1. 29052-PorterJ32.ppt Roger J. Porter, M.D. Consultant Adjunct Professor of Pharmacology, USUHS Adjunct Professor of Neurology, Univ. of Pennsylvania Former Deputy Head, CR&D, Wyeth Research Former Deputy Director, NINDS, NIH Conflicts of Interest in Research: Industry Relationships with the IRB PRIM&R, Boston, MA May 3, 2004

2. 29052-PorterJ32.ppt PHARMACEUTICAL R&D IN THE NEW MILLENNIUM OPPORTUNITY Scientific and Medical Breakthroughs Scientific and Medical Breakthroughs Technology Breakthroughs Technology Breakthroughs CHALLENGE Complexities of Scientific Environment/Regulatory Hurdles Complexities of Scientific Environment/Regulatory Hurdles Cost Containment Cost Containment  D-COST 11,523

3. 29052-PorterJ32.ppt SCIENCE: A TRUTH-SEEKING PROCESS

4. 29052-PorterJ32.ppt BIAS IN RESEARCH: Bias hinders the Search for the truth.

5. 29052-PorterJ32.ppt BIAS IN RESEARCH: Clinical Trials are Experiments—>Designed to Minimize Bias. Conflicts of Interest Induce Bias in Research.

6. 29052-PorterJ32.ppt BIAS IN CLINICAL TRIALS The Investigator The Investigator The Nurse The Nurse The Technician The Technician The Patient The Patient The Patient’s Relatives The Patient’s Relatives The Drug Company The Drug Company

7. 29052-PorterJ32.ppt BIAS IN RESEARCH: One Of The Major Efforts Of The Clinical Protocol Is To Minimize Bias. The IRB Should Be Sufficiently Sophisticated That It Can Recognize A Study With Potential Bias.

8. 29052-PorterJ32.ppt The Industry and the IRB

9. 29052-PorterJ32.ppt The Industry and the IRB Under what circumstances, for a clinical study, does the Industry interact with the IRB? Under what circumstances, for a clinical study, does the Industry interact with the IRB? What kinds of interactions occur? What kinds of interactions occur?

10. 29052-PorterJ32.ppt The Industry and the IRB Two, curiously dichotomous circumstances govern contact by the Industry with the IRB. Two, curiously dichotomous circumstances govern contact by the Industry with the IRB. The path is determined by the identification of the principal investigator. The path is determined by the identification of the principal investigator.

11. 29052-PorterJ32.ppt The Industry and the IRB First Path: In a Phase II or III study, the industry study manager (who might be a clinical scientist or might be a physician) works with a principal investigator (typically an academician) who, in turn, deals with the IRB. The industry study manager would not even think about contacting the IRB.

12. 29052-PorterJ32.ppt The Industry and the IRB Second Path: In a Phase I study, the industry owns its own Clinical Research Unit. The director of the unit (typically a physician) is the principal investigator, and presents each study directly to the IRB. The industry study manager is now the principal investigator; contact with the IRB is expected and natural.

13. 29052-PorterJ32.ppt The Industry and the IRB Issues (I) The IRB needs to have some independence from the principal investigator, whether the IRB is academic, contract, or otherwise. The IRB needs to have some independence from the principal investigator, whether the IRB is academic, contract, or otherwise. The IRB should have some accountability for its actions. The IRB should have some accountability for its actions.

14. 29052-PorterJ32.ppt The Industry and the IRB Issues (II) Should the IRB talk to the principal investigator? OR Should the protocol, etc, be mailed to the IRB for a decision?

15. 29052-PorterJ32.ppt The Industry and the IRB Issues (III) Accreditation is a good idea.

16. 29052-PorterJ32.ppt THE CHAIN OF TRUTH IN DRUG DISCOVERY AND DEVELOPMENT Molecular Development Molecular Development  Synthesis Scale-Up Synthesis Scale-Up  Basic Pharmacology Basic Pharmacology  Early Toxicology Early Toxicology  Pharmaceutical Development Pharmaceutical Development  Phase I in Humans Phase I in Humans  Phase II in Humans Phase II in Humans  Phase III in Humans Phase III in Humans  Registration Registration

17. 29052-PorterJ32.ppt BACKUP SLIDES

18. 29052-PorterJ32.ppt FORCES WHICH MOTIVATE SCIENTISTS: Altruism and Curiosity Fame Fortune

19. 29052-PorterJ32.ppt FORCES WHICH MOTIVATE SCIENTISTS: Altruism and Curiosity Fame Fortune Bias Line

20. 29052-PorterJ32.ppt FORCES WHICH MOTIVATE SCIENTISTS: Curiosity and Altruism Fame Fortune Societal Anxiety Line Research Bias Line