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

Ethical Stakes and Therapeutic Innovation

Yannick PLETAN, MD, MSc, FFPM

Vice-President Pfizer, France

Chief Medical Officer

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


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


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


Penicillin dicovery

SCIENTIFIC PROGRESS

MEDICAL PROGRESS

ECONOMICAL PROGRESS

SOCIETAL PROGRESS

INDIVIDUALS

Fleming, 1943

TECHNICAL PROGRESS= INDUSTRIAL FERMENTATION

Innovation =

Pfizer, 1944

Other antibiotics

Soldiers, 1944Patients

Decrease of mortality (infectious,cardio-vascular, renal, cerebral)Improvement in duration and quality of life

Increased working capacityIndustrial development


Molecule presenting with an important effectOn some mycobacteria

Including tuberculosis agent

Potential options

Tuberculosis treatment(millions of cases in the world)Developing countriesDeprived populationsAffordable daily treatment cost close to nil

Mycobacterium Xenopi treatment,Nosocomial infections agent(hundreds of cases / world)Developped countries, ICUs, specialized wardsNo pre-established financial constraint

A B

Ideally = A + B = 2 distinct developments

What if constraint upon resources ?

= potentialtherapeutic value


0 5 10 15 20 25 30 35

Overall Sickness Impact Profile score

Amyotrophic lateral sclerosis

Chronic pain non-responders

Oxygen dependent COPD

Chronic low back pain

Back pain

Physically disabled adults

Non-oxygen dependent COPD

Rheumatoid arthritis

End-stage hemodialysis

Hypothyroidism

Crohn's

Angina

Myocardial infarct

Ulcerative colitis

Moderate obesity

General population

Cardiac arrest

Group health enrollees

better HRQL lower HRQLBetter 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 lifeThe Sickness Impact Profile: validation of a health status measure.

Bergner M, et al. Med Care 1976.


Treatment aimingat modifying fertility

Population A Population B

Mean age > 45 yearsFecondity index < 1.0Decreasing fertility

Mean Age < 25 yearsFecondity index > 4.0Steep demography

Societalexpectation

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


INNOVATION

SCIENTIFIC PROGRESS

MEDICAL PROGRESS

ECONOMICAL PROGRESS

SOCIETAL PROGRESS

INDIVIDUAL

?

?

??

Responsibilityfor whoundertakes research

Responsibilityfor those whobenefit fromresearch


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

Back-ups


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)


• 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


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

Documents

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