Research Ethics Need for Human Research Subjects Protections

1. Research EthicsNeed for Human Research Subjects Protections Melody Lin, Ph.D. Deputy Director, Office for Human Research Protections Director, International Activities November 2008

2. Objectives • Background • Progress • Public Opinions • Protection • Why We Can Not Fail • Research Suspension & Lesson learned

3. Facts of Historical Evolution • Technology – drugs, biologics, devices • Techniques – transplantation, arthroscopy • Regimens – chemotherapy, diabetes treatment

4. Science Brought to us…… • Better health care • Higher quality of life • Longer life span

5. All these come from….. Researchers’ Innovations + Participants’ Devotion We benefit today from prior research subjects

6. New Idea Research Subjects New Knowledge Better Health Care Improved Quality of Life

7. Public Role in Research • Not interested • Does not understand

8. What do People Think About Participation in Clinical Trial • Tested in humans 83% (believe it is essential) • Not as guinea pigs 24% • Do not admire participants 34% • Gambling with their health 79% Source: Harris Interactive Poll, Feb. 2002 (2031 adults)

9. What do People Think About Participation in Clinical Trial • Unaware of the clinical trial option 85% • For those aware of the option 75% (turn down because suspicious of being a guinea pig) • Excellent cure in participation 97% Source: Harris Interactive Survey, 2001 (6000 cancer patient)

10. Belief in the Need • Important for Economy 94% • Great value for Public Health 68% Source: Research America, 2004 (1000 adults)

11. Belief in the Needof Clinical Trials (CT) • Important 90% • Important for Public Health 60% Source: Western Europe Survey, 2004 (225 Europeans)

12. Public Distrust of (CT) • Very Safe 14% • Somewhat safe 48% Source: Center for information & study on clinical research participation, 2006 (1000 US adults)

13. Public Distrust • Do not trust FDA 27% • FDA is effective (ensure safety) 31% Source: Harris Interactive

14. Public Distrust • Officials in regulatory oversight and drug development 46% • Pharmaceutical & biotechnology co. 42% Source: Harris Interactive

15. Public Distrust • Sponsors to inform public quickly on safety concerns of drug 45% Source: Kaiser Family Foundation, Jan. 2008

16. Public Distrust • Use as guinea pigs without consent White 49% Minority 73% • Doctor will expose them to unnecessary risk in clinical trials White 22% minority 25% Source: Braunstein , Medicine, 87 (1) 2008

17. Public Distrust • Doctors and research team primarily are motivated to recruit s.s. for money & selfish interest 25% American Source: Harris Interactive, 2002

18. Survey in 6 European Countries Unaware of protections 71% • DOH • IRB • I.C. • Government Regulations Source: International Will & Why (BBK Healthcare), 2004 (2300 adults)

19. Survey in United States • Unaware of protections 81% • Federal regulations • International guidelines Source: BBK Healthcare, 2001 (5348) adults

20. After Explanation of Protections Americans & Europeans • More likely to participate 40% • Would participate again 80%

21. Impact of Education • Recruitment depends on educating public about protections • Education impact • More willing to participate • More actual participation

22. What Does “Protection” Mean? • Respect for dignity • Value self and other • Shared responsibilities

23. What Does “Protection” Mean?(2) • Safeguard physical, psychological and social well being • Preserve individual rights to privacy, self determination and safety

24. Who protects Human Subjects? • OHRP • FDA

25. Office of Human Research Protections (OHRP)45 CFR 46

26. Food and Drug Administration Regulations: • Informed Consent - 21 CFR 50 • IRB - 21 CFR 56

27. Health and Human Services (HHS) vs. FDA Regulations (1) Basic requirements for IRBs and for Informed Consent are congruent

28. Health and Human Services (HHS) vs. FDA Regulations (2) • Differences are in applicability • HHS regulations: • Based on federal funding of research • Apply to biomedical and behavioral research • FDA regulations: • Based on use of FDA regulated product: drugs, devices, or biologics • Apply to clinical investigations

29. HHS vs. FDA Regulations HHS FDA IRB DHHS FDA

30. Research Enterprise Government Funding Bodies Dept of Health & Human Services Dept of Defense Dept of Veterans Affairs Dept of Homeland Security Regulatory Bodies Food & Drug Administration Office for Human Research Protection Private Funding Bodies Industry Private Foundations Research Participants Research Settings Contract/ Clinical Research Organizations Site Management Organizations Others The Public Auditing Entities Education Entities Patient Recruitment Firms Data Maintenance Firms Insurance Companies Independent IRBs Accrediting & Certifying Bodies

31. Why We Can Not Fail

32. Government scrutiny of human subjects protection • 1994 Advisory Committee on Human Radiation Experiments - informed consent concerns • 1996 General Accounting Office - heavy workloads, lack of preparedness of IRB, limited resources • 1998 Office of Inspector General, DHHS - IRBs overwhelmed; issued a warning signal • 2001 NBAC report on oversight system • 2001 IOM reports on human research protection 2002 programs

33. Suspensions of U.S. federally supported research • 1998 Rush Presbyterian St. Luke’s Medical Center • 1999 Greater Los Angeles Health Care System, West Los Angeles VAMC • 1999 Duke University Medical Center • 1999 University of Illinois, Chicago

34. Suspensions of U.S. federally supported research • 2000 Virginia Commonwealth University • 2001 University of Oklahoma Health Sciences Center • 2001 Johns Hopkins Medical Institutions

35. Media Attention • Newspapers • Magazines • Television • Radio • Trade Publications

36. Legal Actions • Scheer v. Burke, et al • Hamlet v. Fradin, et al • Steubing v. Kornak, et al • Quinn v. Abiomed, et al • Gelsinger v. University of Pennsylvania • Robertson, et al v. McGee, et al • Wright v. Fred Hutchinson Cancer Research Center, et al • Berman v. Fred Hutchinson Cancer Research Center, et al • Pamel H. Lett and Jim Lett v. The Ohio State University, et al • Aderman v. Trustees of the University of Pennsylvania • Beth Wade v. Oregon Health and Science University • Guckin v. Nagle, et al • D’gosto, Marion v. FHCRC

37. Protections are questioned • Increased government scrutiny and need for a response • Diminished public trust in research • Enrollment issues • Federal support for research

38. Social contract is at risk • Research community must live up to its obligation to conduct research with integrity and ethically • Research community must demonstrate its commitment to ethically sound research

39. Research Suspension&Lessons Learned

40. JHUResearch suspension

41. Healthy volunteer in a • asthma study • Died on July 2, 2001 • inhalation of a non- • approved drug • Lungs were destroyed • Employed at Johns • Hopkins University Ellen Roche 24 years old

42. OHRP Site Visit Plan July 16 & 17, 2001

43. OHRP Site Visit July 16 – 18, 2001

44. Site Visit Team • 5 OHRP Staff • 3 Consultants • 1 FDA Representative

45. Suspension of Assurance July 19, 2001

46. OHRP Findings • IRB not given published toxicity information on the product • The drug was not approved for human use, no IND • Quality of the drug uncertain • IRB inappropriately used expedited review

47. OHRP Findings • IRB did not approve protocol changes • Informed consent: • procedures inadequately described • failed to disclose drug status • inadequately disclose risks

48. OHRP Findings • Inadequate IRB information for continuing review • Inappropriate IRB minutes and backlog • Some IRB members had conflicts of interest

49. OHRP Findings • IRB overloaded, lacking staff • IRB members in need of education

50. Actions Taken OHRP • Suspended assurance, suspending all federally-sponsored research • Required re-evaluation of protocols • Requested a plan to restructure the system for protecting human subjects • Required plan to educate IRB members, staff and researchers