1. Office for Human Research Protections (OHRP) Department of Health and Human Services Office of Public Health and Science Director: Greg Koski, Ph.D. M.D.

2. Office for Human Research Protections (OHRP) Dr. Jeffrey Cohen Associate Director for Education Phone: (301) 402-5552 Fax: (301) 402-2071 E-mail: cohenj@od.nih.gov

3. OHRP Electronic Access n E-mail: ohrp@osophs.dhhs.gov n Web Site: http://ohrp.osophs.dhhs.gov

4. Ethical Principles

5. The Belmont Report 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 Research April 18, 1979

6. The Belmont Report n Respect for Persons –Individual autonomy –Protection of individuals with reduced autonomy n Beneficence –Maximize benefits and minimize harms n Justice –Equitable distribution of research costs and benefits Basic Ethical Principals:

7. Federal Regulations

8. Federal Regulations and Policy 45 CFR 46 - Basic DHHS Policy for Protection of Human Research Subjects Originally adopted May, 1974, Revised January 13, 1981, Revised June 18, 1991 Additional protections for vulnerable populations in Subparts B-D Federal Policy for the Protection of Human Subjects - “The Common Rule” June 18, 1991 Departments of Agriculture, Energy, Commerce, HUD, Justice, Defense, Education, Veterans Affairs, Transportation, and HHS. NSF, NASA, EPA, AID, Social Security Administration, CIA, and the Consumer Product Safety Commission.

9. Federal Regulations and Policy Additional Protections Included in 45 CFR 46: n Subpart B - Additional DHHS Protections Pertaining to Research, Development, and Related Activities Involving Fetuses, Pregnant Women, and Human In Vitro Fertilization n Subpart C - Additional DHHS Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects n Subpart D - Additional DHHS Protections for Children Involved as Subjects in Research

10. Definitions n Research - a systematic investigation designed to develop or contribute to generalizable knowledge. n Human Subject - a living individual about whom an investigator conducting research obtains –data through intervention or interaction with the individual, or –identifiable private information

11. Basic Protections The regulations contain three basic protections for human subjects: n Institutional Assurances n IRB Review n Informed Consent

12. Institutional Assurances

13. Institutional Responsibilities n Institutions bear full responsibility for all research involving human subjects covered under their Assurance n All requirements of 45 CFR 46 must be met for all federally-sponsored research n OHRP strongly encourages institutions to embrace the HHS regulations regardless of sponsorship, and to commit to this standard in their Assurance.

14. Institutional Responsibilities n Designate one or more Institutional Review Boards (IRBs) to review and approve all nonexempt research covered by an the Assurance n Provide sufficient space and staff to support the IRB’s review and record-keeping duties n Establish education and oversight mechanism

15. Institutional Review Board Review

16. IRB Decision Matrix BENEFICENCEJUSTICE RESPECT FOR PERSONS Protection of subjects (especially vulnerable populations) Informed consent Surrogate consent Assent Risk/Benefit Analysis Experimental Design Qualifications of PI Subject selection Inclusion/exclusion Recruitment J. Cooper, Albany Medical Center

17. Social & Psychological Risk Social & Psychological risks are real risks

18. Social & Psychological Risk n Examples –Emotional Distress –Psychological Trauma –Invasion of Privacy –Embarrassment –Loss of Social Status –Loss of Employment

19. Social & Psychological Risk n Risks are TIME and SITUATION specific n Psychological & social risks are very subjective n There is little or no empirical data on the likelihood of risk in behavioral or social research

20. Social & Psychological Risk n In some cases simply participating in the research can cause social or psychological harm –psychological reaction to situation –psychological reaction to questions

21. Social & Psychological Risk n Primary source of social risk results from a breach of confidentiality. –Confidentiality and anonymity are not the same –Names are not the only identifiers –Subjects’ participation in the research may need to be kept confidential as well as their data

22. Informed Consent Beyond the Consent Form

23. The Consent Process Informed consent is not a single event or just a form to be signed -- rather, it is an educational process that takes place between the investigator and the prospective subject. The basic elements of the consent process include: n full disclosure of the nature of the research and the subject's participation, n adequate comprehension on the part of the potential subjects, and n the subject's voluntary choice to participate.

24. Consent vs. Consent Forms n The consent form is merely the documentation of informed consent and does not, in and of itself, constitute informed consent. n Informed consent is a process which is documented by a signed consent form. n The fact that a subject signed a consent form does not mean that he/she understood what was being agreed to or truly gave their voluntary consent.

25. Comprehension n Informed consent is not valid unless the consentor understands the information that has been provided. n It is the responsibility of the investigator to do what he/she can to enhance each prospective subject's comprehension of the information.

26. Tampa Tribune 3/11/00 TAMPA - A lawsuit accusing USF doctors of experimenting on pregnant women without their consent is settled for $3.8 million…. The experiment wasn't considered risky and no adverse effects were documented, plaintiffs in the suit agree. However, the failure to inform … as many as 3,000... pregnant women of various experiments conducted between 1986 and 1990 has cost Tampa General Hospital, USF and the state $3.8 million.

27. Compliance Concerns OPRR Compliance Activities: Common Findings and Guidance http://ohrp.osophs.dhhs.gov/ references/findings.pdf

28. Does the institution support and respect the IRB and its mission? Is there a “culture of compliance”? Are IRB members and investigators knowledgeable about regulatory requirements? Is there adequate documentation of IRB findings and actions?

29. OHRP/FDA/VA Workshops n "Current Human Research Issues & Solutions: Regulatory Overview & Investigator/Institutional Sponsor Partnerships ", May 10-11, 2001, Newark, NJ. n "Current Human Research Issues & Solutions: Regulatory Overview & Hot Topics", June 21-22, 2001, Charleston, SC n "Current Human Research Issues & Solutions: Regulatory Overview & Social/Behavioral Research" July 16-17, 2001, Los Angeles, CA. n "Current Human Research Issues & Solutions: Regulatory Overview & TBD", September 20-21, 2001, Minneapolis, MN.