30 th September 2008 Professor Yuji Sato MD PhD The 8 th Kitasato Harvard t Symposium Centre for Clinical Research Keio University School of Medicine, Japan
Education in preparation for global l trials Issues and Challenges from ongoing global trials Suggestions for future
Provision i of education for global lti trials Three different levels Undergraduate medical students Postgraduate junior doctors and investigators IRB members and other executives
1. Undergraduate d medical education Introductory pharmaceutical medicine i As a part of pharmacology course (3 rd year students) As a part of public health/social medicine course(4 th year students) Clinical trials How to develop a new drug Drug lag issue
2. Postgraduate t education Higher education on clinical i l research Introductory course (twice annually) Advanced course(twice annually) Biostatistics and study design(two series per annum) Attending basic course to be mandatory to all investigators
3. Faculty development For senior professionals Special executive crush course twice per annum IRB members, Ethics committee members Joint course with the University of Minnesota(7 th Feb 2009)
Issues and Challenges from ongoing gg global trials General issues for conducting trials Current situation ti of global l trials il Hurdles for global trial participation
General issues of clinical i l trials il in Japan Enrollment difficulty Enrollment per site is limited, in particular at teaching hospitals Time consuming site set up & slow study progress Complicated in house rules Interdepartmental coordination Investigators: availability & capacity for trials limited Expensive trials despite limited incentives for investigators
Ongoing global l trialsat il at Ki Keio An investigator initiated global trial in gynaecological oncology Sponsored global trials A global trial in haematology A global l trial il in septisaemia i As an investigational site As a coordination center for the investigational sites in Japan
Global l trials: Identified d issues & lessons learned Difficulties i and challenges hll in: 1. Language 2. Communication, i coordination, i collaboration 3. Perception, judgment and decision i making 4. Cost effectiveness, cost performance Time, manpower, experience, incentives
Difficulties and challenges(1): hll () Language English E h documents(protocol, ( case report form, brochure etc) Acceptable to many physicians/specialists p in teaching hospitals Other staffs with varying degree of experience/exposure Interaction, discussion with global centre for trials Tl Teleconferences & meetings Urgent inquiry, protocol amendments Negotiation, clarification and compromise
Difficulties and challenges(2): Communication, coordination &collaboration Site Local sponsor Global HQ IRB Admin Scientist MD Scientist MD Investigator CRC CRA Regulatory QC CRA Regulatory QC Data Manager Data Manager Pt Pt Pt Sales Reps Marketer Sales Reps Marketer Many players, manifold processes, complex reporting lines, unclear accountability
Miscommunication& Discommunication Suggestion from HQ perceived locally as unquestionable demand or reprimand forwarded on to site as an nonnegotiable imperative Rapidly evolving clinical issues: need urgent handling Sense of clinical urgency: difficult to convey and interpret
Difficulties and challenges(3): hll Perception, judgment, decision making Perception gap ~ discrepancy in frame of reference Concern and sensitivity towards details & minutiae as opposed to big picture Japanese Jp minimalism: a double edged sword, risk of degrading ginto trivialism Upside: better data quality, fewer protocol violations & deviations Downside: More time and energy, manpower, overwork and over quality Decision making & clinical judgment Modus operandi different across cultures and countries
Difficulties and challenges(4): hll () Cost Cost effectiveness, C i cost performance High quality data, often swift enrollment despite large N of sites Offset by most expensive study budge Why expensive? Most fees go to sites, not investigators i (de facto indirect expenses) Actual workload and manpower not well reflected Local rule ( point calculation system) at work
How to incentivize i investigators t Participation in global research per se: of academic value Exposure to global standard research Helpful to improve local research activities Access to novel pharmacotherapy tangible clinical advance, benefit for Pts Financial incentive So far very limited in Japan
Comparison of two budget systems Basis Correlation with actual workload Investigator fee In-house distribution Comparability with overseas trials Estimation by points Global budget calculation Points Poor Ca 30% at best Defined in advance No clear breakdowns calculation (points rely (limited by the by contract Only comparable as based on heavily on lab point system) total sum hitherto defined test items format rather than complexity and workload) Global Summation of Good In proportion Not restricted by the Globally comparable actual cost per with respect to details patient per visit Transparent with enrollment, study complexity contract per se; freely defined at investigators discretion
Perceptions among physicians & hospital management Urgency of implementing global trials to improve drug lag Necessity to improve infrastructure Higher education in clinical research methodologies, ethical considerations and related regulations More urgent issues to attend: management crisis Financial i critical ii status of teaching hospitals Medicolegal litigiousness Mounting workload: lack of primary/specialist care distinction teaching g hospitals as mere health care provider Exodus of experienced physicians manpower crisis
Challenges for both academia & industry Global standard operation & business practice Timeline & efficiency consciousness Timely and clear decision making and swift operation Global perspective p versus local preference and customs Big picture against local trivialism and micromanagement Risk taking, positive mindset as opposed to risk averse conservatism Transparent, equal partnership as opposed to subservience Separation between clinical research and sales/promotion aspects Substantial recognition for conflicts of interest cf. c. Eli Lilly: First Pharmaceutical aceut ca Company to Disclose Physician Payments Pfizer Japan: abolishes unrestricted study grant
Challenges hll and critical issues at academia Morale of investigators, CRCs and other staffs: major, and often only, motivation and driver for clinical trials Mounting procedural, operational issues in carrying out global trials: unknown to most investigators & CRCs Understaffed, underfinanced How to ensure manpower, time, infrastructure required in the face of worsening shortage of experienced physicians at teaching hospitals Institutional Review Board: to meet global requirement Training, quality, international accreditation