1. Copyright, 1996 © Dale Carnegie & Associates, Inc. CLINICAL TRIALS AND HUMAN SUBJECT PROTECTION: A PLAINTIFF’S PERSPECTIVE ALAN MILSTEIN SHERMAN SILVERSTEIN KOHL ROSE & PODOLSKY WWW.SSKRPLAW.COM

2. THERAPY VS. RESEARCH EXPERIMENTAL THERAPY VS EXPERIMENT NONTHERAPEUTIC RESEARCH CLINICAL TRIALS CHALLENGE STUDY THERAPEUTIC RESEARCH NEW VS. EXISTING THERAPY NO THERAPEUTIC ALTERNATIVE

3. ETHICAL REQUIREMENTS NUREMBERG CODE HELSINKI DECLARATION BELMONT REPORT THE COMMON RULE FUNDAMENTAL RIGHT TO BE TREATED WITH ESSENTIAL HUMAN DIGNITY

4. WHY ALL THE CONTROVERSY? DEATH OF JESSE GELSINGER DEATH OF ELLEN ROCHE DEATH OF NICOLE WAN UNIVERSITY OF OKLAHOMA MELANOMA TRIAL

6. THE MYTH 0F SUBJECT PROTECTION: EVERYBODY’S WATCHING THE TRUTH: THE RESEARCHER’S ETHICS Currently more than 100,000 trials involving 7- 8,000,000 participants At some major institutions, 4000 current trials 5000 IRBs THE SOLUTION Reduce the number of trials; stop trivial research; devote resources to subject protection

7. CONFLICTS OF INTEREST THE TRUTH Financial and other interests that potentially take the focus away from protection of the subject cannot be managed. THE SOLUTION Institutions and researchers should have no financial stake in the outcome of an experiment or in the decision of the subject to participate.

8. EXPERIMENT MUST BE ETHICALLY DESIGNED PRECLINICAL UNDERSTANDING OF UNIVERSE OF HARM VALID SCIENCE: LIKELIHOOD OF GAINING KNOWLEDGE VALUABLE: FRUITFUL RESULTS FOR GOOD OF SOCIETY RISKS MINIMIZED AND OUTWEIGHED BY BENEFITS NONTHERAPEUTIC: SHOMEIR P’TAYIM THERAPEUTIC: CLINICAL EQUIPOISE ETHICAL USE OF PLACEBOS

9. SELECTION CRITERIA MUST BE EQUITABLE ABSENCE OF COERCION AVOIDS VULNERABLE POPULATIONS

10. INFORMED CONSENT PURPOSE PROCEDURE RISKS BENEFITS SELECTION ALTERNATIVES FINANCIAL INTERESTS

11. UNINFORMED CONSENT:THE MYTH OF INFORMED CONSENT THE TRUTH: The document neither evidences the participant is informed or that he or she consents.

12. THE DOCUMENT Presumes Consent vs Informed Choice Study/Clinical Trial/Research Average time: 10 minutes Conveyed and Understood Competent to give consent Whose role?

13. Therapeutic Misconception  70% believed proven best treatment  50% believed standard treatments and procedures  70% believed best therapeutic alternative  90% believed purpose to benefit them not future patients

15. National Cancer Institute: Reasons to Enroll o Access to new drugs and interventions before widely available o Opportunity to be the first to benefit if approach found helpful o Better care than standard best therapy o Often the best therapeutic alternative

16. SOLUTIONS  Tell it like it is: A human experiment  Use subject advocates  Explain Phase 1, Phase 2, Phase 3  Know whether best therapeutic alternative  Stop selling

17. RESPONSIBLE PROTECTORS OF HUMAN SUBJECTS Investigators IRB members Subject Advocates OHRP RAC FDA All Of Us