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

2. French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN 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

3. French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN 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

4. French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN 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

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

6. French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN Molecule presenting with an important effect On some mycobacteria Including tuberculosis agent Potential options 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 A B Ideally = A + B = 2 distinct developments What if constraint upon resources ? = potential therapeutic value

7. French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN Better QOL Lower 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 Impact of pathologies on quality of life The Sickness Impact Profile: validation of a health status measure. Bergner M, et al. Med Care 1976.

8. French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN Treatment aiming at modifying fertility Population A Population B Mean age > 45 years Fecondity index < 1.0 Decreasing fertility Mean Age < 25 years Fecondity index > 4.0 Steep demography 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

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

10. French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN 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

11. Back-ups

12. French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN 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)

13. French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN 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) Human Research: the most codified activity

14. French-Chinese Meeting - Ethics &- Innovation - Paris - February 23, 2007 - Y.PLETAN 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