1. Ethics of Research

2. History of Regulation of Research n A history of scandals –Nazi experiments, WWII –Beecher expose of US research without consent, 1966 –Tuskegee syphilis study exposed, 1972 –US radiation experiments exposed, 1990s –Japanese WWII experiments on Chinese exposed, 1990s

3. Results n Focus on informed consent n Focus on initial research design n Assume harm comes by being included in experiments n Focus on vulnerable populations of subjects

4. Research in US Today n Some good news n Some bad news

5. Good News n There is a set of Federal guidelines to protect subjects of research n The guidelines have real teeth n The guidelines apply uniformly no matter who funds the research (govt agencies or private)

6. Bad News n This is true only of research involving animals, not humans

7. n “We will not allow human beings to be made into guinea pigs.” n President Clinton n “We should all be so lucky.” n Alta Charo, NBAC

8. The Research Regulation Mess Federally funded research (17 agencies) Private industry

9. A New Scandal n Penn gene therapy experiment n Healthy 20-year-old subject dies as a result of gene transfer therapy n Adverse outcomes in earlier trials concealed n Financial interest of investigators, university in company concealed

10. Lessons from Penn n Focus on initiation of study may lead to inadequate follow-up of actual results n Present system may be inadequate to deal with serious conflicts of interest n Mere existence of review board and regulations did not prevent major problems with informed consent

11. Conflicts of Interest n Genomics industry report to Federal Recombinant DNA Advisory Committee on why reports of adverse events during human trials should be regarded as proprietary secret information--

12. Conflicts of Interest-- II n Reporting adverse event makes our stock go down n Open reporting would allow our competitors to avoid same mistake n Adverse events are rich sources of unanticipated new data n Assess these in light of ethics of protecting human subjects

13. Conclusion n The current heavy reliance on private industry funds to support medical research creates a serious risk to both the values of scientific inquiry and the protection of human subjects n How?

14. Back to Basics n The research enterprise is fundamentally different from the enterprise of treating individual patients n The relationship between health care professional and patient is fundamentally different from the relationship between investigator and subject

15. The Therapy Context n The principal, overriding goal is the benefit to the individual patient n If new knowledge emerges, it is a secondary good, not the aim

16. The Research Context n The principal, overriding goal is generating new knowledge that can be generalized n Any improvement in the health of an individual subject is a secondary good, not the aim

17. “Therapeutic Misconception” n Research subjects encounter people who look like doctors and nurses in a setting that looks like a clinic or hospital n Therefore they assume (despite explicit informed consent) that the overriding goal of the research context is to improve their personal health

18. Ideal Research Subject n Fully informed n High level of understanding n Least vulnerable to outside pressures n Most highly motivated to make the research a success for its own sake n Senses self to be a true partner in the research enterprise n Who is this?

19. Emanuel et al. n The basic ethical question in research on humans is exploitation n The process of informed consent is neither necessary nor sufficient to prevent exploitation n Need detailed list of safeguards based on real ways subjects may be exploited

20. Future? n NBAC draft report on regulation of research (due in 12/00) n Very likely to recommend major overhaul of present regulatory system n More focus on substance of protection and less on paperwork n More focus on ongoing conduct of trial