Policies contributing to Health Reforms leading to improved management of Rare Diseases/ Anaemias/ Haemoglobin Disorders in Europe

Policies contributing to Health Reforms leading to improved management of Rare Diseases/ Anaemias/ Haemoglobin Disorders in Europe A. Eleftheriou, Ph.D Thalassaemia International Federation 4th European Symposium on Rare Anaemias 19 November 2011 Sofia, Bulgaria

Rare Diseases/ Rare Anaemias/ Haemoglobin disorders Policies/programmes: Primary Health Care: Non-Communicable Diseases Genetic Diseases Chronic Diseases Rare Diseases Patients Rights/ Patients Safety Public Health Health Equity Together for Health Health in All Policies Birth Defects: Congenital Malformations, deformations & chromosomal abnormalities, inborn metabolism malfunctions & blood disorders Official Bodies producing Health Policies: Europe World Health Organisation NCDs/ Genetic Diseases/ Chronic Disorders/ Birth Defect programmes Headquarters, Geneva (CH) Executive Meetings Regional Offices WHO EURO World Health Assemblies EU Collaborating Centres Resolutions European Union Rare & Chronic Diseases/ NCDs European Commission European Parliament Council of Ministers Council of Europe Directives/Regulations Recommendations Communications White/Green Papers

WHO Structure WHO HEADQUARTERS GENEVA, SWITZERLAND AFRO: 47 Countries EURO: 53 Countries PAHO: 35 countries EMRO: 23 Countries REGIONAL SEARO: 11 countries OFFICES WPRO: 27 Countries How Does WHO work? Provides guidance and recommendations and has an advisory role to Governments Acts upon requests by the Governments or National Ministries Works with and for the Governments (local, national, regional, headquarters) Support to National Governments is additionally provided by WHO Collaborating Centres (WHOCCs) assigned by WHO based on national expertise and national needs

WHO - Non-Communicable Diseases (NCDs) Impact of NCDs recognised leading threat to human health and development An estimated 35 million deaths - 60% of deaths globally attributed to NCDs In WHO- EURO NCDs cause 86% of deaths & 77% of the disease burden 2010 EU - more than 1/3 suffered from at least 1 chronic disease ( > 90% NCDs) NEED: to increase health care budgets and research funding WHO - Non-Communicable Diseases (NCDs) WHO Department of Sustainable Development and Healthy Environment - SDE Newsletter

WHO - Actions/Events WHO has taken action to address this global health threat: 1. Global Strategies for Prevention and Control of NCDs 53 rd WHA, May 2000 2. Action Plan 2008-2013 for Prevention and Control of NCDs 61 st WHA, May 2008 3. High level UN GA 2010 4. High level UN GA scheduled in September 2011 expected to generate to IMPLEMENT Global Strategy (1) and Action Plan (2) WHO Actions/Events

WHO - List of relevant documents WHO's Genomic Resource Centre - www.who.int/genomics/en WHO, 1989. Report of the fifth WHO working group on the feasibility study on hereditary disease community control programmes (Hereditary anaemias). WHO, Geneva, Switzerland. (WHO/HDP/WG/HA/89.2) WHO, 1991. Guidelines for the Management of Sickle Cell Disease. WHO, Geneva, Switzerland (WHO/HDP/SCD/91.2) WHO, 1993. Report of a joint WHO/TIF meeting on the prevention and control of haemoglobinopathies. WHO, Geneva, Switzerland (WHO/HDP/TIF/WG/93.1) WHO, 1994. Educational materials on prenatal diagnosis for Sickle-cell disorder. WHO, Geneva, Switzerland (WHO/HDP/EM/PN.SCD/94.2). WHO, 1994. Guidelines for the Control of Haemoglobin Disorders. WHO, Geneva, Switzerland (WHO/HDP/HB/GL/94.1). WHO, 1995. Prevention and Control of Haemoglobinopathies. WHO Bulletin, v73(3):375-386. WHO, 1997. Inherited Haemoglobin Disorders: an increasing global health problem. WHO Bulletin, v.75 (3):15-39. WHO, 1999. Services for the Prevention and Management of Genetic Disorders and Birth Defects in Developing Countries. WHO, Geneva, Switzerland (WHO/HGN/WAOPBD/99.1) WHO, 2000. Primary Health Care Approaches for Prevention and Control of Congenital and Genetic Disorders. WHO, Geneva, Switzerland (WHO/HGN/WG/00.1) WHO, 2002. Minutes of a WHO meeting on haemoglobin disorders. WHO, Geneva, Switzerland (WHO/HGN/HB/02.4) WHO, 2002. Report of the Advisory Committee on Health Research. Genomics and World Health. WHO, Geneva, Switzerland (ISBN 92 4 154554 2). WHO, 2003. Genetic Approaches to Haemoglobin Disorders and Primary health Care. WHO, Geneva, Switzerland (WHO/HGN/TIF/CONS/03.1) WHO, 2006. Report by Secretariat to Executive Board: Sickle-cell anaemia. EB117, Doc. EB117/34. WHO, Geneva, Switzerland [ www.who.int/gb ] WHO, 2006. Report by Secretariat to World Health Assembly: Sickle-cell anaemia. WHA59, Doc.A59/9. WHO, Geneva, Switzerland [ www.who.int/gb ] WHO, 2006. Report by Secretariat to Executive Board: Thalassaemia and Other Haemoglobinopathies. EB118, Doc. EB118/5. WHO, Geneva, Switzerland [ www.who.int/gb ] WHO, 2006. Executive Board Resolution on Sickle Cell Anaemia. EB117.R3. WHO, Geneva, Switzerland [ www.who.int/gb ] WHO, 2006. World Health Assembly Resolution on Sickle Cell Anaemia. WHA59.20. WHO, Geneva, Switzerland [ www.who.int/gb ] WHO, 2006. Executive Board Resolution on Thalassaemia and Other Haemoglobinopathies. EB118.R1. WHO, Geneva, Switzerland [ www.who.int/gb ] WHO, 2006. Report of a joint WHO/MOD meeting on Management of Birth Defects and Haemoglobin Disorders. WHO, Geneva, Switzerland. WHO, 2008. Report of a joint WHO-TIF meeting on Management of Haemoglobin Disorders. WHO, Geneva, Switzerland. WHO, 2010. World Health Assembly Resolution on Birth Defects. WHA63.17. WHO, Geneva, Switzerland [ www.who.int/gb WHO - Resolutions on Haemoglobinopathies Thalassaemia and other Urges Member States: Haemoglobinopathies EB118, May 2006 Resolution EB118.R1 Implement and reinforce national programs on HB disorders Evaluate the impact of national programs Intensify the training of all health professionals Promote community education Promote international cooperation Develop and strengthen medical genetic services Sickle cell anaemia Support basic and applied WHA59, May 2006 Resolution WHA59.20 research

WHO - Meeting of Experts Geneva, 17-19 May 2006 Priorities: support continued research for the collection and refinement of data relevant for the control of birth defects and hemoglobin disorders provide practical advice and support for countries wishing to develop medical services for care and prevention of birth defects and haemoglobin disorders promote human resource capacity development and technology transfer WHO TIF Meeting of Experts Nicosia 16-18 November 2007

WHO - Resolutions on Blood Safety Global Health Inequality Government Expenditure on Health WHO The World Health Report Health Systems Financing, the path to universal coverage

% of GDP on Health Expenditure Health Inequality in Europe Premature Mortality in Europe, 2006 Source: WHO EUROPE, Executive Summary, 2010

Health Inequality in Europe Couples living in poverty in EU countries, 2008 Source: WHO EUROPE, Executive Summary, 2010 Health Inequality in Europe A country s progress CANNOT be measured or defined by economic growth on it s own, but by the FAIR DISTRIBUTION OF HEALTH AND WELL-BEING across all settings and regions, and within all population groups

Health Systems & Services in Europe 1 Albania 2 Azerbaijan 3 Armenia 4 Austria 5 Belgium 6 Boznia 7 Bulgaria 8 Croatia 9 Cyprus 10 Denmark 11 France 12 FYROM 13 Germany 14 Georgia 15 Greece 16 Italy 17 Israel 18 Kazakstan 19 Kyskyzsta 20 Malta 21 Netherlands 22 Turkey 23 Portugal 24 Romania 25 Serbia 26 Spain 27 Sweden Health Inequality in Europe There is a widening gap between MS : A five-fold difference in deaths of infants less than 1 year old A 14 and 8 year gap in life expectancy at birth for males and females respectively 10 year shorter life expectancy for vulnerable and socially excluded groups (e.g. migrant & ethnic minorities) Heterogeneity across MS of national policies/programmes for RDs, chronic conditions & NCDs

EUROPEAN UNION COUNCIL OF MINISTERS 27 ministers representing the MS Adoption of legislation and budget EUROPEAN PARLIAMENT Concluding international agreements 754 members representing European citizens Adoption of legislation and budget Democratic supervision EUROPEAN COMMISSION 27 commissioners Right of initiative Implementation of the European policies and budget Europe 2020 Build on lessons learnt, successes achieved & address weaknesses poor implementation, wide heterogeneity Vision: To provide universal good health & well-being Develop high quality health systems Ensure equal access to good quality of care Europe 2020 anticipates to bring: A new kind of growth A stronger governance Tighter economic coordination

Europe 2020: Targets 1. Health Ageing Increase healthy life by at least 2 years RDs/Chronic Diseases/NCDs/ageing g population p major threats 2. R&I 3% of the EU s GDP (public & private) to be invested The challenges the EU faces can only be tackled by breakthroughs that only R&I can deliver 3. Education reduce school drop-outs to below 10%, to get at least 40% of 30-34 year olds to complete tertiary education 4. Poverty/Social exclusion at least 20million fewer people in or at risk of poverty & social exclusion 5. Employment 75% of 20-64 year olds to employed 6. Climate Change/Energy Crisis reduce greenhouse gas emissions to 20% lower than in 1990, 20% of energy to come from renewable sources, 20% increase in energy efficiency EU Budget for Europe 2020 Multiannual Financial Framework (2014 2020) 1,025 billion ~ 1.05% GNI Multiannual Financial Framework Focus: Solidarity & Investment for Sustainable Growth & Employment Agricultural Policy Horizon 2020 Education Budget: 80 billion R&I (Horizon 2020) Target: to constitute 3% GDP Health: may reach 0.3% GDP Research on Health (FP7: 2008 2013) - 6.5 billion More than 7% of the total EU budget will be spent on research by 2013

EU Budget for Europe 2020 Health for Growth Programme (2014 2020) DG SANCO & EAHC Follows on First (2003 2008) & Second (2008 2013) Programme of Community Action in the Field of Health Budget: 446 million ( 125million increase from the 2 nd Programme) Aims to address Health Inequalities by spending: 48% - Innovation & Sustainable Health Systems 22% - Wider access to better & safer healthcare 21% - Control & Prevention of chronic diseases 9% - Protection from cross-border health threats EU focus on Rare Diseases Second Programme of Community Action in the Field of Health (2008-2013) 7 th Framework Programme for Research & Technological Development (2007 2013) RDs are a priority

What are Rare Diseases? 5,000 8,000 distinct RDs 6 8 % of the EU population (50% are children) Affect an estimated 27 36 million individuals across the EU 80% of rare diseases have identified genetic origins Examples of Rare Diseases Rare Cancers Autoimmune disorders Congenital malformations Duchene Muscular Dystrophy Tuberous Sclerosis Complex Haemoglobinopathies Retinitis Pigmentosa

Characteristics of Rare Diseases Chronic, progressive, degenerative, and often life-threatening t i Disabling lack or loss of autonomy affects quality of life of patients High level of pain & suffering for the patient and their family No existing effective cure Majority have identified genetic origins, others are the result of infections (bacterial or viral), allergies and environmental causes Rare Disease Issues Lack of access to correct diagnosis Delay in diagnosis/ misdiagnosis Lack of scientific knowledge & quality information on the disease Heavy social consequences for patients Lack of appropriate quality healthcare Inequities and difficulties in access to treatment and care (where they exist) Additional physical, psychological and intellectual impairments Loss of confidence in the health system

Rare Diseases The Voice of 12,000 Rare Disease Patients EurordisCare2 & EurordisCare3 Survey 2009 40% - delayed or misdiagnosis 28% - dissatisfied with social care system in their country Haemoglobinopathies Patients who wait for transfusion more than 1 hours (118 patients) t Receive treatment Number of patients Percentage Specialised Haemoglobinopathy Centre 44 37,29% General Haematology Department 63 53.39% General Paediatric Department 16 13,56% Private clinic 0 0% Other (mostly oncology) 2 1,69% No answer 1 0,85%

Hb disorders: Time of transfusion Rare Diseases 2011 Research in the UK 46% of patients wait more than 12 months for a diagnosis 12% of patients wait more that 10 years for a diagnosis 46% are misdiagnosed 37% of patients feel that their doctor does not understand them

Rubix Cube of RD management Source:ECRD, 2010 Chronic Conditions Model Source: European Observatory, 2010

Rare Diseases The specificities of RDs single them out as a distinctive domain of very high European added-value Key Policy Documents A. Regulation on Orphan Medicinal Products (EC No 141/2000) Dec 1999 First Community Action Programme on Rare Diseases (1999 2003) Defined the prevalence of rare diseases as affecting no more than 5 per 10 000 persons in the EU Orphan Medicinal Products Regulation EC No 141/2000 Provides incentives for research and development into orphan drugs 10 year market exclusivity is given to MAHs / 12 years for paediatric drugs COMP Established in 2000 at EMA final decision on orphan designation applications 85 positive opinions have been given by COMP 64 of which refer to advanced therapy products 63 orphan-designated products have received MA ( 41% in oncology) average time between designation & authorisation being 2.8 years International Collaboration of EMA & FDA - one single annual report to be submitted for orphan products designated in both the EU & USA

Rare Diseases Key Policy Documents B. Commissions Communication on RDs: Europe s Challenge Nov. 2008 Strategy drafted by EC in collaboration with the RDTF in 2007 & focused on: Improving recognition & visibility of RDs Developing policies/collaborations/coordination/regulation at the EU level Rare Diseases Key Policy Documents C. Council Recommendation on the field of RDs (2009/C, 151/02) June 2009 1. National plans for RDs, in all MS, by the end of 2013 2. Empowerment of patients & patient organisations 3. Definition, Codification & Inventorying of RDs 4. Research 5. Centres of Expertise 6. Gathering of Expertise 7. Sustainability

Council Recommendation on the field of Rare Diseases 1. National plans for RDs Develop & implement plans for RDs in each MS, within the framework of each countries health & social system Preferably by the end of 2013 Through the Europlan project develop recommendations & guidelines to be elaborated & implemented by NHA 15 EU MS have so far developed National Plans for RDs Council Recommendation on the field of Rare Diseases 2. Empowerment of patients & patient organisations Involve patients & patient representatives at all stages of policy-making & decision-taking process Consult policy developments Facilitate access to information Promote patient organisation activities Founding of European Organisation for RD patients - Eurordis

Patient Organisations Patient organisations registered in the OrphaNet database: 2376 disease-specific organisations 1885 national organisations 122 regional organisations 70 European organisations 45 international organisations Eurordis Council of National Alliances Council of European Rare Disease Federations National Alliances of RDs are present in 20 MS including the Bulgarian National Alliance of People with Rare Diseases (NAPRD) Council Recommendation on the field of Rare Diseases 3. Definition, Codification & Inventorying of RDs The Council Recommendation urges the EU to develop a union-wide registry where all RDs are coded & traceable at the national, EU & international level Only 250 RDs have an ICD 10 code (2011) Morbidity & Mortality of RDs is INVISIBLE in health systems ICD 11 will be adopted in 2014 at the World Health Assembly/ EU 3820 diseases will be entered into the ICD 11 (Orphanet WHO partnership) Diseases can be indexed using any one of the existing coding systems (ICD/MIM) or by genes in OrphaNet at the moment

Patient Registries Key instruments to develop clinical research, improve patient care & healthcare planning Until Dec 2010 there were: 514 disease registries in Europe 50 European 29 International 373 National 61 Regional National Registries for Haemoglobin Disorders remain absent from many EU countries (if not most) Source: Orphanet Database Council Recommendation on the field of Rare Diseases At the EU level E-RARE (2006-2010) 16 research consortiums/75 teams/10 countries 9.6 million E-RARE-2 (2010 2014) 9 countries At the MS level in very few countries (e.g. France, Germany, Hungary, Italy, Spain, Netherlands) At the International level IRDiRC Launched in April 2011 Aims to deliver 200 new therapies for RDs by 2020 Objective is to pool together funding & knowledge to progress in providing new diagnostic & therapeutic tools for RDs

Research & Development Funding on the EU Level FP5 (1998 2002) Improving the quality of life & management of living i resources FP6 (2002 2006) Life Sciences, genomics & biotechnology for health 230 million in 59 projects on RDs (including ERA-NET) FP7 (2007 2013) Cooperation 237 million in 50 projects 71 million in 17 projects (Industry independent) 36 million in 8 projects (Orphan Drugs) To be followed by Horizon2020 Council Recommendation on the field of Rare Diseases OrphaNet database 1997 Currently there are 1049 laboratories testing 1764 genes across Europe Germany 1244 genes Netherlands 600 genes France 902 genes Spain 594 genes Italy 643 genes UK 416 genes * Medium-sized countries offer tests ranging from 1 344 genes Therefore testing is heterogenous

Clinical Laboratories 297 genes are tested in one laboratory in the EU (19% of genes) 1189 genes are tested in < 10 countries across the EU (76% of genes) 1088 genes are tested in < 5 countries (69% of genes) 395 genes are tested one country only (25% of genes) 107 labs are accredited for at least part of their diagnostic services 432 participants have gone through 46 EQA organisations in the past 5 years NEED: Coordination at National AND EU level Council Recommendation on the field of Rare Diseases 5. Centres of Expertise / Reference Centres Establish national centres of expertise Participate in European Reference Networks Facilitate cooperation amongst experts/professionals within the country or between countries

European Reference Centres Past Activities & Achievements High Level Group (HLG) on Health Services & Medical Care to promote Patient Mobility HLG & RDTF focused on Reference Centres & Networks 2006 - criteria first identified & defined Based on national experiences (in countries with designation processes) European Reference Centres Officially designated reference centres for RDs exist only in few countries: National Reference Centres - Denmark, France, Norway, Spain & UK Regional Reference Centres Italy Self-declared/Non-designated Reference Centres Austria, Belgium, Czech Republic, Germany, Greece, Hungary, Ireland, the Netherlands, Slovakia & Switzerland Therefore: great HETEROGENIETY Information on Haemoglobinopathy Reference Centres needs to be updates & validated

European Reference Centres Future Action EUCERD focuses on compiling homogenous criteria for reference centres on RDs Other projects & disease- organisations focus on criteria for reference centres for specific groups of diseases e.g. ENERCA, TIF Essential in the context of Cross- Border Healthcare where RDs are specifically mentioned Survival when treated in specialised centres (Forni et al, 2009)

Council Recommendation on the field of Rare Diseases 6. Gathering of Expertise Establish European Reference Networks to foster the diffusion & mobility of expertise & knowledge To develop medical training for more accurate diagnosis & better management To coordinate EU guidelines Minimize delay in access to orphan drugs Share clinical/ therapeutic added-value assessment reports at the Community level European Reference Networks (ERNs) FPs have provided since 1999 funding for 3-year projects on pilot ERNs for RDs including genetic diseases Despite variability European added-value is recognised Most valuable resources have been developed: Shared databases/registries Shared tools for tele-expertise Guidelines & information Training tools/ training sessions Not yet for Haemoglobin disorders Examples of projects include: ECORN-CF (Cystic Fibrosis) NEUROPED (Neurological Paediatric RDs) DYSCERNE (Dysmorphic RDs) CARE-NMD (Duchenne Muscular Dystrophy) ENERCA (Rare Anaemias) EU-CHS (central hyperventilation syndrome)

Rare Diseases EC is assisted by: European Union Committee of Experts on Rare Diseases (EUCERD) Replaced RDTF Formally established by the European Commission Decision 2009/872/EC and supported by the Joint Action Programme 872/EC Rare Diseases outside Europe USA 1983 US Orphan Drug Act FDA OOPD (Office of Orphan Products Development) 1993 NIH ORD (Office of Rare Diseases) 2002 Rare Disease Act - Public Law 107-280 Definition < 1 in 200,000 Asia Japan oldest programme for RD (1972) Research: 130 disease groups Care: 56 diseases 650,000 patients benefit

Rare Diseases outside Europe Singapore 1991 Orphan Drug Policy Taiwan 2000 Orphan Drugs Act Reimbursement gap is at 70% of actual expenditure for RDs & 100% for low income families Korea No national policy or legislation but 1999 Non-Profit Organisations & Orphan Drug Centre supported by Korean Food & Drug Administration definition < 1 in 20,000 2004 Genetic & RD Centre by MOH Research grant for RD 5.5m USD (2008 2012) Rare Diseases outside Europe Australia Orphan Drugs Policy Australian Therapeutic Goods Administration uses information fro US FDA on Orphan Drugs Definition < 1 in 2000 2010 National Strategy for RDs initiated

EU Health Policies Cross Border Healthcare Directive - Directive 2011/24/EU Provision for rare diseases Article 13 The Commission shall support Member States in cooperating in the development of diagnosis and treatment capacity in particular by aiming to: (a) make health professionals aware of the tools available to them at Union level to assist them in the correct diagnosis of rare diseases, in particular the Orphanet database, and the European reference networks; (b) make patients, health professionals and those bodies responsible for the funding of healthcare aware of the possibilities offered by Regulation (EC) No 883/2004 for referral of patients with rare diseases to other Member States even for diagnosis and treatments which are not available in the Member State of affiliation. To be implemented: October 2013 EU Health Policies Clinical Trials Directive Directive 2001/20/EC Currently under revision to be adopted in 2012 Patient safety primary concern Aims to: Develop collaboration (MS, Industry, other stakeholders) Establish cooperation in accessing & following up applications Minimize duplication of efforts better adoption of practical requirements & more harmonized risk adapted approach to procedural aspects of CTs Improve harmonisation in procedural aspects Ensure GCP is performed in CTs outside the EU & recorded in EU registry

EU Health Policies: The Pharmaceutical Package Directive on the prevention of the entry into the legal supply chain of falsified medicinal products - Directive 2011/62/EU Came into force: 21 July 2011 Seeks to harmonize safety & strengthen control measures across EU including: Mandatory features on the outer packaging to demonstrate authenticity Strengthened requirements for the inspection of the manufactures on pharmaceutical ingredients Obligation of manufacturers & distributors to report suspicion of falsified medicines Compulsory logo on legally operating online pharmacies with a link to national registries EU Health Policies: The Pharmaceutical Package Pharmacovigilance policy Regulation (EU) No. 1235/2010 & Directive 2010/84/EU Aims: Enable proactive and independent reporting direct patient reporting Raise awareness on safety issues Increase confidence in safety monitoring Harmonisation of terminology Combat duplication of reporting Will come into effect on 2 July 2012

EU Health Policies Equality in Employment - Directive 2000/78/EC Equal treatment in employment and occupation Prohibition of discrimination of any kind TIF Statement on the Employment Rights of Thalassaemia Patients - August 2011 Revision of Directive on the recognition of Professional Qualifications (2005/36/EC) as applied to the harmonization of haematologist qualifications across the EU Role of Patient Organisations in Health Policy Making Work actively with WHO Regional & local Offices & Collaborating Centres Work with NHA & national focal points & participate in policy-making procedures at the national level Achieve active participation at the EU level & participate in EC consultations Contribute to EU level official organisations (e.g. EMA), committees & fora (e.g. COMP, CAT, PDCO, PCWP, EUCERD etc) Build a strong relationship with national, international & European organsiations like TIF, IAPO, Eurordis

Thank you Dr A. Eleftheriou Executive Director Thalassaemia International Federation Tel: + 357 22 319 129 Email: thalassaemia@cytanet.com.cy