Ethical Stakes and Therapeutic Innovation

1. Ethical Stakes and Therapeutic Innovation Yannick PLETAN, MD, MSc, FFPM Vice-President Pfizer, France Chief Medical Officer

2. A few statements • Novelty is not innovation • There is no unique definition for innovation • Innovation has no societal value per se • Until innovation is recognized as a progress, quest for innovation entails risks rather than benefits, and poses ethical issues • Human Research is the most codified activity in most countries • Newer ethical aspirations surface as we move forward • Seeking innovation imposes choices • Developers may have different perspectives that impact on choices • Context may change the value and outcome of such choices • Any choice in this matter has an ethical dimension or consequence French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN

3. Innovation for some, not for others • The WHO 200-medicine list • Innovation through official awards (Gallien) • Innovation assessed by the Pharmaceutical Industry • An FDA view over Innovation • Evidence Based Medicine • Innovation as the price granted for the new medicines • Innovation, a desperate quest for Rare Diseases French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN

4. A Few Illustrations • From innovation to progress • An example of a development dilemma • Value of innovation depending on posture: public health versus patients’ expectations • Value of innovation depending on context • Responsibility and innovation French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN

5. Penicillin dicovery Innovation = Fleming, 1943 TECHNICAL PROGRESS = INDUSTRIAL FERMENTATION SCIENTIFIC PROGRESS Pfizer, 1944 MEDICAL PROGRESS Other antibiotics INDIVIDUALS Soldiers, 1944 Patients ECONOMICAL PROGRESS Increased working capacity Industrial development SOCIETAL PROGRESS Decrease of mortality (infectious, cardio-vascular, renal, cerebral) Improvement in duration and quality of life French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN

6. Molecule presenting with an important effect On some mycobacteria Including tuberculosis agent = potential therapeutic value Potential options A B Tuberculosis treatment (millions of cases in the world) Developing countries Deprived populations Affordable daily treatment cost close to nil Mycobacterium Xenopi treatment, Nosocomial infections agent (hundreds of cases / world) Developped countries, ICUs, specialized wards No pre-established financial constraint Ideally = A + B = 2 distinct developments What if constraint upon resources ? French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN

7. Impact of pathologies on quality of lifeThe Sickness Impact Profile: validation of a health status measure. Bergner M, et al. Med Care 1976. Lower QOL Better QOL Cardiac Arrest Moderate Obesity Myocardial Infarct Chrohn ’s Disease End-stage Haemodialysis Non-oxygen dependent COPD Back Pain Oxygen Dependent COPD Amyotrophic Lateral Sclerosis French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN

8. Treatment aiming at modifying fertility Population A Population B Mean Age < 25 years Fecondity index > 4.0 Steep demography Mean age > 45 years Fecondity index < 1.0 Decreasing fertility Societal expectation Fertility preferable to contraception Contraception preferable to fertility The choice can be adapted but to context: time, location, fundamental needs for a given population It is not the mission of Ethics to judge over contexts French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN

9. INNOVATION Responsibility for who undertakes research ? SCIENTIFIC PROGRESS ? MEDICAL PROGRESS ? INDIVIDUAL ? ECONOMICAL PROGRESS Responsibility for those who benefit from research SOCIETAL PROGRESS French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN

10. New ethical developments and aspirations • Justice • Right to participate to clinical trials • Equity in sharing benefits and risks • Non exploitation of vulnerable subjects • Coupling research with improvement of medical care • Improvement of Research standards • Relevance of research vis-à-vis local needs • Account for local factors: culture, language • Account for global medical stakes, new or reemerging diseases, worldwide solidarity • Equity with regard to access to health information French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN

11. Back-ups

12. Human Research: the most codified activity • Universal Statements: • World Medical association: Helsinki Declaration (1964) • WHO: Manilla Declaration(1981) • CIOMS : Inuyama Declaration • UNESCO: Universal Declaration on Human Genome and Human Rights (1997) French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN

13. Human Research: the most codified activity • A legislative, regulatory and ethical armamorium: • EU Council: Recommendations • Food & Drug Administration: Code of Federal Regulations • EU Commission: EU Directives and rulings • France: Public Health Bill (2004) • Deontology Code • Patient Rights Bill (2002) • Informatics and Liberties (laws and decrees) • Bioethics Law (2004) • CCNE: Opinions • Individuals Protection Committees (CPP) French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN

14. A very large Scope • Clinical Trials Conduct • Information and consent • Protection of the youngs and adults with incapacity • Trials in emergency situations • Safety statements and protections for specific products • Use of recombinent DNA • Use of human embryos • Genotyping • Patentability of human products • Gene therapy • Non commercialization of human genome • Data protection • Confidentiality French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN