Through the Looking Glass: Reflections of a Research Ethicist or The Collapse of Science and Ethics?

1. Through the Looking Glass:Reflections of a Research EthicistorThe Collapse of Science and Ethics? Michael Goodyear Department of Medicine, Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia, Canada MSMR Waltham MA, June 2006 Goodyear

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3. Alice was sitting curled up in a corner of the great arm-chair, half talking to herself and half asleep Goodyear

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5. Learning Objectives • I: How Did We Get Here From There? • II: Where are We Now? • III: Lessons from TGN1412 • IV: Moving Forward Summary Goodyear

6. “The aim of science is not to open a door to infinite wisdom but to set a limit to infinite error” Brecht B. The Life of Galileo(Leben des Galilei) 1943 Bertolt Brecht (1898 –1956) Goodyear

7. Part I How Did We Get Here From There? Goodyear

8. We All Know Where We Have Come From Or Do We? Goodyear

9. History • Human experimentation since time immemorial • Generally more vulnerable populations • Prisoners, slaves, patients Goodyear

10. History • Thomas Percival (1740-1804) Medical Ethics: a Code of Institutes and Precepts Adapted to the Professional Conduct of Physicians and Surgeons Russell, London 1803 Adopted by AMA 1847, modified many times Goodyear

11. History • Claude Bernard (1813-1878) • Must have potential benefit • Prisoners not considered human Goodyear

12. History • William Osler (1849-1918) • Consent • Animal experimentation • George Bernard Shaw (1856-1950) • “Human Guinea Pigs” (1913)* Goodyear *Disclaimer: No Guinea Pigs were harmed in this production

13. History • Germany • Prussian regulations 1900 • Third Reich 1931 Goodyear

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15. Nürnberg Goodyear

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17. Nuremberg Code 1947 Trials of war criminals before the Nuremberg military tribunals under Control Council Law, No 10, Vol 2. Washington DC: US Government Printing Office, 1949: 181. Goodyear

18. Nuremberg Code 1947 1. Voluntary Consent Essential 2. Must Yield Valid Results 3. Based on Animal Experiments 4. Avoid Physical and Mental Suffering 5. Avoid Injury 6. Risk Proportional to Benefit 7. Subjects Must be Protected 8. Qualified Investigators 9. Voluntary Withdrawal 10. Must be Terminated if Necessary Goodyear Top Secret

19. Nuremberg Code 1947 3. The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study, that the anticipated results will justify the performance of the experiment. Goodyear

20. American Medical Association Judiciary Council • The voluntary consent of the person on whom the experiment is to be performed must be obtained • The experiment must be performed under proper medical protection and management. • The danger of each experiment must be previously investigated by animal experimentation December 10th, 1946 Goodyear

21. Strangers at the Bedside: A history of how law and bioethics transformed medical decision makingNY Basic Books 1991 David Rothman PhD Director, Center for the Study of Society and Medicine Columbia College of Physicians and Surgeons Goodyear

22. “Neither the horrors described at the Nuremberg trial nor the ethical principles that emerged from it had a significant impact on the American research establishment” because they did not seem “directly relevant to the American Scene”Rothman p. 62 Goodyear LF Ross

23. “To most Americans, however, Nuremberg addressed madness, not medicine” Shapiro HT. Waggoner Lecture, U Michigan Dec 5 2001 Ethical Considerations in Research on Human Subjects: A Time for Change…Again Goodyear

24. Tuskegee, Alabama Nürnberg, Germany Goodyear

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26. “I don’t know what they used us for. I ain’t never understood the study” Tuskegee, Alabama (1932 – 1972) RIP Goodyear

27. 1965 Are humans used as guinea pigs not told? Goodyear

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29. “What seem to be breaches of ethical conduct in experimentation are by no means rare, but are almost, one fears, universal” Goodyear

30. “No physician is justified in placing science or the public welfare first and his obligation to the individual, who is his patient or subject, second” “No doctor, however great his capacity or original his ideas, has the right to choose martyrs for science or for the general good”Maurice Pappworth Pappworth M.H. Human Guinea Pigs Penguin 1967, p.27 Goodyear LSwartz

31. The Dark Side • Willowbrook Hepatitis Study • Jewish Hospital Cancer Study • Tearoom Trade Study • Wichita Jury Study • Milgram Obedience Study • San Antonio Contraceptive Study • Radiation Studies • etc………….. Goodyear

32. …and the Light Goodyear

33. Belmont Report1979 Ethical Principles and Guidelines for the Protection of Human Subjects of Research The National Commission for the Protection of Human Subjects of Biomedical and Behavioral ResearchApril 18, 1979 Goodyear

34. So We Fixed it? Right? Goodyear

35. Advisory Committee on Human Radiation Experiments (1994-5) Human Radiation ExperimentsAssociated with theU.S. Department of Energyand Its Predecessors (1944 – 1974) Goodyear X-Files?

36. Unfortunately, however, the government's conduct with respect to some research performed in the past has left a legacy of distrust We did find evidence of some serious problems in the conduct …of human research today 1. Goodyear

37. We realize, however, that regulations and policies are no guarantee of ethical conduct It is essential that the research community come to increasingly value the ethics of research involving human subjects as central to the scientific enterprise 2. Goodyear

38. The revision of regulations that govern human research (and) professional ethics are necessary, but are not sufficient, means to needed reform. Of at least equal import is the development of a more common understanding among the public of research involving human subjects 3. Goodyear

39. Some of what is regrettable about the past happened… because we as citizens let it happen Let the lessons of history remind us all that the best safeguard for the future is an informed and active citizenry Goodyear 4.

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41. Part I Where are We Now? Goodyear

42. The Ongoing Problems • Role Confusion • Mission Creep • Administrivia • The Collapse of Scientific Integrity • Inadequate Resources • Increasing Complexity of Science • Patchwork Quilt • Accountabilty • Inflexible Goodyear

43. Gunsalus CK, Bruner EM, Burbules NC, Dash L, Finkin M, Goldberg JP, Greenough WT, Miller GA, Pratt MG Mission creep in the IRB world.Science. 2006 Jun 9;312(5779):1441. Goodyear

44. Mission Creep in the IRB World • System endangered by excessive paperwork • Overregulation and underprotection • Overwhelmed by procedures and documentation at expense of thoughtful consideration • ‘Ethics Police’ • Researchers equate ‘Human Protection’ • with frustrating delays, expensive paperwork Goodyear

45. Mission Creep in the IRB World • *Ethics a Collective Responsibility • IRBs not a substitute for Ethical Thinking and Behaviour • Should cultivate Ethical Culture • Researchers and IRBs need Support • local • central Goodyear

46. The Ongoing Problems • Role Confusion • The Collapse of Scientific Integrity • A crisis in trust • Inadequate Resources • Increasing Complexity of Science • Patchwork Quilt • Accountabilty • Inflexible Goodyear

47. Why is There a Crisis in Trust? Evidence Based Medicine Archie Cochrane (1909-1988) Goodyear

48. Evidence Based Medicine Goodyear

49. Why is There a Crisis in Trust? • Evidence Based Medicine • Replaced Opinion, Anecdotes and Experts • Based on Systematic Reviews of high quality evidence (RCTs) • Practice Based Guidelines • Graded by Strength of Evidence • So far, so good, BUT Goodyear

50. Why is There a Crisis in Trust? • Evidence Based Medicine A House of Cards Built on Sand? Goodyear