to treatments by patients who need them. On the other hand, improved medical outcomes should also be rewarded appropriately to ensure that private sector companies can recover the huge sums needed to invest in innovative medical research. Three kinds of incentives are required to effectively support innovation: 1) measures to accelerate innovative product discovery through support of R&D efforts (e.g., tax incentives or support for research budgets); 2) appropriate compensation to companies through reasonable and predictable pricing rules and price setting; and 3) the broadest possible access by patients to innovative products and/or services, while being appropriately mindful of costs. Focus on the Practice Lag In recent years, Japan has made significant progress in closing its drug lag, vaccine lag, device lag and diagnostics lag with other developed countries. In many cases, Japan is now on par with other developed countries in expediting the approval of new drug and medical device innovations. The widespread adoption of new innovations is often slowed by existing rules, guidelines, standard practices and social customs. In Japan, this so-called practice lag, the time between the introduction of new medical innovations and their widespread adoption and use, tends, in many cases, to be longer than in most developed countries. The practice lag is not unique to Japan; it is common in countries around the world. Indeed, it is a natural outcome of the desire of physicians to provide safe, proven and effective treatments to their patients. The desire to reduce risk and improve outcomes is a hallmark of the conservative nature of medical practice worldwide. Nevertheless, there has been a rapid evolution in medical treatments and technologies over the past one hundred years with accelerating changes in the past 15 years due to widespread use of digital information technology and global experimentation on solutions. The speed of medical innovation has steadily accelerated, but practices have not evolved as quickly as innovations in screening, diagnostics, treatments and therapeutic options have been introduced. This white paper introduces evidence-based best practices that can help to reduce the practice lag in Japan, deliver improved health outcomes and improve overall cost effectiveness. Healthcare Workers Healthcare workers are the backbone of any healthcare system. What is not well-recognized is that healthcare workers face a wide range of occupational workplace hazards every day. There is room for improvement in the area of safety for healthcare workers by lowering the risk of foreseeable accidents, injuries, and preventable infection, resulting in the 8 Lengthening Healthy Lifespans to Boost Economic Growth

10 increased ability to provide quality care and the reduced incidence of avoidable accidents and injuries. For the prevention and reduction of foreseeable accidents and risks, the government, employers, workers and all other parties concerned must comprehensively implement preventive measures in an integrated manner. This white paper offers several recommendations for improvements of this nature. The aim of this white paper is to highlight innovations in drugs, devices, diagnostics, technology and practices that can yield enhanced patient outcomes and improve overall cost effectiveness of the healthcare system. The ACCJ and EBC look forward to working with all stakeholders in Japan to ensure that Japanese patients continue to have timely access to innovative medical technologies and the best available clinical outcomes within a sustainable healthcare system. References 1. MOF, Japanese Public Finance Fact Sheet, WHO: Global Status Report on Noncommunicable Disease 3. Gender Equality Bureau Cabinet Office, Kyodo-Sankaku, September Health and Global Policy Institute, Research on Health Promotion and Working Women (2016) Lengthening Healthy Lifespans to Boost Economic Growth 9

11 Table of contents Prevention, Early Detection and Treatment 1 Leverage the Full Value of Advanced in Vitro Diagnostic Tests Increase Early Detection Through Comprehensive Eye Exams Health Literacy to Support Eye Health and Healthy Longevity Promote Oral Care to Prevent Periodontal Disease and Dental Caries Increase Sleep Apnea Syndrome Screening Food Functionality and Health Claims in Japan Promoting Self Care and Self Medication Extension of Healthy Life Expectancy and Countermeasures against Frailty Noncommunicable Disease 9 Prevent Chronic Diseases Through Tobacco Control Prevention and Management of Risk Factors for Diabetes Improving Prostate Cancer Treatment Abdominal Aortic Aneurysm Prevent Stroke and Provide Coordinated Care Reduce the Risk of Cerebral Infarction by Early Detection of Carotid Plaque Communicable Disease 15 Stronger Disease Prevention Based on the Stable Implementation of Immunization Policy Increase Hepatitis B Screening, Vaccinations, and Aggressive Treatments Increase Hepatitis C Virus Screening and Promote HCV Treatment Reduce the Spread of Tuberculosis Enhance Basic HIV Policy and Implement Holistic Policy Measures to Control HIV Infection in Japan Accelerating Development of Treatment for Antimicrobial Resistance (AMR) Issues in Diagnosis of Adult Respiratory Infections Including RSV in Japan Mental Health 22 Promotion of Transition of Mentally Disabled Persons to Community Diagnosis and Treatment Prior to Dementia Stage Promoting Proper Use of Hypnotics Lengthening Healthy Lifespans to Boost Economic Growth

12 Women s Health 25 Comprehensive Women s Health Support: An Essential Component to Increase the Participation of Women in Japan s Workforce Reduce the Spread of Sexually Transmitted Infections Increase Cervical Cancer Screening Levels Improvement of Accuracy of Breast Cancer Screening Prevent Fractures Due to Osteoporosis Health IT Home Care 30 Boost Regional Medical and Long-Term Care Collaboration Through Greater Use of Healthcare IT Utilizing Telemedicine to Deliver More Efficient and Effective Healthcare in Japan Improving the Quality of Medical Care, Promoting Team-based Medicine and Supporting Risk Management in Ophthalmological Surgery Improving Home Healthcare Importance of Enhanced Safety and Infection Control 34 Enhance Prevention of Healthcare-associated Infections Improve Infection Control: Closed vs. Open Systems Skin Antisepsis Prevent Bloodstream Infections by Using Appropriate Devices Sepsis Avoid Reuse of Single-use Devices Special Focus Needed on Healthcare Worker Safety 40 Prevent Needle Stick and Sharp Object Injuries Safe Handling of Hazardous Drugs to Protect Healthcare Workers Lengthening Healthy Lifespans to Boost Economic Growth 11

13 01 Leverage the Full Value of Advanced In Vitro Diagnostic Tests Situation Since the 1960s, advances in research and medical technology have led to the development of new diagnostic devices and measuring techniques that enable faster and more accurate diagnostic test results and provide healthcare practitioners with more useful information. Some of these new devices and techniques may cost more to perform than older tests, but they have become recognized around the world as essential in modern medical care because they contribute to improved treatment, faster recovery and greater peace of mind for patients. They can also lead to lower total healthcare costs because they can contribute to more successful treatment, faster patient recovery times and shorter hospital stays. Nevertheless, over the past 20 years, the full value of in vitro diagnostics (IVD) has not always been fully recognized in the Japanese healthcare system, particularly in the levels of medical reimbursement fees. As a result, Japanese patients have not always had timely access to the world s most advanced diagnostic testing. 1 In some cases, patients have undergone older diagnostic tests that are less expensive to conduct, but that may not be as accurate or fast, or provide as much information as newer, more technologically advanced tests. The advantages of laboratory testing, including genetic testing, for accurate diagnosis and preventive medicine have been increasingly recognized by healthcare practitioners. In the 2008, 2010, 2012 and 2014 medical fee revisions, some fees were increased in recognition of the value provided by laboratory testing. Furthermore, in the 2016 revision, a new discussion scheme for IVD s reimbursement system has been implemented in the Central Social Insurance Medical Council. However, there is still room for improvement. Current Policy In recent years, national medical care expenditures have grown due to increased health consciousness of the population, economic growth, the aging of society, and innovations in medical care technology. Recently, medical service fees for diagnostic testing have been steadily reduced, despite significant advances in medical technology, including automation that reduces labor costs while increasing speed and accuracy. Completely new diagnostic testing methodologies that are more sensitive, more accurate, and provide more useful information have been developed. For example, the fee for HIV testing has been steadily reduced, despite the introduction of increasingly advanced testing products that provide greater value. On the other hand, it can be very expensive to develop a new diagnostic testing agent, secure product approval, introduce it to the market, and maintain a system to ensure uninterrupted supply and consistent high quality. As a result of not reflecting the value of improvements in diagnostic testing technology, Japan s low reimbursement fees for diagnostic testing can undermine research and development of new, effective diagnostic testing technology. There are no incentives for innovation. Low reimbursement rates for diagnostic testing can also result in a diagnostic lag that can delay Japanese patient access to new diagnostic tests for several years after they are available in other developed countries. 1 Among the IVD systems currently available in Japan, there remain differences in basic product performance, such as the sensitivity and accuracy of reagents. However, there are cases in which products with higher performance levels, in terms of accuracy and speed, receive the same medical service fees (number of National Health Insurance points) as products with lower performance levels. 12 Lengthening Healthy Lifespans to Boost Economic Growth

14 National Health Insurance reimbursements should be set in a way that reflects the true value of each diagnostic test and reagent, so that more effective (in terms of sensitivity, accuracy, and speed) products are rewarded with higher fees. One example can be found in the case of HIV/AIDS testing in Japan. Among advanced countries, Japan is the only country with an increasing number of people infected with HIV/AIDS. Deficiencies in the existing testing system are a contributing factor in this rise. The testing system should be improved to allow testing of blood, tissue, and DNA samples at the appropriate time and in the most appropriate location. This means that some tests should be conducted quickly on site at the hospital or clinic, while other tests that are less urgent or require more sophisticated examination can be sent off-site to a testing laboratory. Such testing system reform should be conducted as a consistent national policy, rather than at the discretion of local governments. Recommendations Reduce the diagnostic lag through faster IVD product reviews. The period from submission until approval of innovative IVD technology in Japan is unnecessarily long. This increases development costs and slows patient access to the world s most advanced IVD technology that is more sensitive, speedy, and accurate. The applicant and the Pharmaceuticals and Medical Devices Agency (PMDA) should cooperate to effectively, efficiently and speedily implement a Collaboration Plan for IVD review acceleration. Establish a medical reimbursement pricing system that better reflects the clinical value and quality of IVD tests. Laboratory tests should be conducted at medical institutions when faster diagnoses help improve medical treatment or shorten hospital stays. An expert committee in the Central Social Insurance Medical Council should thoroughly evaluate IVD s reimbursement system as well as drugs and devices. Improve the overall quality of IVD tests available and commonly used in Japan. The medical reimbursement system should be revised to reflect differences in the clinical value of various IVD tests, so that healthcare practitioners have an incentive to use more advanced (in terms of sensitivity, accuracy, and speed) tests and so that manufacturers have an incentive to invest in research and development of new testing technology. A system for regular reviews (reevaluation) by a third-party IVD expert organization should be introduced to assess these differences. Establish a consistent national medical screening system to promote screening and follow up for certain diseases like HIV/AIDS, cervical cancer, hepatitis B and hepatitis C that enables early detection and treatment of disease. The system should be consistent nationwide, rather than implemented independently by local governments. The system should also recognize that, although some newer, more accurate, and speedy IVD tests may cost more than older generations of the same test, they can often help to improve cost efficiency by increasing the success rate of treatment and by shortening hospital stays. Reference 1. L.E.K. Consulting LLC IVD review time clock surveys conducted for the Japan Association of Clinical Reagents Industries and the American Medical Devices and Diagnostics Manufacturers Association s In Vitro Diagnostics Committee and Lengthening Healthy Lifespans to Boost Economic Growth 13

15 Wide Disparity in IVD Product Approval Periods (New Product Review Time) Fig. 5 Review Time With Special Consulta7on (10 cases) Special Consultation Max 763 Ave 452 Min 244 Number of Cases Max 1522 Ave 397 Min 144 Without (40 cases) Approval Period (Reviewer Time) Number of Cases Within 6 months Achievement rate With % without % Collaboration Plan for acceleration of IVD product review should be effectively, efficiently and speedily implemented to provide more effective in vitro diagnostic products to clinical practitioners in a more timely manner. Source: Japan Association of Clinical Reagent Industry Association and American Medical Device and Diagnostic Manufacturer Association Joint Time Clock Survey, Positioning of Laboratory Tests in the Healthcare Insurance System Fig Reimbursement Revision: Transitional Change of Total Medical Expenditures and In Vitro Diagnostic (IVD) Testing Fee Level Total Medical Spending IVD Testing Fee Level Recently, IVD testing fees were steadily cut to reduce costs. The true value of the contribution of IVD testing to healthcare has not been reflected. The result of the medical service fee revision from 2008 to 2016 better reflected the value of diagnostic tests. 14 Lengthening Healthy Lifespans to Boost Economic Growth

16 2016 Reimbursement Revision: Full Value of Improved HIV Tests Not Reflected Testing Fee 1 st Gen. HIV-1 2 nd Gen. HIV-1/ HIV2 3 rd Gen. HIV IgM 4 th Gen. HIV Ag Although the quality has improved in each new generation of test, the value of the most advanced tests has not been reflected in insurance reimbursement points. Test Kit Type HIV-1 HIV-1, HIV-2 HIV-1, HIV-2, Group O HIV-1, HIV-2, Group O, Anti-Core Antigen Antibody Antibody / Antigen tested IgG IgG IgG, IgM, IgA IgG, IgM, IgA, Core antigen IVD Example: HIV Test Reimbursement 3 Pricing Does Not Reward Innovation 1 st Gen. 2 nd Gen. 3 rd Gen. 4 th Gen. Year Detected Ab/Ag IgG IgG IgG IgM IgA Target of diagnosis HIV-1 HIV-1 HIV-2 HIV-1 HIV-2 Group O IgG IgM IgA Core Ag HIV-1 HIV-2 Group O Window Period 50 days 50 days 32 days 28 days Fig. NHI points ! !121** * HIV 1 Group O ** 130 from 2008, 127 from 2012, 123 from 2014, 121 from 2016 New generations of HIV tests provide more information in a shorter time frame. However, old and new HIV Ab in vitro testing products with different performance receive the same reimbursement points. Lengthening Healthy Lifespans to Boost Economic Growth 15

17 02 Increase Early Detection Through Comprehensive Eye Exams Situation According to the World Health Organization (WHO), there are 285 million visually impaired people across the globe, of whom 39 million are blind and 246 million have low vision. 1 In Japan, 1,640,000 people are visually impaired, 188,000 of whom are blind and 1,450,000 have low vision. Vision problems result in an estimated social burden of 8.8 trillion yen per year. 2 Today, 72% of those with vision impairment in Japan are aged 60 or over. Due to the population aging, it is estimated that the number of individuals with vision impairment will reach 2 million by 2030 thereby further increasing the financial and social burden on Japan. 2 The underlying causes of vision impairment in Japan in descending order of prevalence include glaucoma (21.0%), diabetic retinopathy (15.6%), retinitis pigmentosa (12.0%), macular degeneration (9.5%) and chorioretinal atrophy (8.4%), and the average age of the affected individuals exceeds 60 years for all the diseases. 3 Comprehensive eye exams by ophthalmologists are critical for the prevention and early diagnosis and treatment of such eye diseases as well as eye coordination problems that can cause a range of conditions from blurry vision to blindness. Comprehensive eye exams by ophthalmologists are also valuable for detecting signs of systemic health problems that show early warning signs in the tiny blood vessels and optic nerves in the eyes, including hypertension, diabetes, high cholesterol, stroke and heart disease. In a large-scale study conducted by the Japan Glaucoma Society in 3,000 individuals aged above 40 years in Tajimi City, one in 20 people (5%) had glaucoma, yet 90% were undiagnosed. 4 For diabetic patients who may develop retinopathy as a complication, the Guidelines for the Treatment of Diabetes recommend retinopathy screening at least on an annual basis. However, another study showed that only 35.6% of diabetic patients underwent annual retinopathy screening, which reveals an issue with eye exams in diabetic patients. A separate international study in adult diabetic patients revealed that approximately 40% of patients in Japan had never received screening for diabetic eye disease while as many as 80% were aware that vision impairment is a complication of diabetes. 7 There is also a challenge in eye exams for children. The School Health and Safety Act requires the boards of education of local governments to conduct health checkups at the time children begin elementary school, while related regulations prescribe that the vision strength of both eyes be checked using a vision chart based on international standards, and that checks be conducted for potential abnormalities. A survey of local boards of education and public and private kindergartens across the country conducted by the Japan Ophthalmologists Association indicated that while 172 of 190 boards (90.5%) conducted the required eye exams, 17 cities and towns in Osaka, Kanagawa and Fukuoka prefectures did not, and that 50.7% of the kindergartens did not conduct a visual test. 8 For contact lenses, although many countries around the world legally require patients purchasing contact lenses to have a prescription showing that they have had their eyes checked by a doctor, in Japan no such legal requirement exists. Thus, there are reports in Japan of serious eye damage, caused by inflammation of the cornea and corneal ulcers, resulting from improper care of contact lenses, the use of contact lenses for excessively long periods, and insufficient explanation of such risks to patients at the time of purchase. 9 Current Policy The Japanese government s Healthy Japan 21 (Phase 2) policy goals do not include any goals specifically related to eye health. 10 By contrast, the U.S. Department of Health and Human Services program, Healthy People 2020, comprising of 10-year 16 Lengthening Healthy Lifespans to Boost Economic Growth

18 goals and objectives for health promotion and disease prevention, includes eight categories related to eyes and vision. 11 Fundus examinations are not currently mandatory in annual special health screenings (tokutei kenshin), which are provided to individuals aged 40 to 74, and are only conducted at the discretion of the physician for selected individuals who meet the criteria. A prescription is not legally required to purchase contact lenses. Recommendations Create a government program to promote adult eye health. Promote comprehensive eye exams by ophthalmologists in order to reduce visual impairment due to diabetic retinopathy, glaucoma, age-related macular degeneration, refractive error and cataracts. In particular, make the provision of comprehensive eye exams, including fundus examination, mandatory for adults aged 40 years old and over to promote early detection of eye health problems related to diabetes. Set numeric goals specific to eye health in the policy goals for the government s Healthy Japan 21 (Phase 2) to promote public health and prevent lifestyle diseases and raise awareness using eye disease prevention programs. Mandate fundus examinations in annual special health screenings (tokutei kenshin). Ensure that each child has a visual test, which is included in health checkups required at school entry by the School Health and Safety Act, and also promote visual testing for preschool children. Ensure that contact lenses are sold based on the guidance of an eye doctor. Reduce potential eye health problems related to contact lenses by ensuring that users have periodic eye exams and are provided information about the risk of eye health problems resulting from improper use. References 1. WHO. Visual impairment and blindness. Fact Sheet No Updated August 日本眼科医会研究班報告 2006~2008. 日本における視覚障害の社会的コスト. 日本の眼科 第 80 巻第 6 号 ( 通巻 578 号 ) 付録平成 21 年 6 月 20 日発行 3. 若生里奈他. 日本における視覚障害の原因と現状. 日眼会誌. 2014; 118: lwase A,Suzuki Y,Araie M,et al. The prevalence of primary open-angle glaucoma in Japanese. The Tajimi Study.Ophthalmology 111: , 日本糖尿病学会. 糖尿病診療ガイドライン 南江堂 Hirokazu Tanaka, Jun Tomio, Takehiro Sugiyama, et al. Process quality of diabetes care under favorable access to healthcare: a 2-year longitudinal study using claims data in Japan. BMJ Open Diabetes Research and Care 2016;4:e International Federation on Aging, International Agency for the Prevention of Blindness, International diabetes Federation, The Diabetic Retinopathy Barometer Report Japan Findings 日本眼科医会学校保健部. 平成 20 年幼稚園ならびに就学時の健康診断の実態に関するアンケート調査 日本の眼科 80: 厚生労働省医薬食品局. コンタクトレンズの適正使用に関する情報提供等の徹底について 薬食発 0718 第 15 号. 平成 24 年 7 月 18 日. 10. 厚生労働省. 健康日本 21( 第二次 ) 公式ホームページ U.S. Healthy People Lengthening Healthy Lifespans to Boost Economic Growth 17

19 Vision Impairment and Associated Social Burden Worldwide: 285 million people are visually impaired Japan: 1.64 million people are visually impaired Blind 39 million Blind 188,000 Low vision 246 million Low vision 1.45 million In Japan, 1.64 million people are visually impaired and the associated annual social burden totals 8.8 trillion yen. Due to population aging, the number of people with vision impairment is estimated to reach 2 million by Sources: WHO. Visual impairment and blindness. Fact Sheet No Updated August 日本眼科医会研究班報告 2006~2008. 日本における視覚障害の社会的コスト. 日本の眼科 第 80 巻第 6 号 ( 通巻 578 号 ) 付録平成 21 年 6 月 20 日発行. Underlying Causes of Vision Impairment The average age of affected individuals is over 60 for all five eye diseases. Macular degeneration 9.5% Chorioretinal atrophy 8.4% Retinitis pigmentosa 12.0% Glaucoma 21.0% Diabetic retinopathy 15.6% Comprehensive eye exams by ophthalmologists are critical for the prevention, early diagnosis, and treatment of eye diseases. Comprehensive eye exams are valuable for detecting signs of systemic health problems that show early warning signs in the tiny blood vessels and optic nerves in the eyes, including hypertension, diabetes, high cholesterol, stroke, and heart disease. Source: 若生里奈他. 日本における視覚障害の原因と現状. 日眼会誌. 2014; 118: Lengthening Healthy Lifespans to Boost Economic Growth

20 Prevalence of Glaucoma and Diabetic Retinopathy Screening Rate Prevalence of glaucoma Annual screening for diabetic retinopathy 5% (one in 20) * 90% undiagnosed No screening Received screening 35.6% Out of 3,000 people age > 40 Out of 7,500 people under treatment for diabetes Sources: lwase A,Suzuki Y,Araie M,et al. The prevalence of primary open angle glaucoma in Japanese. The Tajimi Study. Ophthalmology 111: ,2004. 日本糖尿病学会. 糖尿病診療ガイドライン 南江堂 Hirokazu Tanaka, Jun Tomio, Takehiro Sugiyama, et al. Process quality of diabetes care under favorable access to healthcare: a 2-year longitudinal study using claims data in Japan. BMJ Open Diabetes Research and Care 2016;4:e Lengthening Healthy Lifespans to Boost Economic Growth 19

21 03 Health Literacy to Support Eye Health and Healthy Longevity Eye disease in a super-aging society Healthy Japan 21 (the 2nd term) promotes older persons participation in society and aims to bring the rate of social participation by older persons to 80% by As of 2008, 64.0% of older men and 55.1% of older women were engaged in some type of community activity. 1 In order to promote social participation in this population, the health of sensory organs, especially the eyes, is important. Vision loss or impairment caused by eye diseases, such as cataract and glaucoma, causes a significant drop in quality of life (QOL), making it difficult to participate in society. Also, social costs increase accordingly. 2 It is widely accepted that the risk of eye disease increases with age. The Tajimi Study conducted by the Japan Glaucoma Society revealed that glaucoma prevalence increases with age. The study also found that only 10% of those diagnosed with glaucoma actually went to see an ophthalmologist. 3 This means that 90% of patients do not receive the proper treatment at the proper time, putting them at risk for vision impairment or vision loss that lowers QOL. Significance of health education The fact that 90% of patients do not receive the proper treatment could largely be attributed to a lack of patient knowledge of eye diseases and insufficient access to opportunities to learn about eye diseases. According to the Declaration of Lisbon on the Rights of the Patient adopted by the World Medical Association, patients have a right to medical care of good quality, a right to freedom of choice, and a right to selfdetermination. 4 Adequate health education is essential to support patients in making proper decisions. The fact that 90% of glaucoma patients in the Tajimi Study did not receive adequate treatment and the lack of access to health education appear to be closely correlated. Health literacy depends on exposure to high quality health education from an early age, enabling knowledge to be ingrained so that the knowledge translates into habits. Health education for younger people is an investment with the highest lifetime ROI. Working continuously on health education is the only certain way to achieve the goal set in Healthy Japan 21 (the 2nd term). Japanese citizens have lacked opportunities to access high quality health education on eye health and eye diseases at school, at work, and in the community. 5 It is assumed that this induces eye diseases caused by improper use of contact lenses (CL) by students. Points made by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) and the Japan Ophthalmological Society (JOS) In the report of the Meeting to discuss how future health check-ups should be released by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in December 2013, it is mentioned there are increasing cases of eye trouble including ocular infection due to improper CL usage. 6 It is necessary to make proper CL usage widely known as there are many cases where patients start to use CL from school age. The Japan Ophthalmological Society (JOS) reports on its website that the number of patients diagnosed with an eye disease rapidly increased concurrently with the rapid increase in CL wearers after the launch of disposable CL in It also reports that one in ten CL wearers has an eye disease. According to the JOS, the increased incidence of eye diseases is related to less complicated CL care, the availability of low price CL at retail stores, and increased purchases of CL on the Internet. 7 CL-induced eye diseases are caused by a lack of compliance with usage and lens care 20 Lengthening Healthy Lifespans to Boost Economic Growth

22 guidelines. Irregular check-ups due to the lack of understanding that CL are highly controlled medical devices also have an effect. There are also cases where CL are sold without a prescription from ophthalmologists. 8 There is, therefore, a need for administrative involvement in taking measures and providing health education to secure eye safety and enrichment of lifelong health for CL wearers. Health education in school health on proper behavior and safety regarding CL The Report submitted to School Health Committees released by the Japan Medical Association in March 2014 includes a proposal on eye health education 9 that sets recommended topics for various subsets of the population divided by disease area and school grade: children and students, parents, and teachers. The proposed recommendations for eye health education are shown below in Table 1. High quality health education provided at younger ages will help people develop disciplined lifestyle habit. It also improves health literacy when children reach middle age. The situation will be the opposite when health education is not provided at a young age. Health education in school including proper CL purchase will contribute to the prevention and early detection of eye diseases. In the provision of high quality health education to elementary and high school students, local administrations and the JOA should take the lead in collaborating with schools and parents. This recommendation is based on the report submitted to the Central Education Council in January 2008, which states, we should not take this as a personal challenge. Organizational support in collaboration with schools, households, and the community will have a significant impact. 10 highly convenient framework for execution. As an example, the 2012 activity report of the School Health Problem Solving Support Program shows that the Kyoto Prefectural Administration and the Kyoto Medical Association co-hosted a training session in Kyoto on children s eye health to raise awareness of health concerns. At this session, ophthalmologists gave a lecture on CL to 107 teachers and six school doctors. Participants reported appreciation for the opportunity to learn about eye health and the challenges of CL-use. In Katsuyama City, Fukui Prefecture, a similar program on eye health was held. These two initiatives in Kyoto Prefecture and Fukui Prefecture should be evaluated as an effective way of implementing the philosophy described in the report submitted to the Central Education Council mentioned above. As education on eye health and proper behavior around CL expand across the country, eye health literacy is expected to grow. Recommendations Because eye safety and health is of critical importance to lifelong health and a healthy life expectancy in Japan s fast-aging society, we propose following the policies: Enrichment of health education at school on eye diseases and proper use of CL Creation of opportunities to provide health education on CL in various School Health Committees Improvement of the environment for school ophthalmologists to realize the above (increase resources and budget allocation) Restart of Kadai Kaiketsu Shien Jigyo, or Problem Solving Support Activities Establishment of proper reimbursement fees for CL prescriptions The School Health Problem Solving Support Program presents a useful, effective, and Lengthening Healthy Lifespans to Boost Economic Growth 21

23 Table 1. Health Education Proposal by Ophthalmologists (For elementary and high school students, teachers, and parents) <Excerpt from the School Health Committee of the Japan Medical Association submitted in March 2014> Grade For children and students For teachers For parents Kindergarten Vision of children amblyopia, strabismus Vision of children amblyopia, strabismus Vision of children amblyopia, strabismus Lower grades in elementary school Refractive error (myopia, hyperopia, astigmatism) Amblyopia, strabismus Infectious conjunctivitis (use of swimming goggles) Refractive error (myopia, hyperopia, astigmatism) Amblyopia, strabismus Infectious conjunctivitis (use of swimming goggles) Refractive error (myopia, hyperopia, astigmatism) Amblyopia, strabismus Infectious conjunctivitis (use of swimming goggles) Middle grades in elementary school Refractive error (myopia, hyperopia, astigmatism) Infectious conjunctivitis (use of swimming goggles) Refractive error (myopia, hyperopia, astigmatism) Infectious conjunctivitis (use of swimming goggles) Ocular psychosomatic disease Refractive error (myopia, hyperopia, astigmatism) Infectious conjunctivitis (use of swimming goggles) Ocular psychosomatic disease Upper grades in elementary school Allergic eye diseases, other eye diseases Prevention of ocular trauma (use of swimming goggles) Allergic eye diseases, other eye diseases Prevention of ocular trauma (use of swimming goggles) Ocular psychosomatic disease Allergic eye diseases, other eye diseases Prevention of ocular trauma (use of swimming goggles) Ocular psychosomatic disease 1st year in junior high Contact lens eye diseases Refractive error (myopia, hyperopia, astigmatism) Contact lens eye diseases Refractive error (myopia, hyperopia, astigmatism) Contact lens eye diseases Refractive error (myopia, hyperopia, astigmatism) 2nd year in junior high Prevention of ocular trauma (use of swimming goggles) Eye strain (VDT syndrome etc.) Prevention of ocular trauma (use of swimming goggles) Eye strain (VDT syndrome etc.) Prevention of ocular trauma (use of swimming goggles) Eye strain (VDT syndrome etc.) 3rd year in junior high Eye strain (VDT syndrome etc.) Prevention of ocular trauma (use of swimming goggles) Eye strain (VDT syndrome etc.) Prevention of ocular trauma (use of swimming goggles) Eye strain (VDT syndrome etc.) Accommodotonia Prevention of ocular trauma (use of swimming goggles) 1st year in high school Contact lens eye diseases Allergic eye diseases Contact lens eye diseases Allergic eye diseases Contact lens eye diseases Allergic eye diseases 2nd year in high school Prevention of ocular trauma (use of swimming goggles) Prevention of ocular trauma (use of swimming goggles) Prevention of ocular trauma (use of swimming goggles) 3rd year in high school Eye strain (VDT syndrome etc.) Eye strain (VDT syndrome etc.) Eye strain (VDT syndrome etc.) Accommodotonia 22 Lengthening Healthy Lifespans to Boost Economic Growth

24 References Submitted by the School Health Committee of the Japan Medical Association in March JOS website 8. Same as above 9. Same as above Lengthening Healthy Lifespans to Boost Economic Growth 23

25 04 Promote Oral Care to Prevent Periodontal Disease and Dental Caries Situation Dental health is important not only for chewing food, but also for maintaining a good quality of life that includes enjoying pleasant meals and conversation. Recent scientific evidence suggests that oral health abnormalities also play a role in the deterioration of general health. 1 Reflecting the public s increasing oral health consciousness, the results of the dental disease investigation, which is conducted once every six years by the Ministry of Health, Labour and Welfare (MHLW), indicate that the number of persons brushing their teeth two or three times a day has been increasing yearly. 2 But despite oral hygiene awareness and the improved tooth-brushing habits of Japanese people, more than 70% of the population aged 20 and over have periodontal disease. Moreover, the 2011 rates for the young adult and elderly populations were higher than those in In the United States, as a result of a recommendation by the American Dental Association (ADA) on interdental cleaning and the use of mouthwash as adjuncts to tooth brushing, the usage rate of interdental cleaning tools and mouthwash is higher than in Japan. The difference in daily dental self-care is considered to be one reason for the apparent differences between the U.S. and Japan in the number of natural teeth remaining in the elderly. 3,4 Current Policy The government of Japan s (GOJ) Healthy Japan 21 policy goals set dental policy objectives for the prevention of dental loss and the prevention of dental caries and periodontal disease, which can cause dental loss. In October 2011, the MHLW summarized its final evaluation. The evaluation states that, of the 13 items evaluated with indicators, five items reached their goals: there were more persons in their 60s with at least 24 natural teeth, and in their 80s with 20 natural teeth; there was an increase in the ratio of persons who had received regular dental checkups at least once in the previous year; there were seven items showing a trend toward improvement; and one item had remained unchanged. 5,6 This improvement is thought to be due, in part, to the benefits of fluoride and health promotion campaigns that resulted in positive behavioral changes, such as greater usage of floss and mouthwash. In response to these results, the MHLW reviewed the basic policy of Healthy Japan 21 (stage two), fully revising it in July 2012 to promote a general improvement in public health, and setting up new target values for dental and oral health to In addition, in August 2011 the Dental and Oral Health Promotion Law was promulgated, which includes the recommendation that regular dental checkups be conducted. Rather than simply treating dental caries or areas affected by periodontal disease, many dentists have begun to focus on oral checkups, evaluating the presence of dental caries and periodontal disease, and to perform regular cleaning to maintain oral health. Under the current health insurance reimbursement system, however, the compensation for early intervention and patient education is lower than that for treatment. In 2010, based on a proposal from the National Dental Conference for Support of Motivation in Life, together with the aggressive use of the mass media, progress was made in promoting public awareness regarding preventive dentistry. The public has been broadly and thoroughly informed of the significance of the 80/20 Healthy Long-Lived Society campaign. Recent Progress: Slight Improvement Information on Healthy Japan 21 (the second term) is listed on the MHLW website. Systematic 24 Lengthening Healthy Lifespans to Boost Economic Growth

26 efforts are progressing with the establishment in September 2013 of the Health Promotion Division in the MHLW. 7 Recommendations MHLW should encourage the prevention of periodontal disease, promote instruction in interdental cleaning (interdental brushing and dental flossing) based on the individual s oral condition, the use of chemical plaque control agents (mouthwash), and the provision of conventional coaching in tooth brushing by dentists and dental hygienists. To promote the prevention of gingivitis, which is frequently observed in the young population, MHLW should add to school children s oral hygiene education instruction on interdental cleaning (interdental brushing and dental flossing). Under the health insurance reimbursement system, MHLW should provide higher compensation incentives for dentists to educate their patients in the prevention of dental caries and periodontal disease. To further promote use of fluoride in oral care and prevent cavities, MHLW should revise the Medicated Dentifrice Approval Standard by raising the maximum fluoride concentration allowed in medicated toothpaste (quasi-drug) in conformity with international practice and make it possible in the near term to add fluoride to mouthwash and liquid dentifrice products (quasi-drug). References 1. Japan Dental Hygienists Association Guideline for periodontal disease and general health- physical health begins with prevention of periodontal disease. pp Ministry of Health, Labour and Welfare. Investigation of the actual status of dental disease in American Chamber of Commerce in Japan National survey on prevention, early detection and the economic burden of disease in Japan; and American Chamber of Commerce in Japan Questions concerning oral health, nationwide (n=5,000) Promotion Foundation. International oral health data bank (international comparison of substantial investigations of dental diseases of Japan and other countries). Foundation 5. Healthy Japan 21. Last modified Ministry of Health, Labour and Welfare, Office for Life-Style Related Diseases Control, General Affairs Division, Health Service Bureau Healthy Japan 21. Final evaluation (October 13). 7. On the establishment of the Health Promotion Division (Reference 1). Lengthening Healthy Lifespans to Boost Economic Growth 25

27 Brushing Frequency Has Risen, but Use of Mouthwash, Interdental Cleaning Is Low 日本人の歯磨き回数 Frequency of Teeth Brushing in Japanese Population Not brushing teeth Occasionally brushing teeth Once a day Two times a day Three times a day 16 Investigation of actual status of dental disease 2011 conducted by MHLW Usage rate in Japan and US Teeth brush (twice a day) Interdental cleaning tool Mouthwash 73% 1) 63% 4) 76% 4) 43% 2) 74% 4) 34% 3) 1) Results of investigation of actual status of dental disease in 2011 (MHLW; n=4253) 2) The frequency of using interdental cleaning device is at least 2 times every week and regular checkup is at least once every year --- from Attitude Survey concerning Prevention, Early Detection, and Economic Burden of Disease -- Questions concerning Oral Health by ACCJ, February 2012, Nationwide (n=5000) 3) Investigated by Johnson & Johnson in Nationwide (n=1881). Having used once or more in the past 1 month (%). 4) WHO International Collaborative Study II in Further Measures Required for Periodontal Diseases Centering on Middle-aged and Elderly People Number of teeth More than 70% of people aged 20 or more are still affected by periodontal disease, and the ratio of the affected elderly is rising The number of remaining teeth in the elderly in the US is higher than that of the elderly in Japan Investigation of actual status of dental disease 2011 conducted by MHLW or over Total US Japan International oral health data bank, 8020 Promotion Foundation Lengthening Healthy Lifespans to Boost Economic Growth

28 05 Increase Sleep Apnea Syndrome Screening Situation Early detection is crucial to the health and wellbeing of patients suffering from sleep apnea syndrome (SAS). In 2015, the number of patients with SAS in Japan was more than three million (a prevalence of 2 4% in adults), of whom only approximately 354,000 (about 12%) were undergoing CPAP therapy. 1 That means there is a large pool of latent patients, who are unaware of their condition and do not recognize the symptoms. SAS not only disrupts a person s sleep, causing daily drowsiness, but also contributes to serious cardiovascular disease, such as hypertension, heart failure, stroke, and heart arrhythmia. Several studies have demonstrated that the cumulative survival rate of SAS patients who do not receive proper treatment is significantly lower than that of those who do. 2 While the treatment offered to patients diagnosed with SAS in Japan is in line with that of other developed nations, efforts to bring latent patients to sleep labs for detection are insufficient. Undetected and untreated SAS takes a heavy toll on society. It is estimated that untreated SAS patients cause seven times more traffic accidents than persons who are not suffering from the syndrome. 3 In Japan, a major incident attributed to SAS occurred in 2003, when a bullet train driver dozed off at the controls. The number of patients with SAS who are undergoing continuous positive airway pressure (CPAP) treatment in the United States currently stands at between three and five million, or about 20 to 30 times more than in Japan. 4 This greater number in the United States is due to the more frequent diagnosis of sleep disorders in that country. It is estimated that there is about one sleep lab bed for every 10,000 persons in Japan, while there are five to 10 sleep lab beds for every 10,000 persons in the United States. Also, physicians in the United States have a greater incentive for conducting SAS detection tests where the reimbursement is typically in the range of USD1,000 to USD1,500. Given the severity of the co-morbidities of SAS, preventing and treating it is an investment in public health. Current Policy At present, the Ministry of Health, Labour and Welfare (MHLW) provides reimbursement for SAS testing via full polysomnography (PSG) and simplified portable PSG (without electroencephalography). However, the national health insurance reimbursement amount for full PSG is only JPY33,000 per test (requiring one night in hospital) and does not cover the room charge and the staffing cost of sleep laboratory technicians. This low level of reimbursement does not provide an adequate incentive to physicians. Meanwhile, the significant out-of-pocket costs for patients means that affordability reduces access to SAS testing. In terms of national insurance coverage, CPAP treatment can be prescribed in the United States and major countries in Europe for patients with an apnea-hypopnea index (AHI) of more than five. By contrast, the treatment can be prescribed in Japan only when the AHI is more than 20. Therefore, CPAP treatment cannot be offered to many patients who other countries believe should receive it. Annual health screenings provide an important opportunity to detect lifestyle diseases while they are in their early stages. Untreated, SAS can lead to many lifestyle diseases. To date, in Japan there has been only one official government statement in support of SAS screening. Issued in 2003 by the Ministry of Land, Infrastructure, Transport and Tourism, it recommends the screening for professional drivers. There has been no statement or recommendation for other workers. Many medical practitioners consider SAS screening to be necessary for adult males, of whom 20% have the syndrome. 5 Lengthening Healthy Lifespans to Boost Economic Growth 27

29 In addition, the decrease in female hormone levels causes the incidence of sleep apnea among postmenopausal women to be between two and four times higher than that among premenopausal women. 6 Because SAS in women only rarely produces snoring or sleepiness during the day, it is likely that women may not recognize the possibility that they have the syndrome. Increased efforts for SAS screening are needed because if left untreated, SAS can contribute to various forms of chronic diseases and increase a patient s health risk. Recommendations Raise the level of national health insurance reimbursement for SAS testing by physicians. Revise the criteria for prescribing CPAP treatment to match that of other developed nations where SAS testing is more common. Introduce SAS screening for adult males and postmenopausal women in annual health screenings. References 1. Statistics of Medical Care Activities in Public Health Insurance in 2015: Ministry of Health, Labour and Welfare ( 2. Marin JM et al, Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study, Lancet 2005;365: Findley, L American Review of Respiratory Diseases 138: Young, T., Palta, M., Dempsey, J., Skatrud, J., Weber, S., Badr, S The occurrence of sleep-disordered breathing among middle-aged adults. The New England Journal of Medicine (April) 328(17): (Wisconsin Sleep Cohort Study). 5. Sleep-disordered breathing in the usual lifestyle setting as detected with home monitoring in a population of working men in Japan. Sleep 2008, 31: Yukawa, K., Inoue, Y., Yagyu, H., et al. Gender differences in the clinical characteristics among Japanese patients with obstructive sleep apnea syndrome. Chest 2009, 135: Lengthening Healthy Lifespans to Boost Economic Growth

30 Increase Sleep Apnea Syndrome Screening Over 3 million Sleep Apnea Syndrome patients in Japan 41% no complication (1,230,000 patients) Under Treatment (450,000 patients) 51% have Hypertension (1,530,000 patients) 21% have Cardiovascular diseases (630,000 patients) 13% have Diabetes (390,000 patients) Lengthening Healthy Lifespans to Boost Economic Growth 29

31 06 Food Functionality and Health Claims in Japan Situation The American Chamber of Commerce in Japan (ACCJ) applauds the amendment by the Government of Japan (GOJ) of the existing Foods for Specific Health Uses (FOSHU) regulations and the implementation of revisions on functional claims pertaining to health foods and dietary supplements as Food with Functional Claims (FFC) effective April 1, The Abe Administration believed that obtaining the necessary approval for product claims under the previous FOSHU regulations was too costly and time consuming. In 2013, to resolve some of the regulatory issues, officials recognized the need to establish a new category for claims that recognize health benefits for functional foods. The Prime Minister s Abenomics policies have identified as a potential area of economic growth increased commerce facilitated by recognition of functional claims. The revised regulations do not, however, fully reflect the direction proposed by the Prime Minister, nor do they incorporate global best practices. Modeled after the U.S. dietary supplement regulatory system, Japan s FFC system is supposed to be a notification system. This means that the industry should be required only to notify regulators before the new functional claims are made. In practice, however, the FFC system has become an approval system with the Consumer Affairs Agency (CAA) insisting upon reviewing and evaluating application dossiers for each product submitted by a company. This causes tremendous delay and uncertainty. As a result, industry is impeded from formulating workable business plans, and incurs considerable unnecessary administrative costs. This cumbersome system also prevents Japanese consumers from receiving the benefits of dietary supplementation in a timely manner. The following is a summary of our primary concerns with the 2015 regulations: 1. Ingredient-Use Limitations: Supported by extensive scientific evidence, food components such as vitamins, minerals and other ingredients are globally recognized as providing benefits for consumers in the form of improved health. As such, excluding such ingredients from the government s Food with Functional Claims category would be unreasonable. Under the 2015 regulations, which are based on drug regulations, linkage in this classification to health benefits is limited to a single chemical compound. In reality, the evaluation of an isolated compound by itself without consideration of the various compounds within the same food cannot adequately represent all possible health benefits that the various compounds that make up the food provide when taken all together, since in composite these components work in a way that is more powerful than when used separately. Because nutrients work together to create greater health effects than when they are used separately, industry should be permitted to cite the significant scientific evidence that supports the health benefits from either the food or the food constituents as a basis for making functional claims. 2. Usage Limitations Based on Scientific Evidence: Current regulations prohibit the use of patient data in scientific research studies for the substantiation of claims. This methodology is not in accordance with globally recognized practices and prevents a substantial amount of evidence from being considered ultimately providing a disservice to consumers. 3. Target Audience/Category Limitations: Products specifically targeting minors, pregnant, nursing or prenatal women are banned under the amended regulations. If deemed safe and effective for those 30 Lengthening Healthy Lifespans to Boost Economic Growth

32 categories of consumers, their use should be allowed. This is in keeping with regulatory principles in other developed countries. Furthermore, under the revised regulations, vitamins and minerals are limited to one claim per category. A single given ingredient, such as a particular vitamin or mineral, can have various health benefits. If scientifically warranted, multiple claims should be allowed for a single ingredient. 4. Quality Control Systems Inappropriate, Disadvantage Japanese Exports: When addressing the exportation of goods to foreign markets, regulation of quality control in manufacturing should be based on international best practices. Manufacturing guidelines such as current Good Manufacturing Practice (cgmp), which is used in major markets for dietary supplements, and the Hazard Analysis and Critical Control Points (HACCP) approach to food safety, have been established to conform to regulations set by the U.S. Federal Drug Administration (FDA), World Health Organization (WHO) and other pertinent agencies. In Japan, the quality of health food products is regulated by the Food Sanitation Act. This Japan-specific guideline does not take into account as much as it could in terms of international manufacturing guidelines and standards. It thereby puts the domestic health food and dietary supplement industry at a significant disadvantage in exporting their products. Recommendations The ACCJ and EBC respectfully offer the below recommendations with the sincere belief that Japan will reap a variety of health, social, and economic benefits if it aligns more closely with global standards in the regulation of the health food and dietary supplement industry. The ACCJ and EBC also submit that adoption of the following recommendations would help to improve the competitiveness and efficiency of companies operating in the Japanese market and most important for the health of the Japanese people would enable the market to meet the demand for a greater variety of safe, reasonably priced products. CAA should implement a consultation process prior to dossier submission, through which the applicant can respond to any questions to facilitate rapid dossier consideration and approval. CAA should not mandate third party dossier review in advance, however, because that causes unnecessary delay and expense. In addition, CAA should clarify guidelines for product promotion and advertisement. Guidelines should be flexible and simple to enable and promote informed consumer decisions. Ingredients such as vitamins and minerals are already pre-approved for sale in Japan. Under the new regulations, nutritional ingredients such as vitamins and minerals should not only be deemed eligible as nutrients, but they should be allowed to hold multiple functional claims as well. In addition, Japanese law mandates designating certain substances that are globally recognized as foods as pharmaceuticals. This list should be revised in alignment with global standards to more flexibly allow these substances to be considered functional foods. Eliminating ingredients such as vitamins and minerals proven to deliver added health benefits from the functional claims category renders consumers unable to make informed decisions. In order for consumers to exercise freedom of choice, industry should be permitted to provide information to consumers that notes the scientifically demonstrated links between dietary items and health benefits. We urge Lengthening Healthy Lifespans to Boost Economic Growth 31

33 the GOJ to promptly initiate discussions on the greater use of scientifically backed health-related evidence in the food and dietary supplement industry by forming an expert panel with qualified, decision-making members whose expertise matches the specific needs of the project. In the United States, the FDA sets guidelines, often referencing literature produced by industry. This cooperation between regulators and industry is beneficial for both parties. We urge the GOJ to consider adopting a similar method of working with industry to set standards and publish guidelines for improved quality control systems. We recommend that internationally standardized GMP guidelines be established and mandated, as they would further the promotion of international trade and also aid in assuring consumers that products of low quality are not imported into the Japanese market. In 2013, the Ministry of Health, Labour and Welfare (MHLW) took steps to address these issues by conducting a nationwide survey of GMP compliance. We respectfully request disclosure of the results. The U.S. mandates quality control systems that meet global standards and are much more rigorous than in Japan. Ingredients in dietary supplements that are made in the U.S. and meet global standards should not need to be re-tested in Japan. Japan s guidelines for food regulation should clearly embrace this common-sense principle. Japan s 2015 guidelines limit sources of scientific evidence to healthy people, excluding the possible use of patient data. Nevertheless, dietary supplements can be used in conjunction with prescribed medications for added health benefits. In addition, health claims based on published authoritative statements from agencies operating within the health area, from both within Japan and abroad, should be recognized as sufficient evidence for claim substantiation. Scientific evidence indicates that various health foods and dietary supplements can be useful for all groups, including minors, persons suffering from specified medical conditions, and pregnant, nursing, or prenatal women. The 2015 regulation excludes all claims targeted at these demographics, however. Further clarification regarding who may use the products should be permitted (underlined below): Disclaimer: Although this product has not been formulated for minors, those suffering from disease, and pregnant, nursing, or prenatal women, there is no limitation on usage by these groups of people. As the global dietary supplement market continues to grow and more supply chains form, there is an increasing need for national GMP standards to harmonize with global standards. A compliance deadline for Japan must be set. Furthermore, adherence to global GMP standards should suffice as an index of quality control thus rendering the analysis of specific ingredients unnecessary. Expected Outcome 1. Reductions in Healthcare Costs Scientific research published in the U.S. in 2013 concluded that targeted daily supplement regimes can have substantial health benefits, thus greatly reducing healthcare expenditures. 1 Although further research is needed to address health issues relating to Japanese people, Japan can expect wide-ranging human and societal benefits if consumers take advantage of dietary supplementation as a part of a well-balanced diet. Improved health will benefit individual Japanese citizens, in the first instance, as well as the nation s overburdened healthcare practitioners and insurance systems. 32 Lengthening Healthy Lifespans to Boost Economic Growth

34 2. Prospective Industry Development Allowing dietary supplements to carry statements on their labels that describe the role of a nutrient or dietary ingredient would contribute to informing consumer choices and thereby improving the health of the general population. With Japanese people living longer, many are interested in preventing chronic disease. The demand for information on food and dietary supplements will likely grow as well. Increased sales would improve health outcomes, reduce overall expenditures for medical services, relieve demands on Japan s public and private insurance systems, and spur economic development. Prime Minister Abe s Abenomics economic recovery plan specifically identified the potential for employment opportunities, growing tax revenues, and spurring market growth through international trade by expanding the use of dietary supplements. Insight can be taken from the dietary supplement industry in the U.S., which has quadrupled in size over the last twenty years. The ACCJ and EBC offer the above recommendations in the spirit of partnership with the Government and people of Japan. We are convinced that if the Government of Japan follows global best practices in relation to health food and dietary supplements, as applied in the United States, it will promote a healthier, more prosperous Japan. This outcome will benefit all. References 1. Council for Responsible Nutrition Foundation: Healthcare cost savings resulting from the targeted use of dietary supplements Lengthening Healthy Lifespans to Boost Economic Growth 33

35 Definition of Dietary Supplement Legal status Major Differences in Supplement Systems between Japan and the US Japan (FFC Regulation) No Labeling rule is set under new rule Labeling managed only through food labeling law US Yes DS-specific laws Compliance with manufacturing and quality control standard (cgmp) Voluntarily Mandatory with audit Guideline for manufacturing and quality control Limited to a 5 page outline Detailed guidelines 100% identification test of raw materials when manufactured Optional Mandatory Targeted food and ingredients Structure/Function Claims including organs and body parts Submission of product label claims Required documents for submission Does not cover all foods, Identification of actives necessary, No standard specification, Vitamins and minerals are excluded Possible depending on part Pre-submission at least 60 days before product launch Substantial in comparison to those required in the US Reasonable standards for food, Standard specifications, Vitamins and minerals are included Possible Post-submission within 30 days of product launch 1-2 page letter Severe adverse event report Mandatory Mandatory Market size (as of 2012) $8 billion $32. 5 billion Gap between Prime Minister/Cabinet Decision and Foods with Functional Claims (FFC) Regulation implemented by CAA Prime Minister Abe s idea and Cabinet decision FFC $5 billion? Functional Claims FOSHU $4.3 billion So-called health foods $8.3 billion FOSHU $5.2 billion So-called health foods $4 billion? Unclear area for Functional Claims Functional Claims OK Out of scope from Functional Claims, Left as is Vitamins and Minerals Excluded 34 Lengthening Healthy Lifespans to Boost Economic Growth

36 07 Promoting Self Care and Self Medication Situation According to the World Health Organization (WHO), self-care is what people do for themselves to establish and maintain health, prevent and deal with illness, 1 which includes consideration of a healthy diet, exercise, and hygiene, as well as practicing self-medication. Self-medication is defined as the selection and use of medicines by individuals to treat self-recognized illnesses or symptoms, which includes use of over-the-counter (OTC) drugs to mitigate mild illness or injury as a means of self-health control. With the aim of realizing a healthy-aging society, the Health/Medical Care Working Group of the Regulatory Reform Council has strived to put in place regulatory reforms based on three principles with people s security and safety in mind: 1. improvement of convenience 2. economic revitalization through improvements in medical care and welfare; and 3. the funding of the health insurance system. As a measure to promote self-care / selfmedication, the first step in 2013 enabled the marketing of all OTC drugs on the Internet, and in 2014, the second step was the submission of a report on the early establishment of a system to transfer certain point-of-care (POC) diagnostic products from the medical insurance system to the OTC market. The revised Pharmaceutical Affairs Act which came into force in 2014 permits the marketing of all OTC drugs on the Internet. Combined, these steps have created an environment for the promotion of self-medication. The 2013 Economic Growth Strategy targeted healthy-aging, including promoting industry efforts aimed at extending people s health as they grow older. The June 2013 Japan Revitalization Strategy promoted the use of pharmacies and pharmacists as a community-based hub for health information through the provision of advice on the appropriate use of OTC drugs as well as consultation services and health information. 2 The Ministry of Health, Labour and Welfare (MHLW) 2013 Drug Industry Vision indicated that community-based pharmacists and drugstores should respond appropriately to the needs of the community and should provide patient compliance instructions, consultations, recommendations to seek medical care and advice in connection with the OTC drugs they sell. 3 In promoting the transfer of designated prescription drugs to the OTC category (switch to OTC), the Revised Japan Revitalization Strategy of June 2014 targeted: 1. conducting expedited reviews of each product application using foreign data as a reference; 2. adopting measures to set targets for regulatory review periods at the Pharmaceuticals and Medical Devices Agency (PMDA), in order to shorten review times, and to expand the consultation system; and 3. stablishing a switch to the OTC process that reflects the views of stakeholders, including consumers and the healthcare industry, using as a reference case studies from outside Japan, including from the United States. 4 As the result of the Strategy, the new switch OTC scheme was introduced in April Current Policy The Ministry of Finance 2014 Tax Reform Outline recommended that the tax system be reviewed so that it enhances the delivery of effective preventive care services and recognizes the role and function of pharmacies in contributing to Lengthening Healthy Lifespans to Boost Economic Growth 35

37 the future promotion of self-medication. 5 To enhance the function of primary pharmacies, a total of JPY239 million was allocated in the FY2014 government budget for programs in all 47 prefectures pertaining to the Promotion Project for Health Information Hubs by Exploiting Pharmacies/Pharmacists. In this Project, the Japanese government provides a menu of items that can be selected by each community based on needs, in order to promote and broaden self-medication and home-based medical care. 6 The MHLW also started an initiative in the autumn of 2015 under which community based pharmacies with enhanced consultation systems and facilities were identified. 7 In order to prepare an environment and system that enables people to freely seek health consultations and that further promotes self-medication, the MHLW included in the FY2015 Tax Reform Proposal a provision that would allow a real estate acquisition tax reduction for small and medium-sized pharmacies that have an appropriate marketing system in place. The MHLW also proposed that a tax deduction be established for the purchase of drugs that require a pharmacist s intervention and OTC drugs. 8 In response to this proposal, a tax reduction was established in 2017 for the purchase of pharmacist s intervention required drugs in annual amount of JPY 12,000 or more for households with up to a maximum of JPY 88,000. The Future of Self-Care and Self-Medication Japan has a declining birth rate and an aging population. Each and every citizen must undertake self-care and self-medication, subject to the flexible development of appropriate policies, in order for a financially sound national health insurance system to be passed to the next generation. Because these issues are important and affect future social security benefits and national financial affairs, the promotion of initiatives aimed at enhancing the health of the people, such as Healthy Japan 21 (Second Version) should be encourage and supported. To realize the goal of healthy-aging, the enhancement of the health of each and every inhabitant and worker in the community is exactly what self-care is about. Self-care should be promoted by a Plan-Do-Check-Act ( PDCA ) methodology that encourages the Japanese people to lead a healthy life in order to prevent lifestyle diseases. This can be done by encouraging people to take advantage of various cancer screenings, immunizations, and health checkups and health counseling guidance offered by local governments or health insurance societies, which would lead to appropriate aftercare and self-medication based on a doctor s diagnosis. Furthermore, in order for community inhabitants to approach self-medication as part of a PDCA methodology and to achieve better health literacy, local governments, prefectural and district medical associations, medical institutions and community pharmacies must provide appropriate health education. If self-medication is not accompanied by appropriate health literacy, patients could hold misconceptions and make incorrect choices, leading to mistaken self-diagnoses, inappropriate self-medication or failure to receive timely treatment, which in all cases could lead to serious implications for the health of the patient. While financial and social security demands should be addressed, it is desirable for local governments to act as the facilitators to promote healthy aging by applying best practices in self-care and self-medication as part of their integrated healthcare programs. The PDCA methodology could be achieved through health education and aftercare, 36 Lengthening Healthy Lifespans to Boost Economic Growth

38 including by having healthcare personnel and institutions hold community medical care conferences open to local inhabitants. Useful information could be shared through presentations by community health centers, medical associations, dental associations, pharmaceutical associations, nursing associations, hospital and family doctors, pharmacists and clinical psychologists to name but a few. Promotion of self-care and self-medication and improvement in the health of each and every citizen through this kind of organic cooperation and the use of community based health resources would improve health literacy and contribute to the appropriate allocation of Japan s social security resources. Recommendations In order for self-care and self-medication to be smoothly promoted as a part of the PDCA cycle function of community healthcare, each local government should assume responsibility for acting as a facilitator to promote community healthcare by participating in community health management, for example by establishing and operating conferences between the inhabitants and healthcare personnel who undertake community medical care. As an incentive for inhabitants to maintain and promote their own health, tax reduction for the purchase of OTC drugs (non-prescription drugs) should be further strengthened. The MHLW should promote the transfer of drugs from the prescription category to the non-prescription category (switch to OTC) of those prescription drugs that have been used for an extended period with established efficacy and a proven safety record. In order to expedite regulatory reviews of drugs targeted for a switch to OTC, the current review system should be improved so that foreign efficacy and safety data are actively utilized. In particular, the required volume of clinical trial data should be reduced or eliminated by utilizing existing clinical data, referencing analysis data and referring to appropriate use data from pharmacies, as is the case in Europe and in the United States. In order to expedite regulatory reviews of quasi-drugs, the review systems should also be improved so that foreign efficacy and safety data and data from past cases are utilized, instead of requiring new clinical trials to be conducted in Japan for new quasi-drugs whose safety and efficacy have already been confirmed in Europe and in the United States. Relevant governmental authorities should facilitate and expedite regulatory approvals for dietary supplements and foods with functional claims (FFCs). Dietary supplements and foods with functional claims can play an important role in improving public health in all age ranges, as detailed in Chapter 6 and elsewhere in this White Paper. Lengthening Healthy Lifespans to Boost Economic Growth 37

39 References 1. The role of the pharmacist in self-care and self-medication: Report of the 4th WHO Consultative Group on the Role of Pharmacist, The Hague, The Netherlands, August 26-28, bitstream/10665/65860/1/who_dap_98.13.pdf 2. Japan Revitalization Strategy 3. Ministry of Health, Labour and Welfare Drug Industry Vision Revised Japan Revitalization Strategy 5. Summary of 2014 Tax Reform Shakaihoshoutantou/ pdf 6. Budget Compilation Introduction of Disclosure System of Self M Pharmacies Creating New Standards; Yakuji Nippo, August 1, FY 2015 Ministry of Health, Labour and Welfare, Major Tax Reform Proposals Shakaihoshoutantou/ pdf 38 Lengthening Healthy Lifespans to Boost Economic Growth

40 08 Extension of Healthy Life Expectancy and Countermeasures against Frailty Situation Currently, population dynamics show rapid growth among the elderly and a concurrent shrinking among the younger generation, meaning that Japan has become a fast-aging society. As reported in the news almost every day, Japan is already suffering from various kinds of unfavorable events associated with aging, such as dementia, nursing shortages, and car accidents. Meanwhile, the government of Japan s (GOJ) medical expenditures have been soaring, and currently, 58.6% of total expenses (370.9 billion US dollars; Exchange rate: 1 USD=110 JPY) are attributed to the elderly population, which is defined as those over 65 years of age. 3 Although Japan had been enjoying prosperous economic development through high-paced GDP growth after World War II, the current aging society will negatively impact the GOJ s finances well into the future because growth of the aging population will continue. For example, the elderly population is considered to grow from 33.9 million (26.7% of the total population) in 2015 to 34.6 million (39.9% of the total population) in 2060, meaning that 1 out of every 2.5 people in Japan are over 65 years of age, and that 1 out of every 4 are over 75 years of age. 1, 2 These demographic dynamics are regarded as a significant trend, and Japanese people are increasingly feeling anxiety about their future. However, this anxiety may not be necessary because scientific progress regarding the human body, disease, medication, etc., tells us that aging itself does not necessarily mean a loss of health. This can be justified by a recent statement by the Japan Geriatrics Society (JGS) regarding the definition of elderly people. 5 In their statement, the JGS divided the population of those over 65 into the following three groups: pre-elderly, those between 65 and 74 years of age; elderly, those between 75 and 90 years of age; and super elderly, those over 90 years of age. In addition, because of recent GOJ health policies and improvements in quality of life, such as better exercise habits and improved nourishment owing to more balanced diets, the negative stigma associated with the term aging is diminishing. Current Policy Given this background and with the so-called super-aging society causing concern, in November 2015, the Minister of Health, Labour and Welfare convened a working group made up of knowledgeable, innovative, and relatively younger (those in their 30s and 40s) representatives and selected Ministry of Health, Labour and Welfare (MHLW) staff. This group published a report entitled, Japan Vision Healthcare 2035, which outlines health policies to be implemented to address the healthcare needs of Japan in This report describes five paradigm shifts: quantity expansion to quality improvement, input-centered to patient value-centered, government regulation to autonomy, cure-focused to care-focused, and fragmentation to integration. To execute these five paradigm shifts, the GOJ has developed the following initiatives: empowerment of communities to develop their own medication plans; 22 incentives to engage in self-medication practices; policy guidance to accelerate communities ability to implement an integrated community care system that includes the introduction of new schemes such as the family pharmacy system. 6 Moreover, in terms of specific nutritional interventions to help prevent malnutrition among the elderly, the GOJ has introduced several initiatives, such as providing discounted reimbursement medical fee points for percutaneous endoscopic gastrostomy (PEG) construction and additional medical fee points for PEG closures, encouraging patients to be fed orally during recovery. However, some remaining issues still need to be widely discussed from the standpoints of artificial feeding and life and death. Lengthening Healthy Lifespans to Boost Economic Growth 39

41 In the GOJ s 7th Medical Plan, 22 which will start from fiscal year 2018, frailty, is mentioned for the first time as one of the major target conditions/diseases to be treated as a priority and certain initiatives (medical care specialized for emergencies, disasters, remote areas, perinatal care, and pediatric care). Considering the GOJ s current focus on the integrated community care system, frailty remains in the spotlight. 16 The reason for this is versatility, a characteristic of frailty that has three facets physical, mental, and social and reversibility. Frailty is very attractive from a medical 7, 16 standpoint because of its reversibility. A frail person can regain his/her healthy status even if they once had frail status, which is a 7, 16 sign of risks that could lead to disability. Similar to frailty, metabolic syndrome is an issue for which the GOJ placed significant effort in order to include it in the GOJ s medical policy. 14 Metabolic syndrome had received heavy exposure in front of a large public audience after the eight major academic medical societies (Japan Atherosclerosis Society, Japan Diabetes Society, Japanese Society of Hypertension, Japan Society for the Study of Obesity, Japanese Circulation Society, Japanese Society of Nephrology, Japanese Society on Thrombosis and Hemostasis, and Japanese Society of Internal Medicine) held integrated discussions on the major causes of increased risk for cerebral vessel and coronary-related diseases. These discussions led to the development of diagnosis guidelines that were published in Based on these guidelines, in April 2008, the GOJ made medical checkups mandatory under the health insurance system, and since that time, has been continuing active educational activities. 14 Challenges Although the assessment of frailty can be difficult because of its versatile nature, there is some guidance available for its diagnosis. However, the timing and methods of intervention remain a matter of disagreement among healthcare professionals, as do preventive measures. Among the versatile aspects of frailty, physical frailty is directly associated with decreased physical function in the elderly. The primary reason for this is reported to be malnutrition, which causes individuals to receive insufficient energy and/or nutrient intake. However, both healthcare professionals and the general public have yet to reach a sufficient level of understanding regarding malnutrition, various aspects of nutrition, or metabolism in the elderly. 7 Since an active campaign against metabolic syndrome was initiated in 2005, an undesirable trend has been seen in which people tend to overreact to dietary restrictions, even those who are already a part of the elderly population and thus need to pay more attention to their diet to help prevent frailty. In fact, according to one Japanese cohort study, people with a moderately high body mass index tend to have longer longevity 10 (this is known as the J-Curve phenomenon); however, this phenomenon remains widely unknown. In terms of physical frailty, the major concern is muscle loss, which is caused by the progression of the frailty cycle. 9, 21 Once the level of muscle loss exceeds a certain threshold in terms of skeletal muscle and muscle strength, it is diagnosed as sarcopenia. 11 In the United States, medical expenditures directly related to sarcopenia amounted to 18.5 billion U.S. dollars in 2000, which accounted for approximately 1.5% of total medical expenses. 18 In Japan, the aging of the population is progressing at a faster rate than in the U.S., so it is crucial for the GOJ to take effective countermeasures against sarcopenia in order to avoid a financial crisis caused by the associated soaring medical expenditures. Moreover, the impact of malnutrition, which is considered to be one of the primary causes 40 Lengthening Healthy Lifespans to Boost Economic Growth

42 of sarcopenia, on medical expenditures in Japan is estimated to be much larger than that of other countries. According to one report from the United Kingdom, medical costs associated with malnutrition in the U.K. accounted for approximately 15% of total medical expenditures. 13 Among healthcare professionals, the importance of preventive interventions at the frailty phase is stressed; however, frailty awareness among the general population remains relatively low. A survey conducted in November 2016 targeting both individuals and children with parents over 65 years of age reported that more than 90% of the total respondents had no awareness of frailty. 8 Recommendations 1. Launch a new incentive scheme with medical fee points to help prevent the frail elderly from progressing to sarcopenia. While frailty is a risk factor for other disabilities, it is reversible, meaning that individuals can regain their healthy status. 7 Therefore, appropriate interventions need to be offered in a timely manner, and a systematic approach must be followed to ensure that necessary actions are taken, regardless of person, place, or time. On the other hand, it is difficult to accurately diagnose the correct type of frailty in affected individuals because of its versatility. Considering these difficulties, a new reimbursement medical fee point system accompanied by much clearer diagnostic criteria is needed to help prevent the frail elderly from progressing to sarcopenia. This new scheme, which could be similar to that used for diabetes mellitus dialysis prevention management (350 points), may promote early clinical interventions such as physical exercise and/or nutritional supplementation. Interrupting the frailty cycle that negatively affects the elderly pre-sarcopenia population (frail elderly people) could be expected to increase the robust elderly population (i.e., to extend healthy life expectancy), who are capable of contributing to a more sustainable society by offering additional labor resources. Finally, from a long-term perspective, this could be expected to reduce future medical expenditures. 7 Meanwhile, the actual situation of frailty among the Japanese population, its associations with other diseases, and its economic impact need to be examined and researched further by working across sectors and adopting a strategic approach that moves beyond hospitals, clinics, home care, and nursing homes. Newly developed research methodologies using big data could help in the design and implementation of such an approach. 2. Establish an educational platform that provides family doctors, pharmacists, and home care dieticians with a common understanding of malnutrition among the elderly. It is generally true that the elderly lose skeletal muscle as a result of aging; however, it is also true that elderly individuals with adequate protein intake can minimize muscle loss. 19 Furthermore, even in elderly individuals with strong anabolic resistance, sufficient protein intake combined with physical exercise can improve anabolic response in a similar manner to that of younger populations. 20 In the community setting, it is important that stakeholders who play leading roles in the integrated community care system, including family doctors, family pharmacists, and home care dieticians, share a common understanding regarding the impact of nutrition on metabolic response, the effectiveness of resistance training, and the effects of nutritional supplements on 7, 19, 20 physical frailty among the elderly. Lengthening Healthy Lifespans to Boost Economic Growth 41

43 3. Incorporate geriatric nutrition science into school educational programs. In 2004, the GOJ took action to improve school educational programs about nutrition science by deploying a notice entitled, Enforcement of partial changes in the School Education Law to establish the nutrition teachers system. 17 However, unfortunately, this notice failed to include information on geriatric nutrition. The proportion of the elderly in the total population in Japan continues to grow, so more than ever, children should be given appropriate knowledge about general nutrition science, including geriatric nutrition. Children knowledgeable about nutrition are expected to enhance communication between diverse age groups in the community regarding common topics such as nutrition at home. 4. Foster frailty ambassadors in the community. Every person is responsible for taking their own necessary frailty countermeasures, such as training to prevent frailty and nutrition interventions to prevent malnutrition and maintain/strengthen muscle; we cannot rely solely on healthcare professionals. 7 It is, therefore, recommended that each community take responsibility in fostering their own frailty ambassadors to implement initiatives. A so-called frailty ambassador certification system should be deployed. The GOJ would be able to monitor the number of certificate holders in each prefecture as one of key performance indicators (KPIs) to implement initiatives against frailty. The major criteria to achieve certification as an ambassador should be consistent nationwide, and the scope of scientific knowledge should fit the contents of the aforementioned geriatric nutrition educational platform. Communities are encouraged to utilize frailty ambassadors by taking every opportunity to increase public awareness of frailty, malnutrition, and prevention. Taking this type of grassroots approach with involvement of the local community could improve and reinforce individual knowledge and awareness about frailty and lead to an extension of healthy life expectancy. References 1. Cabinet Office, Government of Japan, Aging Society White Paper 2016 (Summary), chap. 1. Accessed July 12, 2017, 2. National Institute of Population and Social Security Research, Future Estimation of the Japanese Population (Est. January 2012). Accessed July 12, 2017, 3. Ministry of Health, Labour and Welfare, Medical Expenditure Status Accessed July 12, 2017, 4. Ministry of Health, Labour and Welfare, Japan Vision Healthcare Accessed July 12, hokeniryou2035/assets/file/healthcare2035_proposal_ pdf 5. The Japan Geriatrics Society, Statement about the definition and categories of the Elderly by the working group of The Japan Geriatrics Society and The Japan Gerontological Society (Summary). (presented on January 5, 2017). Accessed July 12, 2017, 6. Masanori Miyazaki, Ministry of Health, Labour and Welfare, Summary of Medical Fee Points Revisions (Summary) Paper presented on March 4, Accessed July 12, 2017, 42 Lengthening Healthy Lifespans to Boost Economic Growth

44 7. The Japan Geriatrics Society, Statement about Frailty by the Japan Geriatrics Society. (Presented on May 2014). Accessed July 12, 2017, 8. Pfizer Press Release: Nursing Day: Perception Survey Conducted in 47 Prefectures, Dated November 9, Accessed July 12, 2017, 9. Ministry of Health, Labour and Welfare, 3-2. Pathology and Nutrition in Frailty/Sarcopenia in Report from the Japanese Diet Intake Standards 2015 Development Committee, Accessed July 12, Sasazuki S, et al., Body mass index and mortality from all causes and major causes in Japanese: results of a pooled analysis of 7 large-scale cohort studies, J Epidemiol. 21(6) (2011): The Japan Geriatrics Society, Sarcopenia: Japanese translation of consensus on definition and diagnosis in European Academic Societies with Q&A. Accessed July 12, Bartali B, et al. Low nutrient intake is an essential component of frailty in older persons, J Gerontol A Biol Sci Med Sci. 61 (2006): The British Association for Parental and Enteral Nutrition and National Institute for Health Research Centre, The cost of malnutrition in England and potential cost savings from nutritional interventions (full report) Accessed July 12, 2017, Ministry of Health, Labour and Welfare, Consideration of metabolic syndrome: Image of diagnosis and daily life intervention (Presented at The 3 rd meeting of working group about lifestyle-related diseases and health guidance on August 26, 2000) Accessed July 12, 2017, Ministry of Health, Labour, and Welfare, Policy Report of Specific health checks and specific health guidance Accessed July 12, 2017, Ministry of Health, Labour, and Welfare, Research on health services for the latter-stage elderly (Executive Summary); Health and Labour Science Special Research Initiative 2015 (Presented at the 58 th meeting of Social Security Council Insurance of elderly care on May 25, 2016) Accessed July 12, 2017, Shakaihoshoutantou/ pdf 17. Ministry of Education Culture Sports Science and Technology, Enforcement of partial changes in the School Education Law to establish the nutrition teachers system (Notification dated June30, 2001) Accessed July 12, 2017, Janssen I, et al. The healthcare costs of sarcopenia in the United States. J Am Geriatr Soc. 52 (2004): Houston DK, et al. Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the Health, Aging, and Body Composition (Health ABC) Study, Am J Clin Nutr. 87 (2008): Dideriksen K, et al. Influence of amino acids, dietary protein, and physical activity on muscle mass development in humans, Nutrients. 5 (2013): Xue QL, et al. Initial manifestations of frailty criteria and the development of frailty phenotype in the Women s Health and Aging Study II. J Gerontol A Biol Sci Med Sci 63 (2008): Ministry of Health, Labour, and Welfare, About Medical Plan (Notification to prefectural governors dated July 31, 2017) Accessed August 1, 2017, Lengthening Healthy Lifespans to Boost Economic Growth 43

45 Demographics - Growing Aging Population in Japan 2010 Total Population 127,180 (thousand) 2030 Total Population 115,220 (thousand) 2060 Total Population 89,930 (thousand) 29,410 36,670 36,460 81,280 67,400 45,950 16,480 11,150 7, ,000 40,000 60,000 80, ,000 Age above 65 Age Age ,000 40,000 60,000 80, ,000 Age above 65 Age Age ,000 40,000 60,000 80, ,000 Age above 65 Age Age 0-14 Source: National Institute of Population and Social Security Research, Future Estimation of the Japanese Population (Est. January 2012). Medical Budget - Growing elderly population increases medical expenditures 2014 Medical Expenditure by age group (million US dollars) 2014 Medical Expenditure Distribution by age group 2,500 2,174 2,000 1, % 13% 23% 59% 1, % 20% 40% 60% 80% 100% Age 0-14 Age Age Age above 65 Age 0-14 Age Age Age above 65 Source: Ministry of Health, Labour and Welfare, Medical Expenditure Status Lengthening Healthy Lifespans to Boost Economic Growth

46 Frailty Model - Reversibility of Frailty is the Key Capacity no frailty (Robust) frailty disability Aging Source: Ministry of Health, Labour, and Welfare, Research on health services for the latter-stage elderly (Executive Summary); Health and Labour Science Special Research Initiative 2015 Death Frailty Cycle - Malnutrition accelerates the Vicious Cycle Anorexia Food Intake Total Energy Expenditure Malnutrition Sarcopenia Activity Resting Metabolic Rate Fatigue & Power Disability Walking Speed Strength Source: Ministry of Health, Labour and Welfare, Report from the Japanese Diet Intake Standards 2015 Development Committee. Lengthening Healthy Lifespans to Boost Economic Growth 45

47 Higher protein intake is required for older persons to achieve equivalent muscle protein synthesis to younger persons Muscle protein synthetic response to protein intake Protein response at rest (young and older) Protein response after exercise (young and older) Protein response in immobilized muscle Source: TNT Geriatric 2.0 (Abbott Laboratories) (Dideriksen K, et al. Nutrients. 2013; 5: ) 46 Lengthening Healthy Lifespans to Boost Economic Growth

48 09 Prevent Chronic Diseases Through Tobacco Control Situation It has been scientifically proven that tobacco smoking increases the risk of many diseases such as cancer (including lung cancer), myocardial infarction, stroke, and chronic obstructive pulmonary disease and that abstinence from tobacco can decrease these risks and lead to health improvement. The World Health Organization (WHO) states that tobacco smoking is the single largest preventable cause of disease. 1 Tobacco smoking is classified in the category of mental and behavioral disorders due to psychoactive substance use according to the ICD-10 2 because it is difficult for most smokers to stop smoking by themselves and many require support in overcoming the addiction. Tobacco smoking is now recognized as an addiction in Japan and, since 2006, medical service fees for smoking cessation treatment have been classed as nicotine addiction management fees. 3 The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) conducted a systematic analysis of smoking prevalence and the attributable disease burden in 195 countries and territories between 1990 and The results showed that 11.5% of global deaths in 2015 (6.4 million deaths) were attributable to smoking worldwide. 4 Furthermore, it has been scientifically verified that secondhand smoke increases the risk of various diseases and disorders, as well as death from serious diseases. One effective method of reducing the health risks is banning indoor smoking to prevent exposure to secondhand smoke. The WHO recommends that every indoor workplace and all public spaces be made smoke free. A non-smoking environment in indoor areas is also useful for smokers who want to stop smoking. It has been reported that a policy of smoke-free air in every workplace could reduce the absolute prevalence of smoking. 5 The 2015 National Health and Nutrition Survey reported that the overall prevalence of smoking among Japanese adults is 18.2%. The rate of smoking by men is 30.1% and the rate for women is 7.9%. Rates for both men and women have decreased. However, in particular, the prevalence of smoking by men in their 30s through 50s is between 37 and 41%, respectively, and the rate for women in their 30s through 50s is around 11%. These smoking rates are high. 6 For passive smoking, the rate in all locations is decreasing; however, the passive smoking rate in restaurants, leisure and amusement facilities, and workplaces exceeds 30% and remains high. 6 A survey on the prevention of passive smoking and a smoking ban for indoor workplaces conducted on 8,000 indoor workers in Japan in 2014 showed that 66% of non-smokers desired a total smoking ban and even 25% of smokers also desired the ban. Eighty-one percent of indoor workers expect preventive measures against passive smoking, including measures for the separation of smoking rooms so that smoke does not leak. Sixty-two percent of indoor workers would support a legally-mandated total smoking ban. Only 14% say that the passage of such laws would have a negative impact on their business. Sixty-three percent of indoor workers agreed with the establishment of a passive smoking prevention ordinance by According to one survey, the economic loss per year due to tobacco smoking is estimated at 1.62 trillion JPY in terms of excess medical costs for smokers, 0.14 trillion JPY in excess medical costs for passive smokers, 0.48 trillion JPY in excess nursing care costs, 3.93 trillion JPY in losses related to the labor force, and 0.19 trillion JPY due to fires or extra cleaning of facilities/interior areas. This adds up to a total annual loss of 6.36 trillion JPY. 7 Current Policy In May 2003, the government of Japan Lengthening Healthy Lifespans to Boost Economic Growth 47

49 implemented Article 25 of the Health Promotion Act to eliminate second-hand smoking in public spaces. The law does not stipulate any penalties, specifying only good faith efforts, but it has gradually promoted a voluntary non-smoking movement. Further, with Japan s June 2004 ratification of the WHO Framework Convention on Tobacco Control, which came into force internationally in 2005, efforts to adhere to the treaty including the introduction of the Taspo system to prevent purchases of tobacco by minors have been implemented in Japan. National health insurance coverage for the treatment of nicotine addiction through smoking cessation programs has been provided since In April 2016, the requirement that a person score higher than 200 on the brinkman index, which is calculated by multiplying the daily number of cigarettes smoked by the number of years of smoking, was abolished for persons under 34 years old. A tax reduction was established in 2017 for the purchase of Switch OTC drugs, which includes tobacco cessation OTC drugs, that total 12,000 JPY or more with an upper limit of 88,000 JPY per household. In October 2010, tobacco tax rates were raised, leading to a reduction in tobacco consumption. The demand for taxation revisions made by the Ministry of Health, Labour and Welfare (MHLW) indicates that the increase in the tobacco tax rate is included from the perspective of public health. In the Basic Plan to Promote Cancer Control approved by the Cabinet in June 2012, the first numerical targets adopted were aimed at reducing the national smoking rate to 12% by Further, in stage two of the health promotion goals for Healthy Japan 21, the following targets were set in relation to preventing passive smoking by reducing the opportunities for passive smoking in: 10 Government buildings, from 16.9% in 2008 to 0% by 2022 Medical institutions, from 13.3% in 2008 to 0% by 2022 The workplace, from 64% in 2011 to 0% by 2020 In restaurants, from 50.1% in 2010 to 15% by 2022 If there are opportunities where students can receive education on the negative effects of smoking before they become adults, in particular, as a theme of health education at schools, students will have a chance to acquire health literacy. Such education may contribute to preventing smoking at a young age and reducing smoking rates when these students become adults. With regard to education on the negative effects of smoking provided in school, the Japanese Society of School Health has prepared Materials for Teaching the Prevention of Smoking, Drinking, and Drug Abuse. The materials are expected to be used for teaching the prevention of smoking. The Japan Medical Association proposed political measures under its School Health Committee Report 11 compiled in March 2014 on the health education themes for each school year and clinical department by subject, and the targets of the education would include students, school teachers and staff members, and parents. The report includes a proposal to provide health education on the Negative Effects of Smoking from internal medicine departments and pediatrics departments as a theme for students in the second year of junior high school and higher. The plan is considered effective for the prevention of smoking at a young age as a means of providing health education as a part of school education. The proposal will be linked with school curriculum guidelines issued by the Ministry of Education, Culture, Sports, Science and Technology. 48 Lengthening Healthy Lifespans to Boost Economic Growth

50 In June 2014, the Act for Partial Amendment of the Industrial Safety and Health Act was passed and it included promotion of preventive measures for passive smoking in the workplace by stating that the employer shall strive to take appropriate measures based on the actual conditions of the employer and the work area in order to prevent the passive smoking of workers. In early 2017, MHLW planned to get a bill on smoking ban in public areas to revise the Health Promotion Law passed and in place ahead of the 2020 Tokyo Olympics and Paralympics. The MHLW drafted amendment features a ban on smoking in public institutions, including schools, hospitals, municipal offices, eateries and hotels, as well as other facilities frequented by minors, and imposing penalties on violators. However, the proposal for combating secondhand smoke is weakened by resistance groups, to exempt small bars, and it is yet to be submitted to the Diet. Recommendations In order to protect the public s health and prevent various diseases, seek additional preventive measures against passive smoking, while respecting people s opinions. Implement health education on the negative effects of tobacco for students in school health classes. Consider an increase in the tobacco tax, which is expected to lead to reducing tobacco consumption and thereby improving overall health. Promote and disseminate tobacco cessation drugs to help smokers stop smoking. Lengthening Healthy Lifespans to Boost Economic Growth 49

51 References 1. World Health Organization report on the global tobacco epidemic, World Health Organization. International Statistical Classification of Diseases and Related Health Problems, 10th edition (ICD-10). 3. Ministry of Health, Labour and Welfare, the latest information on tobacco at 4. GBD 2015 Tobacco Collaborators. Smoking prevalence and attributable disease burden in 195 countries and territories, : a systematic analysis from the Global Burden of Disease Study Lancet 2017; 389: Fichtenberg CM, Glantz SA. Effect of smoke-free workplaces on smoking behavior: Systematic review, BMJ 325: , Ministry of Health, Labour and Welfare National Health and Nutrition Survey. kekkagaiyou.pdf 7. Japan-wide survey of 8,000 indoor workers on the prevention of passive smoking and a smoking ban in the workplace, conducted by Johnson & Johnson K.K. Consumer Company, released on May 26, Institute for Health Economics and Policy. Study of anti-smoking measures: Estimate of costs resulting from smoking, July Ministry of Health, Labour and Welfare. Outline of Major Taxation Amendment in file/04-houdouhappyou seisakutoukatsukan-sanjikanshitsu_shakaihoshoutantou/ pdf 10. Reference material for the promotion of Healthy Japan 21 (stage two) by the Regional Public Health Promotion Nutrition Subcommittee, Health Sciences Council, July Ideal Health Education Considered by Doctors in Each Clinical Department (Materials in the back of the book, pp3-5) 50 Lengthening Healthy Lifespans to Boost Economic Growth

52 Lengthening Healthy Lifespans to Boost Economic Growth 51

53 52 Lengthening Healthy Lifespans to Boost Economic Growth

54 10 Prevention and Management of Risk Factors for Diabetes Situation Diabetes is a disease in which preventive medicine plays an important role. According to a 2007 survey, more than 90% of the cases of the disease in Japan were type 2 diabetes, in which patients develop chronic hyperglycemia (high blood glucose) because of insufficient insulin secretion or a lack of insulin activity. As of 2012, 9.5 million people in Japan are estimated to have diabetes, and another 11 million have the potential for developing diabetes. Thus, in addition to those already diagnosed with the disease, an estimated 20.5 million people in Japan may become diabetics. 1 Significant lifestyle changes in recent years are believed to be behind the dramatic increase in the number of people who suffer from diabetes. If a chronic hyperglycemic state persists, it can cause serious complications, such as coronary artery disease, diabetic retinopathy and nephropathy, resulting in a significant decline in quality of life. In serious cases, diabetes may result in loss of sight or the need for limbs to be amputated. Currently, although there are improvements, it is estimated that about 30% of those who are strongly suspected of having diabetes have received almost no treatment. 1 As many as 13,000 people in Japan die each year as a result of having diabetes. 2 This situation caused diabetes-related medical spending in Japan to grow to approximately 1.20 trillion Japanese yen in In the United States, in 2012, diabetes accounted for 176 billion U.S. dollars in direct medical costs and 69 billion U.S. dollars in indirect economic costs, which included disability, work loss and premature mortality. 4 Similar economic cost data are not available for Japan, but the economic burden is estimated to be high and increasing. Diabetes can be prevented by improving lifestyle habits in areas such as nutrition and physical exercise. These improvements not only help prevent the development of diabetes but also help delay the onset of complications in those who already have diabetes. As there are few or no subjective initial symptoms, early detection of diabetes is difficult. Consequently, regular health checkups, including blood glucose level tests and examination of the tiny blood vessels in the back of the eye, are important for the early detection of diabetes. Moreover, if the practice of home-based self-monitoring of blood glucose levels were to become more widespread, this could help prevent the onset of diabetes and assist people in maintaining healthier lifestyles. 5 However, severity and prognosis of diabetes should not be diagnosed solely based on blood glucose level, but instead should be concurrently assessed by the level and progression of the HbA1c, which is an indicator of chronic hyperglycemia. 6 As people with diabetes often have multiple physical disorders such as obesity, lipid metabolism disorders and hypertension, it is necessary to check and comprehensively diagnose the severity of diabetes by analyzing a lipid parameter and blood pressure. 6 Therefore, the establishment of essential diagnostic parameters as well as risk assessment and intervention measures, such as intended health instruction, are needed. In addition, target individuals, in other words persons who should seek prompt consultation, should be encouraged to initiate or continue treatment of diabetes in order to avoid further disease progression. The merits of this approach have been demonstrated by the advanced practices of some municipalities. In the case of Kure City, according to statistical analysis of collected receipt data, the number of patients who initiated dialysis could be reduced by controlling the progress of diabetes. This was achieved by providing individual instruction by specialized nurses to patients Lengthening Healthy Lifespans to Boost Economic Growth 53

55 at-risk. A collaborative approach among doctors, nurses and payers is considered to have contributed to the improvement of the self-management skills of the patients. 7 Amagasaki City also introduced a scientific and population-based approach based on a statistic analysis of receipt data, and could reduce the number of in-patients suffering from cerebral stroke or myocardial infarction, and patients initiating dialysis. 8, 9 These cases show that cooperation between municipalities and payers helped prevent complications in patients with diabetes. Current Policy The government of Japan initiated policy goals designed to reduce the number of diabetics by 25%, and increase the rate of special health screening (tokutei kenshin) to 80% by 2015 as compared with 46.2% in As a method of early detection, a specific medical checkup and health education for metabolic syndrome was introduced in As a result, Japan is believed to be leading the global fight against diabetes. Up until 2008, national health insurance reimbursement for medical treatment relating to the self-monitoring of blood glucose levels was limited to those patients with advanced diabetes requiring insulin injections. However, in April 2008, the national health insurance reimbursement plan was expanded at hospitals with fewer than 200 beds to provide 5,000 Japanese yen per year to cover the cost of self-monitoring of blood glucose levels for diabetic patients not requiring insulin injections. The Japan Revitalization Strategy adopted by the Cabinet on June 14, 2013, requests all corporate health insurance societies to establish and implement a Data Health Plan as a prioritized strategic imperative within their annual business projects. The purpose of the plan is to analyze medical fee receipt data and, using outcomes of the analysis, recommend health maintenance and promotion strategies. The plan also orders individual corporate insurance societies to implement primary to tertiary prevention initiatives for those covered. Local governments are also being asked, as a public insurance societies, to promote data-based health initiatives to maintain and improve the health outcomes of the insured by preventing diabetes or reducing progression of severity and deterioration of diabetes. Diabetes related goals, including those in the updated Healthy Japan 21 program that began in April 2013, have been revised. 11 Reduction of complications. Goal: Reduce the number of people requiring dialysis due to diabetic nephropathy from 16,247 (2010) to 15,000 (2022). Increase the proportion of patients who need to continue medical treatment for diabetes. Goal: Increase the ratio from 63.7% (2010) to 75% (2022). Reduce the proportion of patients unable to control blood glucose to within the JDS HbA1c value of 8%. Goal: Reduce the ratio from 1.2% (2009) to 1% (2022). Curb the increase in the number of diabetics. Goal: Reduce the number of diabetics from 8.9 million (2007) to 10 million (2022) in contrast to the projected 14.1 million. Regarding countermeasures for diabetes, individual target goals for primary, secondary and tertiary preventive care should be set, focusing on indicators of improvement in the ratio of the patients continuing treatment and a decrease in the number of persons with poor blood glucose control. Onset of complications due to diabetes could be deterred by managing blood glucose levels. In particular, decreasing the number of patients who initiate dialysis has been set as a national goal because it would yield a larger financial impact than a reduction in other complications related to diabetes. However, detailed instructions 54 Lengthening Healthy Lifespans to Boost Economic Growth

56 are not provided in the national plan and the determination of actual approaches has been left to the municipalities. By learning from advanced initiatives, such as those conducted in Kure City and Amagasaki City, implementation of approaches based on the unique situation and needs of each region can help the provision of treatment in ways that prevent the deterioration of health conditions. To that end, it is important that central and local governments work with insurers toward the prevention of the progression of diseases such as diabetes. deterioration of diabetes. Have government provide a scheme and budget to support personnel training specialized to data management for municipalities working on prevention and management of diabetes. Recommendations To delay the progress of diabetes in patients who do not require insulin administration, expand health insurance reimbursements to cover self-monitoring of blood glucose levels at home and approve over-thecounter sales of self-testing products. Conduct comprehensive eye screening of persons aged 40 and over to detect early warning signs of diabetes-related eye disease in the fine blood vessels and nerves at the back of the eye. 12 Have the central government and municipalities invest resources in the prevention of the deterioration of diabetes and related complications in ways that are likely to have a major impact on quality of life and cost efficiency. In addition to diabetic nephropathy, set a specific goal to reduce the number of patients with diabetic-related eye diseases, including diabetic retinopathy, within the government initiative to prevent the deterioration of diabetes and related complications. Under the leadership of the central government and municipalities, share all data held by payers among public and private health insurance societies, municipalities, and utilize all such data for the implementation of practical measures based on scientific evidence to prevent the Lengthening Healthy Lifespans to Boost Economic Growth 55

57 References 1. Ministry of Health, Labour and Welfare. The National Health and Nutrition Survey in Japan Ministry of Health, Labour and Welfare Vital Statistics of Japan Ministry of Health, Labour and Welfare National Medical Care Expenditure Centers for Disease Control and Prevention National Diabetes Statistics Report 5. World Health Organization. Fact Sheet 312 (reviewed November 2016) Treatment Guide for Diabetes (excerpt), The Japan Diabetes Society 7. Kure-city s Health Insurance initiative: prevent aggravation such as diabetic nephropathy, Material from 1st Health Investment WG at METI Healthcare Industry Council for Next Generation, February 14, Health-up Strategy AMAGASAKI, Amagasaki-city, 9. The Association for Promotion of Public Local Information and Communication, Homepage Ministry of Health, Labour and Welfare. 2012, Implementation Status of Specific medical examination and Specific health guidance Document Ministry of Health, Labour and Welfare, Health Science Council, Regional Health & Nutrition Promotion Committee, Special Expert Committee on the New National Health Promotion Plan. Reference materials for the promotion of Healthy Japan 21 (stage two), (July 2012) International Diabetes Federation. Diabetes Eye Health: A guide for health professionals 56 Lengthening Healthy Lifespans to Boost Economic Growth

58 Sharp rise in prevalence of Diabetes, Number of those at risk for Diabetes falling in Japan (10,000) million persons highly likely to have diabetes 11.0 million may have diabetes 20.5 million persons at high risk of developing diabetes Source: MHLW, 2012 National Health and Nutrition Survey. Despite improvements, 30% of people thought to have Diabetes receive almost no treatment 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Diabetes Treatment in Japan 29.0% 40.4% 39.2% 47.9% 5.8% 7.7% 5.0% Almost never treated 7.1% Treated, but not now 65.2% 51.9% 55.7% 45.0% Undergoing treatment Source: MHLW 2012 National Health and Nutrition Survey Lengthening Healthy Lifespans to Boost Economic Growth 57

59 Health-up Strategic Program in Amagasaki City This program reduced the number of diabetes patients who required dialysis while also lowering the incidence of cerebral apoplexy and myocardial infraction with a three prong strategy. 1. Promote routine health checkups " Increased consultation rates provided critical information for analysis and subsequent action " Create individualized programs and guidance for high risk patients 2. Apply a population-base approach " Identify high risk patients based on an analysis of health check-up data " Provide tailor-made programs and guidance to high risk patients " Support these patients by collaborating with multiple stakeholders including healthcare providers, insurance associations, private, and public organizations " Help these patients to develop and maintain a more healthy lifestyle 3. Evaluate implementation of the interventions " Modify and upgrade actions and metrics based on updated health check-up data Four New Diabetes Policy Goals were added into Revised Healthy Japan Reduction of complications. Goal: Reduce new annual dialysis patients due to diabetic nephropathy from 16,247 (2010) to 15,000 (2022). 2. Increase ratio of patients continuing treatment. Goal: Raise from 63.7% (2010) to 75% (2022). 3. Reduce ratio of patients unable to control blood sugar to within JDS HbA1c value of 8.0%. Goal: Reduce from 1.2% (2009) to 1% (2022). 4. Reduce increase in diabetes patients. Goal: Limit number of patients (8.9 million in 2007) to 10 million in 2022, compared with the projected 14.1 million. Source: MHLW, Reference Materials for the Promotion of Healthy Japan 21 (Stage Two), July Lengthening Healthy Lifespans to Boost Economic Growth

60 11 Improving Prostate Cancer Treatment Situation The number of prostate cancer patients in Japan is increasing. In 2012, prostate cancer was the fourth most prevalent male cancer, with the incidence expected to increase making it the most prevalent male cancer by The most strongly associated risk factors include age, ethnicity, family history, hormones, and obesity. 2 Because morbidity and death rates start increasing from the age of 50 while individuals are still working, future economic losses are considered to be significant. Therefore, countermeasures should be sought. 1 Current Policy Recently, a new pathological concept for castration-resistant prostate cancer (CRPC) is being used. Because prostate cancer is androgen dependent, cytoreduction can result from androgen ablation from the testis through surgical or medical castration. Other initial treatments include prostatic specific antigen (PSA) monitoring, surgery and combination of endocrine and radiation therapies. Various treatment options are recommended depending on the risk stratification. 3 In Japan, the combination of LH-RH analogue, also known as medical castration, and antiandrogen (combined antiandrogen therapy) is widely used as endocrine therapy. Although the response rate of the initial endocrine therapy by androgen ablation is as high as 85 to 90%, more than half of patients show resistance to the therapy over the five years following treatment resulting in disease progression, which may be associated with an elevated PSA. Such resistant prostate cancer is characterized as CRPC, which is defined as a condition with disease progression or an elevated PSA after surgical or medical castration while the serum testosterone level falls below 50ng/dL, regardless of the use of antiandrogen. 4,5 Once resistance is observed, the prognosis worsens rapidly where there are unmet medical needs. Four drugs for the treatment of CRPC with global track records, including bone metastatic CRPC, were introduced to Japan recently (three in 2014 and one in 2016). These drugs are expected to improve the prognosis of patients with CRPC dramatically. Currently, there are nearly 30,000 patients with CRPC and both the number and the incidence are increasing. Early CRPC is often found in men in their 50s to 60s who are still working, so these treatments can enable them to continue to contribute to society while they are receiving treatment, if the symptoms permit. In 2009, the United States Food and Drug Administration proposed in the Journal of Clinical Oncology that emphasis be placed on the assembly of data through the use of on patient reported outcomes (PROs) for the entire cancer therapeutic area. 6 PROs enable patients to directly report their health status without interpretation by a clinician or any other party. 7 PROs can be used to analyze patients assessments of their QOL, making medical care from the patient s point of view even more important. It is clear from the Journal of Urology s 2013 report on prostate cancer that physicians and patients do not share similar perceptions about the peripheral symptoms of prostate cancer, such as pain and fatigue, and that the gap in perception remains. 8 While prostate cancer data reported in journals mainly focused on the basis of PSA (prostate-specific antigen), in recent years, there is increased recognition of the importance of evaluation by diagnostic imaging related mainly to bone lesions, alleviation of symptoms relating mainly to pain, and evaluations related to QOL. 9 To achieve the important therapeutic goal of maintaining the quality of life of prostate cancer patients, it is important to improve PRO-conscious communication between patients and physicians. Because this disease Lengthening Healthy Lifespans to Boost Economic Growth 59

61 largely affects men in their 50s an age when people are still working and contributing to society treatments with less impact on daily life are important to both patients and the Japanese economy. Recommendations Promote proven treatments that enable the maintenance of quality of life in order to improve outcomes for prostate cancer, in particular castration-resistant prostate cancer. Place a higher emphasis on QoL and PROs as well as imaging and symptom assessments, in addition to PSA measurements in the treatment of prostate cancer. Recommend that the perspective of PROs be taken into account in evaluating for future clinical study endpoints and in developing guidelines on the use of cancer medications. Establish a mechanism to adopt PROs in actual clinical settings. Identify steps to ease patient burden during hospital visits, which is critical for patients to continue treatment and allow employed patients to lead a normal daily life, and promote understanding by physicians and employers. Include more disease-specific questions in patient interviewing. Engage cancer-certified pharmacists and nurses in cancer patient communications. References 1. Hori M, Matsuda T, Shibata A, Katanoda K, Sobue T, Nishimoto H, et al. Cancer incidence and incidence rates in Japan in 2009: a study of 32 population-based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project. Japanese journal of clinical oncology. 2015;45(9): International Agency for Research in Cancer (IARC). EPIC Study. The Prostate Cancer Working Group 植村元秀他 :Mebio, Vol 31, No.9, 2014, p 寺田直樹他 :Mebio, Vol 31, No.9, 2014, p 今本敬他 :Mebio, Vol 31, No.9, 2014, p Ethan Basch et al., Recommendations for Incorporating Patient-Reported Outcomes Into Clinical Comparative Effectiveness Research in Adult Oncology. DOI: /JCO Journal of Clinical Oncology 30, no. 34 (December 2012) US Department of Health and Human Services, Food and Drug Administration. Guidance for Industry Patient- Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims; Dec. 2009, p6. 8. THE JOURNAL OF UROLOGY, Vol. 189, S59-S65, January Cookson M., et al. Castration-resistant prostate cancer: AUA Guideline The Journal of Urology 190(2); Lengthening Healthy Lifespans to Boost Economic Growth

62 Male Cancer Prevalence in Japan Top Five Male Cancers (2012) Site 1 Stomach 2 Colorectal 3 Lung 4 Prostate 5 Liver Estimated Prevalence of Male Cancers (2016) Site Prevalence Prostate 92,600 Stomach 91,300 Lung 90,600 Colorectal 84,700 Liver 29,000 Hori M, Matsuda T, Shibata A, Katanoda K, Sobue T, Nishimoto H, et al. Cancer incidence and incidence rates in Japan in 2009: a study of 32 population-based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project. Japanese Journal of Clinical Oncology. 2015; 45(9): Perception Gaps of QOL between Patients and Doctors Has Yet Improved. Patient-requested QOL Improvements Should be Considered a Treatment Goal Urinary Incontinence Rectal Urgency Fatigue Pain Diarrhea Libido Impotence Physician % Patient Physician Patient Differing Perceptions of Quality of Life in Patients With Prostate Cancer and Their Doctors THE JOURNAL OF UROLOGY Vol. 189, January 2013 Lengthening Healthy Lifespans to Boost Economic Growth 61

63 PRO Measures Used in Prostate Cancer Cancer-Specific Instruments 1. European Organiza9on for Research and Treatment of Cancer Quality of Life Ques9onnaire (EORTC QLQ-C30) 2. European Organiza9on for Research and Treatment of Cancer Quality of Life Ques9onnaire Prostate Module (EORTC QLQ-PR25) 3. Func9onal Assessment of Cancer Therapy General Version (FACT-G) 4. Func9onal Assessment of Cancer Therapy Prostate Version (FACT-P) 5. FACT Advanced Prostate Symptom Index (FAPSI-8) 6. Prostate Cancer Treatment Outcomes Ques9onnaire (PCTO-Q) 7. University of California-Los Angeles Prostate Cancer Index (UCLA-PCI) 8. Expanded Prostate Index Composite (EPIC) 9. Prostate Cancer-Quality of Life (PC-QoL) 10. Pa9ent Oriented Prostate U9lity Scales (PORPUS-P and PORPUS-U I ) Reference: Morris C., Gibbons, E., Fitzpatrick, R. A structured review of Patient-Reported Outcome Measures for men with prostate cancer. Report to the Department of Health Patient-reported Outcome Measurement Group, Department of Health, University of Oxford, pp Lengthening Healthy Lifespans to Boost Economic Growth

64 12 Abdominal Aortic Aneurysm Situation One disease area for which early detection has the potential to reduce the mortality rate in Japan s aging society is Abdominal Aortic Aneurysm (AAA). AAA is a disease where localized dilatation (ballooning) of the abdominal aorta exceeds the normal diameter. In many cases, the dilation occurs gradually. The risk is highest for male smokers over the age of 65 who have hypertension. The most effective means of AAA prevention is reduction of risk factors: smoking cessation and control of high blood pressure and high cholesterol. AAA patients rarely experience symptoms besides pain in the abdomen or lower back. The risk of rupture depends on extent of dilation of the patient s abdominal aorta. The normal diameter of an abdominal aorta is 1.5 to 2 centimeters. However, if the diameter exceeds 3 centimeters (150% of normal), abdominal aorta is defined as an aneurysm with risk of rupture. In general, any AAA over 5 centimeters in diameter is a candidate for surgery. If the abdominal aorta ruptures, the risk of death is up to 90%. AAA can be diagnosed with noninvasive imaging tests including ultrasound and computed tomography (CT) scan. Results of the Multicentre Aneurysm Screening Study undertaken in the U.K. over a four-year period provide reliable evidence of the benefit from screening for AAA based upon the National Health Service criteria for quality of life and mortality. The study found 53% reduction in aneurysm-related deaths for those who attended screening. screening, and the actual prevalence of AAA in the Japanese population is unknown. Recommendations 1. Promote better understanding of AAA among citizens and health professionals through regular check-ups in order to increase the rate of early detection of AAA among the high-risk population and provide adequate disease management. 2. Introduce incentives, such as reimbursement, for abdominal ultrasound screening or early detection of AAA. 3. Support the development of clinical guidelines for screening and diagnosis of AAA by academic societies. Case Study: The AAA Japan Study The AAA Japan Study is a large scale multi-facility cohort study targeting Japanese hypertension patients over the age of 60 using pocket-size ultrasound devices to identify AAA. The research results show that 4.1% of Japanese hypertension patients over the age of 60 who participated in the study had AAA. Key findings follow below: 5.7% of females in their 80s had AAA. Treatment ratio remains low with only 16,000 patients out of the estimated 197,000 patients undertaking surgical treatment annually who were the target for this case study. Therefore, it is assumed that a significant number of AAA cases exist in Japan. It is important that undetected and untreated AAA be detected and treated early. The estimated number of patients with AAA in Japan exceeds 1,100,000. However, only 16,000 people undergo surgical treatment annually, and many patients are brought into the hospital as a result of sudden rupture. In most cases, AAA is found as a result of an unexpected detection through abdominal ultrasound Lengthening Healthy Lifespans to Boost Economic Growth 63

65 References 1. Ashton H.A., Buxton M.J., Day N.E., Kim L.G., Marteau T.M., Scott R.A., Thompson S.G., Walker N.M., Multicentre Aneurysm Screening Study Group, The Multicentre Aneurysm Screening Study (MASS) into the effect of abdominal aortic aneurysm screening on mortality in men: a randomised controlled trial, The Lancet (2002), 360(9345): Surgical Care Associates Medtronic. Abdominal Echocardiography. Last modified April 21, Statistics Bureau. Ministry of Internal Affairs and Communications. March 21, 2013 Population Estimate. 5. Fukuda S., Watanabe H., Iwakura K., Daimon D., Ito H., and Yoshikawa J., Multicenter Investigations of the Prevalence of Abdominal Aortic Aneurysm in Elderly Japanese Patients with Hypertension, The AAA Japan Study Investigators (Circ. J 2015): 79: Lengthening Healthy Lifespans to Boost Economic Growth

66 Abdominal Aortic Aneurysm Enlarged area in the lower part of the aorta, the major blood vessel that supplies blood to the kidney. and Abdominal Aortic Aneurysm 1.2 million patients Source: Medtronic Japan Untreated AAA increase risk of sudden rupture % risk of AAA rupture within 5 years if not treated 25% 35% 75% 5-5.9cm 6-7cm >7cm Size of the AAA Estimated figures based on Ministry of Internal Affairs and Communications demographic statistics (March 2014) 82% of AAA sudden ruptures result in death. Up to 50% of untreated AAA exceeding 5.5 cm will result in death with sudden rupture. One screening could identify clinically significant AAA and reduce mortality rate by approximately 70%. Upon arrival to the hospital for emergency care, only 50% of patients survive. 50% of those who survive do so after surgery. Lengthening Healthy Lifespans to Boost Economic Growth 65

67 AAA Screening saves lives Source: Medtronic Japan One screening can detect clinically critical AAA, which can potentially reduce morality rate by 70%. Mortality rate comparison for males aged by screened and control group AAA Deaths Screened group (n = 2,212) Control group (n = 3,058) Years Since Entry 21 R. A. P. Scott, et al. Eur J Vasc Endovasc Surg 2001; 21: AAA Japan Study Estimated AAA patients from the AAA Japan Study According to the 2014 hypertension treatment guideline, the number of hypertension patients over the age of 60 is estimated to be 26.9 million. The AAA Japan Study suggests that 4.1% of that group may have AAA, which means that there are likely approximately 1.1 million patients. Risk factors: Age, male, smoking, 1,100,000 patients Estimated AAA patients (over 60) Treatment Ratio 197,000 patients Patients required for surgical treatment(over 60) 16,000 patients Annual patients treated hypertension, family history 16,000 AAA patients treated: from Japan Stent 2013 Estimated 1.1 million patients: prediction using 4.1% of hypertension patients over 60. Source: Fukuda S, Watanabe H, Iwakura K, Daimon M, Ito H, Yoshikawa J, for the AAA Japan Study Investigators. Multicenter Investigations of the Prevalence of Abdominal Aortic Aneurysm in Elderly Japanese Patients With Hypertension - The AAA Japan Study -. Circ J 2015; 79: Lengthening Healthy Lifespans to Boost Economic Growth

68 13 Prevent Stroke and Provide Coordinated Care Situation Stroke (cerebrovascular disease) was once the number one cause of death in Japan. Since the 1970s, the number of deaths from stroke has been gradually decreasing and stroke is currently the fourth leading cause of death (following malignant neoplasm, cardiovascular disease, and pneumonia). 1 However, over 110,000 people still die from stroke every year. It is estimated that over 300,000 people develop stroke every year and the number of stroke patients in Japan exceeds 2.8 million. 2 While thrombolytic therapy (clot busting) with recombinant tissue plasminogen activator (rtpa) must be provided within 4.5 hours from the onset of a stroke, the prevalence of the therapy among all cerebral infarction cases is as low as 5% and varies by region due to the shortage and uneven distribution of physicians, coupled with inadequate utilization of information technology (IT), which often results in uncoordinated emergency care. 3 Without access to expert care, patients who suffer a stroke can be left immobile, incontinent, and unable to speak. As a result, stroke is the most common cause of bedridden care, accounting for one in three bedridden patients in Japan. 4 Stroke care creates a significant economic burden and lost productivity for the supporting families and communities as a whole. The annual healthcare costs for stroke total 1,782 billion Japanese yen, accounting for 4.4% of national health expenditures, while the average hospital stay for discharged patients with stroke lasts 90 days, four times or more longer than patients being treated for malignant neoplasm and cardiovascular disease. 5,6 Among several sub-types, cardiac cerebral embolism, or stroke caused by atrial fibrillation (AF), is the most severe stroke with poor prognosis where one in three AF-related strokes results in death of the patient (12%) or the patient being bedridden (19%). 7 AF, or absolute arrhythmia, is the most common heart rhythm abnormality and causes one in five strokes with the proportion increasing to one in three in those over the age of 80 as AF is more prevalent in older populations. 7 Strong government leadership and adequate investments for stroke prevention are desperately needed. Japan is aging to an unprecedented level, which will pose an unbearable burden of stroke in clinical, societal, and economic terms, if action for stroke prevention is not taken immediately. According to a national public opinion survey conducted in 2011, 80.3% of survey respondents would like more information about strokes and stroke prevention. Eight percent of survey respondents reported being satisfied with the stroke emergency network in their region, while 22.9% reported being dissatisfied and 44.1% said they do not have enough information about it. 8 Much needs to be done for stroke prevention. Among other things, special attention needs to be paid to the prevention of AF-related strokes, which tend to be more severe and cause greater disability than other types of strokes. Although effective therapies exist, such as oral anticoagulation therapy (OAC), which lowers stroke risk by two-thirds if appropriately used, 9 significant challenges remain. These challenges include: 1) many AF patients are likely undetected in fact stroke is the first manifestation of AF for half of all AF-related stroke cases; 10 2) half of all AF patients do not receive OAC; 11 and 3) even if they receive OAC, the treatment is often sub-optimal because OAC may be under-dosed, 11 or patients may not adhere to the treatment. 12,13,14 Current Policy Since 2008 when stroke was positioned as one of the four diseases of focus (currently one of five) in the fifth regional healthcare plan, the Lengthening Healthy Lifespans to Boost Economic Growth 67

69 development of care coordination at a regional level has become a key issue. At present, discussion is underway for the seventh regional healthcare plan to be implemented in This plan will aim to build a comprehensive care system as part of the regional healthcare vision currently under development by prefectural governments and establish a seamless medical and nursing care system from acute care to chronic care, including nursing and welfare facilities, ambulatory nursing care and visiting care. Stroke prevention is in general high on the agenda of national and regional health policy, but without a comprehensive national policy framework, local governments rarely have dedicated strategies on the prevention of AF-related stroke. Electrocardiograph (ECG) tests are essential and effective for AF detection, especially among the elderly, but health check-ups for the elderly commonly do not include ECG or pulse checks. The government of Japan promotes Data Health, healthcare services based on data analysis, and is trying to reinforce the capability of payers to prevent and manage diseases leveraging their health check-up/claim/nursing care data, where public health and healthcare collaboration is expected to play an increasing role. Payers encourage patients with AF or an irregular pulse detected through health check-ups to consult physicians, and support subsequent patient management by sharing patient information with physicians. Regional Medical Associations and Pharmacist Associations collaborate in developing care coordination between general practitioners (GPs), cardiologists, and pharmacists to ensure optimal AF management. The case studies selected below point to the right direction. However, such coordination is rarely in place without a national policy framework and practical guidance to encourage and facilitate a coordinated approach to care. Recommendations Establish a basic law and develop a national health plan for stroke prevention and care. Raise societal awareness of the need to adopt monitoring, early diagnosis, and intervention for stroke, as well as the importance of stroke prevention, detection and management of risk factors including AF. Encourage patients at high risk for cardiovascular disease to seek medical care and intervention on a regular basis. Drive AF early detection by including pulse checks and ECG tests in health check-ups for the elderly, and make sure AF patients identified through the checkups receive optimal OAC treatment as appropriate by facilitating public health and healthcare collaboration. Integrate pulse checks into clinical practice GPs and specialists should opportunistically screen all their patients aged 65 and over for AF, by pulse palpation, followed by ECG if irregular pulse is detected. Promote a regional network for stroke prevention and care, integrating AF management by fostering and rewarding better collaboration between GPs, hospitals, pharmacists, and nursing care services for long-term care. Initiatives for Disease Control Together with 19 academic societies, the Japan Stroke Society and the Japanese Circulation Society jointly developed and released the Five-Year Plan for Overcoming Stroke and Cardiovascular Disease in Two major goals of the Plan include reduction of age-adjusted mortality from stroke and cardiovascular disease by 5% in five years and by 10% in 10 years, and extension of healthy life span. Control of stroke, the number one cause of bedridden care in Japan, is identified as a critical issue to address among others. Furthermore, initiatives are ongoing for 68 Lengthening Healthy Lifespans to Boost Economic Growth

70 enactment of the Basic Bill to Control Stroke, Cardiac Disease and Other Cardiovascular Disease to Extend Healthy Life Span. 17 Case Study 1: Ontario Stroke Network 18 Ontario is the second-largest province in Canada by area and, with a population of 13 million, it accounts for one-third of Canada s total population. Approximately 25,000 people have a stroke each year, 15,300 of whom remain hospitalized. In total, more than 90,000 patients are living with a strokerelated disability. Stroke care accounts for over 3% of the total healthcare cost in Canada, which is much lower than Japan s 10%. The Ontario Stroke Network (OSN) is an innovative, collaborative organization committed to enhancing stroke prevention and care for all Ontarians. The OSN is the credible advisor for the Ontario Stroke System and leads provincial initiatives and programs. The network is a responsive partner in integrated strategies aimed at improving patient outcomes, system efficiency, and access to care. It comprises nine Regional Stroke Centers that are connected to 16 District Stroke Centers, spread across other regional primary care centers. The annual ageand sex-adjusted in-hospital mortality rates due to stroke decreased 6% between April 2003 and August Case Study 2: Shizuoka E2 Net 19 Since 2007, Shizuoka Hospital and Shizuoka/ Shimizu Medical Associations have been expanding E2 Net, an AF care coordination network between the hospital and GPs. As of October 2014, about 200 GPs were involved and 1,000 AF patients were registered. Before the initiative started, complexity of AF management was preventing GPs from actively utilizing OAC therapy, leaving many AF patients untreated or sub-optimally treated, while hospitals were overloaded with AF patients. This situation triggered an initiative in which 1) GPs voluntarily participating in the network refer AF patients to the hospital; 2) the hospital assesses the patients, develops treatment strategy, and starts OAC as appropriate; 3) the hospital refers the patients back to GPs, where patients receive follow-up care according to the treatment strategy; and 4) re-assessment at the hospital is repeated once a year. The network, which covers the majority of GPs in the region, contributed to reducing hospital burden and improving OAC treatment, with approximately 90% of AF patients registered now receiving OAC therapy. Case Study 3: Izumisano Public Health Activities 20 Regional governments and public health centers in Izumisano, Osaka, have been working on stroke prevention because it was identified as causing the most significant socioeconomic burden in the region. In 2014, in addition to public campaigns primarily focusing on hypertension, they decided to develop practical guidance on public health activities for prevention of AF-related stroke, the deadliest and most debilitating, but preventable form of stroke. The Izumisano- Sennan Medical Association was also engaged in this development. The joint workinggroup discussed what could be done for AF-related stroke prevention under the current health checkup system, where ECG is not necessarily included, without incurring significant additional costs. The guidance proposed included: 1) ECG and/or pulse checks by doctors or nurses; 2) referring patients with AF or irregular pulse detected to doctors; 3) establishing care coordination network for AF management; and 4) key measurements for assessment (details are publicly available at Prevention of AF-related stroke in the region is being promoted based on the proposed guidance, and more municipalities now include ECG for every individual in the designated health checkup system. It has been confirmed that the diagnosis rate of AF improves when ECG is conducted in every individual subject Lengthening Healthy Lifespans to Boost Economic Growth 69

71 to the designated health checkup. In order to further enforce the initiative, it is important to promote cross-functional collaboration among medical institutions, governments and public health centers. References 1. 厚生労働省平成 27 年 (2015) 人口動態統計月報年計 ( 概数 ) の概況 2. 脳卒中有病者数と脳卒中による要介護者数の推定 厚生労働科学研究費補助金健康科学総合研究事業 地域脳卒中発症登録を利用した脳卒中医療の質の評価に関する研究 ( 主任研究者 : 鈴木一夫 ) 文部科学省科学研究費補助金( 基盤研究 (B)) 循環器疾患発症の長期推移と地域のリスク要因の推移との関連に関する研究 ( 主任研究者 : 喜多義邦 ) 3. 日本脳卒中学会 rt-pa( アルテプラーゼ ) 静注療法適正治療指針第二版 (2016 年 9 月一部改訂 ) 4. 厚生労働省平成 25 年国民生活基礎調査の概況 5. 厚生労働省平成 26 年度国民医療費の概況 6. 厚生労働省平成 26 年 (2014) 患者調査の概況 7. 脳卒中データバンク 2015 小林祥泰編集 8. ACCJ 疾病の予防 早期発見および経済的負担に関する意識調査: 報告書 2011 年 11 月 9. Hart RG, et al. Ann Intern Med 2007; 146: Hannon N, et al. Cerebrovasc Dis 2010; 29: Akao M, et al. Circ J. 2014; 78: Fang MC, et al. J Am Coll Cardiol 2008; 51: Reynolds MR, et al. Am J Cardiol 2006; 97: Parker CS, et al. J Gen Intern Med 2007; 22: 厚生労働省保険局健康保険組合連合会 データヘルス計画作成の手引き ( 平成 26 年 12 月 ) 16. 日本脳卒中学会ホームページ 日本循環器学会ホームページ 脳卒中 循環器病対策基本法の成立を求める会ホームページ Ontario Stroke Network 脳卒中予防への提言書- 心原性脳塞栓症の制圧を目指して - の第二版, 心房細動による脳卒中を予防するプロジェクト実行委員会 ( 山口武典ほか ) 20. 脳卒中予防への提言書- 心原性脳塞栓症の制圧を目指して - の第三版, 心房細動による脳卒中を予防するプロジェクト実行委員会 ( 山口武典ほか ) 70 Lengthening Healthy Lifespans to Boost Economic Growth

72 Seven Recommendations to Prevent AF-related Stroke Early AF detection Promote proper treatment for stroke prevention in AF patients Incorporate opportunistic AF screening (pulse check followed by ECG) into clinical practice Promote care coordination between GPs and Specialists in AF management Promote self-pulse check Daily Life Specialists GPs Leverage Health Checkups (pulse check, ECG, training for self-pulse check) Health Check-ups Pharmacists Promote integrated community action to drive AF detection and management Drive Public Health and Healthcare collaboration Drive Pharmacist-Physician collaboration in ensuring optimal anticoagulation therapy Source: TASK-AF Report ver available at Lengthening Healthy Lifespans to Boost Economic Growth 71

73 14 Reduce the Risk of Cerebral Infarction by Early Detection of Carotid Plaque Situation Cerebrovascular diseases was the leading cause of death in Japan for three decades after World War II. However, with public education efforts aimed at preventing high blood pressure along with the development of innovative technologies for diagnostic imaging, minimally invasive treatment and medicines, the number of deaths from these diseases has been decreasing since the early 1970s. Data from the Ministry of Health, Labour, and Welfare (MHLW) shows that the number of deaths related to cerebrovascular diseases has fallen by 15.5% between 2000 and 2015, and the number of patients with cerebrovascular disease fell by 20% between 1999 and 2014, showing a correlation between the decline in the number of deaths and the incidence of cerebrovascular disease. On the other hand, the proportion of cerebrovascular disease-related deaths that encompass a cerebral infarction has been increasing year by year. It was 13.3% in 1960 and up to 57.6% in The spread of the western food culture and the increasing numbers of diabetes and hyperlipemia patients are recognized as general causes for the increase. In addition, cerebral infarction patients make up a large part of the total number of patients suffering from cerebrovascular diseases, comprising approximately 66% in Patients with cerebral infarction are more likely to need in-hospital treatment when compared to patients with other types of cerebrovascular diseases. Therefore, the government of Japan recognizes cerebral infarction as a disease that must be addressed in order to slow rising medical expenses. In the area of nursing care, patients and caregivers responded to a survey conducted by the MHLW by saying that the main reasons for receiving or providing nursing care are related to cerebrovascular diseases. Thus, the issue of cerebral infarction relates to another subject of the government s future healthcare policy: the transfer from in-hospital care to home healthcare (nursing care). The main causes of cerebral infarction are stenosis or occlusion of vascular lumen by atherosclerotic plaque and arterial embolism by vulnerable plaque. The carotid artery is one of the body parts where atherosclerosis occurs more frequently and it is well recognized that the use of MRI and ultrasound systems are effective to examine the condition of the plaque, and even its vulnerability. Furthermore, a diagnosis provided by these two systems gives important information to doctors who decide on surgical treatment. Patients also benefit from the minimally invasive nature of the examinations. The validity of diagnostic imaging with MRI and ultrasound to detect the causes of cerebral infarction in the early stage is gaining support among doctors. Working groups organized by medical specialists of the Japan Brain Dock Society and the Japan Academy of Nurosonology are currently making efforts on improving the precision of the examinations and spreading the use of MRI and ultrasound to hospitals and clinics. Current Policy The government of Japan continues to organize public education activities for prevention and early detection of cerebral infarction. Some local governments provide citizens with subsidies for brain examinations, and private sector companies and health insurance associations prepare package programs of financial support for examination of cerebral infarction. However, opportunities for examination are not accessible to all eligible in Japan due to geographic maldistribution of examination facilities or local government budget restraints. Moreover, when compared to the government s enthusiasm for building public awareness of the importance of using ultrasound systems for breast cancer screening, there is much work to be done in providing 72 Lengthening Healthy Lifespans to Boost Economic Growth

74 access to, and standardizing, examinations of carotid plaque in all regions of Japan. Recommendations To promote early detection of carotid plaque and to maximize quality of life of all citizens, increase public awareness of the importance of carotid plaque examinations by organizing public lectures and through public media campaigns. Develop more financial support programs for carotid plaque examinations to provide equal healthcare opportunities across the country References 1. e-stat, 脳血管疾患の病類別にみた性 年次別死亡数 百分率 粗死亡率及び年齢調整死亡率 ( 人口 10 万対 )5-27, Last modified December 5, 2016, disp=other&requestsender=dsearch 2. Ministry of Health, Labour and Welfare, 目次タブ内 > 脳血管疾患 ( 脳卒中 ) 参照, last modified 2014, go.jp/toukei/saikin/hw/kanja/10syoubyo/ 3. Ibid. 4. Franzetti, F., et al Effectiveness of switching from open to closed infusion system for reducing central vascular associated bloodstream infections in an Italian hospital. American Journal of Infection Control 35(5): e67-e Salomao, R., et al Probability of developing a central vascular catheter-associated bloodstream infection when comparing open and closed infusion systems in Brazil. Proceedings and abstracts of the 47th annual scientific meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, United States (September 17 20). 6. Rosenthal, V.D., et al Am J Infect Control. 7. Higuera, F., et al Attributable cost and length of stay for patients with central venous catheter-associated bloodstream infection in Mexico City intensive care units. Inf Control Hosp Epidemiology 28: Salomao, R., et al The attributable cost, and length of hospital stay of patients with central line-associated blood stream infection in intensive care units in Brazil. Am J Infect Control 34: e22. Lengthening Healthy Lifespans to Boost Economic Growth 73

75 Deaths Caused by Cerebrovascular Diseases Aubarachnoid hemorrhage Cerebral hemorrhage Cerebral infarc=on Others Aubarachnoid hemorrhage Cerebral hemorrhage Cerebral infarc=on Others Source: Ministry of Health, Labour and Welfare Deaths and Patients of Cerebrovascular Diseases # of Pa=ents # of Deaths Source: Ministry of Health, Labour and Welfare 74 Lengthening Healthy Lifespans to Boost Economic Growth

76 Vessel Wall Imaging Done by MRI Lengthening Healthy Lifespans to Boost Economic Growth 75

77 15 Stronger Disease Prevention Based on the Stable Implementation of Immunization Policy Situation In recent years, many new vaccines have become available in Japan, and the number of diseases targeted by the national immunization program have increased. As the number of vaccine targets have increased, immunization schedules have become crowded, particularly the immunization schedule for infants, which requires nine classes of vaccinations in the Japanese National Immunization Program. Because simultaneous vaccinations are not yet standard in Japan, this places a great burden on both the infant and the accompanying guardian. The vaccination rate for pediatric vaccines that have been introduced in the National Immunization Program remains stable and high, at over 95%. In contrast, the vaccination rate for Category B diseases such as influenza and pneumococcal pneumonia for elderly people is only around 40-50%. 1 In addition, the vaccination rate for HPV, for which active recommendation was discontinued in June 2013 is 0.5%. 1 Not every disease that is targeted for the National Immunization Program achieves high vaccination rates. Issues have also been identified regarding the stable supply of vaccines. In 2016, the Ministry of Health, Labour and Welfare (MHLW) issued requests to local governments for cooperation in ensuring the stable supply of hepatitis B and MR vaccines. 2,3 These requests were caused by unexpected circumstances such as natural disasters that led to sudden increases in demand. However, unless vaccines can be supplied in a stable manner, the National Immunization Program s operations are at risk for disruption. In 2015, Japan was certified by the World Health Organization (WHO) as a country where measles has been eliminated. Although there have been no reported cases of domestic origin since then, there have been outbreaks due to imported viruses, and in 2016 there were several such cases including an outbreak centered near the Kansai International Airport. 4 With international events including the 2019 Rugby World Cup and the 2020 Olympics and Paralympic Games approaching, the number of travelers will continue to increase. Therefore, the need for immunization to prevent infectious diseases is also increasing. Current Policy Based on the immunization law that was revised in April 2013, Japan s first national immunization plan, The Basic Plan for Vaccination, took effect in April The plan clearly stated the basic philosophy behind Japan s immunization policy, which is that vaccinations should be provided for diseases that can be prevented through immunization and vaccines. There has been great progress in discussions on introducing new vaccines into the national immunization program to achieve the priority goal of the Basic Plan, which is to eliminate vaccination gaps. Since the 2013 revisions to the immunization law, coverage has been added for six diseases (HPV, Hib, pediatric pneumococcus, elderly pneumococcus, varicella, and hepatitis B). However, discussions continue on the National Immunization Program and rotavirus vaccine, Haemophilus influenzae type b sediment vaccine, Diphtheria pertussis tetanus combination vaccine second stage (for year olds), and the effectiveness in adults of the Pneumococcal vaccine (13-valent conjugate) and the varicella vaccine. Deliberations on the rotavirus vaccine are taking the longest time, with no final conclusions reached even after 5 years of discussions. Although combination vaccines, including vaccines that contain both Measles and Rubella antigens, are mentioned as a high development priority in the Basic Plan for Vaccination, there has been no progress toward their introduction. Since the implementation of the Basic Plan for Vaccination, the Task Force on Vaccines and Blood Products was set up in January 2016 in response to concerns of the Chemo-Sero- 76 Lengthening Healthy Lifespans to Boost Economic Growth

78 Therapeutic Research Institute. The purpose of this Task Force is to look into drastic measures, including the role of industry, to address issues related to the stable supply of vaccines and blood products. In October 2016, they presented policy proposals on the vaccine industry and vaccine administration. 6 Issues The ACCJ and EBC greatly appreciate such governmental efforts to improve vaccination policy in this way. However, concerns remain about the following issues. The examination schedule for having a vaccine introduced into the National Immunization Program is unclear. Because of this, predictability is low regarding how a vaccine becomes part of the National Immunization Program, which in turn makes it difficult to create development and production plans for new vaccines. In order to introduce a new vaccine into the National Immunization Program, it is necessary to secure funding in the national budget. This is a separate process from council that evaluates whether a vaccine should be included in the National Immunization Program from a scientific point of view. Therefore, even when the council presents its findings, the vaccine may never become part of the National Immunization Program unless funding is secured in the government budget. Even if a vaccine is included in the National Immunization Program, its supply planning and distribution are basically left up to the manufacturers and market forces. There are a number of processes involved in producing a vaccine, from manufacturing to shipment. Because it takes about a year to complete these processes, a reduction in supply due to unexpected problems or a sudden increase in demand due to an outbreak can lead to a vaccine being in short supply when it is needed. In spite of this, long-term measures at the national level to ensure a stable supply have not been considered. Introducing a new vaccine into the National Immunization Program requires the collection and evaluation of basic data to assess its effectiveness and safety. However, at present, while there is a council that conducts evaluations, the system for collecting and maintaining basic data is insufficient, making it difficult to conduct evaluations and analysis in a timely manner. Immediately after the HPV vaccine was added to the regular vaccination program, reports of adverse effects were received, and active recommendation of the vaccine was suspended in June 2013 so that experts could quickly carry out assessments. However, because data such as the epidemiological information and vaccination records required to scientifically examine the reported events were not collected and maintained, studies to evaluate the causal relationship between the vaccine and adverse events are taking a great deal of time. As of July 2017, the results of the scientific evaluation had still not been obtained, leaving no effective means to address the increased risk of HPV infection. This situation has caused confusion and concern among healthcare workers, municipalities, and people in Japan. Because Japan s quality standards and regulations related to the development of mixed vaccines differ from those of other countries, there has been no progress in introducing mixed vaccines that are routinely used overseas. Japan also has unique quality standards for existing vaccines. Because of these, in some cases vaccines that are widely distributed overseas are manufactured separately for Japan. As a result, when a shortage occurs in Japan, even if the vaccine is available overseas it cannot Lengthening Healthy Lifespans to Boost Economic Growth 77

79 be distributed in Japan, so there is the risk that Japan alone may experience related shortages. Although the number of vaccines in the National Immunization Program is increasing, the government does not offer information on the usefulness of immunization for individuals and society or information on risks that, while rare, are possible in a way that is easy for people to understand. As a result, it has become difficult for guardians and those being inoculated to make decisions regarding vaccinations based on accurate information. Recommendations Create clear requirements and criteria, along with a standard review schedule, so that a new vaccine can be promptly included in Japan s National Immunization Program after obtaining approval under the Pharmaceutical Affairs Law. Provide complete government financial support for all vaccines. In addition, establish a structure to secure permanent financial resources for that purpose. Establish a system to allow the acquisition of information on disease incidence trends, epidemiological data, and disease burden in order to scientifically evaluate the effectiveness of vaccines. Information on the background incidence rates of various diseases required for safety evaluations should also be included. To ensure a stable supply of the vaccines included in the National Immunization Program, build a national vaccine stockpiling system based on discussions and collaboration between industry, the government and academia. Promote the harmonization of vaccine approval requirements, regulations related to development, and quality standards across major countries and regions. Because public understanding is extremely important in promoting immunization, the national government should actively transmit information on an ongoing basis that is easy for people to understand in order to strengthen public awareness of the importance of immunization and of the immunization system itself. At the same time, they should establish a system to implement appropriate communication regarding risks in the event of an emergency. Case study: The US pediatric vaccine stockpiling system 7 In the United States, there is a national stockpiling system in place for all vaccines used in regular pediatric vaccinations. This system, funded by the CDC (Centers for Disease Control and Prevention), began in By 1998, they had accumulated a six-month stockpile of most pediatric vaccines, including combination vaccines. Currently, it operates on funding from the national government s Vaccines for Children Program (VCP). All pediatric vaccines are covered, including combination vaccines. Seasonal influenza vaccines, for which stocks change every year, are purchased for stockpiles once per year for the second half of the season (December January) using government funds. The amounts of each vaccine used are monitored frequently and adjusted appropriately. In addition, the manufacturers manage expiry dates by replacing the stockpiled vaccines as appropriate. When a supply shortage occurs, the manufacturer of the vaccine involved borrows stock from the government s stockpile to fill orders for regular vaccinations or other needs. After the supply shortage has been resolved, the manufacturer replaces the amount of vaccine borrowed. Information on vaccines that have had supply problems is published periodically on the websites of the Advisory Committee on Immunization Practices (ACIP) and the Centers for Diseases 78 Lengthening Healthy Lifespans to Boost Economic Growth

80 Control and Prevention (CDC), and the government, manufacturers, and other related parties maintain close communication and cooperation, discussing and responding to vaccine supply issues. References 1. The 18 th Committee on Immunization Policy, Reference No Request for cooperation; About the stable supply of HepB vaccine, 29 th Sep Request; About proactive recommendation of MR vaccine for Phase 2 subjects in NIP, and the stable supply of MR vaccine, etc., 27 th Jan The case of outbreaks of measles in Kansai Airport A Basic Plan for Vaccinations March 28, 2014 (viewed on March 30, 2017) Recommendations from the Vaccine / Blood Products Industry Task Force advisors October 18, 2016 (viewed on March 30, 2017) Kimberly S. Lane et al., Clinical Infectious Diseases 2006; 42:S125 9 Lengthening Healthy Lifespans to Boost Economic Growth 79

81 Policy proposals for the vaccine industry and vaccine policy by the Taskforce on Vaccines and Blood Products Policy proposals for the vaccine industry and vaccine policy! Promote evidence-based vaccination policy! Implement company size/market structural reforms! Secure a stable supply! Harmonize the approval system internationally! Expand the research and development/production system! Promote international expansion Members of the Taskforce on Vaccines and Blood Products Shigeru Omi, President, Incorporated Administrative Agency, Japan Community Health Care Organization Jugo Hanai, Director, Nonprofit Organization, Medical Care and Human Rights Network Kenji Shibuya, Professor, Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo Tatsuya Kondo, Chief Executive, Incorporated Administrative Agency, Pharmaceuticals and Medical Devices Agency (PMDA) Proposals by consultants of the Taskforce on Vaccines and Blood Product, 18 th October, 2016 A mechanism for scientific implementation is necessary for evaluation of the efficacy and safety of vaccination. Policy proposals for the vaccine industry and vaccine policy An excerpt from Promotion of evidence-based vaccination policy! We should enhance the activity of collecting and analyzing active epidemiological data using the information and communication technology (ICT) based medical information network. Especially in the case of adverse events, reports should lead to immediate epidemiological investigations to prevent people from refusing vaccinations, in line with the Vaccine Adverse Event Reporting System (VAERS), which is a system for vaccine recipients to report adverse events that is implemented in the U.S. Proposals by consultants of the Taskforce on Vaccines and Blood Products, October 18, Lengthening Healthy Lifespans to Boost Economic Growth

82 International harmonization is necessary for vaccine approvals, development regulations, and quality standards. Policy proposals for the vaccine industry and vaccine policy Excerpts from International harmonization of the approval system! Harmonization of regulations including the approval system and quality management, which vary between different countries, should be promoted to support international expansion of domestic suppliers and create a suitable domestic environment for foreign suppliers to enter the market.! Regulatory authorities in each country should cooperate to develop new vaccines simultaneously in global collaborative studies to achieve efficient development from the viewpoint of international harmonization and cooperation.! We should discuss the concept of national examinations and improve the efficiency and speed of the approval process. Proposals by consultants of the Taskforce on Vaccines and Blood Product, 18 th October, 2016 Lengthening Healthy Lifespans to Boost Economic Growth 81

83 16 Increase Hepatitis B Screening, Vaccinations, and Aggressive Treatments Situation Viral hepatitis is considered to be the most common contagious disease in Japan. Of the estimated 2.1 to 2.8 million patients and carriers of viral hepatitis B (HBV) and hepatitis C (HCV), 1.1 to 1.25 million people (approximately 1% of the Japanese population) are thought to be persistently infected with HBV. 1 Chronic HBV and HCV infection significantly increases risk of hepatic carcinoma. The number of deaths from liver cancer in Japan has been rising rapidly since 1975, and, as of 2015, stood at about 30,000 per year although it has recently begun to decline. About 15-20% of these cases are due to infection with HBV. There are few subjective symptoms associated with HBV infection, and the disease can progress without a person being aware they are infected. Epidemiological data show that nearly one million carriers, approximately 70 to 80% of the total HBV positive patient population, are not aware of their HBV infection. 2,3 Therefore, it is important for those infected with HBV and HCV to become aware of their status, access appropriate treatments, and periodically monitor their disease status, which could significantly reduce potential risks associated with hepatocellular carcinomas. However, public awareness of these facts remains low, despite efforts to educate the public about the disease that have been repeated over the years. The main reason that awareness remains low is because risk of infection, ways to prevent infection, and comprehensive hospital education that could enhance awareness of diagnostic and treatment options have not been sufficiently shared with the public. Additionally, there are new treatments, which have been included in the list of drugs eligible for reimbursement since 2014, available that can eliminate HCV from the body thereby curing HCV induced chronic hepatitis. In contrast, the latest clinically available HBV treatment drugs cannot eliminate HBV from the human body, although they can bring HBV down to a quiescent level. As a result, those infected with HBV have less motivation to access aggressive clinical treatment options when compared to HCV patients, even if they are aware of their HBV infection. Epidemiological studies suggest that consistent suppression of HBV virus in the body may improve liver functioning and could reverse cirrhosis caused by the virus. Therefore, aggressive treatment of HBV with the latest treatment options is critical even with the currently available treatments. Hepatitis caused by chronic HBV infection, as well as with chronic HCV infection, continues to progress through to cirrhosis, decompensation, and hepatocellular carcinomas. Furthermore, HBV infection, unlike HCV, can induce fulminant hepatitis within a short period of time after infection, and some case reports indicate that these patients occasionally require plasma exchange or liver transplantation. Therefore, it is essential not only to prevent HBV infection, but also to detect HBV infection as early as possible, followed by adequate medical treatments at the appropriate time. HBV, like HCV, can be easily detected with a blood test. Therefore, once hepatitis screening tests are accelerated, HBV infection could be identified at an earlier stage, allowing patients to get appropriate diagnostic tests, followed by adequate treatment options provided by hepatologists before significant liver damage can occur. Hepatitis screening tests are currently voluntary, and are available as a supplemental option associated with regular or special annual health check-up programs, or as an independent screening test. However, the ratio of hepatitis screening tests still remains low.4 Given that conventional hepatitis screening tests can detect HBV infection together with that of HCV, it is quite essential to require 82 Lengthening Healthy Lifespans to Boost Economic Growth

84 acceleration of hepatitis screening tests not only from patients treatment perspective, but from a public health point of view. Although elimination of HBV from the human body cannot currently be achieved, the latest HBV treatments can maintain HBV viral load levels below detectable limits at doses that are one tenth of those required of previously available treatments. Newer treatments better target liver hepatocytes, reducing the effective dose and significantly reducing the adverse effects of treatment when used for a chronic treatment over a longer period of time. Even with improved treatments, R&D efforts to pursue an HBV cure continue. For these reasons, it is even more critical to accelerate hepatitis screening tests to detect HBV infection as early as possible. In May 2016, the World Health Organization (WHO) General Assembly unanimously adopted a strategy to eliminate viral hepatitis from every member country by 2030, and declared aggressive implementation of policy measures to control hepatitis across the globe. 5 Amidst increased global focus on this issue, it is more critical than ever to take more aggressive approaches to accelerate HBV patient identification and treatment in Japan. HBV Prevention Since HBV induced hepatitis has been linked to liver cancer, this type of cancer is considered preventable. HBV infection can be primarily prevented by HBV vaccines. Therefore, aggressive HBV vaccination has been proposed to date. HBV is transmitted via blood and bodily fluids. Even in the form of dried blood, HBV remains infectious for more than one week. 3 Many people have been infected without realizing it because of the various possible modes of transmission, including mother-to-child transmission, transmission through repeated use of an injection syringe or needle (i.e., for mass vaccinations), and sexual transmission. In 1986, a Mother-to-Child Transmission Prevention Program was started in Japan as an HBV infection control measure whereby newborn babies of mothers carrying HBV were vaccinated. Following introduction of the program, the HBV carrier rate declined to 0.04%. However, infection caused by other modes of transmission, including father-to-child transmission and child-to-child horizontal transmission at childcare centers, remains an issue. Further, in recent years, an acute viral inflammation via sexual transmission brought the HBV of genotype A into Japan from other countries. Acute infection with HBV genotype A is a growing public health concern, as genotype A has a higher rate of persistent infection than other genotypes, and has been spreading in Japan. Furthermore, it has been reported that when some patients with a history of HBV received chemotherapy and immunosuppressive therapy, the HBV was reactivated even after it was successfully controlled for years, and at times severe or lethal hepatitis resulted. 5 Only HBV vaccination can completely prevent this type of unexpected reaction. The WHO recommends that universal HBV immunization should be conducted in all nations. Most countries have introduced universal vaccination programs for children (newborn babies and school children). In Japan, a universal vaccination program for all newborns after April 1, 2016, has been implemented since October 1, There is no catch-up vaccination program to cover children and adolescents who were born before April Hepatitis Screening Tests Current available hepatitis screening tests can generally detect HBV and HCV infection Lengthening Healthy Lifespans to Boost Economic Growth 83

85 at the same time. The number of screened people has remained around 1.1 to 1.2 million annually and the screening rate continues to be low, especially among employees. This is the same trend as HCV screening tests. Some employee insurance organizations provide free and voluntary hepatitis screening tests for their members and spouses, but organization are not asked to provide mandatory hepatitis screening services to members. After implementing and executing the Basic Hepatitis Control Act, policy measures to control hepatitis including HBV have been aggressively deployed. However, these efforts have not led to a dramatic increase in the hepatitis screening test ratio yet. HBV Treatment Interferon (IFN) has been used to treat chronic hepatitis since 1986, and antiviral treatments using nucleic acid analogues have been administered since IFN treatment duration was originally restricted to four weeks, and was extended to six months in In 2008, self-injection of IFN-alpha received regulatory approval, and, since 2011, 12 month treatments with Peg-INF-alpha2a products have been available. INF-based treatments are widely effective for younger HBV patients and patients with genotype A or B HBV infection. These treatments can effectively reduce the volume of anti-hbs antigens as well as those of HBV DNA. INF-based treatments are, therefore, efficient treatment options for some patients in preventing HBV induced hepatocellular carcinoma. Among nucleic acid analogues, Lamivudine was firstly launched in 2000 for HBV treatment. However, it increased the risk of developing drug-resistance. Other new nucleic acid analogues were introduced in 2004, 2006 and 2014 to provide various clinical treatment options. These wider options can now control even those patients who have developed resistance to some anti-hbv nucleic acid drugs. Adequate treatment using these anti-viral drugs can modify the disease status of HBV induced chronic hepatitis and cirrhosis, and prevent hepatocellular carcinoma, through reversing cirrhosis with treatment. 7,8 The latest nucleic acid analogue launched in 2017 provides equivalent clinical efficacies to control HBV with one tenth dose than the previous drug. This option provides a new paradigm for treatment of HBV induced hepatitis with less concerns about adverse effects of the drug under longer duration of treatment. Aid for Medical Expenses Beginning in 2009, the government of Japan (GOJ) began disbursing aid for medical expenses for hepatitis. Since January 2010, after implementing Basic Act on Hepatitis Measures, this system was upgraded so that in principle the out-of-pocket cost to each patient for treatment is only 10,000 or 20,000 yen per month. Subsequently, newly developed antiviral medications for HBV have been added to the list of covered treatments under the existing system. Current Policy A vaccination program to prevent motherto-child HBV infection has been effective in preventing the vertical transmission of HBV from mothers to infants. However, vaccinations for the rest of the infant and child population has not been introduced as a part of the regular vaccination program. Therefore, horizontal HBV transmission persists and effective vaccination of these populations has become a public health issue. Unless tested, it is very difficult for patients to recognize that they have HBV, but the screening ratio of hepatitis tests still remains low. Under these circumstances, in January 2015, the Immunizations and Vaccines Sub-council of the Health Science Council recommended introducing universal vaccination of infants. The program has been implemented and vaccinations to all children born after April 1, 2016, have included the HBV vaccine in the regular vaccination program Lengthening Healthy Lifespans to Boost Economic Growth

86 However, the HBV vaccination catch-up program that provides vaccinations to infants and children over one year old (those born before April 1, 2016) remains voluntary. On November 30, 2009, the Hepatitis Basic Law was enacted because hepatitis diseases are considered to be the most contagious diseases in Japan. Under this law, comprehensive hepatitis control measures have been executed as a health policy strategy. The law defines the basic principles of hepatitis control and clarifies the responsibilities of Japanese national and local governments in terms of ensuring comprehensive execution of measures for hepatitis prevention, early detection and control disease progressions. The law also defines policies for the provision of economic support for the treatment of infected patients. In May 2011, the MHLW revised the basic guidelines for hepatitis testing to enable hepatitis screening tests to be included in employees annual medical checkups as a voluntary option. At the same time, the MHLW issued fundamental guidelines for the promotion of hepatitis virus screening that state all Japanese should receive the screening test at least once in their life and a system to provide broad screening services, and urge people to use the services, needs to be established. Free screening is, however, still not available for employees who receive health insurance coverage through the health insurance associations of private employers. There is also concern about potential discrimination or bias against employees who are found to be infected with the hepatitis virus. Therefore, only a limited increase in the screening rate was expected even under current conditions. Under these circumstances, in June 2016, the MHLW drastically revised the existing Basic Strategies to Control Hepatic Diseases, followed by a major revision of 10 year strategic initiatives for measuring hepatic diseases in December These upgraded policy strategies and initiatives could accelerate aggressive promotion of hepatitis screening tests, together with appropriate execution of adequate medical treatments to viral hepatitis patients by liver disease specialists. Recommendations Vaccination is the most important and secure means of HBV infection control. Although a regular vaccination program for newborns has been executed, the population of infants and children who have not been vaccinated under the voluntary HBV vaccination program still face risk of HBV infection. As of today, there are no cure options to eliminate HBV from an infected human body. Therefore, careful considerations of the cost effectiveness and supply capabilities of vaccine manufacturers strongly suggest that the GOJ should consider aggressive implementation of the HBV vaccination catch-up program aimed at infants and adolescents as the most effective HBV infection prevention program. GOJ should implement measures to further increase hepatitis screening levels among the general public in Japan, which can result in a decrease in the prevalence of HBV induced cirrhosis and hepatocellular carcinoma: Introduce effective hepatitis education programs across Japan for adults and students, based on public-private sector collaboration. Implement hepatitis screening tests as a standard item in employees annual health checkups. Currently, hepatitis screening tests are only recommended for employees medical checkups, but they should become mandatory requirements. Public funds should be provided so that there is no need for individuals to pay a co-payment or fee. Lengthening Healthy Lifespans to Boost Economic Growth 85

87 National and local numeric goals should be set for hepatitis screening rates for those covered by both employer-based insurance and resident-based insurance, respectively. GOJ should ask each prefectural government to establish and strengthen collaborative clinical treatment systems and flows involving appropriate local stakeholders to provide adequate treatment measures to HBV carriers in a timely manner, and track the execution progress of these measures annually. GOJ should work cooperatively with private companies, health insurance payers, and health advisors to establish a public health education system to deliver accurate and easy-to-understand information on HBV induced liver diseases and the latest medical treatment options. They should also work together to allow HBV carriers to access appropriate medical treatment options without discrimination when someone tests positive for the hepatitis virus. References 1. MHLW National Execution Program for Promoting Comprehensive Hepatitis Measures Let s Know Hepatitis Project, accessed March 28, 2017: 2. Ministry of Health, Labour, and Welfare National Cancer Center Cancer Information Service, Hepatocellular Carcinoma, accessed February 16, 2017: 4. Ministry of Health, Labour and Welfare Hepatitis B Vaccine Task Force Japan National Institute of Infectious Diseases Hepatitis V Vaccine Fact Sheet (July 7). and forpatient_hbv.html. 6. Ministry of Health Labour and Welfare Japanese Society of Hepatology: White Paper of Liver Cancer, European Association for the Study of the Liver, 2017 EASL Clinical Practice Guidelines on the management of hepatitis B virus infection: 86 Lengthening Healthy Lifespans to Boost Economic Growth

88 Regular HB Vaccination to Newborn Babies! Program Launch Date: October 1, 2016! Objective: Hepatitis B is an infectious disease. To prevent its occurrence and transmission from person to person, and considering its seriousness or severity, the preventive vaccination should be recommended. 1! Target for vaccination: Babies born after April 1,, 2016 before the first birthday! Schedules: Standard schedule- three times (at 2 months, 3 months, and 7-8 months of age). 2 " No regular catch-up programs for babies born before April 1, 2016 Source 1: MHLW 4 th Vaccination Policy Committee, material 1-1 Source 2: Clinical Guidance on National Immunization Program Historical Trends in Persistent Infections with Hepatitis B Virus Policy Research Project to Conquer Hepatitis Units: 10,000 people (estimate) Total number of infected Undiagnosed patients Patients Special summary from patient study 33.2 Insurance claims No continued treatment New infections Cured Died *Deaths from all causes 22.8 Partial excerpt from materials submitted by committee-member Tanaka, Document 3, MHLW th Council for Anti-Hepatitis Strategy, On Trends in Persistent Infections with Hepatitis C Virus, 2/26/2017 More people are being tested for the hepatitis virus, and the number of unaware undiagnosed patients is decreasing. A newly recognized problem is the increasing number of infected patients categorized as not continuing treatment. Lengthening Healthy Lifespans to Boost Economic Growth 87

89 Providing Hepatitis Screening as Part of Annual Health Checkups is Most Effective # A majority of people 38.2% who have been screened for the hepatitis virus cite that they were screened because it was offered as a part of their annual health checkup. However, most annual health checkups in Japan do not include the hepatitis screening test as a standard option. # The best way to increase the screening rate is to provide free screening tests nationwide along with regular annual health checkups for people aged 40 or over within a specific period of time while carefully protecting personal information. Reason Screened It was in the menu of my regular health checkup Tested at time of surgery, pregnancy or endoscopic test 40 Received a notice from my local government health office Tested when gave blood Because friend or family member had hepatitis / HP Learned of free screening program from municipal government pamphlet or website Few people tested in current free screening program (%) 38.2 Source: MHLW 2011 Status of Participation in Hepatitis Screening: Understanding the Reality Initiative (National study with 74,000 Japanese between 20 and 79 years of age); August 2012 Presentation of Report (unofficial translation of , ) Indications for selecting ETV or TAF over TDF* " ETV, TAF and TDF as monotherapy are preferred first line treatment " Patients on TDF at risk of development and/or with underlying renal or bone disease should be offered the option to switch to ETV or TAF 1. Age >60 years 2. Bone disease Chronic steroid use or use of other medications that worsen bone density History of fragility fracture Osteoporosis 3. Renal alteration** egfr <60 ml/min/1.73 m 2 Albuminuria >30 mg/24 h or moderate dipstick proteinuria Low phosphate (<2.5 mg/dl) Hemodialysis * TAF should be preferred to ETV in patients with previous exposure to nucleoside analogues. ** ETV dose needs to be adjusted if egfr <50 ml/min; no dose adjustment of TAF is required in adults or adolescents (aged at least 12 years and of at least 35 kg body weight) with estimated creatinine clearance (CrCl) >15 ml/min or in patients with CrCl <15 ml/min who are receiving hemodialysis. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection 88 Lengthening Healthy Lifespans to Boost Economic Growth

90 17 Increase Hepatitis C Virus Screening and Promote HCV Treatment Situation The number of deaths from liver cancer in Japan has been rising rapidly since As of 2015, this figure stood at about 30,000 per year and has recently begun to decline. About 60% of these cases are due to infection with the hepatitis C virus (HCV). 1 The group with the highest prevalence are those over 60 years old, with an estimated 1 to 1.5 million carriers (as of 2011). 2 Most infections in this group are due to medical procedures before the 1980s, when disposable medical implements had not become widespread, or result from contaminated blood transfusions prior to 1989, when the HCV test was introduced to check blood to be transfused. There are few subjective symptoms associated with hepatitis C infection, and the disease can progress from chronic hepatitis to hepatic cirrhosis to liver cancer without the patient being aware of the infection. 3 However, HCV can be easily detected with a blood test. Therefore, it is important for everyone to be screened for HCV as early as possible before chronic hepatitis progresses into advanced stages, such as compensated/decompensated cirrhosis or hepatocellar carcinoma. Those who are infected should receive appropriate treatment as soon as possible to prevent continued damage to the liver. Hepatitis screening tests are currently voluntary, and are available as a supplemental option associated with regular or special annual health check-up programs, or as an independent screening test. Yet, hepatitis screening rates remain low. 4 The treatment paradigm of HCV has drastically changed in Japan since It is now possible to eliminate HCV more quickly and reliably, with shorter treatment duration and higher elimination rates compared to previous treatment options. In May 2016, the World Health Organization (WHO) general assembly unanimously adopted a strategy to eliminate viral hepatitis from every member country by 2030 and declared aggressive implementation of policy measures to control hepatitis across the globe. 5 To date, it is estimated that approximately 70-80% of those who are HCV positive have been diagnosed, leaving 20 30% unaware of their infection. 6 Furthermore, at least one third of the 80% of patients who are aware of their HCV status have not been treated, enabling their disease to silently progress toward liver failure. Hepatitis Viral Test In 2002, the government of Japan offered hepatitis viral testing through health examinations provided by local governments nationwide as part of the Health and Medical Service Act for the Aged. About 100,000 HCV carriers were detected out of more than 8.5 million who received the test. 6 Subsequent efforts to increase convenience of testing by extending free testing to healthcare centers, clinics, and hospitals have been recognized as effective because of a steadily increasing number of people being tested. 6 The number of those infected with HCV who were unaware of their infection was estimated to be 880,000 in This figure fell to an estimated 296,000 by The nearly 300,000 HCV carriers who are unaware of their HCV status are considered at risk of developing liver disease. Therefore, it is critical for public health providers to establish systems going forward to facilitate routine or incidental hepatitis C testing for the entire adult population. Between 2011 and 2014, the number of HCV tests provided annually by local governments remained constant at 1.1 to 1.2 million. 8 One long-cited problem is the low rate of hepatitis tests provided by employer-based health Lengthening Healthy Lifespans to Boost Economic Growth 89

91 insurance organizations, which are not currently required to provide HCV screenings as a part of the current health checkup program. In an attitude survey published by the Ministry of Health, Labour and Welfare (MHLW) in 2012, nearly one half of survey respondents stated that they had not received a hepatitis viral test. The top two reasons cited were, No opportunity to receive the test, followed by, Not included in my regular health examination program. 9 Only about 50% of health insurance unions, in which most employees of large corporations are enrolled, perform hepatitis viral testing as a part of their regular health examination programs. The actual number of employees in large and small-medium size corporations who received hepatitis viral testing in 2014 was 140,000 and 210,000, respectively, which shows that implementation of hepatitis testing in these sectors have been significantly delayed compared with local government programs. In addition, a 2014 report says that 530,000 people (250,000 in the case of HCV) with positive results of hepatitis testing have not received confirmed diagnosis or appropriate medical treatments. This clearly suggests that follow-up initiatives for HCV positive patients after hepatitis testing are critical to promote appropriate measures to prevent disease progression. 7 HCV carriers are not usually aware of minor changes in their disease condition and feel healthy unless their chronic hepatitis status progresses significantly. Therefore, traditional disease awareness campaigns or promotion initiatives to accelerate hepatitis testing have not resulted in behavior change. Under these circumstances, payers should take proactive and aggressive action to accelerate hepatitis screening among their members and caregivers, in addition to conventional disease awareness campaigns, in order to accelerate identification of HCV patients who are unaware of their diagnosis and disease status. Hepatitis C Treatment Innovative new drugs have been continuously developed recently. Since 2013, new classes of drugs have also been developed and approved for clinical use in Japan for HCV patients. These first Direct Acting Antiviral regimens (DAAs) required concomitant use of Interferon and ribavirin for 48 weeks of treatment and required an injection every week, while only achieving a 50% cure rate. Second generation DAAs, with interferon, have achieved 85 90% cure rates among treated patients. However, adverse reactions to these regimens mainly due to interferon injections still caused some patients to discontinue treatment. This more effective combination regimen was not recommended for elderly patients because of concerns about the potential adverse reactions that interferon could cause. Since 2014, with careful attention on reducing adverse reactions and improving tolerability, innovative all-oral regimens have been developed that can cure HCV without interferon for almost all patients in as little as 12 weeks. These options expand the treatment paradigm to provide promising treatment outcomes for chronic patients and possibly prevent disease progression into hepatic cirrhosis and even liver cancer. 7 Aid for Medical Expenses Beginning in 2009, the government of Japan began disbursing aid for medical expenses for hepatitis. Since January 2010 after implementing Basic Act on Hepatitis Measures, this system was upgraded so that in principle the out-of-pocket cost to each patient for treatment is only 10,000 or 20,000 Japanese yen per month. Subsequently, newly developed antiviral medications have been added to the list of covered treatments under the existing system. Current Policy According to Basic strategies for promoting hepatitis measures (established May 16, 2011, and updated June 30, 2016), Japan is implementing 90 Lengthening Healthy Lifespans to Boost Economic Growth

92 policies to address hepatitis with leadership and ownership delegated to the prefectures. Based on the 2016 revision of basic strategies, the following points are designated as budget proposal priorities for the 2017 fiscal year: 1. Fostering environments to promote hepatitis measures (Medical expense subsidies) 2. Increasing hepatitis screening rates (Accelerating hepatitis viral detecting test rates especially focusing on employees and their caregivers, follow-up initiatives toward identified HCV carriers) 3. Strengthening regional collaboration to treat and support hepatitis patients (Strengthening collaborative relationships among local stakeholders led by prefectural governments and the core hepatitis treatment hospitals; developing and educating human resources who treat and care for hepatitis patients; supporting hepatitis patients in their daily social lives or supporting their ability to remain in the workforce; introducing an incentive mechanism to promote innovative initiatives conducted by prefectural governments) 4. Promoting disease awareness with correct information to the public (Promoting disease awareness through the Let s Learn Hepatitis project, a national campaign to promote comprehensive hepatitis measures) 5. Promoting research (Developing new treatment options for hepatitis) Efforts to promote hepatitis viral testing have yielded certain benefits over the long term. Innovative new drugs for HCV patients and ongoing efforts by medical professionals have increased cure rates. In addition, expanded aid programs for treatment expenses have enabled HCV positive patients to fully access curable treatment options. The efficacy of improved medical technologies and strategies to eliminate liver cancer, however, ultimately depends on the effective identification of infected individuals through testing and the adoption of efficient treatment options to prevent disease progression by infected individuals. A pilot project that provides follow-up to HCV positive patients has been established through both the Project to Prevent Progression and the Policy Research Project to Conquer Hepatitis. For example, social marketing approaches led by the Saga Prefectural Government have resulted in brochures designed to promote the importance and urgency of hepatitis treatment to those with HCV, which could succeed in increasing hepatitis treatment rates. 10 Extending this type of effort nationwide could lead many HCV patients to access appropriate medical care, and would be a great and impactful example of a successful hepatitis prevention policy to be used globally. Recommendations Through appropriate law revisions, GOJ should support regulations to allow National Health Insurance (NHI) payers to implement mandatory hepatitis screening tests as part of their annual health checkups or special health check-ups for those over 40, and establish effective processes to accelerate the identification of HCV carriers among non-diagnosed people as early as possible. In collaboration with each prefectural government, the GOJ should arrange efficient systems that enable HCV positive carriers identified through hepatitis screening tests to access information on the latest available treatment options in their area for eradicating the HCV virus effectively and efficiently. Further the twin goals of promoting hepatitis viral testing and expanding access to hepatitis curable treatments by establishing a medical system that works collaboratively and includes primary care physicians, not only local governments and hepatic disease center hospitals. Lengthening Healthy Lifespans to Boost Economic Growth 91

93 Plan and lead cutting edge policy measures to change both patient and prescriber attitudes and behaviors, and to make elimination of HCV and related liver diseases a priority. Continue to secure sufficient budget for executing eradication initiatives against viral hepatitis, and promote comprehensive approaches toward HCV eradication. Furthermore, advocate for a policy to control hepatitis as a best practice for preventing or controlling other diseases. References 1. National Cancer Center Cancer Information Service, Hepatocellular Carcinoma, accessed on February, 16, 2017: 2. MHLW National Execution Program for Promoting Comprehensive Hepatitis Measures Let s Know Hepatitis Project, accessed on March, 28: 3. Excerpted from materials submitted by committee-member Tanaka, Document 8, MHLW st Council for Anti-Hepatitis Strategy, accessed on February 16, 2017: 4. Kaishima, et al. Study of the issues of receiving hepatitis screening and the rate of consulting hospitals. Kanzo 2016; 57: MHLW Quarantine Report FORTH Latest HCV hepatitis treatments (Fact Sheet) updated on July, 2017 (Translated from WHO original document by MHLW), accessed on March 28, 2017: 6. Excerpted from materials submitted by committee-member Tanaka, Document 3, MHLW th Council for Anti-Hepatitis Strategy, accessed on February 16, 2017: 7. Excerpted from materials submitted by committee-member Tanaka, Document 3, MHLW th Council for Anti-Hepatitis Strategy accessed on February 16, 2017: 8. Document 2, MHLW th Council for Anti-Hepatitis Strategy accessed on June 22, 2017: 9. MHLW FY2011 Project to Assess Hepatitis Testing Status, Project Report for 12/2011 to 01/2012, Published 08/2012, accessed on March 28, 2017: Summary and Section reports 2015 on MHLW funded Policy Research Grand Project on Hepatitis Demining Policy Initiatives Research for establishing effective follow-up systems for hepatitis virus positive carriers diagnosed through hepatitis screening tests 92 Lengthening Healthy Lifespans to Boost Economic Growth

94 Liver Cancer Kills 30,000 People Every Year, >80% of Cancer Cases are Due to Hepatitis 1! MHLW indicates million people are infected with the hepatitis C virus and million are infected with the hepatitis B virus. 1! Yet, most people infected with viral hepatitis have no symptoms and are unaware until they develop liver cancer or liver disease many years later. 1 40,000 30,000 Deaths Due to Liver Cancer Total Male Cause of Deaths Due to Liver Cancer Others about 17% 20,000 10,000 Female HBV about 15% HCV about 68% Source: Cancer Registry and Statistics. Cancer Information Service, National Cancer Center, Japan. Source: The 18 th Follow-up Survey on Primary Liver Cancer in National Center for Global Health and Medicine, Information Center for Hepatitis Map of Hepatitis screening check Historical Trends in Persistent Infections with Hepatitis C Virus Policy Research Project to Conquer Hepatitis Units: 10,000 people (estimate) Total number of infected Undiagnosed patients Patients Special summary from patient study 46.9 Insurance claims No continued treatment New infections Cured Died *Deaths from all causes Partial excerpt from materials submitted by committee-member Tanaka, Document 3, MHLW th Council for Anti-Hepatitis Strategy, On Trends in Persistent Infections with Hepatitis C Virus, 2/26/2015 More people are being tested for the hepatitis virus, and the number of unknowing undiagnosed patients is decreasing, but a newly recognized problem is the increasing number of infected patients categorized as no continued treatment. Lengthening Healthy Lifespans to Boost Economic Growth 93

95 Transition of therapies for Chronic Hepatitis C and Rate of Sustained Virological Response IFN : Interferon Peg : Polyethylene glycol DAAs : Direct Acting Anti-virus Agents 70&80% over,90% 50% 25% 5% Recommendation for consultation to people positive for hepatitis virus test: Case study in Saga prefecture Interview people positive for hepatitis who reached to treatment Keywords were provided which made those with hepatitis go to hospital Created a leaflet for Call to Action Leaflet which describes: Necessity of treatment (Hepatitis should be treated even though no symptoms are found) Importance of treatment (Hepatitis may cause hepatic cirrhosis or cancer) Emergency (If patient starts treatment earlier, possibility of permanent cure increases) Distributed to people with hepatitis The rate of those who received treatment increased Excerpt from FY2015 annual report of MHLW grant research Study for construction of efficient follow-up system for hepatitis virus positive test person 94 Lengthening Healthy Lifespans to Boost Economic Growth

96 18 Reduce the Spread of Tuberculosis Situation In 2015, 10.4 million people became Tuberculosis (TB) and 1.8 million died from TB. Most TB deaths occur in developing countries, including India, Indonesia, China, Nigeria, Pakistan and South Africa. And among those diagnosed with TB, 480,000 were estimated to have multidrug-resistant TB (MDR-TB). The number of TB patients has decreased by an average of 1.5% per year since We have to accelerate this rate of decrease to enable achievement of the 2020 milestones of identified by the End TB Strategy. 1 TB was once rampant in Japan; however, the number of persons with TB fell significantly after World War II as a result of the national government s commitment to implement countermeasures, including the enforcement of the Tuberculosis Prevention Act. However, awareness of TB among the general public, as well as among medical professionals, has been decreasing in recent years. In fact, the falling new case rate slowed after the 1980s. As a result, 18,280 patients were newly diagnosed with TB in 2015 in Japan. 2 Japan remains a country with a moderate risk for TB infection, having higher rates of morbidity and mortality than other developed countries. For example, Japan has an infection rate 3.5 times that of Canada, 5.5 times that of the United States, and 2.4 times that of Sweden. 2 With the number of reported TB infections still high, in order to eradicate TB in Japan there is an urgent need for both rapid diagnosis and aggressive treatment. Current Policy The Tuberculosis Prevention Law was integrated into the Infectious Disease Law in 2006, and the new law was enacted in Under the new law, TB is classified as a Category II disease, and all cases must be reported immediately. In the diagnosis of TB, rapid reporting of test results is necessary. Based on the advice of the U.S. Centers for Disease Control and Prevention (CDC), a new TB diagnosis guideline was completed in 2016 by the Japanese Society for Tuberculosis. According to this guideline, liquid testing media are recommended to meet the need for rapid reporting. However, under the Japanese medical system, use of liquid media is not mandated. The lack of rapid and accurate TB diagnoses leads to an unacceptable burden on patients and a waste of precious healthcare resources. Rapid and accurate diagnosis is at the core of the international effort to halt the spread of TB. Recommendations Encourage rapid diagnosis to prevent the spread of TB by: Mandating the use of liquid testing media under the existing Japanese Society for Tuberculosis diagnosis guideline, in order to enhance the speed and accuracy of TB diagnosis in Japan. Cultivating initial culture samples on liquid media which are more rapid and sensitive than other media and have a higher detection rate in order to reduce the rate of delayed diagnosis and treatment and ultimately to help reduce the length of hospitalization. References 1. World Health Organization Tuberculosis fact sheet. (March) Statistics of TB Japan Anti-Tuberculosis Association Lengthening Healthy Lifespans to Boost Economic Growth 95

97 Current Situation of TB in Japan Japan is Still a Country with Moderate Risk of Tuberculosis Year Number Rate Number Rate Number Rate Number Rate Number Rate Pop. (*1,000) 127, , , , ,298 Total cases 24, , , , , Pulmonary 18, , , , , Sputum smear (+) 9, , , , , Extrapulmonary 5, , , , , Latent TB infeclon 4, , , , , Reference: Tuberculosis Year Book, Japan AnL-Tuberculosis AssociaLon Updated Sep. 2014! The rate of decrease slowed down aver the 1980 s! In Japan, over 20,000 palents are newly reported annually slll higher than over developed countries Japan TB Infection Rates Remain High Japan is Still a Country with Moderate Risk of Tuberculosis 96 Lengthening Healthy Lifespans to Boost Economic Growth

98 Tuberculosis Notifications Rates, All Cases (per 100,000) 2013 Source: JATA/The Tuberculosis Surveillance Center, 2015 Usefulness of Liquid Media! Current liquid media deteclon technology is 10 to 14 days faster than solid media.! Liquid media are recommended in the inilal culture, where it is superior in rapidity and sensilvity/deteclon rate.! Liquid media are recommended due to the possibility of shortening expensive hospital stays. Number of days required to detect smear (+) vs. smear (-) # of days Liquid Solid Liquid Solid Smear (+) Smear (-) Source: ExaminaLon Guideline on Mycobacterium Tuberculosis, 2007 (edited by the Japanese Society for Tuberculosis, Exploratory Commiaee for Acid-Fast Bacillus ExaminaLon Method, 2007). Acid-fast Bacillus ExaminaLon Inspected by BACTEC MGIT960 (Kayako Shimizu, 2001). Lengthening Healthy Lifespans to Boost Economic Growth 97

99 19 Enhance Basic HIV Policy and Implement Holistic Policy Measures to Control HIV Infection in Japan Situation The total number of those infected with HIV in Japan has been steadily increasing, reaching 25,995 at the end of 2015 based on a report from the Ministry of Health, Labour and Welfare (MHLW). The total number of new HIV infections has exceeded 1,000 per year since 2004, peaking at 1,590 in There have been more than 1,400 new infections each year since ,2 About 30% of those newly diagnosed with HIV have a sudden onset of AIDS due to HIV disease progression, and this figure does not seem to be improving. This results from people not being tested for HIV, which prevents them from learning about their status at an earlier disease stage. The incidence of sudden onset of AIDS is higher in areas where both healthcare professionals and examination subjects are poorly informed and are less cautious concerning HIV infection, though the absolute number of new HIV diagnoses is greater in high prevalence areas such as Tokyo, Osaka, Aichi, Kanagawa, Chiba, Fukuoka and Okinawa than other prefectures. These trends have not changed for a decade. 3 A national network has been established that offers free, anonymous HIV testing at public health centers for persons who are aware of HIV infection risk and strive to undergo HIV testing voluntarily. In recent years, however, only approximately 140,000 people are tested annually, with this figure declining year by year. A recent research paper has revealed that alternative methods of HIV testing for high risk populations in clinics or through the mail have become popular. When these three options are combined, a total of 248,339 tests were performed in Testing among the high risk population has resulted in 32% of new HIV diagnoses, with a 0.15 to 0.35 detection ratio. 1 In 2014, 7.6 million pre-screening tests occurred at a hospital or diagnostic institute prior to medical procedures, and detected the remaining 68% of new HIV cases identified. The detection ratio of these pre-screening tests is 0.075%. 4 The effectiveness of the examination system and the methods for encouraging its use are, therefore, uncertain. Determining how to discover those infected with HIV who are unaware of their infection is a key to reducing the spread of HIV infection. HIV infection has become a disease that can be controlled as a chronic disorder, and recent innovations can provide appropriate treatment options with a better long-term safety profile if administered at an earlier stage of disease. However, the prognosis for patients with sudden onset of AIDS remains poor. Early identification of those infected with HIV is crucial to preventing the spread of HIV and boosting the quality of life of those with HIV. International guidelines recommend immediate treatment of persons with HIV, with no delay based on their CD4 level. Therefore, steps must be taken to widen the base for testing, identifying, and treating people who are unaware of their infection risk especially in high prevalence regions. To effectively control HIV/AIDS in Japan, several issues must be addressed, including: 1) decreasing testing budgets, 2) less aggressive and status quo HIV education and testing promotion for at-risk populations, especially in high prevalence areas, 3) lack of an aggressive HIV/AIDS educational program to increase general understanding about the latest HIV/AIDS treatments and measures, and 4) less active promotions to share global standards on how to control HIV/AIDS infection and their outcomes compared with the situation in Japan. For individuals at high risk for HIV who test negative, the World Health Organization (WHO) recommends comprehensive education of prevention strategies as an important tool in lowering the risk of infection. In addition, use of antiviral medications for Pre-Exposure Prophylaxis (PrEP) can reduce the risk of 98 Lengthening Healthy Lifespans to Boost Economic Growth

100 infection further when offered in conjunction with comprehensive education. WHO recommends offering antiviral therapies for PrEP among those at highest risk for HIV infection. 5 Current Policy To date, free and anonymous HIV testing has been conducted at public health centers and testing facilities within medical institutions as part of a testing consulting system with user convenience in mind. Thirty percent of all new HIV cases are discovered at such public health centers despite the fact that tests conducted at public health centers make up only 2% of nationwide testing. 4 Between fiscal years 2006 and 2010, the Strategic Study for the Prevention of AIDS, based on a Health and Labour Sciences Research Grant (project for AIDS-related issues) strove to double the number of those being tested for HIV and reduce the number of people diagnosed with AIDS by 25% over a five-year period (ending at the close of 2010). Unfortunately, these goals have not been achieved, and the percent of patients with AIDS at time of diagnosis remains at or above 30% annually. This case shows the limits of a policy that is dependent on the voluntary action of people who are not aware of their infection risk and who must voluntarily undergo examinations without a recognized need to be tested. It also shows that healthcare professionals and others need to help promote awareness among people at risk and support them in accessing HIV testing. Advanced countries have implemented targeted screening programs in select high prevalence areas to increase HIV testing rates in collaboration with experienced STD specialists, urologists and therapists in the region. 6 best practices outside of Japan as potential policy options. 7 Recommendations The Government of Japan (GOJ) should set a comprehensive HIV/AIDS national strategy that outlines control and monitoring methods of HIV/AIDS infections to prevent new HIV infections according to the WHO target. Implementation of the updated HIV/AIDS Prevention Strategies now under discussion at the AIDS and STD sub-committee should be accelerated. GOJ should accelerate appropriate screening programs to identify HIV infections effectively and efficiently, collaborating with private institutes where physicians and healthcare experts are familiar with working with those at high risk for HIV as well as those with HIV. GOJ, in collaboration with prefectures with a high HIV prevalence, should allocate screening and education budgets disproportionally to raise public (including those who are HIV positive, but unaware of their infection) awareness of HIV/AIDS screening, the latest treatment options, and expected health outcomes of treatments. GOJ should consider implementing Pre-Exposure Prophylaxis (PrEP) programs in high prevalence areas to prevent high risk people from contracting HIV. GOJ should aggressively challenge social stigma around HIV/AIDS through its public affairs efforts in collaboration with the groups within the private and public sectors that are motivated to support those with HIV. HIV screening tests like those of HCV, HBV and syphilis should be reimbursed under daily clinical practices at healthcare facilities. In 2017, the MHLW AIDS and STD Sub-Committee started to update HIV/AIDS prevention strategies, which include the latest policy measures and Lengthening Healthy Lifespans to Boost Economic Growth 99

101 References 1. Chairperson s summary report on 2015 HIV/AIDS Surveillance committee reviews dated on May 25, 2016 (Annual summary report as of June 5, 2017): 2. MHLW HIV/AIDS Surveillance Committee 2015 full report: 3. Chairperson Comments of MHLW AIDS Surveillance Committee on the latest HIV/AIDS Surveillance Flash Report in March, 2017: 4. Ichiro ITODA, HIV Testing in Healthcare Facilities: Journal of AIDS Research, 17, , CDC published guidelines for PrEP use that define the risk categories (May 14, 2015): 6. CDC modeled and presented data at CROI 2016 that showed that in the US, if PrEP use is increased among high-risk populations in the current test-and-treat rates for HIV, there are an additional 48,221 infections averted by The number of infections averted that are attributable to PrEP declines if you also expand testing and treatment to achieve National HIV/AIDS Strategy Goals (because successful viral suppression also reduces transmission), however it still shows value. Achieving NHAS goals for both treatment AND PrEP averts 168K from treatment and an additional 17K from PrEP.: 7. Reference 1 at 4 th AIDS and STD Sub-Committee meeting on April, 11, 2017: Lengthening Healthy Lifespans to Boost Economic Growth

102 Annual Changes of Newly Identified HIV and AIDS Patients # Accumulated number to ,995 Definition HIV: Diagnosed before AIDS AIDS: Detected after AIDS 1,434 1, HIV AIDS Total 2015 Annual AIDS Surveilance Report) The Number of HIV Tests and HIV Positive Patients in , % 25, % 77, % 4,999, %?? 1,451,541 1, % The Journal of AIDS Research Vol. 17 No , 2015 Lengthening Healthy Lifespans to Boost Economic Growth 101

103 US CDC published Guidelines for PrEP Use Fast Facts Pre-exposure prophylaxis, or PrEP, is a way to help prevent HIV by taking a pill every day. People who are at substantial risk for HIV should talk to their doctor about PrEP. PrEP must be taken every day to be most effective. Resources Basic PrEP Q&As ( Clinical Practice Guidelines ( Clinical Practice Guidelines Providers Supplement ( PrEPProviderSupplement2014.pdf) Basic PEP Q&As ( Four Four Scenarios of the Potential Impact Impact of Expanded of Expanded HIV Testing, HIV Testing, Treatment Treatment and PrEP and in PrEP the United in the States, United States, Lengthening Healthy Lifespans to Boost Economic Growth

104 20 Accelerating Development of Treatment for Antimicrobial Resistance (AMR) Situation The public health and social economic impact of antimicrobial resistance (AMR) has posed a serious global threat. In Japan, healthcare-associated infections have been spreading, caused by antimicrobial-resistant Gram-positive cocci including Methicillinresistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococci (VRE) as well as antimicrobial-resistant Gram-negative bacilli including multidrug-resistant Pseudomonas aeruginosa (MDRP) and multidrug-resistant Acinetobacter spp. (MDRA) (Figure 1). 1 While the spread of these healthcare-associated infections is a significant problem, communityacquired antimicrobial-resistant infections are also increasing. 1 Outside Japan, the rise of AMR is not confined to general bacterial infections. Malaria parasites have become resistant to artesunate, a drug known as a specific medicine against malaria. 1 In addition, multidrug-resistant and extensively drug-resistant tuberculosis has spread around the world. Addressing the rising threat of AMR requires a holistic and multi-sectoral (One Health) approach because antimicrobials used to treat various infectious diseases in animals may be the same or be similar to those used in humans. 1 Resistant bacteria arising in humans, animals or the environment may spread from one to the other, and from one country to another. AMR does not recognize geographic or human/animal borders. The Centers for Disease Prevention and Control (CDC) reports that each year in the United States more than 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die. 2 According to a report by a committee appointed by the former UK Prime Minister David Cameron, if the situation is left untreated, AMR may claim 10 million lives per year globally by 2050, leading to an expected GDP loss of 100 trillion U.S. dollars. 3 For the aforementioned reasons, there is an urgent need to adopt a global One Health approach against AMR, which addresses both human and animal health together. In fighting against AMR, top priority should be given to preventing the increase, transmission, and spread of antimicrobial-resistant bacteria, and developing effective new treatments (including vaccines and diagnostics) against such bacteria (Figure 2). Since the 1960s, with the development of many powerful antimicrobial drugs, the leading cause of deaths in developed countries has shifted from infectious diseases to non-communicable diseases. As pharmaceutical companies have also shifted their focus, the development of new antimicrobials has declined since the 1980s (Figure 3). There are relatively few novel antibiotics in the pipeline for several reasons: the discovery of antibiotics is difficult, clinical development of antibiotics is constrained and costly, and economic return on new antibiotics is generally poor. The economic return is poor because the use of novel antibiotics is usually restricted to preserve effectiveness, resistant infections are initially rare, and reimbursement systems undervalue novel antibiotics relative to their societal value and public health benefits. These factors contribute to limited returns for novel antimicrobials relative to other therapeutic areas and less investment in antimicrobial research and development. Current Policy The World Health Organization (WHO) highlighted AMR on World Health Day 2011 and called upon the international community to devote global efforts under the One Health approach. 4 In 2015, the World Health Assembly endorsed the Global Action Plan on Antimicrobial Resistance and urged all member states to develop relevant national action plans within two years. 5 At the following G7 Summit 2015 in Schloss Elmau, Germany, 6 the G7 Health Ministers Meeting 2015 in Berlin, 7 the G7 Ise Shima Summit 2016, 8 and the Lengthening Healthy Lifespans to Boost Economic Growth 103

105 G7 Health Ministers Meeting 2016 in Kobe, 9 member states agreed to work together on AMR as a global priority. At the United Nations high-level meeting on AMR held in September 2016, leaders reaffirmed the issue of AMR and showed a commitment to working on AMR on the national and international levels. 10 In Japan, led by Prime Minister Abe and his Cabinet, the AMR national action plan was developed in April 2016 ahead of other countries and implementation of cross-ministry initiatives is underway. 1 The action plan defines objectives, as well as strategies and specific initiatives in six areas: (1) improving public awareness/understanding, (2) surveillance and monitoring, (3) preventing/controlling infections, (4) promoting adequate use of antimicrobials, (5) promoting research and development/drug discovery, and (6) enhancing global collaboration. Based on this action plan, special committees have been established quickly for improving public awareness, surveillance, and promoting adequate use. They are already working toward the objectives. For accelerating the development of new treatments (including vaccines and diagnostics) against antimicrobial-resistant bacteria, no specific measures have been taken yet, and discussions have started slowly about establishing international clinical evaluation guidelines and a priority review system. Discussion on how to secure predictability of financial return, which is crucial for pharmaceutical companies to start development in this area, has not even started. Recommendations As discussed above, addressing AMR infections is an urgent challenge as the spread of AMR infections is very likely to pose a significant threat to public health in Japan. However, in Japan, discussions on and initiatives for promoting the development of treatments (including vaccines and diagnostics) against antimicrobial-resistant bacteria have not been fully initiated. It is possible that, when AMR infections emerge in Japan, antimicrobials against those infections may not be available in Japan alone. To avoid such a critical situation, the following measures should be taken: Implement post-approval incentives that improve companies profit predictability and motivation and promote research and development of new treatments for AMR infections in Japan. Effective incentives include: Market entry rewards: Government or other relevant body pays an adequate incentive to a company that has developed and received an approval for a new AMR treatment so that the company can secure adequate profit. Extended market exclusivity that can be applied to other products (transferable exclusivity): A company that has developed and received an approval for a new AMR treatment is granted the right to extend the market exclusivity period for a drug of its choice for up to 12 months (by postponing generic entry). National purchase: Government and other organizations buy new AMR drugs for appropriate prices after marketing approval. (Consider possible purchase for stockpile as needed.) Accelerate ongoing discussions on international common clinical evaluation guidelines and a priority review program for AMR drugs and implement them promptly. In creating the guidelines, the following matters should be considered: From the viewpoint of feasibility and early development, drugs should be reviewed based on the minimum efficacy/safety data packages rather than requiring conventional assessment by organ and non-inferiority studies. Minimum shared criteria in Japan, the U.S. and Europe should be clarified to 104 Lengthening Healthy Lifespans to Boost Economic Growth

106 enable the use of common efficacy/ safety data in each country. Government and scientific organizations should lead the initiative to build registries for effectively collecting efficacy/safety information after marketing, thus building an environment where valuable data are collected consistently from development through post-marketing stages. References 1. The Government of Japan National Action Plan on Antimicrobial Resistance (AMR) Ministerial Conference to Strengthening Measures on Emerging Infectious Diseases Antimicrobial Resistance (AMR) Action Plan Antibiotic Resistance Threats in the United States 2013: 3. The Review on Antimicrobial Resistance Tackling Drug-Resistant Infections Globally: final report and recommendations 4. WHO World Health Day April WHO Global Action Plan on Antimicrobial Resistance 6. Leaders Declaration G7 Elmau Summit blob=publicationfile&v=3 7. Declaration G7 Berlin Health Ministers Meeting Declaration_AMR_and_EBOLA.pdf 8. Leaders Declaration G7 Ise-Shima Summit 9. Declaration G7 Kobe Health Ministers Meeting United Nations high-level meeting on antimicrobial resistance, 21 September Lengthening Healthy Lifespans to Boost Economic Growth 105

107 Trend of Drug Resistant Gram-negative Bacteria Figure 1 Drug resistant bacteria that have no effective antimicrobials are gradually increasing 4.0% 3.5% 3.0% 2.5% 2.0% 1.5% 1.0% 0.5% 0.0% Carbapenem-resistant Enterobacteriaceae (CRE) Carbapenem-resistant Pseudomonas aeruginos 3rd-Generation Cephalosporin-resistant Klebsiella pneumoniae 3rd-Generation Cephalosporin-resistant Escherichia coli Fluoroquinoloneresistance Escherichia coli Multidrug-resistant Pseudomonas aeruginosa Source: JANIS, Annual report in Threat Level of Antibiotic Resistant Bacteria Figure 2 Threat label Antibiotic resistant bacteria (Category 5 ID) Urgent Clostridium difficile (C. difficile) Carbapenem-resistant Enterobacteriaceae (CRE) Drug-resistant Neisseria gonorrhoeae (cephalosporin resistance) Serious Multidrug-resistant Acinetobacter Drug-resistant Campylobacter Fluconazole-resistant Candida (a fungus) Extended spectrum β-lactamase producing Enterobacteriaceae (ESBLs) Vancomycin-resistant Enterococcus (VRE) Multidrug-resistant Pseudomonas aeruginosa Drug-resistant Non-typhoidal Salmonella Drug-resistant Salmonella Typhi Drug-resistant Shigella Methicillin-resistant Staphylococcus aureus (MRSA) Drug-resistant Streptococcus pneumonia Drug-resistant tuberculosis (MDR and XDR) Concerning Vancomycin-resistant Staphylococcus aureus (VRSA) Erythromycin-resistant Streptococcus Group A Clindamycin-resistant Streptococcus Group B Source: CDC, Antibiotic Resistance Threats in the United States, Lengthening Healthy Lifespans to Boost Economic Growth

108 The Number of Approved Antibiotics in Japan Figure 3 Only three new antibiotics have been approved since Sources: Product information of each antibiotic product (excludes antifungals and antituberculosis products) Lengthening Healthy Lifespans to Boost Economic Growth 107

109 21 Issues in Diagnosis of Adult Respiratory Infections Including RSV in Japan Situation In recent years, the morbidity of pneumonia has been increasing with the aging of the Japanese population, with pneumonia now ranked the third leading cause of death in Japan. 1 However, pathogens that cause pneumonia and respiratory infections are not accurately diagnosed in Japan. RS Virus Infection RS virus (RSV) infects more than 50% of infants within a year after birth, and infects nearly 100% by the age of 2 years. However, permanent immunity against RSV is not acquired; 6 to 83% of children are repeatedly infected with RSV every year as it often spreads in households or childcare facilities. 2 Respiratory symptoms may be severe in high-risk infants with underlying diseases, including chronic pulmonary disorder and congenital heart disease, and thereby they can be life threatening. Reports indicate that RSV accounts for approximately 50% of all pneumonia cases and 50 to 90% of infant cases of bronchiolitis. 3 RSV is recognized as a significant pathogen that causes severe lower respiratory tract infection, encephalopathy/ encephalitis, and neonatal apneic events even in infants with no additional issues outside of RSV infection. 2 The risk of severe RSV infection is present not only in infants but also in the elderly, immunocompromised patients, and patients with cardiopulmonary complications. Similar to other viral respiratory infections, it has been suggested that RSV may exacerbate chronic obstructive pulmonary disorder (COPD) and asthma, 4 and can ultimately lead to death in patients with these conditions. The number of patients with COPD in Japan was estimated to be 5.3 million in a large-scale national epidemiologic study, the NICE Study (published in 2001), 5 and it is currently the 10th leading cause of death in Japan. 1 In a study in the United States, RSV infection was noted in 10.6% of patients who were admitted to the hospital for pneumonia, 11.4% of patients with COPD, 5.4% of patients with congestive heart failure, and 7.2% of patients with asthma. 6 It is estimated that in the U.S. 2 10% of elderly people living in the community and 5 10% of elderly patients living in care facilities, such as nursing facilities, develop RSV infection. It is reported that more than 10,000 elderly patients in the U.S. die each year due to complications related to RSV infection. 7 Although epidemiological data on RSV infection in Japanese adults is limited, respiratory viruses were detected in 7 out of 70 patients (10%) who required hospitalization for suspected respiratory infection in a 5 month period and RSV was detected in 3 of these patients (2 with COPD and 1 with asthma) in an observational study by Kurai et al. In addition, a patient with COPD in whom RSV was detected required mechanical ventilation and died due to respiratory failure. 8 Also, in the 2-season investigation by Takahashi et al., the number of patients with influenza pneumonia was 13 and 11 in the first and second seasons, respectively, which were lower than those with RSV pneumonia (28 and 14, respectively), and it was demonstrated that the significance of RSV as the cause of pneumonia was equal to or exceeded that of influenza. 9 However, the annual average number of deaths due to RSV infection in Japan is reported to be 31.4 ( Mean from data collected between 2008 and 2012). 10 The majority of cases involved children, and the statistics of the number of deaths were considerably different from those in other countries. Also, more than 90% of reported cases involved patients aged 3 years or less, indicating the absence of manifestation of RSV infections in Japanese adults. 108 Lengthening Healthy Lifespans to Boost Economic Growth

110 Difference in the Method of Diagnosis Compared to Other Countries Among adults in Japan, the reported number of individuals with RSV infection is extremely low. One reason for this is the lack of established diagnostic methods that allow accurate diagnosis of the cause of respiratory infection in adults. Currently in Japan, health insurance reimbursement is approved for a brief test by immunochromatographic assay, primarily used in clinical practice in pediatric departments. However, although effective for over half of child cases where the nasal mucosa has a large amount of virus, diagnosis is still difficult in adults where the amount of virus in the nasal mucosa is typically less than that of children. Outside of Japan, there is increasing use of diagnostics, including polymerase chain reaction (PCR), which are able to detect RSV in adults with high sensitivity. The use of improved gene-based diagnostic methods by real-time PCR (RT-PCR) (including Multi- Plex) is also increasing. However, health insurance reimbursement for these tests has not yet been approved in Japan, and they are currently not being used for routine treatment of lower respiratory tract infection in adults. Also, since there are currently no therapeutic drugs against RSV infection, diagnosis is not actively made in adults, in particular, and the gene-based diagnostic method is not commonly used in medical practice. 11 Screening and diagnosis remain low because RSV is regarded as a disorder that occurs only in children and RSV infection and its disease burden in adults is not accurately recognized in Japan. As such, the number of adult patients in Japan is not adequately understood. Current Policy The gene-based test agents for respiratory infections symptomatic of pneumonia and severe lower respiratory tract infection that are commonly used in other countries are not covered by Japanese health insurance, and, as a result, accurate tests and diagnoses are not performed for respiratory infection in adults. There is a lag in adoption of diagnosis technologies and practices compared to the U.S. and Europe. In addition, the existing qualitative test for RS virus antigens (brief test by immunochromatographic assay) is covered by Japanese health insurance only in inpatients, infants aged less than a year, and patients in whom palivizumab preparations are indicated, although detection is difficult in adults, and there are currently no diagnostic agents that can be used in the routine treatment of high-risk, adult patients. The government of Japan (GOJ) has proposed the Action Plan against Antimicrobial Resistance (AMR) and has been engaged in efforts to reduce by 2020 the daily amount of use of antimicrobials per 1,000 population by two thirds of that in On the other hand, antimicrobials that are ineffective against viruses are empirically used without identifying the responsible bacteria or viruses in lower respiratory tract infection and pneumonia, and there is concern this practice could lead to drug resistance. Recommendations The GOJ should take initiative to educate not only children, but also adults and the elderly on the risks of RSV infection, in addition to accelerating epidemiologic studies. Health insurance reimbursement should be approved for gene-based test agents including Multi-Plex, which has been increasingly used in Europe and the U.S. in respiratory disorders. A system should be established to identify the viruses or bacteria in patients and administer a therapeutic drug according to the test Lengthening Healthy Lifespans to Boost Economic Growth 109

111 results, instead of empirically administering antibiotics to the majority of patients. There is currently no antiviral drug for RSV infection available. After a drug is developed, it should be made available to high-risk patients, including pediatric inpatients and elderly patients as soon as possible. References 1. MHLW, Population Survey Report (2015), Accessed July 11, Kusuda S, Know RS virus infection, RS virus infection x palivizumab DATA BOOK (1st edition) published by Medical Review Co., Ltd., 2014: p National Institute of Infectious Diseases, Particular infectious disease: influence and RS virus infection, IDWR 2014:48, 4. Kurai D, et al. Virus-induced exacerbations in asthma and COPD. Front Microbiol. 2013;1(4): GOLD Japan committee, COPD information site 6. Falsey AR, et al. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med. 2005;352(17): Branche AR, et al. Respiratory syncytial virus infection in older adults: an under-recognized problem. Drugs Aging. 2015;32(4): National Institute of Infectious Diseases, Importance of RS virus infection in adults and the elderly IASR, 2014:35,147-8, 9. Takahashi et al. Onset of adult RS virus infection in 2 winter seasons (conference minutes) The Journal of the Japanese association for infectious diseases, 2014;88(2): National Institute of Infectious Diseases, Particular infectious disease: RS virus infection, IDWR 2013:36, Casiano-Colón AE, et al. Lack of sensitivity of rapid antigen tests for the diagnosis of respiratory syncytial virus infection in adults. J Clin Virol. 2003;28(2): Ministerial Conference on Infectious Disease Control Measures to be an International Threat AMR action plan (Apr 5, 2016) p Lengthening Healthy Lifespans to Boost Economic Growth

112 Environment surrounding diagnosis of RS virus! Respiratory syncytial virus (RSV) infects nearly 100% of children by age 2. Permanent immunity against RSV is not acquired and repeatedly infected.! RSV is thought to affect patients with exacerbation of chronic obstructive pulmonary disorder (COPD) and asthma, and it is a factor associated with direct causes of death in these patients. " The number of patients with COPD in Japan was estimated to be 5.3 million. It is currently the 10 th leading cause of death in Japanese.! However, the majority of the reported death cases caused by RSV infection in Japan involved children, indicating the absence of manifestation of RSV infections in adults.! As the background reason for this, diagnostic methods that allow accurate diagnosis of RSV infection in adults have not yet been approved for reimbursement in Japan.! Rapid antigen based tests for RSV are covered by the National Health Insurance, but the target patient group for reimbursement is limited (hospitalized, <1 Yr pediatrics etc.). Also because detecting adult RSV requires a test with high sensitivity, there are currently no diagnostic agents that can be used in the routine treatment of high-risk, adult patients. RSV is a commonly detected pathogen found in hospitalized elderly who have community-acquired pneumonia in the US. Seema J, et. al. N Engl J Med 373:415-42, 2015 Lengthening Healthy Lifespans to Boost Economic Growth 111

113 Comparison of RSV infection and influenza patients who required inpatient treatment RSV infection in adults was thought to exhibit common cold-like symptoms and considered a self-limited illness. However, mortality rate in elderly hospitalized patients with RSV is similar to those with influenza. RSV Infection (n=132 2), 607 3) ) Influenza (n=144 2), 547 3) ) Average Age (Years) Pneumonia (%) Short-term Fatal Rate (%) Chronic respiratory disease merger (%) Ventilator Use (%) ) and 3) 1) Daisuke Kurai, IASR Vol. 35 p : June ) Falsey AR, et al., N Engl J Med 352: , ) Lee N, et al., Clin Infect Dis 57: , Lengthening Healthy Lifespans to Boost Economic Growth

114 22 Promotion of Transition of Mentally Disabled Persons to the Community* Situation In 2014, the total number of patients with mental disabilities in Japan was estimated to be million, which is more than the number of patients with the so-called four major disorders (cancer, stroke, acute myocardial infarction, and diabetes mellitus). 313,000 of those with a mental disability are inpatients, more than half (166,000) of whom have schizophrenia, which is more common than dementia or mood disorder. 1 Schizophrenia is a serious disorder associated with particularly severe impairment. It frequently occurs in younger people at the age when they start to live independently from their parents; the average age at onset is the early to mid-20s in women and somewhat earlier in men; about 40% of males have their first episode before age 20. It can take a long time before a definitive diagnosis is made, and the initiation of treatment may be delayed by years in practice. 2,3,4 Also, schizophrenia is a disorder that repeatedly recurs/relapses, and symptoms are exacerbated after each recurrence/relapse. 5,6 At present, there is no complete cure for schizophrenia. However, it is possible to control the symptoms and reduce the risks of recurrence/relapse through treatment, including psychotherapy and medication. Although several factors are related to recurrence/relapse, a decrease in medication compliance has particularly been associated with recurrence/relapse. If medication is not appropriately taken, 70-80% of patients relapse within a year. The harmful effects of relapse include: 1) mental deterioration and reduced social function, 2) difficulty in achieving the effects of the drugs, resulting in increased doses, and 3) re-hospitalization. 7,8 In psychiatric wards, long-term hospitalization has surfaced as an issue. The mean duration of hospitalization is 281 days in patients who are discharged from psychiatric wards, and there are efforts to reduce the average length of hospitalization. However, 100,000 of inpatients have been hospitalized for 5 years or longer, and 85,000 patients for a period of 1-5 years. 1 Current Policy In order to reduce long-term hospitalizations, the government of Japan (GOJ) presented various statements, including the Vision for Renovation of Mental Health Welfare, in Unfortunately, the goals outlined in this policy were not achieved. However, after the ratification of the Convention on the Rights of Persons with Disabilities in 2013, the GOJ again presented policies to reduce long-term hospitalizations and promote the transition of patients into the community, and the Revised Mental Health Act took effect in In the guidelines issued by the Minister of Health, Labour and Welfare in March 2014 based on the above act ( Guidelines for Ensuring Provision of Good and Appropriate Medical Care for Mentally Disabled Persons ), the GOJ declared it will promote functional differentiation of the psychiatric ward and promote the transition of mentally disabled persons into the community. To implement these measures, the Plan for Welfare of Persons with Disabilities, which is based on the Comprehensive Support Law for Persons with Disabilities, will be utilized. Municipalities and prefectures have been asked to establish and implement a Plan for Welfare of Persons with Disabilities every 3 years in accordance with the basic guidelines specified by the GOJ. 9 To support the transition of mentally disabled persons into the community, the GOJ plans to request that municipalities strive to achieve the following target goals in the Plan for Welfare of Persons with Disabilities in the following term (the 5th term, ). 10 In principle, a place for discussion among healthcare and welfare professionals Lengthening Healthy Lifespans to Boost Economic Growth 113

115 should be established in each healthcare area for persons with disabilities or in each municipality (city, town and village) by the end of fiscal year Each local government should decide the number of patients that will be admitted to psychiatric wards long term (one year or longer) Each local government should set rates of early discharge from psychiatric wards (at 3 months, 6 months, and one year after hospitalization) In 2017, municipalities and prefectures will promote the establishment of the 5th Plan for Welfare of Persons with Disabilities in accordance with the above basic guidelines. The GOJ has already shared national target values for the number of welfare services provided for patients (bases) based on target figures for patients who have transitioned into the community: 46,000-35,000 people by the end of March 2021, and 98,000-79,000 in In April 2020, three plans, including the 5th Plan for Welfare of Persons with Disabilities mentioned above as well as the 7th Medical Plan and 7th Insured Long-Term Care Service Plan, will simultaneously be initiated. The systems for payment for medical services, nursing care, and disabilities will also simultaneously be revised, in addition to the revision of the Handicapped Persons Employment Promotion Law (described below). 10 We propose that the GOJ promote the following measures to advance effective approaches for the mentally disabled to transition into the community and ensure achievement of these goals in each area. Measures to Consider When Developing Effective Approaches 1. Support for Municipal Leadership In order to achieve the transition of mentally disabled persons into the community, leadership and the effectiveness of the Plan for Welfare of Persons with Disabilities in each municipality will be critical. However, municipalities do not always have adequate expertise or ideas for how to facilitate and support mentally disabled persons living in the community. In many cases, the number of responsible persons who are assigned to each municipality health center or office is insufficient, and there is a concern that this initiative will not progress if it is solely dependent on voluntary efforts by municipalities. The GOJ must provide adequate support and advice to the municipalities to enable them to exert full leadership in establishing policies for mental health, including the transition of mentally disabled persons into the community. The establishment of policies by the municipalities would be smoother and more efficient if the GOJ provides detailed and appropriate advice on methods for 1) networking among multiple occupations and parties, and 2) promoting discussions in the Places of discussion requested in the GOJ s Plan for Welfare of Persons with Disabilities. Moreover, the GOJ should introduce successful examples from various regions. 2. Development of Human Resources for Support of Mentally Disabled Persons Living in the Community The transition of long-term inpatients into the community requires that human resources be secured to support patients living in the community. Human resources across a variety of occupations are needed; therefore, a support system for mentally disabled persons has not been adequately established at present. As patients start to transition into their communities, the number of hospital beds will fall and human resources for inpatient nursing/ care may be redistributed to support those living in the community. However, there is concern that the supply of human resources will not meet demand because psychiatric wards have been allowed to function with 114 Lengthening Healthy Lifespans to Boost Economic Growth

116 fewer staff compared to general wards as a result of so-called, special cases for psychiatric departments. In addition, although it is expected that psychiatric social workers (PSW) in hospitals would principally be responsible for planning and supporting the transition of inpatients into the community, the absolute number of PSWs is not sufficient and many psychiatric hospitals have difficulty finding PSWs. There is an urgent need to secure and develop human resources to nurse, care, and support patients living in the community. 3. Elimination of Stigma in the Community If patients with mental disabilities are encouraged to live in the community, psychological resistance from community members is expected to be an obstacle. In order to eliminate discrimination and stigma against patients with mental disability, the government must actively educate community members to foster an accurate and thorough understanding of various mental disabilities and illnesses and the significance of the policies being implemented Maintenance of Appropriate Medication Compliance Recurrence/relapse due to poor medication compliance is another concern related to the promotion of transition of patients into the community. Because, in principle, the patient will have to control their medication usage after the discharge, there is a possibility that appropriate medication compliance may not be maintained. As described above, schizophrenia is a disorder that repeatedly recurs/relapses, and it is said that 70-80% of patients relapse within a year if appropriate the medication is not taken. 7,8 Post-discharge maintenance of medication compliance is a critical factor in the promotion of transition into the community. One of the means for the maintenance of medication compliance is confirmation and guidance on medication by home care services. In addition, utilization of long-acting injections (LAI) that are administered every 2 to 4 weeks would be an effective approach, instead of oral agents. Since patients would receive injections during visits to the hospital and the medication remains effective until the next visit, patients will not be required to control their medication by themselves. However, the use of LAIs is hindered by the current medical service payment system. This is because it is necessary to administer LAIs to the patients before discharge. However, fees for chronic hospitalization in a psychiatric ward are a bundled per day payment that includes drug expenses, and it is difficult for medical institutions to recover the costs for LAIs provided to a patient being discharged because the payment is for inpatient treatment. As such, LAIs cannot be introduced at the end of hospitalization prior to discharge, and this has been identified as the cause of delay of the transition of patients to the community in some cases. In order to avoid such situations, payment for LAIs used to promote the transition of patients into the community should be prescription based so that costs are recoverable. 5. Support for Employment of Mentally Disabled Persons Who Live in the Community Social participation is critical for mentally disabled persons to maintain their lives in the community. Having a role in the community can lead to stabilization of symptoms as well as daily life. At present, patients spend their days primarily in day care at a psychiatric department after discharge; however, extended opportunities for employment would be important for the promotion of transition into the community. The Handicapped Persons Employment Promotion Law mandates that the rate of employment of disabled persons by each employer must be equal to or higher than the statutory employment rate (the statutory Lengthening Healthy Lifespans to Boost Economic Growth 115

117 employment rate for private enterprises was 2.0% as of 2017). Although this system has only included physically and intellectually disabled persons thus far, the rate will be calculated to include mentally disabled persons after April 2018, and an increase in the statutory employment rate is anticipated. 11 (As a note, employers have been allowed to include mentally disabled persons they hire in the rate of employment of disabled persons since 2006.) In advance of these actions, employment of mentally disabled persons has been increased considerably in recent years. Although less than 2,000 in 2006, employment increased to 42,000 in 2016 and, between 2015 and 2016, increased by 21.3%. 11 However, mentally disabled persons tend to terminate employment earlier than physically or intellectually disabled persons. According to the statistics, in 2013, the mean length of employment of mentally disabled persons was 4 years and 3 months, which was shorter than that of physically disabled persons (average employment of 10 years and 0 months) and that of intellectually disabled persons (average employment of 7 years and 9 months). 12 The characteristics of mental disabilities and illnesses, suitability for operation, and the process for mastering tasks differ considerably by disorder. Therefore, if the employer and co-workers do not have adequate knowledge/ understanding of these aspects, appropriate assignments and considerations may not be given to workers with mental disabilities, which may lead to incompatibility at the workplace and early resignation. There is also a concern that the employer may avoid hiring other mentally disabled persons once early resignation occurs. In order to promote the transition of mentally disabled persons into the community in the future, it is necessary to further develop opportunities for employment, and support those with mental disabilities and their employers to ensure stable employment. Although labor offices such as the Public Employment Security Office have been providing support, it is necessary to provide further support by those who are familiar with the characteristics of mental disabilities. For persons with mental disabilities, establishment of an environment where peer support, including consultations, is provided by others with mental disabilities who have already been employed would also be beneficial. For employers, it is important to provide adequate advice on detailed considerations to be taken in response to the characteristics of mental disabilities. It is also important to establish a place for patients who have transitioned into the community to work actively in the community and an environment to prevent relapses of a disorder. As a possible measure, healthcare centers and psychiatric hospitals with mental health specialists may provide consultations to employers for the care of persons with mental disabilities and mediate opportunities for employers to consult the patients physicians in charge. 6. Precautions for Promotion of the Transition into the Community Although it is favorable that patients with mental disabilities continue their lives in areas familiar to them, there are some concerns about the promotion of these policies. As described above, the transition into the community can only be achieved based on the following premises: appropriate involvement of the municipality, patient support from various professionals, understanding by the community, maintenance of medication compliance, establishment of opportunities for employment and social participation, and accommodation/ support systems. However, unfortunately, these systems have not been fully established in all municipalities. Future promotion of the transition into the community must be performed with care, taking into account the 116 Lengthening Healthy Lifespans to Boost Economic Growth

118 state of these systems in each municipality. If transition into the community is implemented hastily in the absence of adequate systems, patient conditions may be exacerbated, resulting in an increased psychological burden on patients and their families. In order to realize transition policies, it is necessary to promote them while considering the status of these support systems, rather than being constrained to the numerical goals of transition. Transition into the community should be promoted with care and flexibility, taking into account the development status of each municipality s systems. Recommendations The GOJ should provide appropriate advice and support to municipalities to enable them to exert leadership in realizing the Plan for Welfare of Persons with Disabilities. Compared to inpatient treatment, more human resources will be required to support those living in the community with mental disabilities. Therefore, establishment and development of human resources for nursing, care, and support should promptly be promoted to advance transition into the community. The GOJ should promote accurate knowledge of mental disabilities to eliminate stigma related to mental disabilities in the community, which may interfere with efforts to support the transition of patients into the community. Since a reduction in medication compliance often leads to recurrence/relapse of disorder, more consideration should be given to measures for maintenance of medication compliance, such as utilization of LAIs. In addition, issues related to the system for payment for medical services related to transition should also be addressed. In addition to promoting the establishment of opportunities for employment of patients with mental disabilities who have started to live in the community, an effective support system should be established for patients and their employers to ensure stable employment. Lengthening Healthy Lifespans to Boost Economic Growth 117

119 References 1. MHLW, Patient survey (2014), tallied by Department of Health and Welfare for Persons with Disabilities, MHLW 2. The MSD Manual professional version schizophrenia (monitored on July 3, 2017) 3. Higuchi. T, J. Clinical Pharmacology, 11 (3) Watanabe. K, J. Clinical Pharmacology, 13 (7) Molina.JD.et.al J Exp Clin.Med 2012;4 6. Koyama. T, J. Clinical Pharmacology, 11 (4) Ozaki. N, J. Clinical Pharmacology, 11 (6) Robinson,D.et al;arch Gen Psychiatry 56, Basic guidelines for ensuring welfare service for handicapped people and consultation support, development of the provision system of community life support projects of municipalities and prefectures, and ensuring smooth implementation of independence support benefits and community life support projects 10. The 83rd meeting of Committee on Handicapped People, Social Security Council, MHLW (Jan 6, 2017) 11. Employment Measures for Persons with Disabilities Division, MHLW, Total result of employment situation of persons with disabilities (Dec 13, 2016) 12. Employment Measures for Persons with Disabilities Division, MHLW, Employment situation survey result report for persons with disabilities (FY2013) *The government of Japan uses the term, mental disability, to refer to those diagnosed with a mental disorder or mental illness. Persons with intellectual disabilities are not included in this category. 118 Lengthening Healthy Lifespans to Boost Economic Growth

120 ! After the ratification of the Convention on the Rights of Persons with Disabilities in 2013, the Revised Mental Health Act took effect in 2014.! In the guidelines issued by the Health Minister in 2014 based on the above act, it was declared that the GOJ will promote functional differentiation of psychiatric wards in addition to promoting the transition of mentally disabled persons to the local community.! To implement these measures, the Plan for Welfare of Persons with Disabilities for FY will be utilized. Local governments will be requested to establish and implement plans in accordance with the basic guidelines specified by the GOJ. Development of community care Early discharge of new inpatients Discharge rate of new inpatients for 2021 within 3 months: 69% within 6 months: 84% within 1 year: 90% Promotion of current inpatients moving back to community Number of inpatients who have been hospitalized more than 1 year Current: 185,000 By the end of FY2020: 146, ,000 By 2025: 97, ,000 Future reduction of number of psychiatric beds Reference: MHLW Guidelines for Ensuring Provision of Good and Appropriate Medical Care for Mentally Disabled Persons (issued in Mar 2014), MHLW commijee on the future psychiatric medical and welfare and (Dec 22, 2016) Lengthening Healthy Lifespans to Boost Economic Growth 119

121 Source: MHLW PaOent survey! Patients in psychiatric wards in Japan tend to be hospitalized long-term in Japan. Number of psych beds Number of inpatients Number of long-term hospitalized patients Average length of stay Source: MHLW Medical insotuoon survey, PaOent survey, Mental health welfare material, Hospital report (2014) 120 Lengthening Healthy Lifespans to Boost Economic Growth

122 (1,000 patients) Source: MHLW PaOent survey (1,000 patients) Source: MHLW PaOent survey Lengthening Healthy Lifespans to Boost Economic Growth 121

123 (1,000 patients) Source: MHLW PaOent survey, MHLW commijee on the future psychiatric medical and welfare and (Dec 22, 2016) (projected) 122 Lengthening Healthy Lifespans to Boost Economic Growth

124 23 Diagnosis and Treatment Prior to Dementia Stage Situation The current number of patients with dementia in Japan has exceeded 4 million, and with the progression of the aging population, it is estimated that the number will increase to 7 million by The social cost for dementia reached 14.5 trillion Japanese yen annually in 2014, and it is projected that this will increase to 19.4 trillion in Dementia is a term for various disease types, and Alzheimer s disease (AD) accounts for more than one half of all dementia. AD is a gradually progressing and irreversible disease, and onset often occurs with memory disorder followed by various impairments of cognitive functions. Eventually, it leads to impairments in activities of daily living and social life becomes difficult. Behavioral and psychiatric symptoms such as hallucination and delusion, which often appear with disease progression, can become a large burden on caregivers and family. For this reason, social costs also increase alongside disease progression. 1 With recent advances in imaging and biomarker research, it has become possible to capture pathological changes occurring in the brain (e.g., accumulation of pathogenic protein) from a relatively early stage, even before the onset of dementia. These findings led to the recent proposal of new diagnostic criteria before the onset of dementia based on clinical symptoms and pathological conditions. Specifically, asymptomatic AD has been proposed to refer to conditions in which there are no clinical symptoms but there are AD pathological characteristics, and mild cognitive impairment (MCI) due to AD has been proposed to refer to conditions in which AD pathological characteristics are present and the patient experiences progressive memory disorder that does not impact the performance of daily activities. 2 The development of new drugs for AD is being actively pursued globally, but no drug has been approved since the approval of Memantine hydrochloride in 2003 (2011 in Japan). The drugs currently being developed for AD can be divided broadly into two categories: 1) symptomatic therapy drugs for the cognitive impairments (core symptoms) and behavioral and psychiatric symptoms (peripheral symptoms) and 2) disease modifying therapy drugs for pathological change to delay or stop disease progression. Many of the drugs recently being developed are disease modifying therapy drugs. However, unfortunately, no large-scale studies yet exist which confirm their efficacy. However, beneficial knowledge has been obtained through the results of past clinical studies and imaging/biomarker research. For example, there is awareness of the importance of intervention prior to the onset of dementia when neuronal cell death may be limited, and there is also awareness of the importance of AD diagnosis using imaging/biomarkers. Many large-scale clinical studies are therefore now being conducted using biomarkers related to MCI due to AD and asymptomatic AD before the onset of dementia. In United States, it is estimated that successful early intervention with the potential to delay the onset of dementia for 5 years could reduce 33% of the dementia related social costs over the next 25 years. 3 Current Policy A national strategy for dementia in Japan, the Comprehensive Strategy to Accelerate Dementia Measures (New Orange Plan), was formulated in 2015 by the Ministry of Health, Labour and Welfare (MHLW) in collaboration with relevant ministries and agencies. 4 The provision of timely and appropriate medical/ nursing care in accordance with the condition of dementia was established as one of the seven pillars of the plan. In an effort to achieve this goal by 2025, a comprehensive and cyclical care mechanism centered on early diagnosis and preemptive measures is incorporated. The goal is to deliver a mechanism that enables Lengthening Healthy Lifespans to Boost Economic Growth 123

125 medical and caring professionals to organically collaborate to provide timely and appropriate medical and nursing care seamlessly and in the most suitable setting for each stage of dementia, from prevention to the final stage of life. Furtherance of research and development of methods of prevention, methods of diagnosis, methods of treatment, rehabilitation model, and nursing care model and dissemination of the results of research and development was also included as a pillar of the plan, calling for research and development related to dementia and dissemination of the results. In the U.S., the National Alzheimer s Project Act, a national strategy addressing AD, was enacted in The goal of this strategy is to develop effective treatment and prevention methods for AD by In order to achieve this goal, the Act prioritizes research by setting milestones, expanding research of methods to treat and inhibit progression of AD, accelerating research of early and asymptomatic AD, fostering global coordination of research, and bridging the results of research to actual clinical practice. As each part of this plan is being implemented, details related to these areas as well as progress is being disclosed. Recommendations Hereafter, when large-scale clinical studies have confirmed the effect of intervention of AD in the early stage and new drugs are expected to be available, there is a possibility that dissociations between clinical studies settings and actual clinical practice may arise (for example, diagnostic criteria and access to biomarker testing). In addition, the availability and demand for early treatment intervention if a new drug is marketed has potential to greatly impact the fiscal sustainability of the healthcare system. For this reason, the ACCJ and EBC believe that it is necessary to resolve the following policy issues: Develop new disease concept and new diagnostic criteria, and disseminate information related to the condition that precedes the onset of dementia First, disease concepts and diagnostic criteria in regard to mild cognitive impairment (MCI) due to AD and asymptomatic AD which are disease stages before the onset of dementia should be clarified and established. Then, awareness of these disease concepts and diagnostic criteria should be increased through various mechanisms and access to the necessary diagnostic tests should be promoted to support those with limited symptoms to access care. Enhance global guidance related to the development of drugs for MCI due to AD and asymptomatic AD MCI due to AD and asymptomatic AD affects populations that have not yet been subjects of dementia research. Therefore, to efficiently accelerate the development of new drugs, guidance on how this new target population can be identified as well as efficacy endpoints is required. Development will likely take place at the global level, so the formation of a global consensus is essential. Enable costs for imaging/biomarker tests for early detection and for early intervention drug treatment to be reimbursed by insurance In order to promote early diagnosis and early intervention treatment, costs related to imaging/biomarker testing and drug treatment for inhibiting the onset of dementia need to be reimbursed by National Health Insurance. 124 Lengthening Healthy Lifespans to Boost Economic Growth

126 References 1. 佐渡充洋 : 平成 26 年度厚生労働科学研究費補助金 ( 認知症対策総合研究事業 ) わが国における認知症の経済的影響に関する研究 平成 26 年度総括 分担研究報告書. 厚生労働省, 東京 (2015) 2. McKhann GM, Knopmann DS, Chertlkow H, et al. The diagnosis of dementia due to Alzheimer s disease: recommendations from the National Institute on Aging-Alzheimer s Association workgroups on diagnostic guidelines for Alzheimer s disease. Alzheimer Dement 2011; 7: Changing the Trajectory of Alzheimer s Disease: How a Treatment by 2025 Saves Lives and Dollars. (2015) Available at: 4. 厚生労働省 : 資料 認知症施策推進総合戦略 ( 新オレンジプラン )~ 認知症高齢者等にやさしい地域づくりに向けて ~ の概要. (2015) Available at: aiboushitaisakusuishinshitsu/02_1.pdf 5. Alzheimer s Association: The National Alzheimer s Project Act (NAPA). (2011). Available at: Lengthening Healthy Lifespans to Boost Economic Growth 125

127 Estimated Number of Patients with Dementia Pa#ents (x 10000) (year) Es#mated Number of Pa#ents with Demen#a by Demen#a type Source: Research on projection of elderly with dementia in Japan; FY2014 Health and Labour Sciences Research Grants, Public Administration Policy (trillion yen) Estimated Social Cost (year) (year) Source Research on economic impact of dementia in Japan; FY2014 Health and Labour Sciences Research Grants, Measures for Diseases and Disorders Social Cost of Demen#a is es#mated as JPY14.5 trillion/year in 2014 and projected to increase to JPY19.4 trillion/year by Lengthening Healthy Lifespans to Boost Economic Growth

128 Economic Effect by Early Intervention Changing the Trajectory of Alzheimer s Disease: How a Treatment by 2025 Saves Lives and Dollars IMPORTANT: Early diagnosis using image tests/ biomarkers, or Early interven?on by disease-modifying therapies before the onset of demen?a Initiatives by Countries (including Early Diagnosis) Japan Comprehensive Strategy to Accelerate Dementia Measures (New Orange Plan) (2015) A National Strategy for Dementia established by the MHLW in collaboration with the related administrative agencies US The National Alzheimer s Project Act (2011) Enacted a Law of National Strategy to overcome AD Issues that may rise when clinical utility is demonstrated by Early Diagnosis / Early Intervention in clinical studies Environmental divergence between clinical study setting and actual medical practice (e.g., diagnostic criteria, access to biomarker testing) Impact on national insurance finances by early treatment intervention Lengthening Healthy Lifespans to Boost Economic Growth 127

129 Policy Recommendations Create new disease concept, establish criteria, and disseminate information of probable conditions before the onset of dementia Prepare global guidance on the development of drugs for MCI due to AD and asymptomatic AD Reimburse costs by insurance for imaging/ biomarker tests for early detection and for early intervention drug treatment 128 Lengthening Healthy Lifespans to Boost Economic Growth

130 24 Promoting Proper Use of Hypnotics Situation Insomnia is an all too common disease, causing one in five adults to experience one or more of the following symptoms: difficulty falling asleep; difficulty maintaining sleep; or early-morning wakings. 1 In addition to increasing the risks of psychiatric diseases such as depression, insomnia is also associated with the onset of a wider range of diseases including hypertension and diabetes. 2 Insomnia also causes social and economic losses including increased long-term absences from work, additional medical expenses, decreased productivity, and higher rates of industrial accidents. The health, economic and social impact of this disease must be addressed through improved treatment. 3 Under such circumstances, the prescription rate of hypnotics in Japan has consistently increased. The proportion of adults who receive a prescription for a hypnotic at least once in three months has reached 4.8%, which means that 1 in 20 Japanese people are taking hypnotics. 4 Major hypnotics prescribed include benzodiazepine (BZ) hypnotics, non-bz hypnotics, melatonin receptor agonists and orexin receptor antagonists. BZ receptor agonists (including BZ and non-bz hypnotics) are the most commonly prescribed hypnotics. BZ receptor agonists are widely prescribed in every clinical department as well as in psychiatric departments due in part to convenience. These drugs have various indications (e.g., hypnotic sedative, treatment for anxiety), are highly effective, and cause relatively few side effects. According to a report of United Nations International Narcotics Control Board, the amount of BZ receptor agonists used in Japan is significantly higher than other countries; it is about twice as high as that in the Europe and about six times as high as that of the Americas. 5 While the number of hypnotic prescriptions has increased as described above, dependency and abuse (overdose) by long-term use, highdose use and polypharmacy in some patients has become a social problem. According to the Fact-Finding Survey on Drug-Related Psychiatric Diseases in Psychiatric Medical Institutions in Japan, psychiatric drugs such as hypnotics and anti-anxiety drugs are the second most widely abused drugs after illegal stimulants such as methamphetamine. 6 Among hypnotics, side effects that have been associated with the use of BZ receptor agonists in particular because of their mechanism of action include dependency, unsteadiness and fall caused by the muscle-relaxing effect carrying over to the next day, memory disorder, and delirium. The incidence of these adverse reactions increases as the dose increases. Additionally, BZ receptor agonists increase the risk of fracture in the elderly by 26% and long-term use can cause a permanent decrease in a wide range of cognitive functions, damage that cannot be reversed. 7, 8 In this context, The Japanese Society of Sleep Research issued Guidelines for Proper Hypnotic Use/Withdrawal in The guidelines focus on the proper use of hypnotics and provide explanations to patients and evidence-based recommendations for prescribing physicians on the optimization of treatment for insomnia, utilization of non-drug therapy such as sleep hygiene instructions and cognitive behavioral therapy, treatment goal setting, and methods of hypnotic reduction/ withdrawal. The Guidelines for Medical Treatment and its Safety in the Elderly, issued by The Japan Geriatrics Society, places BZ drugs in the List of drugs that requires particularly careful administration. 10 The most important point in the proper use of hypnotics is evaluating the adequacy of medication as needed and avoiding unnecessary long-term or high-dose use. Insomnia treatment should improve the daytime function and life of a patient medical Lengthening Healthy Lifespans to Boost Economic Growth 129

131 practitioners need to verify that a treatment regimen achieves this objective, balancing the risk and benefits. Current Policy The Ministry of Health, Labour and Welfare (MHLW) took measures to promote the proper prescription of psychotropic drugs, including hypnotics. One measure was a decrease in the medical fee when a physician prescribes a certain number of anti-anxiety drugs or hypnotics during one doctor s visit. However, this action alone has not been sufficient. An investigation of prescriptions provided by the psychiatric departments in 2014, the third year after the introduction of revised measures, revealed that 2.1% of patients received BZ receptor agonists at up to three times the maximum clinically recommended dose. In addition, the proportion of high-dose prescription of 33 different BZ receptor agonists did not show a tendency to decrease after the medical fee revision. Regarding polypharmacy 32.2% of psychiatric outpatients received a prescription for two or more BZ receptor agonists. 11 In response to the situation, MHLW provided a direction to revise package inserts of 44 pharmaceuticals that are used as hypnotics, anti-anxiety drugs and antiepileptic drugs, including BZ receptor agonists, in March It calls attention to dependency and withdrawal symptoms caused by continuous drug use even within the range of approved dose. The new policy also requires careful observation because BZ receptor agonists may cause irritable excitation or confusion in a range of patients. MHLW also encouraged the promotion of proper psychotropic prescription by supporting the formation of the psychiatric department liaison team. Hospitals that establish these special liaison teams are eligible to receive an additional fee to promote prevention and early intervention for delirium and other psychiatric conditions. The actual number of institutions that filed to receive this additional support was small. Thus, MHLW increased the additional points for medical fees and relaxed the standards for institutions to further promote the formation of the liaison teams. Recommendations As stated above, measures for proper use of hypnotics have been started by academic societies and MHLW in recent years, but in fact their long-term use, high-dose use and polypharmacy have not decreased as much as expected. While the current situation is dire, it may grow even worse as Japan sees a rise in the number of patients diagnosed with insomnia unless we are able to decrease the over prescription of hypnotics. The following actions and policies could promote more appropriate prescription and use of hypnotics. 1. Introduction of non-drug therapy evaluation on medical fees Non-drug therapies such as sleep hygiene instruction are one alternative to hypnotics. Physicians should be eligible to receive a fee for the provision of non-drug therapy. 2. Introduction of appropriate withdrawal/ reduction evaluation on medical fees The treatment goal for insomnia patients is to sleep steadily without using hypnotics. Reimbursement practice should lead to the gradual reduction of hypnotics use by individual patients. Tapering and alternate day prescriptions require additional physician explanation, time and support medical fees should recognize the time and effort required to reduce hypnotic consumption. 3. Reinforcement of measures for limiting the prescription of BZ drugs The current action on medical fees against polypharmacy of psychotropic drugs has not resulted in the reduction of polypharmacy of BZ receptor agonists, 130 Lengthening Healthy Lifespans to Boost Economic Growth

132 which are categorized as both anti-anxiety drugs and hypnotics, because anti-anxiety drugs and hypnotics are separately counted when the number of drugs is counted in the action. To improve the situation, measures to limit the prescription of BZ receptor agonists should be considered. Options may include the addition of evaluation by subtracting points for BZ receptor agonist polypharmacy, and the amendment of reimbursement regulations that currently target all hypnotics, so that physicians are not penalized when they prescribe a safer alternative. 4. Promotion of measures for delirium by the psychiatric liaison team The intervention of psychiatrists is said to be useful to prevent delirium caused by the unnecessary use of BZ receptor agonists. Therefore, the current situation in which it is difficult to obtain the additional fee for the psychiatric liaison team should be improved. Currently, many institutions cannot fulfill the institutional standards for the formation of the liaison team because recruiting qualified full-time nurses and specialists is difficult. Further measures should be taken after sufficiently verifying the results of medical fee revisions in Education of healthcare professionals on proper use of hypnotics Opportunities should be created to increase understanding around the proper use of hypnotics through cooperation between industry, government and academia. This could include the preparation of educational materials and training for healthcare professionals, including physicians. References 1. Kaneita Y et al., Excessive daytime sleepiness among the Japanese general population. J Epidemiol 15(1), 1-8(2005) 2. Taylor DJ et al., Comorbidity of chronic insomnia with medical problems. Sleep 2007:30(2): Doi Y et al., Impact and Correlates of Poor Sleep Quality in Japanese White-Collar Employees Sleep 26(4), (2003) 4. Mishima K et al., Health Labour Science Research Grant, Special Research International Comparison of Psychotropic Medication Prescription Patterns , United Nations, Report of the International Narcotics Control Board on the Availability of Internationally Controlled Drugs: Ensuring Adequate Access for Medical and Scientific Purposes, Matsumoto T, Problems of psychiatric pharmacotherapy in view of clinical practices for drug dependence: Findings from the National Survey for Patients with Drug-relates disorder in Psychiatric Hospitals. Japanese Journal of Psychiatric Treatment 2012;27(1): Xing D et al. Association between use of benzodiazepines and risk of fractures: a meta-analysis. Osteoporos Int 2014; 25: Banno M et al., Effect of hypnotics on cognitive performance. Jpn.J.Clin. Psychopharmacol 19(1),49-59(2016) 9. The Japanese Society of Sleep Research, Guidelines for Proper Hypnotic Use/Withdrawal The Japan Geriatrics Society, Guidelines for Medical Treatment and its Safety in the Elderly Okumura Y et al., Changes in high-dose combined anxiolytic-hypnotic prescription in outpatient psychiatric practice after regulatory action. Jpn. J. Clin. Psychopharmacol 2015; 18(9): Lengthening Healthy Lifespans to Boost Economic Growth 131

133 List of hypnotics GABA/BZ receptor agonist Category Benzodiazepines Non-benzodiazepines Generic name Launch Year triazolam 1983 etizolam 1984 brotizolam 1988 flunitrazepam 1984 quazepam 1999 flurazepam 1975 haloxazolam 1981 Melatonin receptor agonist ramelteon 2010 Orexin receptor antagonist suvorexant 2014 Notes Guidelines for Medical Treatment and its Safety in the Elderly 2015 places BZ drugs in the List of drugs that requires particularly careful administration. Major side-effect and reason: Oversedation, Cognitive function decline, Delirium, Fall/Fracture, Hypokinesia zolpidem zopiclone Guidelines for Medical Treatment and its Safety in the Elderly 2015 places BZ drugs in the List of drugs that requires particularly eszopiclene 2012 careful administration. Major side-effect and reason: Fall/Fracture, Possibility of other side-effect similar to Benzodiazepines Source : Package inserts, Guidelines for Medical Treatment and its Safety in the Elderly Average consumption of benzodiazepines * (sedative-hypnotics) The amount of benzodiazepines used in Japan is significantly higher than in Europe and the Americas S-DDD ** per 1,000 inhabitants per day Europe Americas Japan Approximate consumption calculated by the Board S-DDD (defined daily doses for statistical purposes) United Nations, Report of the International Narcotics Control Board on the Availability of Internationally Controlled Drugs: Ensuring Adequate Access for Medical and Scientific Purposes, Lengthening Healthy Lifespans to Boost Economic Growth

134 Trends in prescription rate of high-dose benzodiazepines Prescription rate of high-dose benzodiazepines constantly decreased by 0.29% a year, but did not show significant changes in the trends after medical service fee revision Rx rate of high-dose benzodiazepines Dose of diazepam equivalent mg/day mg/day >45 mg/day Note: The maximum clinically recommended dose is to not exceed 15mg for outpatients (Source: diazepam package insert) Objective Investigate changes in high-dose and combined anxiolytic-hypnotic prescription in outpatient psychiatric practice before/after biennial medical service fee revision Methods Based on prescription data from Japan Medical Research Institute CO.,LTD., conduct secondary analysis on 1,102,575 prescription issued by psychiatric practice from Apr 2011 to Nov 2014 Okumura Y et al., Jpn J Clin Pharmacol. 2015;18: Trends in polypharmacy rate benzodiazepines of Polypharmacy rate of benzodiazepines Polypharmacy rate of >5 benzodiazepines decreased by 1.03%, but did not show significant changes in those of 2~4 benzodiazepines drugs 3 drugs 4 drugs 5 drugs Objective Investigate changes in high-dose and combined anxiolytic-hypnotic prescription in outpatient psychiatric practice before/after biennial medical service fee revision Methods Based on prescription data from Japan Medical Research Institute CO.,LTD., conduct secondary analysis on 1,102,575 prescription issued by psychiatric practice from Apr 2011 to Nov 2014 Okumura Y et al., Jpn J Clin Pharmacol. 2015;18: Lengthening Healthy Lifespans to Boost Economic Growth 133

135 25 Comprehensive Women s Health Support: An Essential Component to Increase the Participation of Women in Japan s Workforce Situation Prime Minister Abe s administration has made the advancement of women a key element of its economic growth strategy. Compared to other advanced economies, however, Japan has a significant gap in economic and career advancement opportunities for women versus men. For example, Japan ranked 111 out of 144 countries in the World Economic Forum s 2016 Global Gender Gap Index, declining from the previous year. 1 Recognizing this gap, Prime Minister Abe noted that women are Japan s most underutilized resource, 2 and has cited the enhancement of women s participation and advancement in the workforce as one of the key pillars of Abenomics necessary for the economic revitalization of Japan. To date, the government s main policy focus as it relates to women s issues has been on reforms to support working mothers and to increase the number of women in managerial positions. Complementary to these structural and social reforms is the critical, yet overlooked, need to improve the prevention and treatment of female-specific health risks to ensure women stay healthy throughout their working lives. Mirroring the gap in economic opportunities for women, Japan also lags behind other developed countries in the provision of comprehensive measures to prevent and treat female-specific health risks. Ensuring that Japanese women are aware of such risks and have convenient access to screening and treatment is essential to ensure that they stay healthy throughout their working lives. Healthcare-related measures are, therefore, critical to the attainment of the government s gender equality goals and should go handin-hand with structural and social reforms. Meeting these healthcare challenges will not only be beneficial to Japanese women, but will also strengthen the economy and society as a whole. Increased Comprehensive Screening Can Decrease Women s Health Risks Women experience a changing and complex set of health risks throughout their lives, including menstrual symptoms, cervical and breast cancer, as well as later life conditions such as osteoporosis. Working women also face the challenge of balancing career development opportunities and the timing of childbearing. With lifestyles changing, today s women experience their first menstruation at a younger age and bear children at a later age and fewer times. This results in fewer interruptions in menstruation than in the past. Because of the increased number of menstruations that women now experience in their life, health risks associated with menstruation, including endometriosis and dysmenorrhea, are on the increase. Although menstrual symptoms (e.g., pain, bleeding) may be considered neither severe nor critical compared to cancer or other diseases, the vast majority of Japanese women suffer from menstrual symptoms every month, which when severe, lead to significant pain, distress and work loss. Indeed, it has been reported that more than 70% of Japanese women suffer from menstrual problems, which could be indicative of, or lead to, more serious health problems; yet, few of them consult a gynecologist about their symptoms. 3 It is estimated that the economic burden associated with menstrual symptoms reaches 680 billion Japanese yen annually, 72% of which is associated with work productivity loss. 3 If menstrual symptoms are left untreated, the risks of infertility and ovarian cancer may increase. Furthermore, it is estimated that the socioeconomic losses related to certain femalespecific diseases in employed women total 6.37 trillion Japanese yen. 4 Educational Intervention to Improve Health Literacy and Support Women s Advancement While women s advancement in business is ever more anticipated, balancing work and family 134 Lengthening Healthy Lifespans to Boost Economic Growth

136 presents challenges. However, many Japanese women do not have the support needed to pursue these critical dual roles. Women s health education is particularly important for women as awareness can not only prevent disease, but can also empower women to make better informed decisions about their life plans and to further achieve their career aspirations. Strikingly, in a study of 79 countries, Japanese women scored the lowest among countries within the very high Human Development Index (HDI) category with regard to comprehensive fertility knowledge; Japanese women s comprehensive fertility knowledge score of less than 40% was far below the average score of 64.3% for very high HDI countries. 5 Japanese women s knowledge was even below the 44.9% average for countries in the non-very high HDI category. 5 This lack of fertility knowledge has serious implications. For example, more than 40% of women in Japan mistakenly believe that a woman in her 40s has a similar chance to conceive as a woman in her 30s. 6 A separate survey of Japanese adolescents revealed that 82% did not know that menstrual disorder and dysmenorrhea may be attributed to endometriosis. 7 This broad lack of fertility knowledge reinforces the social stigma Japanese women face both in seeing a gynecologist and in openly discussing the health challenges they face. Current Policy Currently, a lack of guidelines for comprehensive health checks for women may lead to a situation in which otherwise treatable women s life cycle changes remain undiagnosed and, therefore, are not managed, leading to a possible increased risk of infertility, breast cancer, ovarian cancer and cervical cancer. Indeed, the incidence of ovarian cancer in Japanese women is 2.5 times higher compared to 35 years ago. 8 It is, therefore, critical to facilitate access to women s healthcare services and enhance comprehensive support for women s health to minimize such health risks. Education policies have not kept up with the needs of modern society where the government of Japan (GOJ) aims to accelerate women s participation in the workforce and women tend to delay childbearing. In many cases, primary and secondary school education does not place sufficient focus on healthrelated topics, especially women s health risks and fertility decline. Recommendations Facilitate greater access to women s healthcare services and encourage women to regularly consult a gynecologist by requiring annual gynecological check-ups from the onset of puberty a standard practice in most other developed countries. Amend laws and policies, as needed, to support greater access to gynecological care by, for example, adding gynecological disease prevention to the Health Promotion Act, and including gynecological check-ups in the regular health examination as an optout rather than an opt-in item under the Industrial Safety and Health Act. Offer appropriate women s health education depending on each woman s life stage at schools and universities to enable women to be more aware of, and better manage, changing health risks. The GOJ should ensure that women s health education is included under the School Health and Safety Act. Enhance women s health awareness and encourage women to take action to better plan their lives and improve their worklife-health balance. For example, the GOJ should encourage employers and municipalities to promote women s health through the issuing of new guidelines adopted under the Women s Advancement Promotion Law. Lengthening Healthy Lifespans to Boost Economic Growth 135

137 References 1. World Economic Forum Global Gender Gap Report Accessed May Retrieved from 2. Prime Minister of Japan and His Cabinet Speech on Growth Strategy by Prime Minister Shinzo Abe at the Japan National Press Club, April 19, Tanaka et al. Burden of menstrual symptoms in Japanese women: results from a survey-based study. Journal of Medical Economics 2013, 1-12, Informa Healthcare 4. Health and Global Policy Institute. Research on Health Promotion and Working Women Bunting L, Tsibulsky I, Boivin J Fertility knowledge and beliefs about fertility treatment: findings from the International Fertility Decision-making Study. Human Reproduction, 28: Maeda E, et al A cross sectional study on fertility knowledge in Japan, measured with the Japanese version of Cardiff Fertility Knowledge Scale (CFKS-J). Reproductive Health, 12: Bayer Yakuhin, Ltd. Survey about women s health in 2,083 students aged 15 to 18 years. Nikkei Inc. October Retrieved from 8. Matsuda A, Matsuda T, Shibata A, Katanoda K, Sobue T, Nishimoto H, and The Japan Cancer Surveillance Research Group Cancer Incidence and Incidence Rates in Japan in 2008: A Study of 25 Population-based Cancer Registries for the Monitoring of Cancer Incidence in Japan (MCIJ) Project. Japanese Journal of Clinical Oncology, 44(4): Lengthening Healthy Lifespans to Boost Economic Growth

138 Experienced Bothersome Symptoms during Menstrual Period n=18,174 Source: Adapted from Table 1, Journal of Medical Economics 2013, 1-12, Informa Healthcare Economic Burden Associated with Menstrual Symptoms in Japan Source: Adapted from Table 2, Journal of Medical Economics 2013, 1-12, Informa Healthcare Lengthening Healthy Lifespans to Boost Economic Growth 137

139 Improvement of Daily Life by Gynecologist Consultation Level of inhibition and limitation of daily life associated with menstrual symptoms (%) Women with gynecologist consultation (n=274) 100% 80% 60% 40% 20% 0% 59.1% McNemar s test p< % 0% Before consultation After consultation Before OTC use After OTC use A great deal Women without gynecologist consultation (n=500) 100% 80% 60% 40% 20% Quite a bit 77.1% 76.8% Source: Adapted from Figure 5, International Journal of Women s Health 2014: , Dove Medical Press International Comparison of Fertility Knowledge Source: Figure 1, Human Reproduction, 2013;28: Lengthening Healthy Lifespans to Boost Economic Growth

140 Limited Women s Health Literacy in Adolescents Survey in 2,083 students aged 15 to 18 years Source: Bayer Yakuhin, Ltd. Survey about women s health in 2,083 students aged 15 to 18 years. Nikkei Inc. October Retrieved from Limited Women s Health Literacy in Adolescents Survey in 2,083 students aged 15 to 18 years Source: Bayer Yakuhin, Ltd. Survey about women s health in 2,083 students aged 15 to 18 years. Nikkei Inc. October Retrieved from Lengthening Healthy Lifespans to Boost Economic Growth 139

141 26 Reduce the Spread of Sexually Transmitted Infections Situation The incidence of sexually transmitted infections (STIs) remains high in most of the world, despite diagnostic and therapeutic advances that can rapidly render patients with many STIs noninfectious and cure most STIs. In many cultures, changing attitudes toward sexual and the use of oral contraceptives have reduced traditional sexual restraints, especially for women, yet both physicians and patients have difficulty dealing openly and candidly with sexual issues. Additionally, the development and spread of drug-resistant bacteria (e.g., penicillin-resistant gonococci) is making some STIs harder to cure. The World Health Organization reported that more than one million STIs are acquired every day worldwide. 1 The highest rates is among year olds, followed by year olds. It is estimated that one in 20 young persons contract a STI each year, not including HIV and other viral infections. 2 The WHO estimates that, in 2012, there were million new infections of the four curable STIs chlamydia (130.9 million), gonorrhea (78.3 million), syphilis (5.6 million) and trichomoniasis (142.6 million). 3 The commonly reported prevalence of STIs among sexually active adolescent girls, both with and without lower genital tract symptoms, include Chlamydia (10 25%), gonorrhoea (3 18%), syphilis (0 3%), trichomoniasis (8 16%), and herpes simplex virus infection (2 12%). Among adolescent boys with no symptoms of urethritis, isolation rates include Chlamydia (9 11%) and gonorrhoea (2 3%). In the US, adolescents ages account for nearly half of the 20 million new cases of STI s each year. 4 Among STIs, the reported number of genital Chlamydia infections in Japan is extremely high, especially among young men and women. 5 In many cases, Chlamydia is asymptomatic. Of Japanese high school girls who have participated in sexual intercourse, 13% have asymptomatic Chlamydia. 6 Untreated Chlamydia in women can cause pelvic peritonitis in 20 40% of cases. It also can lead to infertility or ectopic pregnancy in a woman who becomes pregnant. Some women with untreated Chlamydia may have difficulty becoming pregnant. 7, 8, 9, 10 Chlamydia is associated with a five-fold risk for contracting the human immunodeficiency virus (HIV) and a five-fold risk for human papillomavirus (HPV) infection, which can cause cervical cancer. 11 Furthermore, Chlamydia infection during pregnancy can cause chorioamnionitis, premature delivery and abortion, as well as Chlamydia pneumonia and Chlamydia conjunctivitis in the newborn through 12, 13, 14, 15 fetomaternal infection. By detecting Chlamydia infections at an early stage, treatment is possible with regular antibiotics. Delay in detection, however, can lengthen the course of treatment and raise the cost. Women who have been infected with Chlamydia for a long time may require expensive fertility treatment to conceive. This can entail a high cost for the patient or for those local governments that subsidize these treatments. Women of child-bearing age should receive regular Chlamydia screening. It is important to note that Chlamydia remains contagious as long as it remains untreated. It has been reported that the total cost resulting from Chlamydia can be reduced by conducting annual screening tests for women between the ages of 15 and An additional outcome of screening may be an increase in the extremely low birth rate in Japan. The CDC recommends annual Chlamydia screening for women under the age of 25, and for those women over 25 who have recently changed sexual partners or have a partner who has an STI. In addition to the annual Chlamydia screening as recommended by the CDC, the screening is advised by many other organizations, including the American 140 Lengthening Healthy Lifespans to Boost Economic Growth

142 Academy of Family Physicians (AAFP), American College of Obstetricians and Gynecologists (ACOG), American College of Preventive Medicine (ACPM), Canadian Task Force on Preventive Healthcare, European Centre for Disease Prevention and Control (ECDC), and the Health Technology Assessment Programme in the U.K. Based on these recommendations, free screening tests are provided in many countries, including the United States, the U.K., Sweden, and Australia. Current Policy In Japan, many local governments provide free Chlamydia tests. However, the percentage of people who take the tests remains very low. In addition, the tests are conducted using blood samples, making it difficult to judge whether a positive result shows a past infection or a current infection. Additionally, the blood screening test suffers from low sensitivity and false negative results. Recommendations Subsidize Chlamydia screening tests for women of childbearing age (roughly years of age). In order to realize a high rate of testing and to reduce the cost burden to women, conduct Chlamydia screening at the same time as screening for cervical cancer for women in their twenties and thirties. Use a test based on nucleic acid amplification technology with endocervical swab specimens, instead of blood screening for the antibody which has a problem in sensitivity. Detect Chlamydia and start treatment at an early stage to increase quality of life for women and reduce the total cost to the public health insurance system of infertility treatment. Lengthening Healthy Lifespans to Boost Economic Growth 141

143 References 1. WHO. Sexually transmitted infections (STIs) Fact sheet (Updated August 2016) WHO. Sexually Transmitted Infections among adolescents WHO. Report on global sexually transmitted infection surveillance CDC. (2014). Reported STDs in the United States. Atlanta, GA: National Center for HIV/AIDS, Viral Hepatitis, STD & TB Prevention, Centers for Disease Control and Prevention. - PDF 5. Okabe, N., Tada, Y STD trend in Japan suggested by the investigation of infectious disease trends, and the study of the promotion of specific infectious diseases prevention guidelines, pp The Japanese Association for sex education. (2012) The current status and prevention of sexually transmitted diseases among young people. 2012(6) Kohl, K.S., Markowitz, L.E., Koumans, E.H Developments in the screening for chlamydia trachomatis: a review. Obstet Gynecol Clin North Am 30: Eschenbach, D. Acute pelvic inflammatory disease Glob Libr Women s Med (ISSN: ) doi /GLOWM Weström, L., Joesoef, R., Reynolds, G., Hagdu, A., Thompson, S.E Pelvic inflammatory disease and fertility: a cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results. Sex Transm Dis 19: Røttingen, J.A., Cameron, D.W., Garnett, G.P A systematic review of the epidemiologic interactions between classic sexually transmitted diseases and HIV. Sex Transm Dis 28: Campbell, K.P., Lentine, D Sexually transmitted infections (STIs) evidence-statement: screening and counseling. In Campbell, K.P., Lanza, A., Dixon, R., Chattopadhyay, S., Molinari, N., Finch, R.A., eds. A Purchaser s Guide to Clinical Preventive Services: Moving Science into Coverage. Washington, DC: National Business Group on Health. 12. Di Bartolomeo, S., Mirta, D.H., Janer, M., Fermepin, M.R., Sauka, D., Magarinos, F., de Torres, R.A Incidence of chlamydia trachomatis and other potential pathogens in neonatal conjunctivitis. Int J Infect Dis 5: Frommell, G.T., Rothenberg, R., Wang, S.P., McIntosh, K Chlamydial infection of mothers and their infants. J Pediatr 95: Schachter, J., Grossman, M., Sweet, R.L., Holt, J., Jordan, C., Bishop, E Prospective study of perinatal transmission of Chlamydia trachomatis. JAMA 255: Hu, D., Hook, E.W., Goldie, S.J Screening for Chlamydia trachomatis in women 15 to 29 years of age: a cost-effectiveness analysis. Ann Intern Med 141: Lengthening Healthy Lifespans to Boost Economic Growth

144 Why Screen for Chlamydia? Chlamydia is Spreading Among Young Japanese Epidemiological surveillance of genital Chlamydia infections in Japan Annual morbidity rate per 100,000 MEN WOMEN Yoshiaki Kumamoto, JJSTI 15:17-45, 2004 Chlamydia is the most common sexually transmitted disease. Lengthening Healthy Lifespans to Boost Economic Growth 143

145 Multiple types of test from one sample collection Two different types of sample collection are required Liquid Cytology based Test Chlamydia trachomatis Blood test Cytology detection Liquid Cytology based Test Cytology One sample collection in LBC for three types of test Chlamydia trachomatis Nucleic Acid Amplification Tests HPV Nucleic Acid Amplification Tests* Japan Association of Obstetricians and Gynecologists Co-testing of Cytology and HPV is recommended for those over 30 years of age. 144 Lengthening Healthy Lifespans to Boost Economic Growth

146 27 Increase Cervical Cancer Screening Levels Situation Early detection and early intervention are critical for the prevention of cervical cancer. According to the 2016 Projected Cancer Statistics, out of the 12,100 annual cases of cervical cancer diagnosed, roughly 3,000 women are expected to die from the disease. 1 Japan has seen a sharp rise in the number of patients with cervical cancer in their twenties and thirties, and a growing mortality rate. Cervical cancer is the only type of cancer whose incidence can be reduced with a vaccine, which is already in use in more than 100 countries and has recently become available in Japan. Because the human papilloma virus (HPV) is the dominant cause of cervical cancer, regular Pap testing, early HPV testing when recommended, and early vaccination can work together effectively to prevent cervical cancer. In the United States, regular Pap testing has been successfully adopted and recognized as one of the most effective cancer screening tests. Current Policy In 2009, the government of Japan (GOJ) made progress in improving cervical cancer screening by announcing a new five-year program to send coupons for free screening to women aged 20, 25, 30, 35, and 40. To date, only a small fraction of the target group has been receiving free screening due to low public awareness and the fact that the free screening cannot be received as part of the annual screenings provided by private health insurance associations. In 2011, the GOJ took a further step by funding the implementation of a National Cancer Initiative, targeting breast, colon, and cervical cancer. To further enhance cervical cancer prevention, HPV vaccination for girls between 10 and 14 years of age was also funded. In 2010, the cervical cancer screening rate in Japan was only 24.3%, less than half the Organization for Economic Co-operation and Development (OECD) average for member countries. 2 Recent efforts combined with various national and regional awareness initiatives have helped to increase the screening rate to 27.5% in 2013; however, Japan s cervical cancer screening rate remains low compared to the OECD average and especially when compared to other developed countries which have screening rates of over 80%. Widespread public confusion remains concerning how vaccination and cervical cancer testing combine to prevent cervical cancer. Recommendations Amend the National Health Insurance Law of Japan to fund and include cervical cancer testing in health exams for all women between the ages of 20 and 40. Increase funding for raising cervical cancer awareness to meet Japan s goal of a 50% cervical cancer screening rate as soon as possible. Increase funding to better educate women on how the three latest technologies to fight cervical cancer HPV vaccination, HPV testing, and Pap testing based on liquidbased cytology (LBC), all currently available in Japan can work together to achieve comprehensive cervical cancer prevention. Promote use of the latest cervical cancerfighting technologies, including HPV vaccination, HPV testing and, most critically, LBC cancer cell screening, to increase accuracy and reduce the amount of retesting for cervical cancer. In particular, the combined use of HPV testing and cytology has become a trend in recent years. Therefore, it is recommended that the conventional cytology method be converted to liquid-based cytology as soon as possible as a first step toward more universal adoption. Promote the use of automated screening systems, which are commonly used in the United States and Europe to ensure accuracy control; and promote streamlined operations for the increased manpower expected in labs as a result of an increased screening rate in the future. Lengthening Healthy Lifespans to Boost Economic Growth 145

147 References 1. Projected Cancer Statistics, 2016, Center Information Service, Center for Cancer Control and Information Services, National Cancer Center 2. Ministry of Health, Labour and Welfare National lifestyle basic research report (July 12) Lengthening Healthy Lifespans to Boost Economic Growth

148 Incidence Rate of Cervical Cancer (including intraepithelial carcinoma) Per 100, Age Source: Cancer Information Service, National Cancer Center, Japan Cervical Cancer Screening Rate in Developed Countries Japan s Cervical Cancer Prevention Problem is the Low Screening Rate United States ² Austria ² Germany ² Sweden ¹ Norway ¹ New Zealand ¹ Switzerland ² Canada ² Slovenia ¹ France ² Finland ¹ Greece ² Poland ² United Kingdom ¹ Spain ² Denmark ¹ Netherlands ¹ Iceland ¹* Ireland ¹ Belgium ¹ OECD24 Chile ¹ Australia ¹ Portugal ² Estonia ¹ Czech Rep. ¹ Korea ¹ Luxembourg ¹* Italy ¹ Japan ² Hungary ¹ Slovak Rep. ¹ Mexico ¹ Turkey ¹ Source: OECD, % of women screened The screening rate has improved since 2010; however, it remains low compared to the OECD average and other developed countries. Lengthening Healthy Lifespans to Boost Economic Growth 147

149 Comprehensive Cervical Cancer Prevention Three Technologies Work Together Percentage of Women for all 10-14, yrs. where possible Starting at 20 every 1-2 years for all women When recommended 10 Woman s Age Comprehensive Cervical Cancer Prevention After Age 10: Get HPV Vaccination! After Age 20: Get Periodic Screening! Woman s Age 148 Lengthening Healthy Lifespans to Boost Economic Growth

150 28 Improvement of Accuracy of Breast Cancer Screening Situation Female breast cancer morbidity related to age starts to increase at age 30, peaks between 45 and 65 years of age, and then gradually decreases. The morbidity and mortality of female breast cancer has consistently been increasing year by year and statistics show that, in 2015, there were an estimated 13,584 breast cancer related deaths and, in 2016, over 90,000 women in Japan diagnosed with breast cancer. 1 The rate of breast cancer screening is 80.4% in the United States and 74.1% in South Korea. However, in Japan the breast cancer screening rate is only 36.4%, a rate markedly lower than those of other developed countries. 2 In the U.S., an advanced country in terms of breast cancer screening, patient advocacy groups have highlighted that regular mammography screening cannot detect cancer in some cases because of dense breast tissue, leading to the risk of failing to detect the tumor until after it has progressed. This has now become a social problem. Therefore, since 2009, 32 states have adopted the Breast Density Notification Law, which requires that examinees by mammography alone be informed that there is a limit on the cancer detection rate of mammography in women with highly dense breast tissue and, furthermore, that ultrasonography, digital breast tomosynthesis, and magnetic resonance imaging (MRI) are available as testing options in addition to mammography. 3 According to a survey conducted in 2017, in the case of Japan, the ratio of municipalities that receive information on breast density from organizations that conducted mammography examinations is 31% (527/1700). Among these, 230 municipalities notified patients with dense breasts and 95 of those municipalities recommended ultrasonography screening to examinees with high breast density. 4 In Japan, there is a high rate of dense breast tissue for women in their 40s, the peak age for breast cancer. Thus, the proportion of local governments using ultrasonography for their screening programs is 32.3% (559 of 1731 municipalities). 5 However, there is no scientific evidence demonstrating that breast ultrasonography screening decreases mortality. Therefore, the first RCT conducted worldwide, A Randomized Controlled Trial to Verify the Efficacy of the Use of Ultrasonography in Breast Cancer Screening Aged (J-START: Japan Strategic Anticancer Randomized Trial), was conducted with a grant for the third term of the Ministry of Health, Labour and Welfare s (MHLW) Comprehensive Control Research for Cancer. The study results showed that ultrasonography contributes to the detection of Stage 0 or 1 cancers. However, the results also showed an increase in the number of additional invasive tests (e.g. needle biopsy), which is an increase in the negative impact of the examination. 6 While it is critical to thoroughly scrutinize the relative balance between the positive and negative impact of ultrasonography being integrated into municipally-administered examination process, the Japan Central Organization on Quality Assurance of Breast Cancer Screening began to develop a quality assurance system for ultrasonography screening and work-up in 2013, with a focus on future needs. As of the end of March 2017, 19,188 doctors and 19,857 technologists had participated in the mammography training program, whereas only 2,625 (vs MMG: 14%) doctors and 3,370 technologists (vs MMG: 17%) had in participated the ultrasonography training program. Thus, we consider human resource development an urgent need in order to fully introduce breast ultrasonography screening. 7 In 2012, the Japanese Association of Breast Cancer Screening developed Guidelines for the Use of Breast Magnetic Resonance Imaging Lengthening Healthy Lifespans to Boost Economic Growth 149

151 (MRI) for Breast Cancer Screening in High Risk Women to reduce deaths from breast cancer among high-risk women. This has led to a gradual increase in institutions conducting MRI screening as an optional examination. Health insurance society funding for MRI screening has also been reported. Guidelines in Europe and the U.S. state that MRI should not be performed at institutions where MRI-guided biopsy cannot be performed because MRI breast cancer screening requires a biopsy when lesions of the mammary glands can only be detected by MRI alone. However, in Japan, access to MRI-guided biopsy remains limited because it is not covered by insurance. MRI-guided biopsy is available in only 19 institutions across the country of breast ultrasonography screening in order to support the fully introduction of this technology. Add technical fee reimbursement for digital breast tomosynthesis. Add technical fee reimbursement for MRIguided biopsy to assure the accuracy of MRI breast cancer screening. In the U.S., the Centers for Medicare & Medicaid Services established national average payment rates for digital breast tomosynthesis (DBT) that went into effect January 1, 2015, because breast cancer detection rates by DBT are higher than that of conventional digital mammography. In Japan as well, there has been an increase in the number of institutions that recognize the clinical accuracy of DBT and are considering its introduction for the purpose of accurate diagnosis. However, DBT has not become widely used because it is more expensive than conventional digital mammography. 13 Current Policy Since 2009, the government has distributed a free coupon to women and has encouraged them to be screened for breast cancer. This initiative resulted in increased screening rates, but has not been effective enough to meet the government target of 50% screening rate. Recommendations Continue to distribute coupons and provide financial support encouraging women to have breast cancer screening. Fund human resource development projects to enhance the quality assurance 150 Lengthening Healthy Lifespans to Boost Economic Growth

152 References 1. Japan Cancer Society. Pink Ribbon Festival. (Japanese) 2. Cancer Statistics Cancer Information Service. (Japanese) 3. Are You Dense? Last modified Cancer Screening Document 2: Current Status of Breast Cancer Screening, The 21 st Meeting of the Council on Efficient Conduct of Cancer Screening, March 27, (Japanese) 5. Cancer Screening Document 3: Current Status of Breast Cancer Screening in Local Government, Document presented at the 19 th Meeting of the Council on Efficient Conduct of Cancer Screening, September 23, (Japanese) 6. J-START. Last modified April 24, (Japanese) 7. The Japan Central Organization on Quality Assurance of Breast Cancer Screening. Last modified (Japanese) 8. Guideline of Breast MRI Screening for High Risk Group of Breast Cancer guideline_fix.pdf (Japanese) 9. Terumo Corporation. Promotion of Awareness For Breast Cancer Screening and Extend Subsidies for Breast MRI Screening For Female Employees and Spouses in Terumo Corporation October 28, terumo.co.jp/pressrelease/detail/ /140 (Japanese) 10. Saslow, D., Boetes, C., Burke, W., Harms, S., Leach, M. O., Lehman, C. D., Morris, E., Pisano, E., Schnall, M., Sener, S., Smith, R. A., Warner, E., Yaffe, M., Andrews, K. S., Russell, C. A. and for the American Cancer Society Breast Cancer Advisory Group (2007), American Cancer Society Guidelines for Breast Screening with MRI as an Adjunct to Mammography, CA: A Cancer Journal for Clinicians, 57: doi: /canjclin Mann, R.M., Kuhl, C.K., Kinkel, K., and Boets, C., Breast MRI: Guidelines from the European Society of Breast Imaging, European Radiology (2008): 18: doi: /s BIG READS Group. Breast Imaging Research and Diagnostic Support Group. (Japanese) 13. Department of Health and Human Services. Centers for Medicare & Medicaid Services. Medical Learning Network. Preventive and Screening Services Update- Intensive Behavioral Therapy for Obesity, Screen Digital Tomosynthesis Mammography, and Anesthesia Associated with Screening Colonoscopy (Updated August 31, 2015). downloads/mm8874.pdf Lengthening Healthy Lifespans to Boost Economic Growth 151

153 (%) The rate of breast cancer screening in Japan is among the lowest in OECD countries International Comparison of Screening Rate Breast cancer screening (50-69 years old) US (2010) France (2010) Korea (2012) UK (2011) Germany (2009) Australia (2011) Japan (2010) Source: OECD Health Data 2013 Source: Actual Situation of Breast Cancer Screening, etc., Document by Division for Promotion of Measures against Cancers and Health Promotion, Health Service Bureau, Ministry of Health, Labour and Welfare November 13, Breast density no-fica-on requires a framework to support women with dense breast -ssue Report to municipalities from screening centers Respondents: 1700 municipalities Notification to examinees 69% 31% Reported Not reported No#fies Does not no#fy Reporting based on discretionary judgement by screening centers are not included. Source: The 21st meeting of the Council on Efficient Conduct of Cancer Screening, dated March 27, 2017: Document 2 Current status of Breast Cancer Screening (in Japanese) Lengthening Healthy Lifespans to Boost Economic Growth

154 Adding ultrasonography to mammography screening results in 1.5 x higher detec-on rate for early stage breast cancer Source:Ohuchi N, Suzuki A, Sobue T, et al. Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a randomised controlled trial. Lancet Jan 23;387(10016): doi: /S (15) Epub 2015 Nov 5 Human resource development projects on breast ultrasonography screening are not enough The number of persons attending the training program by the Japan Central Organization on Quality Assurance of Breast Cancer Screening (Persons) Mammography Ultrasonography Doctors Technologists Source :Data from The Japan Central Organization on Quality Assurance of Breast Cancer Screening as of March 31, Lengthening Healthy Lifespans to Boost Economic Growth 153

155 29 Prevent Fractures Due to Osteoporosis Situation Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fractures. The World Health Organization (WHO) defines osteoporosis as a disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. According to the 2011 Japanese guidelines for prevention and treatment of osteoporosis, the estimated number of osteoporotic patients aged 40 or over in Japan is 12,800,000 (3,000,000 men and 9,800,000 women). 1 In order to retain their strength, bones are constantly rebuilding through a cycle of breaking down old bone (bone remodeling) and building new bone (bone formation). However, for a variety of reasons including aging, menopause, poor diet, and lack of exercise, the bone turnover balance can become disrupted, causing bone resorption to outpace bone formation, resulting in an overall decrease in bone mass. Therefore, the incidence of osteoporosis dramatically increases in women during the first half of their fifties, after menopause, and in men during the latter half of their sixties. 1 In most cases, osteoporosis progresses without obvious symptoms. However, with the progression of bone mass decrease and microcracks, subtle symptoms, such as a slight loss of height and lower back pain, begin to appear. Decreased bone mass and micro-cracks increase the risk of fractures, even from relatively small impacts, such as from falls. Fractures due to osteoporosis mainly occur in the vertebrae, femoral neck of the hip, and radius of the arm. Due to the rapidly aging population in Japan, femoral neck hip fractures which cause elderly people to become bedridden or require nursing care are continuing to increase. 2 (Figure 1) Fractures due to osteoporosis are becoming an increasing financial burden on the Japanese healthcare system. The estimated entire annual healthcare and nursing care cost is one trillion yen and about 80% of this cost is driven by femoral neck hip fractures. 3 (Figure 2) In addition to the healthcare cost burden, osteoporosis causes a severe decline in quality of life for patients. Life expectancy is markedly reduced and the chance of spending the rest of one s life bedridden is significantly higher for elderly patients who suffer hip fractures. 4,5 Moreover, research shows that, once a fracture occurs due to osteoporosis, a woman is five times more likely to suffer another facture within a year. (Figure 3) Therefore, in order to reduce the likelihood of a woman becoming bedridden there is a particular need to ensure that these high-risk patients have access to effective treatments. It is well known that the prevention of primary fractures is critical and education and awareness about the significance of early diagnosis and treatment are essential. 6,7,8,9 Recent trends in hip fractures around the world, show a decline in North America and Europe as well as Australia, New Zealand and Singapore. In Asia, other than in Hong Kong, the rate of increase is also declining significantly. In Japan however, a country where the aging of the population is progressing, the rate continues to increase. 10 While Japan needs immediate countermeasures to address this issue, the osteoporosis screening rate still hovers around five percent. The correlation between the osteoporosis screening rate and percentage of the elderly population with nursing care needs suggests that the higher the screening rate, the lower the eventual nursing care needs. 11 (Figure 4) For this reason, increasing the screening rate is important for Japan. Nonetheless, aggressive intervention to prevent primary fractures among at-risk patients is also crucial, 154 Lengthening Healthy Lifespans to Boost Economic Growth

156 including through the use of medication and improvements in lifestyle. Underappreciated is the importance of prompt diagnosis and treatment for those patients who have already experienced a fracture, as their risk of experiencing a second fracture within one or two years increases over 5 times. 12 (Figure 3) Innovative medicines that have been developed provide a wide range of alternatives to treat osteoporosis, including ones that prevent bone resorption and others that stimulate bone formation. Prompt initiation of treatment for osteoporosis is important to prevent loss of quality of life due to bone fractures. Current Policy The Ministry of Health, Labour and Welfare (MHLW) considers osteoporosis screening to be one of the pillars of its health-promotion projects for people over the age of 40. Currently, osteoporosis screenings are being conducted nationwide at five-year intervals for women between the ages of 40 and 70, but the screening rate is relatively low. In April 2013, the MHLW launched a revision to its Healthy Japan 21 goals that included a target to increase the public awareness rate of locomotive syndrome, a term for various musculoskeletal disorders, including osteoporosis, that contribute to a heightened risk of needing nursing care or becoming bedridden, to 80% by 2022 from the base rate of 17.3% in In addition, it is also important to increase awareness of both the necessity of proactive intervention when bone density screening shows increased bone fracture risk and to the presence of an existing fracture. Leadership from both the central government and local municipal governments will be important to introduce measures for the prevention and treatment of osteoporosis promptly. local governments should pay particular attention to awareness programs that focus on the importance of prevention and treatment of osteoporosis as a way to avoid serious bone fractures. Local governments should incorporate various osteoporosis awareness and prevention programs into community-based healthcare programs throughout Japan. It is very important for health officials of local governments to include information on the importance of prevention, early screening and treatment of osteoporosis in such programs. Japan should incorporate programs that focus on diagnosing and promptly treating patients who have already experienced a fracture given their higher risk of experiencing additional fractures. Healthcare professionals and nursing care providers should improve their health literacy in relation to osteoporosis and collaborate across the spectrum from screening to treatment in the framework of community-based comprehensive healthcare systems. Recommendations The current health policy for bone health is focused on improving awareness of locomotive syndrome. Within this effort, Lengthening Healthy Lifespans to Boost Economic Growth 155

157 References 1. Japanese 2011 guidelines for prevention and treatment of osteoporosis 2. Hagino H et al. J Orthop Sci 2010; 15: Harada A, Japanese Journal of Geriatrics, 42; , Cooper C, et al. 1993; American Journal of Epidemiology 137(3): Effect of hip fracture on mortality in elderly women: the EPIDOS prospective study. Empana JP, Dargent-Molina P, Bréart G; EPIDOS Group Ettinger B, et al : Journal of the American Medical Association 282(7), , Black DM, et al : Journal Bone Miner Res. 14(5), , Ross PD, et al : Osteoporosis Int. 3(3), , Lindsay R.: Journal of the American Medical Association, 285, Ballane G et al. J Bone Miner Res 2014; 29(8): Yamauchi H., et al: Nippon Rinsho 69; , van Geel TACM, et al. Ann Rheum Dis. 2009; 68: Healthy Japan 21(The second term) Ministry of Health, Labour and Welfare (MHLW) Lengthening Healthy Lifespans to Boost Economic Growth

158 Trend of Proximal Femoral Fractures Figure 1 ( ) Femoral neck fractures are increasing in Japan due to the growing aging population 40,000 35,000 Femoral neck fracture Intertrochanteric femoral fracture Number of Patients 30,000 25,000 20,000 15,000 10,000 5, Year Healthcare and Nursing Care Costs of Osteoporotic Fractures Figure 2 Healthcare and nursing care costs are estimated to reach up to 1 trillion yen, about 80% of which are for proximal femoral fractures Health and nursing care costs 797.4~989.5 billion yen (The graph was created using the maximum value of the trial calculation.) Health and nursing care costs Femoral Neck 678.6~811.4 billion yen Spine 118.8~178.1 billion yen 0 2,000 4,000 6,000 8,000 10,000 (billion yen) Atsushi Harada et al. Japanese journal of Geriatrics 2005: 42; Lengthening Healthy Lifespans to Boost Economic Growth 157

159 Importance of Early Intervention to Prevent a Second Fracture Fracture Risk Increases Over 5 times in the First 2 Years Following Initial Osteoporotic Fracture 6 Figure 3 Relative Risk of Subsequent Fracture Follow-up, in years Average over the entire follow-up period = 2.1 Cross-sectional study with 4,140 postmenopausal women years old with known fracture history van Geel TACM, et al. Ann Rheum Dis. 2009;68: Osteoporosis Screening Figure 4 The higher the osteoporosis screening rate, the lower the nursing care needs. Osteoporosis screening rate is still low and does not seem to be improving in Japan. Osteoporosis screening rate by prefecture and (%) the level of nursing care needs 16 (%) 8 Trend of osteoporosis screening rate in Japan Osteoporosis screening rate R= P<0.05 Osteoporosis screening rate (%) Level of nursing care needs Screening rate =No. of screened people/ Female population (Age 40, 45, 50, 55, 60, 65,70 Hirose Yamauchi et al. Nippon Rinsho 2011: 69; Lengthening Healthy Lifespans to Boost Economic Growth

160 30 Boost Regional Medical and Long-Term Care Collaboration Through Greater Use of Healthcare IT Situation With the declining birthrate and rapid growth of the elderly population, coupled with issues such as the serious shortage of doctors, uneven distribution of specialized physicians and regional gaps in healthcare distribution, Japan must consider a fundamental change in how healthcare services are delivered to its citizens. In such circumstances, healthcare information, communication and technology (ICT) will be at the core of this change, providing improved efficiency, better outcomes, and a higher quality of life. Many governments of other countries are investing heavily in healthcare ICT, and are already gaining tangible benefits. The aftermath of the 2011 Great East Japan Earthquake highlighted the importance of electronic healthcare records (EHR), storage of health information, disaster preparedness, service continuity, and regional medical and long-term care collaboration. Based on this experience, and, with access to the world s leading medical technologies and ICT appropriately integrated with rapidly emerging IoT and AI related technologies, Japan has the potential to innovate and to become the global leader in healthcare ICT. Since the introduction of the IT Basic Law in 2000, healthcare IT has been a priority for the government of Japan (GOJ). As a result, 98% of large hospitals have implemented the so-called electronic receipt system (as of 2017 March) 1, a nationwide electronic billing system. However, the current process still requires some manual operations between organizations, and does not provide the full benefits of electronic throughput. Meanwhile, EHR penetration in hospitals has increased to 30.2% as of 2016, 2 but utilization varies between different sized hospitals and remains low among older clinics, and interoperability remains a challenge. Despite various government-sponsored policies and practices for telemedicine, implementation has been relatively slow due to the lack of appropriate inventive models and guidelines. Hereafter, with advancing methodologies such as cloud technologies, data analysis, AI and deep learning, appropriate utilization should be considered for quality and efficiency improvements in diagnosis and treatments, reduction of the gap in regional medical care, and optimal allocation of limited resources. For this purpose, healthcare ICT system tools should be designed not only for individual hospitals, but with the idea of connecting all hospitals (i.e., as a secondary medical region ) to function as a component of the broader social infrastructure. For example, a holistic IT system among multiple medical and long-term care facilities and care providers that encompasses not only acute care but the whole pathway of prevention, long-term hospital stay and homecare, is required with optimized range and granularity for utilization. Information systems should be interoperable and comprehensive (i.e., to include text, image, and sensing data), providing availability and scalability that can be shared in real time both internally and externally between facilities. Security should be also taken into consideration to increase emergency response readiness. In addition, such infrastructure will not be sustainable if supplementary funding is limited to initial costs and does not cover running costs for maintenance, if productivity is not improved, and if incentives are not provided through medical and long-term care reimbursement. Both the installation and the sustainable management of systems should be achieved. Furthermore, the GOJ should actively promote standardization of Japan s healthcare IT based on the experience and merits of global standards, with an eye to the continued introduction of global best practices into Japan. The need for efficiency and flexibility of large-scale and multi-layer systems that can be supported by a wide range of stakeholders Lengthening Healthy Lifespans to Boost Economic Growth 159

161 in regional collaboration should also be taken into consideration. The government should introduce a comprehensive and holistic policy for the implementation and management of a sustainable ICT infrastructure that promotes adoption of global standards and incorporation of best practices from many players in an independent and prompt manner. Current Policy While the Regional Health Revitalization Fund, introduced in 2009 will be terminated, the GOJ has enacted a comprehensive new law that aims to maintain and promote regional medical and long-term care (the Comprehensive Medical and Longterm Care Promotion Law ). As a result, funds from the increased consumption tax now support the new fund. At the same time, local governments were required to create a regional health vision that describes the future of regional health provision by the end of Fiscal Year In order to build a mechanism for functional distribution and collaboration of healthcare envisioned by the Medical and Long-term Care Promotion Law, accelerated utilization of ICT is required. A system that enables information sharing of EHR and regional medical and long-term care data, with telemedicine capability, will become a part of Japan s healthcare critical infrastructure. By utilizing analysis and insights from accumulated big data and cloud computing infrastructure for information sharing, improvements are expected in practical actions contributing to population health, such as acute care, early diagnosis, control of noncommunicable disease, homecare, clinical decision support, research, reduced workload of medical practitioners, effective operations management of medical and nursing care, optimized resource allocation, and quality assurance. Similarly, in 2014, the new Medical Device Law was enacted, and medical software can now be regulated independently from hardware. In addition, various health software applications that can be used in a clinical setting, as well as for personal health, are available in the market. While some software may not be regulated by the Medical Device Law, the industry is working on a self-guideline that takes into account its intended use and risk. With the greater use of ICT in healthcare, increasing awareness among developers and users will become more and more important. Recommendations Make strategic investment plans for EHR, medical imaging information systems, and regional healthcare collaboration. Build incentive models to facilitate ICT investment through medical and longterm care reimbursement and sustainable funding. Ensure interoperability based on global standards to facilitate regional medical and long-term care collaboration. Promote external storage and effective analysis of healthcare information based on cloud computing, with adequate rules for privacy and security. Cultivate understanding and agreement on use of data, including comprehensive consent, for secondary use of data with a variety of methods. Implement financial incentives for initiatives to develop evidence-based insights from data analysis, contributing to effective and adequate operations management of medical and long-term care. Raise awareness, among healthcare providers and the members of the general public, regarding the benefits of using healthcare ICT. Continue to develop and evaluate new rules on medical software that promote the healthcare industry as well as public health. Introduce a legal framework for medical 160 Lengthening Healthy Lifespans to Boost Economic Growth

162 information and Medical IDs based on global standards that take into account the balance between adequate protection and effective utilization of medical information. References 1. Health Insurance Claims Review & Reimbursement Services. Billing status by receipt request form (2017 March) (In Japanese) 2. Japanese Association of Healthcare Information Systems Industry The Report on EHR Penetration 2016 (in Japanese) Lengthening Healthy Lifespans to Boost Economic Growth 161

163 Regional Medical and Long-Term Care Collaboration Through IT(1) Drivers Building regional care toward 2025 Collect information from the full care continuum, including prevention, acute care, recovery, homecare and prescription, to provide adequate care Use IT as a tool to communicate among various medical and care professionals. The number of Regional Medical and Long-Term Care Collabora7on (Including es7ma7on) Revitaliza7on plan(accumulated) Tradi7onal (accumulated) Revitaliza7on plan of local medical New fund New fund: new financial support system (fund) Challenges Source:JMARI Working Paper No.368 Overview of regional medical collaboration using IT (2015 version) published October! Management sustainability! How to measure outcome vs cost! Agree on level and standard and format of the data to be shared! Define and optimize patient ID, user authentication, and security 1 Regional Medical and Long-Term Care Collaboration Through IT(2) Drivers To facilitate smooth transition of patients among hospital and clinics, information should include not only summary of discharge but also imaging data. IT can potentially fill the regional and professional gaps between medical and long-term care providers. Challenges! Patient consent! Procedures for secondary use such as analysis of data format, and communication protocol. Provided service (including future plan) Sharing image info. Home-care collaboration Summary at discharge Nursing care collaboration Comm. with mobile-device Info. Sharing (SNS etc.) Image diagnostic service E-letter of introduction Collabo. about health check Mail / m-magazine Remote conference Collab with diagno-center Remote medication Reservation E-note of drug prescription Patient ID Card PC service for patients Mobile service for patients Info. about empty bed E-prescription paper Self-managing system for pt. E-note of DM monitoring Providing Plan Source:JMARI Working Paper No.368 Overview of regional medical collaboration using IT (2015 version) published October Lengthening Healthy Lifespans to Boost Economic Growth

164 31 Utilizing Telemedicine to Deliver More Efficient and Effective Healthcare in Japan Situation Governments and healthcare providers are under significant pressure to lower the costs of delivering healthcare services. One way to achieve this imperative is to integrate new infrastructure, information systems and emerging technologies that support an increasingly broad healthcare ecosystem. Telemedicine is one such solution. Telemedicine is a dynamic and important method of delivering healthcare services that holds the potential to benefit the Japanese healthcare community, patients, the government and the broader economy as a whole, by virtue of its ability to enhance traditional medical services and, in some cases, improve access to healthcare in a more affordable way. Telemedicine is formally defined by the American Telemedicine Association (ATA) as the use of medical information exchanged from one site to another via electronic communications to improve a patient s clinical health status. Telemedicine includes a growing variety of applications and services using two-way video, , smartphones, wireless tools and other forms of telecommunications technology. Telemedicine encompasses a wide range of remote healthcare services such as patient consultations via video conferencing, transmission of still images, e-health including patient portals, remote monitoring of vital signs, continuing medical education, consumer-focused wireless applications and nursing call centers, among other applications. Benefits derived from telemedicine are numerous and typically fall into one of four categories: (1) enhanced efficiency; (2) improvement in patient satisfaction and quality of life (QOL); (3) greater access to healthcare; and (4) contributions to clinical safety and reduction of medical errors. Although there are few if any objective statistics on the application and delivery of telemedicine services in Japan or, for that matter, around the world, many experts in the field believe that there is a wide gap between (i) the technological capabilities of Japanese manufacturers and service providers, and the advanced infrastructure within the country and (ii) the utilization of telemedicine amongst healthcare practitioners and patients here in Japan. Current Policy The ACCJ and EBC have identified a number of issues that we believe represent obstacles to the growth of telemedicine in Japan, including: Ambiguity of Article 20 of the Medical Practictioners Act The current wording makes no mention of telemedicine and contains language that many legal professionals and academics believe could be interpreted to prohibit telemedicine. The ordinance issued by the Ministry Health, Labour and Welfare (MHLW) on March 31, 2011, shortly after the Great East Japan Earthquake, and the notice on July 14, 2017, however, accepted telemedicine under the same conditions as face-to-face treatment. Thus, Article 20 should be revised in the manner that reflects the MHLW notice and announcement and incorporates reference to telemedicine. Uncertainty as to Who Can Implement Telemedicine Because no official guidelines for telemedicine exist in Japan, it is unclear who is authorized to implement it. The primary interpretation is that only medical doctors can implement telemedicine, but, for the full benefits to be realized, other medical professionals can and should be allowed to participate. Given the shortage of physicians, particularly in rural areas, the MHLW should implement a system that expands the services that nurses, psychiatrists, clinical engineers and other healthcare professionals can provide under a doctor s remote Lengthening Healthy Lifespans to Boost Economic Growth 163

165 guidance. In the United States, credentialing for telemedicine clearly designates the persons who can implement specific telemedicine treatments and operate specific devices. Both the government and the medical sector are active in educating, training and monitoring telemedicine practice in U.S. medical institutions. Limitations of the Current Reimbursement System Teleradiology, telepathology, telephone consultation, guidance and management for use of a pacemaker, and asthma treatment at home (telemonitoring) are some rare examples of telemedicine services whose costs are clearly approved for reimbursement. It is uncertain whether other telemedicine practices qualify for reimbursement or not. This differs greatly from the U.S., where Medicare protocols clarify which treatments are subject to reimbursement in a simple way by using CPT (Current Procedural Terminology) or HCPCS (Healthcare Common Procedure Coding System) codes. For example, Medicare in the U.S. accepts the costs of telemonitoring, guidance and education on diabetes and dialysis treatment in its reimbursement scheme. Telemedicine is also suitable for health management in ways other than direct treatment, such as for continuous monitoring of a patient s condition, consultation by medical specialists, disease-management, prevention of the worsening of illnesses, and guidance and education for patients. The ACCJ and EBC submit that the costs of these telemedicine practices should also be reimbursed, and that the government of Japan (GOJ) should do more to lower the cost of ongoing monitoring by facilitating utilization of the Internet of Things (IoT) and machine to machine (M2M). Limited Utilization of Electronic Health Records (EHR) Especially in Small and Medium-sized Clinics and Hospitals During the aftermath of the 2011 Tohoku disasters, many believed that had there been an efficient electronic healthcare record (EHR) system in place, emergency medical care would have been much easier for doctors to deliver and patients to receive. Based on this experience, and as one of the world s leading IT economies, Japan has the potential to innovate and lead the future of healthcare IT globally. It is estimated that, as of 2014, 77.5% of large hospitals (hospitals with over 400 beds) and only 35% of all clinics in Japan utilize EHR. In addition, many healthcare IT systems in Japan are designed only for individual hospitals, not with the idea of connecting hospitals to function as a component of the broader social infrastructure (i.e., as a secondary medical region ). EHR allows patient records to be securely shared amongst healthcare practitioners, increasing accuracy, convenience and coordination while reducing the chance of error and lowering costs. Telemedicine and Health Information Exchanges (HIE), along with integrated data from EHR, are at the heart of a patient-centered team care delivery model. Limits on Data Centers and Cloud Computing Services Related to Healthcare Including Big Data Cloud computing enables not only large hospitals but also small/medium-size hospitals, clinics, pharmacies and nursing care services to access and utilize big data integrated from EHR, HIE and other resources at low cost and as needed. However, rules regarding security, privacy and personal information protection in healthcare often differ by government body (e.g., METI, MHLW, MIC and local governments). As a result, cloud services providers face challenges in meeting each set of requirements. To optimize the merits of big data and analytics in the entire healthcare value chain, it is essential to develop common rules related to privacy and personal information protection, applicable to both the healthcare providers and the cloud services providers, and to fully 164 Lengthening Healthy Lifespans to Boost Economic Growth

166 implement the National ID or Common ID number system. Cross-border harmonization in the healthcare IT sector is also essential. Recommendations The ACCJ and EBC believe that the GOJ can and should do more to promote the utilization of telemedicine via a combination of deregulation and economic promotion. This is consistent with Prime Minister Abe s emphasis on the importance of ICT applications in the medical field in Japan s growth strategy. Specifically, the ACCJ and EBC urge the government to: Amend Article 20 of the Medical Practitioners Act in a way that defines which telemedicine practices can be accepted under the same conditions as face-to-face treatment and allows medical practitioners to easily understand who can implement telemedicine. Clearly define reimbursement qualifications and expand reimbursement to include actions other than direct treatment, including consultation between medical specialists, patient education, disease management and, in particular, monitoring of patients at home. Such bio-data monitoring of patients and the elderly can help those with chronic health conditions, and can also be used to prevent diseases and maintain health helping to further reduce medical expenditures. Lower the cost of ongoing health data monitoring by facilitating growth and utilization of IoT and M2M by ensuring that service fees charged by the mobile carriers are rationalized. Speed up the implementation of the Regional Cooperation Medical Information Network, based on the Dokodemo MY Byouin (My Hospital Everywhere) Project. Make further efforts and provide greater incentives to increase EHR penetration and ensure greater data interoperability. Harmonize rules related to privacy and personal information protection among relevant government bodies for utilization of big data and healthcare analytics in cloud computing. Introduce a policy framework that promotes delivery of telemedicine services and supports companies willing to invest and develop new business models in this emerging sector; improve coordination across the various ministries involved in regulating telemedicine. Implement existing global standards and assume a leadership role in the ongoing development of telemedicine s future global standards. Notes and References 1. Ordinance issued by the Ministry Health, Labour and Welfare (MHLW) on March 31, 2011, and the announcement on July 14, 2017, stated: Although treatment delivered via telemedicine is not the same as face-to-face treatment, telemedicine does not automatically conflict with Article 20 of the Medical Practitioners Act if it enables useful information on the physical and mental condition of patient to be obtained in a sufficiently substitutable manner. 2. Regarding Promotion of Healthcare IT, The Ministry of Health, Labour and Welfare Accessed April 2017 Lengthening Healthy Lifespans to Boost Economic Growth 165

167 Percentage of Home Care Agencies Using Disease Management Telehealth Programs Telehealth is used in the U.S. to help manage various chronic diseases. The 2014 National State of the Home Care Industry Study included over 1,100 home health agencies of all sizes, all auspices, rural and urban, forprofit and not-for-profit, hospital-based and freestanding. Homecare agencies report that they use their telehealth systems to serve patients with one or more chronic disease. 35% Diseases addressed by telemedicine in home health agencies in the U.S. 30% 25% 20% 15% 10% 5% 0% Other Diabetes Other Cardiac COPD Heart Failure National State of the Home Care Industry Study 2014 Telehealth Global Forecast The global telehealth market is expected to grow by more than a factor of 10 from 2013 to 2018, as medical providers increasingly employ remote communications and monitoring technology to reduce costs and improve the quality of care, according to IHS Technology. Global Forecast of Telehealth Patients and Device and Service Revenue (Thousands of Patients Revenue in Million of US Dollars) Millions of US Dollars Thousands of Pa3ents Device & Service(in Millions of US Dollars) Total Pa3ents (in Thousands) Source IHS Technology January, Lengthening Healthy Lifespans to Boost Economic Growth

168 32 Improving the Quality of Medical Care, Promoting Team-based Medicine and Supporting Risk Management in Ophthalmological Surgery Situation In conventional ophthalmological surgery, especially in vitreoretinal surgery, surgeons utilize an optical microscope that requires them to assume an unnatural posture for long periods of time (Picture 1). This method also limits the ability to view the intra-ocular surgical field in real-time and in 3D to surgeons and their assistants. Therefore, surgery status is not shared in real-time with other staff in the operating room, such as junior doctors, medical interns, orthoptists, nurses and staff because they cannot see simultaneously see the surgical field on the same screen that the surgeon sees. Opportunities for staff to improve their skills are limited as result. As conventional surgery only allows a limited number of people to have simultaneous vision under the microscope, in cases of emergency, the ability to immediately intervene is impeded due to the time needed to inform others of the current status of surgery and allow them to make critical decisions. Recently, an ophthalmic surgery visual system with a 3D visualization system was developed. This system uses a camera attached to the binocular part of the microscope to enable the display of real-time surgical images on a 3D monitor. Introduction has begun in medical facilities (Picture-2). This technology makes it possible for all staff in the OR to simultaneously have real time vision of the surgical field condition and surgical progress on a large screen. As a result, this technology has been recognized by medical professionals to have a high level of efficacy in the field of education. With the 3D visualization system, a digital filter makes it easy to visualize the tissue involved in detail. Expanded depth of field and vision also makes detailed treatment easier. In conventional surgery with an optical microscope, junior doctors and other staff were unable to observe the surgical field in real-time. With this system, they will be able to make real time observations during ophthalmological surgeries, including vitreoretinal surgeries. This will increase opportunities for professionals to improve their skills. It is also expected that this 3D visualization system will bring ergonomic benefit to surgeons. Conventional surgery using microscope requires surgeons to look into the microscope for a long time. It is reported that 70% of ophthalmology surgeons who are over 55 years old feel pain in their neck, back, and shoulders. 1 The newly developed system enables surgeons to perform long surgeries in a relaxed posture, which can reduce the risks caused by poor posture during conventional microscopic surgery. This technology will improve the surgical skills of doctors and co-medicals engaged in ophthalmological surgery, leading to improvement and possible standardization of the quality of ophthalmological medical care. We also expect that introduction of this technology will improve the quality of ophthalmological treatment provided to older persons in Japan s rapidly aging society, improving their QOL and contributing to a longer healthy life expectancy. Use of this technology is also expected to contribute to increased transparency when discussing ophthalmological surgeries with patients and their families. While the success rate of ophthalmological surgery has a significant impact on post-operative QOL, the current healthcare fee system does not reflect elements such as improved quality of medicine, medical education, and transparency provided to patients. This gap creates a problem for both for doctors and patients. Doctors are often not able to begin utilization of new technologies in a timely manner because of high installation costs. Patients, as a result, have limited access to surgeries in which the latest surgical equipment is utilized, increasing safety and transparency. Lengthening Healthy Lifespans to Boost Economic Growth 167

169 Recommendations The technology mentioned above will contribute to improving the quality of medical care by increasing opportunities for doctors and co-medicals to learn. It will also greatly contribute to the effective implementation of team-based medicine and risk management. Other benefits include improving the sense of unity in the operating room by sharing real-time surgical information and enabling qualified professionals to take emergency measures and provide support during surgery. The technology will also mitigate the excessive physical burden faced by surgeons on their cervical spine, shoulders and back during conventional surgeries using an optical microscope. Use of this technology and the creation of a visual record will also improve surgical transparency and accountability. Considering these benefits, this technology should be promoted for use in medical facilities conducting vitreous surgery, including educational facilities, as basic equipment for future ophthalmological surgeries (in particular, in vitreoretinal surgeries). In order for this technology to offer the benefits mentioned above, we believe that assessment of healthcare fees for ophthalmological surgeries using this equipment should be carried out and include a particular focus on vitreoretinal surgeries. References 1. Gauba V, Tsangaris P, Tossounis C, Mitra A, McLean C, Saleh GM. Human reliability analysis of cataract surgery. Arch Ophthalmol. 2008;126(2): Lengthening Healthy Lifespans to Boost Economic Growth

170 Picture 1. Surgeons in conven1onal surgery Picture 2. 3D visualiza1on system enabling real 1me sharing of surgical progress Lengthening Healthy Lifespans to Boost Economic Growth 169

171 33 Improving Home Healthcare Situation In 2017, the government of Japan (GOJ) forecasted that the population aged 65 and over would increase from 27.3% of the population in 2016 to 30.0% by 2025 and 38.1% by Healthcare expenditures for these persons accounted for 58.6% 1 of the total healthcare expenditure in Japan, or 40.8 trillion Japanese yen in This is expected to increase to 54.0 trillion Japanese yen in In 2012, average healthcare spending was four times higher for people aged 65 (JPY717,200 per person) than for those under 65 versus (JPY177,100 per person). Given that elderly people need more medical services, in the absence of reform, the growth of this population will result in a considerable strain on the financial stability of the healthcare system further. Promotion of home healthcare will be one of the key policy reforms needed to optimize healthcare resource allocation for the next years. A survey of elderly people conducted by the Japanese Cabinet Office in 2007 showed that more than 41% hoped to have nursing care at home. Under the current Japanese system, healthcare service outcomes, as measured by life expectancy, and healthcare availability, as measured by the number of nurses and doctors per 1,000, are comparable to other OECD countries. 3 However, the average hospital stay in Japan is 31.2 days, remarkably higher than 6.1 days in the United States and 5.5 to 12.6 days in European OECD countries. With the highest life expectancy in the world, demand by Japanese people for healthcare services is shifting from quantity of life to quality of life, to include features that enable living and being treated in their homes. The GOJ is also supporting the demand shift from hospitals to communities under the community based integrated care system and has introduced financial incentives for hospitals to send their patients to community care as part of the 2016 biennial healthcare reform. However, some of the most effective medicines, devices and services needed to support home healthcare are still not available in Japan. The GOJ has initiated a series of high level healthcare and welfare reforms. Prime Minister Shinzo Abe has highlighted home healthcare as a core third arrow policy of Abenomics. More practically, the Ministry of Health, Labour and Welfare (MHLW) issued its Home Healthcare/ Nursing Care Acceleration Project 2012 (Zaitaku Iryo/Kaigo Suishin Project 2012). The GOJ is planning to distribute 2.7 trillion Japanese yen in social security funding, under the Comprehensive Reform of Social Security and Tax, 4 of which 1.5 trillion Japanese yen is earmarked for medical and long-term care. Expanding home healthcare is one of the key strategies to increase the efficient allocation of healthcare resources within budget limitations. Budget allocation for home healthcare has been planned to (1) educate healthcare professionals (JPY0.1 billion), (2) prepare infrastructure (JPY2.3 billion), and (3) support unique needs in treating different diseases (JPY1.1 billion). 5 The ACCJ and the EBC applaud the efforts by the MHLW to promote home healthcare, and are ready to tackle these challenges together with other stakeholders. Current Policy While the ACCJ and EBC welcome Japan s increased focus in improving home healthcare, to date, this focus has been predominantly on the terminally ill. An expanded definition of home healthcare to include chronic illnesses, sub-acute illness and pediatric disease is needed to facilitate the uptake of the full range of treatments that can be delivered safely at home, while helping to control healthcare expenditures and improve patient QOL. Reimbursement of home healthcare is still under development in Japan. Although in practice advanced technology allows patients 170 Lengthening Healthy Lifespans to Boost Economic Growth

172 to have the right treatment at the right place at the right time, the current National Health Insurance (NHI) system is designed to cover population based medicine provided in the medical setting, which at times does not meet personal needs. Medical treatment at home often requires some sort of modification in a patient s medical support to meet their daily life. Neither NHI nor long term care insurance, which is designed to cover assistance for daily activities at home, provides full and comprehensive coverage for home medical treatment. Furthermore, under the current system, a comprehensive personalized home medical treatment plan is not possible, as a care plan developed by a care manager is not integrated with the medical plan done by the medical doctor in the hospital. To provide efficient medical and care services at home, it is imperative that sufficient infrastructure is established that leverages various existent technologies, such as remote medical care management and information sharing through the Internet. Those technologies greatly reduce the burden of distance and empower individual patients to treat themselves at home. Society has already seen the advantages of these technologies and is equipped to deal adequately with safety and privacy issues in practice. However, in healthcare, regulation and reimbursement rules for those technologies are not well developed, which prevents available technologies from being used within Japan s healthcare system. Under the current tight regulatory rules, individual manufacturers for home healthcare devices often need to develop and establish an infrastructure to communicate between medical professionals and patients, without or with limited reimbursement coverage. As leaders in developing and supplying innovative and life-saving pharmaceuticals and medical devices, ACCJ and EBC companies understand the particular challenges of creating products for home use. In particular, drugs and devices developed and designed for use in hospitals often require modification and testing to ensure ease and safe use by patients and caregivers. However, the modification of medical devices for home use is not appropriately valued under the current regulatory process, nor reimbursed under the current pricing and reimbursement rules. Because of this, the health insurance reimbursement system does not sufficiently incentivize manufacturers to develop medical products with functionality specific for home use in Japan. Recommendations The ACCJ and EBC support the MHLW s strategy for the future of healthcare in Japan, which describes community based healthcare service in cooperation with clinical services at hospitals. As the Japanese society is aging faster than any other developed country, we urge the MHLW to adopt the following recommendations to improve and expand access to home healthcare in Japan: Expand the scope and focus of home healthcare from primarily treating the terminally ill to include monitoring and treating a wide range of chronic illnesses, sub-acute illness and pediatric disease. Significantly expand the reimbursement for monitoring and access to treatments that can be delivered safely at home. Introduce a system whereby a specialist or team plans and manages comprehensive personalized medical and care plans on an individual basis. Review capabilities and responsibilities of all team members, including doctors, clinical technologists, nurses, and caregivers, and explore ways to optimize resource allocation for better home healthcare. Encourage increased private sector participation in the creation of innovative Lengthening Healthy Lifespans to Boost Economic Growth 171

173 treatment modalities by promoting greater use of public-private partnerships, especially in the development of remote medical care and information sharing. Incentivize medical device manufacturers to invest in modifying medical devices for home use by creating regulatory evaluation criteria and pricing/reimbursement rules specific to devices designed for home use. Ensure that maintenance fees for medical devices for home use are fully reimbursed under the physicians fee system. References 1. MHLW. 平成 26 年度国民医療費の概要. Accessed April MHLW. 平成 24 年 3 月社会保障に係る費用の将来推計の改定について. Accessed April MHLW, OECD 加盟国の医療費の状況 (2012 年 ), Accessed April MHLW 社会保障 税一体改革. Accessed April MHLW. 在宅医療 介護推進プロジェクト. Accessed April Lengthening Healthy Lifespans to Boost Economic Growth

174 Over Prepared Hospital Based Care, Not Enough Room in Community Average hospital stay (days) # of doctors/1000 populaeon # of nurses/1000 populaeon US UK Germany France Sweden Japan Average in OECD 6.1* * Not given 2.5* ** 3.9* ** * 8.7** 11.1* Source: OECD Health Data 2014, provided by MHLW *2011 data **including HCPs in educaeon and research Average in OECD was taken from Health at a Glance 2013 The health care system is strongly oriented toward curaeve care. Although there is a desire to pivot the system toward primary care, the quality architecture is not in place to support expansion of this sector. OECD Review of Health Care Quality, JAPAN, Nov. 5, 2014 hxp:// Design Considerations for Devices Intended for Home Use -FDA in 2014 Environmental Considera>ons! LocaEon! Contaminants! Water Supply! Temperature! Dampness and Humidity! Atmospheric Pressure Changes! Air Flow! Travel and InternaEonal Use! Fluid Exposure! Storage User Considera>ons! Physical! Sensory/Perceptual! CogniEve! EmoEonal Design Considera>ons! Lock-out Mechanisms! Maintenance! CalibraEon! Mechanical! Electrical Issues Supply Mains Internal Electrical Power Source Permanently Installed Devices Outlets and Adapters Power Outages ElectromagneEc CompaEbility Wireless Technology Alarm Systems Source: FDA Design consideraeons for devices intended for home use November 2014 Lengthening Healthy Lifespans to Boost Economic Growth 173

175 Expanding Home Healthcare Use: Increasing Visits for Pediatric Patients Increase rate: rate of increase based on 2001=1 Increase rate= number of user(age: 0-9) % in Total The number of community nurse visits for pediatric paeents was 842 in 2001, and increased to 2,928 in 2009 (a 3.5 fold increase in the last 8 years) Source: Kangoshienkyokai hxp:// accessed Dec Enhanced Security of Medical/Long-term Care Services Source: hxp:// 174 Lengthening Healthy Lifespans to Boost Economic Growth

176 34 Enhance Prevention of Healthcare-associated Infections Situation A healthcare-associated infection (HAI), also known as a nosocomial infection, is an infection that a patient contracts while receiving treatment for another condition in a healthcare facility. 1 Patients who are hospitalized, especially patients in critical care units, are constantly at risk of developing nosocomial infections. Patients who incur these infections are hospitalized longer as a result of the infection, and require treatment, leading to higher overall costs for hospitals and payers. 2,3 A 2011 study reported on stroke patients in 36 Japanese hospitals showed a HAI incidence rate of 16.4%. Patients who contracted HAIs paid on average the equivalent of an additional $3,067 in medical fees and remained hospitalized for an additional 16.3 days. 4 HAIs are preventable. A study evaluating 30 reports on HAIs concluded that great potential exists to decrease nosocomial infection rates, from a minimum reduction effect of 10% to a maximum reduction effect of 70%. 5 It is well documented that the adoption and implementation of infection control guidelines and programs by hospitals reduces the HAI infection rate, thereby reducing the attributed length of stay and associated costs. 6 According to the Agency for Healthcare Research and Quality (AHRQ), a research agency within the U.S. Department of Health and Human Services (HHS), serious HAIs that lead to extended hospital stays, and ultimately increased cost and risk of mortality, include bloodstream infections (BSIs), catheter-associated urinary tract infections (CAUTIs), surgical site infections (SSIs), and ventilator-associated pneumonia (VAP). These four infections account for more than 80% of all HAIs. 7 Many of these infections are resistant to treatment with antibiotics, leading to serious illnesses, debilitating post-treatment effects, and in some cases death. Some bacteria that cause HAIs can survive in the healthcare environment, including on medical devices, surgical tools, unwashed hands, and the clothing of hospital personnel, and are easily transmitted from patient to patient when healthcare professionals do not observe good infection control practices. Active surveillance and bundled infection control practices are the solution for preventing HAIs. By knowing in advance that a patient is a carrier of an infectious pathogen, healthcare workers and facilities are better able to take appropriate actions to control and prevent the spread of infection. Special infection prevention programs, such as decontamination before surgery, can help protect patients. Active surveillance is most effective when all hospital in-patients are screened at the time of admission. And it is most important for patients in intensive care units and emergency rooms and for all high-risk patients, such as those who are immunocompromised or undergoing long-term hospitalization. Active surveillance is not intended to serve as a substitute for the diagnosis of infection. Rather, active surveillance has been found to be an effective tool that healthcare facilities can use for the detection and control of infectious pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), the human immunodeficiency virus (HIV), and hepatitis viruses. Current Policy In April 2007, the medical law of Japan was amended to obligate all healthcare institutions in Japan to take measures to secure safety in operation with regard to HAIs. The enforcement ordinance for this amendment includes four core mandates: 1. Execute hospital infection prevention guidelines. 2. Hold hospital infection prevention committee meetings. Lengthening Healthy Lifespans to Boost Economic Growth 175

177 3. Implement infection prevention training for employees. 4. Report infectious disease incidence status. Healthcare institutions not implementing these infection prevention methods may be inspected. In addition, the Ministry of Health, Labour and Welfare (MHLW) Ministerial Ordinance Official Notice for Infection Prevention in Healthcare Facilities was issued on June 17, The notice contains guidance regarding the following: 1. Establishing an infection control team and its role. 2. Collaboration between institutions for cases that individual institutions cannot handle, including outbreaks caused by multidrug-resistant bacteria. 3. Criteria on suspected outbreaks and requirements for reporting to health centers. However, the problem remains that, should there be an outbreak of infection at a noncompliant hospital, there is no penalty other than a reprimand for not upholding social responsibility. Stronger infectious disease control mandates are needed. Government statements support stronger mandated infection control. The ACCJ and EBC welcome the statement made on June 21, 2010, by Assistant Minister for Global Health Masato Mugitani, on behalf of the MHLW, pledging support to address healthcare associated infection. 7 One of the objectives of this pledge is to promote the highest standards of practice and behavior to reduce the risks of healthcare-associated infection. We commend the measures taken by the MHLW to meet this objective, in particular the steps taken to establish a national infectious disease surveillance system and the instructions to hospitals on infection control reporting. Since 2000, Japan Nosocomial Infections Surveillance (JANIS), a Ministry of Health, Labour and Welfare (MHLW) national surveillance program, has targeted infection reporting at approximately 2,100 hospitals with >200 beds. Currently over 1,990 hospitals (including over 90% of all hospitals with >500 beds) voluntarily participate in the JANIS program. Since 2008, the ACCJ targeted the need for increasing hospital resources to implement enhanced infection prevention and control and to expand mandated HAI surveillance. In April 2010, for the first time, the MHLW established Infection prevention and control additional fee, a 1,000 yen per patient upon admission medical fee for hospitals with >300 beds in an effort to encourage enhance infection prevention and control. In April 2012, this fee was increased five-fold to a maximum of 5,000 yen for hospitals known as Infection prevention and control additional fee 1 hospitals and expanded to include smaller hospitals known as Infection prevention and control additional fee 2 hospitals at 1,000 yen per patient upon admission. Further progress was made in January 2014, when the scope of the JANIS program was expanded to cover the over 5,500 smaller hospitals of <200 beds. Though hospital infection reporting remains voluntary for hospital <300 beds, it is now mandatory for hospitals classified as Infection prevention and control additional fee 1 hospitals in order to qualify for the up to 5,000 yen per patient upon admission medical fee targeting implementation of enhanced infection prevention and control. Continued government funding of infection prevention and control and the expansion the JANIS program from 2,100 larger hospitals to as many as 7,600 hospitals, large and small, should increase surveillance and enhance infection prevention and control practices at hospitals in Japan. 176 Lengthening Healthy Lifespans to Boost Economic Growth

178 A further milestone was reached in April 2014 when MHLW for the first time mandated infection reporting by Infection prevention and control additional fee 1 hospitals as a requirement for continued qualification for the per patient reimbursement fee. This mandate to report is the first such mandate by the MHLW and the first directive to ensure that at least some of portion of per patient fee is being used to actually enhance infection prevention and control. The Infection Reporting will also allow the MHLW to measure infection incidence at large hospitals with Infection prevention and control additional fee 1 hospital status and in time hopefully mandate further actions to enhance infection prevention and control and reduce infection incidences over time. Recommendations Develop a comprehensive HAI prevention strategy, including bundling of proven infection control practices, education, and cultural change. Such a strategy should consider the impact that enabling technologies, such as rapid molecular diagnostic testing and novel medical devices, have in improving patient safety and reducing HAIs. Information technology should also be utilized to enhance implementation of HAI surveillance and prevention. Based on JANIS data, clearly define reasonable HAI prevention targets for healthcare institutions and measure progress over time. Wherever possible, establish baseline HAI incidence rates, using standardized metrics to allow measurement of hospital-specific progress in achieving prevention targets. Provide incentives, including rewards and penalties, to promote compliance with HAI prevention targets. Every healthcare facility should develop and maintain a comprehensive HAI control and reduction plan that is consistent with current standards of care and best practices. Facilities that fail to develop, implement, and maintain a current HAI control and reduction plan should face sanctions until they are compliant. Coordinate efforts at government and institutional levels with stakeholder support. Prevention and reduction of HAIs will require a concerted effort by all healthcare institutions, with engagement and leadership from policy-setting bodies at different levels of government and with the support of stakeholder organizations. Provide the Japanese government with adequate resources, in addition to international, local, and institutional efforts. This also includes identifying and prioritizing gaps in HAI research. Implement active surveillance, early screening, detection, and monitoring in the healthcare setting of infectious pathogens, such as multidrug-resistant organisms and bacteria, as well as the well-known pathogens, MRSA, VRE, Clostridium difficile, HIV, and hepatitis viruses. Develop reimbursement incentives for facilities that implement active surveillance and periodic environmental monitoring for microbial contaminants such as MRSA. On a broader regional scale, the ACCJ and the EBC commend the government of Japan s acknowledgement of the work by the World Health Organization World Alliance for Patient Safety. The ACCJ and EBC recommend optimizing international cooperation to exchange best practices and encourage Japan and all 21 Asia Pacific Economic Cooperation (APEC) member economies to support the current effort by the APEC Life Sciences Innovation Forum to fight HAIs through enhanced infection prevention and control region wide. Lengthening Healthy Lifespans to Boost Economic Growth 177

179 References 1. U.S. HHS. Agency for Healthcare Research and Quality, 2. Lee, J., Imanaka, Y., Sekimoto, M., Ikai, H., Otsubo, T Healthcare-associated infections in acute ischaemic stroke patients from 36 Japanese hospitals: risk-adjusted economic and clinical outcomes. Int J Stroke 6: Chen, Y., et al Incidence rate and variable cost of nosocomial infections in different types of intensive care units, Infect Control Hosp Epidemiol 30: Lee, J., et al. Op. cit. 5. Harbarth, S The preventable proportion of nosocomial infections: an overview of published reports, Journal of hospital infection 54: Victor Daniel Rosenthal MD,CIC,Msc (2016). International nosocomial infection control consortium (INICC) resources: INICC multidimensional approach and INICC surveillance online system. American Journal of Infection Control 44 (2016) e81-e Lengthening Healthy Lifespans to Boost Economic Growth

180 Healthcare Associated Infections: A Global Healthcare Issue 8 6 Millions of Infections ! Nearly 7 million HAIs in 2015 in the U.S., Europe, and Japan! Over 2 million cases and 99,000 deaths in the U.S Source: Inhibitex Japan Europe U.S.! In some developing countries, more than 25% of patients admitted to hospitals acquire HAIs! Hundreds of millions of patients impacted worldwide each year Summary Report of MRSA HAI Surveillance in 2009 Medical Expense of Patients with and without MRSA Infection wo MRSA w MRSA (n =) 60, Ave days in Hospital Medical expense - Patient/day 51,779 55,843 Total medical expense resulting from MRSA infections 1. Total number of inpatients per day 39,953 (2008) 2. Average rate of inpatients who develop MRSA 0.4 % 3. Approximate MRSA infection rate (incident/day) 160/day 4. From above, average medical expense w MRSA: 55,843 X = 5,364,837 wo MRSA: 51,779 X = 817, Difference 5,364, ,072.6 = 4,547, Total = difference X incident/day X 365 day 4,500,000 X 160 X 365 = approximately 265,000,000,000 yen Total of more than 265 billion yen is likely spent as a result of MRSA HAI s. The average patient w/ HAI stays more than 80 days longer. Source: Kobayashi H., et al Journal of Japanese Environmental Infection Vol. 26, No.2, Note: Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium that has developed resistance to standard types of antibiotics, which makes infections more difficult to treat and thus more dangerous. Lengthening Healthy Lifespans to Boost Economic Growth 179

181 Bundles of Best Practices Comprehensive Bundles of Best Practices include:! Screening patients for multi-resistant organisms! Hand hygiene! Isolation and contact precautions! Improved environmental cleaning! Antibiotic stewardship! Optimal management of safety-engineered vascular access devices There are various guidelines for preventing HAIs such as SHEA Guideline (2003 CDC/HICPAC Guideline Nov Best practice guide for preventing MRSA infection by APIC March 2007 Guidelines for the control and prevention of MRSA in healthcare facilities by HIS, UK (2006) Must Improve Japanese System for Preventing HAIs " No HAI prevention strategy " No HAI data " No HAI prevention target " No incentive to prevent HAI " HAI prevention strategy, including bundles of proven infection control practices " Require regular reports as a way to grasp actual situation " Define reasonable HAI prevention targets " Provide incentives, including rewards and penalties, to promote compliance with HAI prevention targets. 180 Lengthening Healthy Lifespans to Boost Economic Growth

182 35 Improve Infection Control: Closed vs. Open Systems Situation Many nosocomial infections occur when medication/fluids are administered via an intravascular device. 1 A common example of infections caused by exposure to air and contamination via intravenous (IV) systems are bloodstream infections (BSIs). BSIs have a significant influence on patient outcomes because these infections can either be the patient s primary cause of death, or exacerbate the patient s primary condition, which could lead to death. A surveillance study by the International Nosocomial Infection Control Consortium (INICC), conducted in intensive care units (ICUs) in Latin America, Asia, Africa, and Europe, demonstrated that the mortality rate of patients with BSIs was 29.6%. 2 Most bloodstream infections and their associated risks can be prevented. The use of innovative medical products can play an effective role in BSI prevention. For example, closed intravenous systems have a proven record of reducing BSIs, thereby potentially improving patient safety and reducing costs of associated longer hospital stays and treatment. In a closed IV system, the fluid is not exposed to the outside air, which significantly reduces the risk of contamination and infections. Studies have shown that BSI rates were reduced when changing from an open to a closed system. In Mexico, the BSI rate was reduced by more than 80%, 3 in Argentina by 64%, 4 in Italy by 61%, 5 and in Brazil by 55%. 6 The results of a clinical study conducted in Argentina demonstrate that the mortality rate associated with BSIs can be reduced by 91% if patients receive fluids via a closed IV system. 7 The reduction of BSI rates lowers costs by shortening ICU length of stay and reducing the use of antibiotics and other medications required to treat BSIs. Studies conducted in Mexico and Brazil have shown that reducing BSI rates may lead to significant cost savings. 8,9 Recognition of closed system safety innovation through higher reimbursement would also encourage the use of newer closed system devices over existing older open system devices that sacrifice safety for a lower unit cost. Current Policy In Japan, the medical fees set for many types of cases do not assume use of closed systems. Indeed, there is no distinction between open and closed systems in medical fee reimbursement schedules. As a result, medical institutions must bear the additional associated costs of purchasing and using advanced closed system medical devices. The pricing rules for Special Treatment Materials also lack incentives for using closed systems: the distinction between open and closed systems is not established in existing reimbursement categories. This results in the pricing of closed system devices that are designed for enhanced safety and infection control being set at the same level as the older, less innovative, and less safe open systems. Recommendations The Japanese government should encourage hospitals to make the use of innovative medical products, such as closed intravenous systems, an integral part of hospital infection control policy. Revise medical fees to reflect the cost and use of closed system medical devices in both inpatient and outpatient settings. To further enhance safety and the practice of infection control, establish a clear distinction between open and closed systems through the creation of new functional categories. Lengthening Healthy Lifespans to Boost Economic Growth 181

183 References 1. Maki, D., et al The risk of bloodstream infection in adults with different intravascular devices: a systematic review of 200 published prospective studies, Mayo Clin Proc 81: Rosenthal, V., et al International nosocomial infection control consortium (INICC) report, data summary for , American Journal of Infection Control 36: Frausto, S.R., et al Blue Ribbon Abstract Award: Cost effectiveness of switching from an open IV infusion system on rates of central venous catheter-associated bloodstream infection in three Mexican hospitals. Am J Infect Control 33:e54 e Rosenthal, V.D., et al Am J Infect Control. 5. Franzetti, F., et al Effectiveness of switching from open to closed infusion system for reducing central vascular associated bloodstream infections in an Italian hospital. American Journal of Infection Control 35(5):e67-e Salomao, R., et al Probability of developing a central vascular catheter-associated bloodstream infection when comparing open and closed infusion systems in Brazil. Proceedings and abstracts of the 47th annual scientific meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, United States (September 17 20). 7. Rosenthal, V.D., et al Am J Infect Control. 8. Higuera, F., et al Attributable cost and length of stay for patients with central venous catheter-associated bloodstream infection in Mexico City intensive care units. Inf Control Hosp Epidemiology 28: Salomao, R., et al The attributable cost, and length of hospital stay of patients with central line-associated blood stream infection in intensive care units in Brazil. Am J Infect Control 34:e Lengthening Healthy Lifespans to Boost Economic Growth

184 Closed System in Infusion Line Use of all in one system with IV catheter, extension tube, and fixed plate and closed IV system enable reduction of blood stream infections. Closed system devices Closed IV catheter system Development of Closed Cap Main line Piggy line With open three-way stopcock Need to release the end cap when connecting -> possibility of bacterial infections CV Catheter Main line Piggy line With closed three-way stopcock By closing the connectors, infection risk is reduced CV Catheter Lengthening Healthy Lifespans to Boost Economic Growth 183

185 History of Infusion System Devices Mechanical valve Cannula access split septum Closed system Split septum Luer access split septum 184 Lengthening Healthy Lifespans to Boost Economic Growth

186 36 Skin Antisepsis Situation The prevention and control of infections represent one of the most important safety initiatives for a healthcare organization. Infections can be acquired in any healthcare setting, transferred between healthcare institutions, or brought in from the community. Because infections are a significant safety risk for patients and healthcare workers (HCWs), infection prevention and control must be high on every organization s list of priorities. Hand in hand with robust hand hygiene and environmental disinfection, skin antisepsis is fundamental to the prevention of healthcareassociated infection and is a critical component of an effective infection prevention and control program. While many antiseptics have been used over the years, clorhexidine gluconate (CHG) is increasingly becoming the standard of care for skin antisepsis for the prevention of HAIs on a global basis. CHG is a broad-spectrum skin antisepsis compound that, when used in appropriate concentrations, has rapid and long-term antiseptic properties. A large and growing base of scientific evidence supports the efficacy of CHG in reducing both gram-positive and gram-negative bacteria. As a result, CHG is increasingly considered the standard of care for skin antisepsis in countries with developed infection control practices. The overwhelming body of clinical evidence supporting the safety and efficacy of CHG has led to growing awareness and adoption globally. CHG is recommended in HAI guidelines in a growing number of countries and is a compulsory component of the patient care bundles or interventions for prevention of the most costly and deadly device-related HAIs catheter-related bloodstream infections (CRBSIs), surgical site infections (SSIs), and ventilator-associated pneumonia (VAP). While allergic reactions can occur, according to the WHO, the U.S. Centers for Disease Control and Prevention (CDC) and other influential health organizations, CHG is considered to be both safe and effective. Many key Japanese opinion leaders favor use of CHG to prevent all device-related infections. Current Policy In Japan, although there are some guidelines recommending that using 0.5% chlorhexidine solution has the same efficacy as a 10% povidone iodine or 70% alcohol solution for skin antisepsis, there is no specific national guideline to recommend the specific use of applications of more than 0.5% chlorhexidine. Those healthcare practitioners leading infection prevention in Japan recognize the CDC guidelines and are aware of the Institute for Healthcare Improvement (IHI) care bundles, and some health institutions are following these recommended practices. Actual practice is often inconsistent with these recommendations, however, because of the fear of allergy and the perceived relatively high cost of single-dose applicators. To better ensure infection prevention in Japan, evidence-based general skin antisepsis protocols should include, at a minimum, those globally recognized best practices being employed worldwide to reduce and prevent HAIs. Recommendations In line with global best practices, basic skin antisepsis guidelines should include, at a minimum, the following protocols: Skin antisepsis for the insertion and maintenance (dressing changes) of central venous catheters, peripherally inserted central catheters (PICCs) and peripheral catheters (arterial or venous). Preparation of clean skin with a >0.5% chlorhexidine preparation with alcohol before central venous catheter and peripheral arterial catheter insertion, and during dressing changes. If there is a contraindication to chlorhexidine, Lengthening Healthy Lifespans to Boost Economic Growth 185

187 tincture of iodine, an iodophor, or 1, 2, 3, 70% alcohol can be used as alternatives. Preparation of clean skin with an antiseptic (70% alcohol, tincture of iodine, an iodophor, or CHG) before peripheral venous catheter insertion. 1, 2 CHG may be more effective in preserving the IV site, increasing its longevity, decreasing sample (blood) contaminant, and preserving sample integrity. Skin antisepsis for patient presurgical bathing and presurgical skin prep. Use 2% chlorhexidine wash for daily skin 1, 4, 5, 6 cleansing to reduce the chance of SSI. Skin antisepsis for surgical skin prepping (pre-operating room, and can be inclusive of cut-down procedures for the placement of central venous catheters [CVCs], such as tunneled dialysis catheters, and subcutaneous ports). Use 2 4% chlorhexidine as an antimicrobial agent for surgical skin prepping (not for use on eyes, ears, mucous membranes). 7 Single-dose applicators for skin antisepsis as they: Eliminate contamination of multi-use bulk solution bottles Increase compliance with skin antisepsis guidelines Reduce the need for skin antisepsis solution, durable materials, and sterile reprocessing Reduce procedure time Lower both the direct cost of skin antisepsis practices and indirect costs (labor and time). Avoidance of bulk solutions for skin antisepsis, due to the risk of contamination. While single-dose applicators are not specifically called for in the CDC guidelines, they have the earlier-mentioned benefits. 186 Lengthening Healthy Lifespans to Boost Economic Growth

188 References 1. Centers for Disease Control and Prevention. April 1, 2011 Guidelines for the Prevention of Intravascular Catheter-Related Infections Maki, D.G., Ringer, M., Alvarado, C.J Prospective randomized trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters. Lancet 338: Mimoz, O., Pieroni, L., Lawrence, C., et al Prospective, randomized trial of two antiseptic solutions for prevention of central venous or arterial catheter colonization and infection in intensive care unit patients. Crit Care Med 24: Bleasdale, S.C., Trick, W.E., Gonzalez, I.M., Lyles, R.D., Hayden, M.K., Weinstein, R.A Effectiveness of chlorhexidine bathing to reduce catheter associated bloodstream infections in medical intensive care unit patients. Arch Intern Med 167: Munoz-Price, L.S., Hota, B., Stemer, A., Weinstein, R.A Prevention of bloodstream infections by use of daily chlorhexidine baths for patients at a long-term acute care hospital. Infect Control Hosp Epidemiol 30: Popovich, K.J., Hota, B., Hayes, R., Weinstein, R.A., Hayden, M.K Effectiveness of routine patient cleansing with chlorhexidine gluconate for infection prevention in the medical intensive care unit. Infect Control Hosp Epidemiol 30: WHO. Guidelines for safe surgery 2009: Safe surgery saves lives. ISBN Additional References a. Resar, R., Griffin, F.A., Haraden, C., Nolan, T.W Using care bundles to improve healthcare quality. IHI Innovation Series white paper. Cambridge, MA: Institute for Healthcare Improvement. b. Anderson, D.J., Kaye, K.S., et al Strategies to prevent surgical site infections in acute care hospitals. Infect Control Hosp Epidemiol 29 Suppl 1:S c. Al-Tawfiq, J.A. and Abed, M.S Decreasing ventilator-associated pneumonia in adult intensive care units using the Institute for Healthcare Improvement bundle. Am J Infect Control. d. Flanders, S.A., Collard, H.R., Saint, S Nosocomial pneumonia: state of the science. Am J Infect Control 34: e. Rosenthal, V.D., Guzman, S., Crnich, C Impact of an infection control program on rates of ventilator-associated pneumonia in intensive care units in 2 Argentinean hospitals. Am J Infect Control 34: f. Siempos, I.I., Vardakas, K.Z., Falagas, M.E Closed tracheal suction systems for prevention of ventilator-associated pneumonia. Br J Anaesth, 100(3): g. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia Am J Respir Crit Care Med 171: h. Institute for Healthcare Improvement. Sepsis Resuscitation Bundle. Lengthening Healthy Lifespans to Boost Economic Growth 187

189 Antiseptic solution recommended in HAI guidelines in a growing number of countries CDC Guidelines for the prevention of intravascular catheter-related infections Prepare clean skin with a >0.5% chlorhexidine preparation with alcohol before central venous catheter and peripheral arterial catheter insertion and during dressing changes. If there is a contraindication to chlorhexidine, tincture of iodine, an iodophor, or 70% alcohol can be used as alternatives. Use a 2% chlorhexidine wash for daily skin cleansing to reduce CRBSI. WHO Guidelines for safe surgery 2009: Safe surgery saves lives: ISBN Use of 2 4% chlorhexidine as an antimicrobial agent for surgical skin prepping (not for use on eyes, ears, mucous membranes). Skin Antisepsis in the Clinical Context SSI/CRBSI: Non Single-Dose SSI/CRBSI: Single-Dose Products 1.Sterile forceps (reprocess cost) 2.Sterile bowl (reprocess cost) 3.Sterile drape (for cart not pt) 4.Sterile gauze / cotton balls (5) 5.Sterile solution (40ml) 6.Extra cart/tray for product = 0$ capital 7.Sterile Gloves Procedure Steps 1. Gather product(s) (x6) 2. Drape cart 3. Set up bowl, cotton balls and forceps 4. Place compound liquid into bowl 5. Place cart/tray near patient 6. Put on sterile gloves 7. Pick up forceps 8. Pick up cotton balls with forceps 9. Dip cotton ball in solution 10. Apply solution with cotton ball to patient 11. Drop cotton balls on tray 12. Pick up new cotton ball 13. Apply solution with cotton ball to patient (repeat) 14. Remove cart/tray from patient side 15. Dispose of leftover solution 16. Remove forceps/bowls 17. Transport forceps/bowls to sterilization area 18. Dispose of drape and cotton balls 19. Clean cart 20. Deliver forceps/bowl to central sterilization 21. Sterilize forceps; bowl (up to 48 additional steps 7 ) 22. Package sterilized forceps/bowls 23. Store sterilized forceps; bowl = $ (range up to $15) = $ (range up to $15) = $ ; (range up to $ ) = $ = $0.96/ml 9 = 0$ capital = $ Products 1. Sterile CHG single dose applicator (26ml) = $ Sterile Gloves = $ Procedures Steps 1. Gather product(s) 2. Open single dose package 3. Drop on sterile field 4. Put on sterile gloves 5. Break liquid seal 6. Apply CHG to pt. 7. Dispose the applicator Time for prep = 13 minutes 8 Product cost = $8.98 (Low estimate) Time for prep = 5 minutes 8 Product cost = $7.58 Single dose applicator reduces steps, time and is more cost effective Wound care Manufacturer s cost (confirm); Lionser CHG2% 65ml $1.35: $ /ml x 40ml =$ (Advention); 3M CHG 2% 70ml $1.90: $ ml x 40ml = $ : Averaged =$ GHX 2011: 26ml Chloraprep; 11. Advention finding/model pricing for SSI Japan 188 Lengthening Healthy Lifespans to Boost Economic Growth

190 Antiseptic Solutions Currently Used Main antiseptic solutions used by type of procedure, 2012 % of procedures 100% 80% 5% 28% 7% Legend Other (sterile water, soap) 60% 40% 20% 0% 63% 4% 28% CVC skin prep 46% 3% 23% PVC/AVC skin prep 80% 1% 12% Surg skin prep 100% Surg prebathing 95% 5% Oral care Alcohol Iodine CHG 1% CHG <1% CHG is becoming more common for catheter-related procedures, while adoption for surgical skin prep appears to be emerging 1% CHG is new in Japan, KOLs anticipate it will become the next standard Source: Advention BP Lengthening Healthy Lifespans to Boost Economic Growth 189

191 37 Prevent Bloodstream Infections by Using Appropriate Devices Situation Potential Factors in Catheter Infection Catheter-associated infections include exit, tunnel, pocket and bloodstream infections. 1 In the United States, these kinds of infections extend the length of hospital stays by an average of 12 days and result in an additional cost of some $18,432 per patient. As reported by the U.S. Centers for Disease Control (CDC), some 250,000 bloodstream infections (BSIs) resulting from central vascular catheter (CVCs) have been estimated to occur annually, 2 with an estimated death rate of some 12 25% (30,000 62,500) as a result of catheter-related bloodstream infections (CRBSIs). The prevention of CRBSIs is important for improving patient outcomes, and depends on having appropriate medical care, product guidelines, and infection control. Examples of the potential factor related to the catheter infection risk include: 1. The length of time catheters remains inserted. 2. The frequency with which catheters are inserted and removed. 3. The use of multiple-lumen catheters. 4. Immunosuppression. Local infection often arises in such areas as the catheter insertion site, or the tunnel for, or pocket of, an implanted port, and can occur concurrently with a BSI. The indications include local oppressive pain, the sensation of heat, sweating, hardened areas, and pus discharge. These can be identified by visual examination and by lightly tapping the dressing over an insertion site, tunnel, or port pocket. Should any abnormality be detected, the dressing should be removed and the site carefully inspected. 3 Evaluating Catheter-related BSIs Regularly check catheter insertion sites. 3 Observe a patient s general condition (including for fever, chills, sweating, malaise, lassitude, muscular pain, weakening, tachycardia, changes in consciousness, and sharp pain). 3 Pay attention to immunosuppressed patients, because symptoms of infection are not readily apparent. 3 When infection is suspected, promptly start treatment (with blood culture, antibiotics) as instructed by the doctor. It has been estimated that fatalities exceed 50% for patients not treated within 24 hours of the onset of infection. 3 Reduce CRBSIs with Needleless Systems Use of needleless systems is included in the 2011 CDC guidelines for preventing intravascular catheter-related infections: a split septum valve may be preferred over a mechanical valve due to increased risk of infection with some mechanical valves. 1 The recommendation was added because the CDC found evidence that the structure of needleless systems affects the incidence of CRBSIs. 4 A study provides strong evidence that both positive- and negative-pressure mechanical valves are linked to increases in CRBSIs, in conditions where the CRBSIs, surveillance methods, and infection prevention measure are the same. 1 When switching from a split septum to a positive- or negativepressure mechanical valve, an increase in CRBSIs was observed in all ICUs and wards. In addition, switching the valves back to a split septum resulted in a significant decrease in CRBSIs in 14 ICU rooms. When planning the introduction of a closed type IV needleless system, hospital staff should keep an eye on CRBSIs to ascertain whether they result from use of mechanical valves. 1 Efficacy of PICCs in Reducing CLABSIs The peripherally inserted central catheter (PICC) is a central vascular catheter (CVC) that is inserted through elbow, forearm, or upper arm veins and places the catheter tip into the central vein. According to Morikane 190 Lengthening Healthy Lifespans to Boost Economic Growth

192 et al. (2009), it has been reported that PICC procedures reduce the rate of central line-associated bloodstream infection (CLABSI) by approximately 45% compared with that of CVC procedures through the subclavian vein or internal jugular vein. In addition, the total cost of treatment per hospitalization decreases, given that the CLABSI-related cost of antibiotics (some 410,000 per infection) and additional hospitalization (about 22 days per infection) can be avoided. The use of PICCs does not only reduce the incidence of infection on insertion, but can ensure safety. The anti-reflux PICC reportedly decreases the risk of catheter occlusion caused by the anti-reflux valve, which is designed to resist backflow when the catheter is not being used Furthermore, the safety of PICC is receiving increased recognition. Japan Medical Safety Investigation Organization issues the first report as Analysis on deaths related to complications associated with central venous access on March According to the Suggestion 1 in the report, it is recommended to consider the alternative use of PICC in order to lower the risk of complications by the insertion of Central Venous Catheter. Recommendations The Japanese government should encourage medical institutions to use innovative medical products as an integral part of their infection control policies. Medical fees should reflect the cost and use of medical devices and materials, in both inpatient and outpatient settings. References 1. Centers for Disease Control and Prevention. April 1, Guidelines for the Prevention of Intravascular Catheter-Related Infections Yokoe, D.S., Classen, D Improving patient safety through infection control: A new healthcare imperative. Infection Control Hospital Epidemiology 29:S3 S Infusion nursing standards of practice Journal of Infusion Nursing 29(1S): Jarvis, W.R., Murphy, C., Hall, K.K., et al. 2009, Healthcare-associated bloodstream infections associated with negative- or positive-pressure or displacement mechanical valve needleless connectors. Clin Infect Dis 49: Crnich, Christopher J., Dennis, Maki G The promise of novel technology for the prevention of intravascular device-related bloodstream infection. II. Long-term devices. Clinical Infectious Disease (May 15) 34: Morikane, Keita, et al Multifaceted comparison of peripherally inserted central catheters (PICCs) with conventional central venous catheters (CVCs). Japanese Journal of Environmental Infections 24: McGee, David C., et al Preventing complications of central venous catheterization. New England Journal of Medicine (Mar 23) pp National Institute for Health and Clinical Excellence Technology Appraisal Guidance on the use of ultrasound locating devices for placing central venous catheters (TA49). 9. Japanese Society for Quality and Safety in Healthcare Committee. Pursuing safety for procedures with serious risk creating and complying with a safety policy of CVC procedures How to Guide, ver. 2. Joint Commission on Medical Safety and Collective Action Plans in Japan. 10. Hinson, Edith Kathryn, Blough, Lauren D Skilled IV therapy clinicians product evaluation of open-ended versus closed-ended valve PICC lines a cost savings clinical report. Journal of Intravenous Nursing (July/Aug) 19(4): Lengthening Healthy Lifespans to Boost Economic Growth 191

193 11. Low infection rate from PICCs (evidence Level I). In the Guidelines for the prevention of intravascular catheter-related infections (2002), use of PICCs was reported to have caused fewer instances of CRBSI than conventional CVCs. In the meta-analysis by Crnich et al. (2002), it was reported that, when catheter insertion exceeds 1,000 days, PICCs had a statistically lower rate of CRBSI occurrence (0.4) than non-tunnel CVCs without coating (2.3). 12. Lower infection rate for anti-reflux valve PICCs (domestic, evidence Level II). According to Morikane et al. (2009), the number of CRBSIs occurring when catheter placement exceeds 1,000 days is 5.6 for anti-reflux valve PICCs and 7.0 for non-tunnel CVCs. When a logistic regression analysis was conducted on CRBSI factors, it was reported that anti-reflux valve PICCs were a factor (odds ratio 0.55, p = 0.019) that significantly reduced the risks of CRBSI occurrence. (The infection rate with 100 units can be translated into 17.8% for CVCs and 9.8% for PICCs.) 13. Safety of PICC insertion (evidence Level I III). According to McGee et al. (2003), it is said there is roughly a 10% possibility of mechanical complications (including arterial puncture, hematoma, pneumothorax, and hemothorax) occurring for each CVC placement inserted through subclavian, internal jugular, and femoral veins (evidence Level I). Furthermore, the British National Health Service (2002) reported one fatality from among 3,000 CVC procedures as a result of a procedure-induced pneumothorax. Based on these findings, in 2008 the Japanese joint commission on medical safety and collective action plans published the second version of a how-to guide, in order to prevent fatalities attributable to mechanical complications. The book recommends that insertion through the subclavian or internal jugular vein should be avoided, and that the procedure should, instead, be from the upper arm, where safety can be assured, with mechanical complications reduced 10%, safety ensured, medical costs resulting from complications reduced, adverse physician patient relations avoided, and the overall quality of healthcare improved. PICCs are considered extremely safe, both theoretically and clinically, and can be inserted without serious complications. In fact, Morikane s multicentre trials reported no serious complications following insertion of anti-reflux valve PICCs. 14. Low occlusion rate and simple care and maintenance with anti-reflux valve PICCs (evidence Level III). According to a cost savings clinical report (evidence Level III) by Hinson et al., (1996), anti-reflux valve PICCs have a lower catheter occlusion rate compared with standard PICCs. In addition, with the lower frequency of medication use to prevent occlusions and fewer catheter replacements, cost relative to care and maintenance reportedly can be reduced. Furthermore, since a heparin lock is not necessary, anti-reflux valve PICCs are suitable for intermittent chemotherapy and infusion therapy by homecare workers. 15. Analysis on deaths related to complications associated with central venous access by Japan Medical Safety Investigation Organization first report March Lengthening Healthy Lifespans to Boost Economic Growth

194 Guidelines on Prevention of Catheter Related Blood Stream Infections 2008 SHEA, IDSA Strategies to prevent central line-associated bloodstream infec?ons (CLABSI) in acute care Do not rou?nely use posi?ve-pressure needleless connectors with mechanical valves before a thorough assessment of risks, benefits, and educa?on regarding proper use (B-II) (Maragakis et al., 2006; Field et al., 2007; Salgado et al., 2007; Rupp et al., 2007). Rou?ne use of the currently marketed devices that are associated with an increased risk of CLABSI is not recommended CDC - Guidelines for the preven?on of intravascular catheter-related infec?ons When needleless systems are used, a split septum valve may be preferred over some mechanical valves due to increased risk of infec?on with the mechanical valves [ ]. Category II From the above, increases of BSI is thought to be caused by inappropriate infec?on preven?on, device design, or both, and it is necessary to understand the features of each device when selec?ng and using the device. It is necessary to reconfirm the management of infusion both in terms of sozware and hardware, e.g. whether or not CRBSI can be achieved, what is the appropriate use of the device, whether other measure for infec?on preven?on is fully considered. Lengthening Healthy Lifespans to Boost Economic Growth 193

195 38 Sepsis Situation Sepsis is a serious and life-threatening condition in which the body s tissues and organs are damaged due to the immune system s overwhelming response to an infection. Sepsis is the leading cause of death from infection, affecting all age and lifestyle groups without discrimination between developed and developing areas of the world. 1 A report from the American Journal of Respiratory and Critical Care Medicine analyzed the worldwide incidence and mortality of sepsis based on available data and estimated that globally there are 31.5 million cases of sepsis and potentially 5.3 million deaths annually. 2 In the U.S. alone, over 1.6 million people are affected by sepsis, with about 258,000 deaths, which leads it to be the number one cause of death in U.S. hospitals. 3 In 2011, incidence of sepsis in Japan was estimated at more than 380,000 cases annually. 4 A study in Japan of 3,195 ICU-treated sepsis patients estimated that the survival rates of these patients to be 56.3% at 28 days and 73.6% at 90 days after being admitted to the ICU. 5 However, even those who recover from sepsis are left with long-lasting physical and mental effects, including amputations, organ deterioration, memory loss, anxiety, and depression. 3 As the most vulnerable age groups tend to be infants and the elderly, in a rapidly aging Japan, an increase in patients with sepsis is expected. In addition, the emergence of multi-drug resistant organisms may increase the number of those infected with sepsis. Current Policy In an attempt to stop the rise of sepsis related deaths, the U.S. and European societies of Critical Care Medicine took the lead in initiating the Surviving Sepsis Campaign in 2002 and globally promulgated the concept and treatment of sepsis in 2004 through the Surviving Sepsis Campaign Guideline (SSCG). In 2010, a non-profit organization called Global Sepsis Alliance (GSA) was created. Since then, the GSA has been actively engaged in educating not only healthcare providers but also the worldwide public about the prevention and earlier detection of sepsis with the aim of reducing sepsis deaths by 20% by Under the GSA vision of, A World Free of Sepsis, the following five goals were created to be achieved by 2020: 6 1. Fewer sepsis cases globally due to effective prevention strategies 2. Rise in sepsis survival around the world for adults, children, and newborns 3. Better access to rehabilitation services 4. Rise of public and professional understanding and awareness of sepsis 5. Better measurement of the global burden of sepsis and the positive impact of sepsis control and management interventions To achieve these goals, the GSA designated September 13 as World Sepsis Day and holds sepsis-related events worldwide. 7 The Japanese Society of Intensive Care Medicine (JSICM) joined the GSA in 2012 and since 2013, World Sepsis Day events have also been held in Japan. In addition, JSICM created its own website ( 敗血症.com) to educate the public about sepsis. In 2016, at the 45th General Meeting of the U.S. Society of Critical Care Medicine (SCCM), a new definition of sepsis (Sepsis-3) was released: sepsis is a life-threatening condition that arises when the body s response to infection injures its own tissues. 8 In 2017, Surviving Sepsis Campaign Guidelines 2016 (SSCG 2016) and the Japanese-version Guidelines for Sepsis Care (prepared jointly by JSICM and Japanese Association for Acute Medicine) were released, supporting global efforts to improve sepsis treatment. 9 Most recently, due to the joint efforts of the GSA, the World Health Organization (WHO), and others, on May 26, 2017, the World Health Assembly (WHA) and the WHO designated sepsis as a global health priority and adopted a resolution to prompt 194 Lengthening Healthy Lifespans to Boost Economic Growth

196 action. 10 The resolution requests that the Director General of the WHO: 1. Publish a report on sepsis and its global consequences by the end of Support the Member States adequately 3. Collaborate with other UN organizations 4. Report to the 2020 WHA on the implementation of this resolution disseminated. In addition, providers should also consider accelerating the clinical process for prompt treatment after a blood culture turns positive. These measures will lead to a more appropriate use of antibiotics in clinical settings and will contribute to the improvement of prognoses in patients with sepsis. Recommendations Because sepsis is triggered by an infection, it is of great importance for sepsis treatment to diagnose the infection itself, and microbiological testing plays a pivotal role in assessing the clinical conditions of a patient. Above all, it is extremely important to detect causative organisms of sepsis by using a blood culture test. Such blood cultures may enable identification of causative organisms, information about the source of infection, drug susceptibility testing, and determination of a period for administering antimicrobials and other procedures. Results obtained from identification of causative organisms and drug susceptibility testing makes it possible to avoid the inappropriate use of antibiotics and optimize sepsis treatment. In a world where anti-microbial resistance (AMR) is becoming a key medical issue, effective blood culture testing is essential. Recommendations of blood cultures in multiple guidelines Similar recommendations are provided in multiple guidelines including the Surviving Sepsis Campaign Guidelines 2016 (SSCG 2016) and the Japanese-version Guidelines for Sepsis Care. 11 Future state of blood culture New systems, such as a way in which to promptly load blood culture bottles (containing collected blood) into medical equipment in clinical settings, which will cause no delay in optimal treatment, should be developed and Lengthening Healthy Lifespans to Boost Economic Growth 195

197 References 1. World Sepsis Day, Basic Material 2017 The World Sepsis Fact Sheet, Carolin Fleischam, et al., Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations, American Journal of Respiratory and Critical Care Medicine (February 1, 2016): Vol. 193, No. 3. Accessed July 13, 2017, doi: /rccm oc 3. Sepsis Alliance, Sepsis Fact Sheet, 2016, 4. Eisai, Phase III Study for Sever Sepsis Treatment Eritoran (E5564) Does Not Meet Primary EndPoint, January 25, 2011, 5. Mineji Hayakawa, et al., Characteristics, treatments, and outcomes of severe sepsis of 3195 ICU-treated adult patients throughout Japan during Journal of Intensive Care (July 12, 2016) 4:44 Accessed July 13, 2017, doi: /s Global Sepsis Alliance A World Free of Sepsis, Global Sepsis Alliance, Accessed July 13, World Sepsis Day Organization, World Sepsis Day, Accessed July 13, Mervyn Singer, Clifford S. Deutschman, and Christopher Warren Seymour et al., The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) The JAMA Network (February 23, 2016) Accessed July 13, 2017 doi: /jama Surviving Sepsis Campaign Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2016, Fourth Edition. Accessed July 13, Global Sepsis Alliance, WHA Adopts Resolution on Sepsis, May 26, Accessed July 13, The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock Clinical and Laboratory Standard (CLSI) Principles and Procedures for Blood Cultures; Approved Guideline. Clinical and Laboratory Standard Institute Wayne. PA., USA Dennis L. Steves, et al., Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America (IDSA) Clinical Infectious Disease (July 15, 2014) 59 (2):e10-e52. doi: /cid/ciu Lengthening Healthy Lifespans to Boost Economic Growth

198 World Sepsis Day September 13 th World Sepsis Day September 13 th Lengthening Healthy Lifespans to Boost Economic Growth 197

199 World Sepsis Day September 13 th World Sepsis Day September 13 th 198 Lengthening Healthy Lifespans to Boost Economic Growth

200 39 Avoid Reuse of Single-use Devices Situation Single-use medical devices (SUDs) are designed to be discarded after one use and should not be reused under any circumstances. The one-time use of a SUD ensures function and sterility, while preventing cross-contamination and infection. Only SUDs that have gone through appropriate reprocessing, including cleaning, functional testing, repackaging, relabeling, disinfection and sterilization should ever be reused. However, some healthcare personnel are unaware of, do not understand, or do not adhere to the guidelines for the appropriate use of SUDs The health risks of reusing an SUD depend to a great extent on the type of device and the way it interacts with the patient s body. 11 SUDs are often classed as critical, semi-critical, and non-critical, according to a set of criteria known as the Spaulding definitions. 12 Under these definitions, critical SUDs are those that are intended to contact normally sterile tissue or body spaces during use. Semi-critical SUDs are intended to contact intact mucous membranes and not penetrate normally sterile areas of the body. Non-critical SUDs are intended to make topical contact and not penetrate intact skin. Most non-critical devices, like compression sleeves, can be cleaned and reused with minimal risk. Opened but unused sterile instruments can sometimes be re-sterilized, provided the materials can withstand the sterilization procedure. However, some invasive SUDs, especially those with long lumens, hinged parts, or crevices between components, are difficult or impossible to clean once body fluids or tissues have entered them. Reusing SUDs carries with it the obvious risk of cross-patient infection, but also the increased probability that the device could malfunction due to the adverse effects of reprocessing on materials or delicate components. 11 Inappropriate reuse of SUDs poses a serious health risk to patients. The reuse and reprocessing of SUDs also raises legal and ethical questions. The small number of studies that have considered the clinical outcomes associated with the use of reprocessed SUDs are of variable quality and provide insufficient evidence to establish the safety and efficacy of their use. Use of several types of reprocessed SUDs is cost-saving only if it is assumed that there are no adverse effects. However, there is insufficient data to establish the cost-effectiveness of re-using SUDs. Those who fund and use SUDs should consider the relevant legal, ethical, and psychosocial issues. In hospital settings in Japan, infection control personnel are employed to conduct surveillance, monitor practices, and provide education and training on appropriate infection control practices. However, specific infection control resources have traditionally been lacking in outpatient settings Current Policy In December 2007, the Ministry of Health, Labour and Welfare (MHLW) issued an official notice on the incidence of nosocomial infections related to medical treatment and the importance of thorough safety management structure. 17 The notice, a follow-up to one issued in 2004, was intended to highlight the problem of SUD reuse and to enhance healthcare facility prevention measures from a medical safety and infection prevention perspective. 18 Since 2001, the government of Japan (GOJ) has directed the drive for the specification of single use in SUD package inserts. Recommendations Enforce compliance with best practice infection control guidelines. National regulations should be developed to ensure that outpatient facilities adhere to standard infection control precautions and aseptic techniques regarding the transmission of infectious disease in healthcare settings. Increase oversight of healthcare facilities Lengthening Healthy Lifespans to Boost Economic Growth 199

201 to ensure implementation of best practices. National standards for oversight should be developed and enforced to enhance inspection and regulation of healthcare facilities. Enhance education and training of healthcare workers on infection prevention techniques. In order to address the inconsistencies in adherence to infection control guidelines, infection prevention education and training programs should be developed that include the proper use and handling of SUDs and are targeted to healthcare workers in outpatient settings. Encourage adoption of technologies to prevent SUD reuse. Efforts should be made to enhance uptake of existing technologies designed to prevent reuse and support development of new technologies to address this problem. Conduct outreach efforts to enhance patient awareness of appropriate use of SUDs. Public outreach initiatives should be developed to educate patients about the appropriate use of needles, syringes, and other-use devices. 200 Lengthening Healthy Lifespans to Boost Economic Growth

202 References 1. Yamaguchi University Medical Association The current state of re-sterilization of single-use equipment in the operating room. Yamaguchi Medical Journal 58(5): The risk of re-sterilization and the safe use of disposable products. Yamaguchi Medical Journal 58(5): Japanese Society of Medical Instrumentation Survey on the use of re-sterilized single-use equipment. The Japanese Journal of Medical Instrumentation 74(6): The current state of re-sterilization of single-use medical equipment. The Japanese Journal of Medical Instrumentation 74(4): Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy Japanese Journal of Gynecologic and Obstetric Endoscopy 21(1): Japanese Association for Operative Medicine Journal of Japanese Association for Operating Room Technology 25(2): Japanese Society of Medical Instrumentation The issue of reusing single-use equipment. The Japanese Journal of Medical Instrumentation 72(4): The Japanese Journal of Medical Instrumentation 73(4): Akita Association of Rural Medicine Akita Journal of Rural Medicine 48(2): Medtronic Japan Co., Ltd Risk of use of worn tool bar for craniotomy. 11. Canadian Reprocessing of Reusable and Single-Use Medical Devices, July 30, Spaulding, EH, The Role of Chemical Disinfection in the Prevention of Nonsocomial Infections, PS Brachman and TC Eickof (ed), Proceedings of International Conference on Nonsocomial Infections, 1970, American Hospital Association, Chicago, IL 1971: Thompson, N.D., Perz, J.F., Moorman, A.C., Holmberg, S.D Nonhospital healthcare-associated hepatitis B and C virus transmission: United States, Annals of Internal Medicine 150: U.S. Food and Drug Administration, Center for Devices and Radiological Health Guidance for industry and for FDA staff: Enforcement priorities for single-use devices reprocessed by third parties and hospitals. Appendix B: Definition of terms. Rockville, MD: U.S. Food and Drug Administration Miller, M.A., et al Canada communicable disease report 27(23): Canadian Healthcare Association The reuse of single-use medical devices: Guidelines for healthcare facilities. Ottawa: CHA Press. 17. Ontario Hospital Association Executive summary. Reuse of single-use medical devices (Jan 12) Day, P What is the evidence on the safety and effectiveness of the reuse of medical devices labeled as single use only? NZHTA Tech Brief Series 3(2). Christchurch, N.Z.: New Zealand Health Technology Assessment Ministry of Health, Labour and Welfare Iseishihatsu # (December 28). 20. Ministry of Health, Labour and Welfare Iseishihatsu # (February 9). Lengthening Healthy Lifespans to Boost Economic Growth 201

203 40 Prevent Needle Stick and Sharp Object Injuries Situation Needle stick and sharp object injuries pose a serious occupational risk to healthcare workers. The provision of a safe and healthy working environment is a fundamental right of every employee in Japan. Duty of care provisions within occupational health and safety legislation aim to protect people from all types of hazards and risks arising from work activities. Therefore, it is reasonable to expect that healthcare workers should be protected from exposure to dangerous blood-borne viruses, including hepatitis B and C viruses and HIV. Even the smallest puncture of the skin can expose a healthcare worker to more than 30 blood-borne pathogens, 1 bacteria, and parasites, any of which can cause serious and potentially life-threatening infections. Nurses and doctors suffer a majority of these injuries, which occur in patient rooms and operating rooms. However, other medical staff can also become victims. Ancillary staff such as hospital orderlies, cleaners and laundry staff, and other downstream workers also suffer needle stick injuries. In Japan, it is estimated that between 450,000 and 600,000 sharp object injuries occur every year, which is equivalent to one in two doctors or nurses experiencing sharp object injuries every year. According to the Research Group of Occupational Infection Control and Prevention, in Japan in 2014, among the reported sharp object injuries, 50% were nurses and 36% were doctors, with the percentage increasing for doctors. 2 Categorized by profession, incident rates were 14.4 for residents, 4.6 for doctors, 3.0 for nurses and clinical technologists, with the degree of risk being higher for residents and doctors, calculated as (number of needle stick injuries per year for profession A) / (number of full time equivalent staff in profession A) x (100). In terms of the number of reported cases, in 2010 the incidence of needle stick injuries was 6.4 per 100 occupied beds, with a significantly higher (p<0.01) rate of 7.9 at university hospitals compared with 5.3 at other hospitals. However, in 2012, the rate was 6.2 per 100 occupied beds (7.5 at university hospitals and 5.5 at other hospitals), which does not represent an evident decrease. There has been a continuous notable increase in the number of sharp object injuries caused by pre-filled cartridge needles (insulin injection pen needles). Injuries caused by delay in the universal utilization of safety-engineered devices for various types of sharps was identified in a 2014 report as a persistent problem in Japan. 3 Current Policy In June 2011, a ministerial ordinance official notice was issued by the Ministry of Health, Labour and Welfare (MHLW) regarding infection prevention in healthcare facilities. It made specific recommendations for occupational safety regarding the prevention of sharp object injuries, which include prohibiting the recapping of needles; requiring puncture-resistant sharp object collectors at bedsides; and recommending the use of safety devices. 4 These are the same as the recommendations issued in February 2005, which was the first time that the recommended use of safety devices was incorporated into an official health ministry notification. Policy Changes in the Past Year Despite repeated efforts to enhance safety and infection control, there are no mandated public policies or legislation requiring the use of safety-engineered devices or enforcement of the health ministry s notification to prevent sharp object injuries in Japan. Recommendations Educate and train healthcare workers in infection control techniques. In order to encourage compliance with infection control guidelines, infection prevention 202 Lengthening Healthy Lifespans to Boost Economic Growth

204 education and training programs must be developed that target healthcare workers and address sharp object injury prevention and proper disposal programs. Mandate safer working practices. Employers must develop and implement an exposure control plan to eliminate or minimize worker exposure to blood-borne pathogens if workers are required to handle, use, or produce an infectious material or organisms, or if they are likely to be exposed to such a material or organisms at a place of employment. Require the use and assessment of appropriate medical devices that incorporate safety engineered technology to prevent sharp object injury. The use of devices incorporating such technology can greatly reduce the incidence of needle stick injuries and exposure to blood-borne pathogens. Healthcare facilities should be required to adopt and regularly evaluate engineering controls designed to prevent percutaneous injuries. Promote the use of blunt suture needles to prevent needle stick injuries in operating rooms. Promote the use of safety engineered insulin pen needle devices to prevent needle stick injuries during in-patient care of diabetic patients. Provide additional medical fees to cover the cost of enhanced safety. Eliminate the use of needles where safe and effective alternatives are available. Whenever possible, encourage the use of devices that eliminate the need for needles in order to reduce the potential for occupational exposure to blood-borne pathogens due to percutaneous injuries from contaminated sharp objects. The United States, the 26 countries of the EU, as well as Canada and Taiwan have all enacted laws that provide a safer workplace for healthcare workers by reducing the risk of deadly blood-borne infection transmissions. Many other countries around the world are now considering similar healthcare work occupational health and safety legislation. There is an urgent need for Japan to enact and enforce occupational health and safety legislation that mandates the use of safety-engineered devices whenever possible. References 1. Tarantola, A., Abiteboul, D., Rachline, A Infection risks following accidental exposure to blood or body fluids in healthcare workers: A review of pathogens transmitted in published cases. American Journal of Infection Control. 34: Kimura, S Research of the status of needlestick injuries and prevention among healthcare workers. Japan Ministry of Health, Labour, and Welfare science research grant project (March): Japan-EPINet Survey Working Group Summary of the survey published by the Research Group of Occupational Infection Control and Prevention in Japan Ministry of Health, Labour and Welfare. Iseishihatsu Lengthening Healthy Lifespans to Boost Economic Growth 203

205 Low Market Penetration Level of Safety Engineered Devices is an Issue Penetration level of safety engineered devices at hospitals that participated in EPINet TM survey (%) The research group of occupational infection control and prevention in Japan (JRRGOICP) h"p://jrgoicp.umin.ac.jp/ EPINet Japan Survey JSE2015 The importance of ensuring safer safety devices Needle stick injuries (NSI) occur with safety devices, especially winged steel needles. Therefore, a system to evaluate safer safety devices is needed. # of NSI/ 100beds Incidence of needle stick injuries per 100 beds Unknown Non- Safety device Safety device Winged steel needle (N=250) IV catheter (N=151) Other Injection Needle (N=751) Suture needle (N=539) The research group of occupational infection control and prevention in Japan (JRRGOICP) h"p://jrgoicp.umin.ac.jp/ EPINet Japan Survey JSE Lengthening Healthy Lifespans to Boost Economic Growth