1. Human Research Protection Program 101 July 19-20, 2007 Milwaukee, WI

2. Consideration of Risks and Benefits at Initial Review Presented by: John C. Hudson MS Presented by: John C. Hudson MS

3. A story of two investigators…

4. Consideration of Risks and Benefits Fulfill regulatory requirements set forth in Common Rule (VA: 38 CFR 16.111; DHHS: 45 CFR 46.111) And as described in 1200.5 (Para.7: IRB Responsibilities and Authority) More than just regs: CONSIDERATION OF RISKS TO SUBJECTS AND POSSIBLE BENEFITS OF RESULTS IS CENTRAL TO THE REVIEW OF HUMAN SUBJECTS RESEARCH

5. Why Consider Risks & Benefits  The main charge of an IRB is their responsibility to protect the RIGHTS and WELFARE of human subjects in research  Practical aspect: in addition to the ethical/moral responsibilities there is a legal aspect  NOT protecting the rights and welfare of human subjects invites bad press, lawsuit, even the shutting down of an institution  Point to consider: Weighing of Risks and Benefits is WHY we have IRB review

6. BUT WHAT DO WE MEAN BY THE RISKS AND BENEFITS OF HUMAN SUBJECTS RESEARCH?

7. Risk: What is it?  The probability of harm or injury occurring as a result of participation in a research study  Prediction of some future occurrence of harm  Consideration of probabilities: what has happened before?

8. Risks: Types of Risk  Physical  Psychological  Social  Economic  Legal

9. Risks: Types of Risk  Physical  Psychological Emotional Loss of dignity Embarrassment  Social Loss of confidentiality Loss of social status Threat to privacy Harassment  Economic Threat to employment Insurability and insurance costs

10. Social and Psychological Risks are REAL Risks  Social and Psychological risks are TIME and SITUATION specific Pregnancy in minors v. in adults Known Alzheimer’s at less risk than some one not yet identified Offspring at risk if genetically-linked  Social and Psychological risks are subjective

11. Benefit: What is it?  A valued or desired outcome; an advantage  The probability of hoped for benefits

12. Benefit: Hoped for benefits?  Two Major Categories: Benefits to participants Benefits to society  Research may have: Therapeutic intent (intend to affect a medical condition or understand that condition) Nontherapeutic (increase knowledge; basic research)

13. Risk/Benefit Analysis  Risks and benefits are not parallel ideas Risks: often individual, immediate, measurable Benefit: often elusive, future, potential  Need to maintain a favorable balance

14. What the Codes and Regulations Say  The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment (Nuremberg 6)  Biomedical research involving human subjects cannot legitimately be carried out unless the importance of the objective is in proportion to the inherent risk to the subject (Helsinki I.4)  Risks to the subjects [must be] reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result (45 CFR 46.111a)

15. Belmont Report: it’s all about risk Three basic ethical principles in the Belmont Report guide the conduct of research with human subjects: 1.Respect for Persons: Includes honoring the privacy of individuals and maintaining their confidentiality. 2.Beneficence: Should maximize potential benefits to subjects; minimize potential risks. If any risks may result from participation then there must be benefits: to the subject, to humanity, or to society in general. 3.Justice: Subjects selected fairly and that the risks and benefits of research are distributed equitably. Precautions to not select subjects simply because of the subjects’ easy availability, their compromised position, or because of racial, sexual, economic, or cultural biases in society.

16. Identifying risks and benefits?  NO ONE can be objective about their own work  Underestimate risks  Overestimate benefits  IRB acts as objective referee

17. The Role of the IRB  Review potential risks, discomforts, hazards, or inconveniences of protocol Probability, magnitude, duration, reversibility of risks  Separate risks of research from standard of care risks e.g. Risks of surgery already scheduled  Give special consideration to risks for research involving vulnerable populations Children, mentally impaired, prisoners, others

18. The Role of the IRB (cont.)  Consider hoped for benefits Benefits can take the form of therapy, education, information, resources or empowerment Benefits can be directed at participants, their community, society, medical knowledge, medical technology  Consider if risks reasonable in relation to possible benefits Balancing potential risks to participant/others against possible benefits to participant/society

19. The IRB: Balancing potential risks  No benefit requires no risk to participants  Little benefit requires low risk  High risk studies require showing of significant benefit to participants  To determine balance consider type of risk Physical, psychological, social, economic

20. Special Categories of Risk

21. Minimal Risk Risk level is determined by the IRB A risk is minimal where the probability and magnitude of harm or discomfort anticipated in the proposed research are not greater, in and of themselves, than those ordinarily encountered in daily life or during the performance of routine or psychological examinations or tests. (45 CFR 46.102i)  For research to be exempt from IRB review it MUST be minimal risk

22. Significant/Non-significant Risk  FDA Device studies rules: Significant risk is when there is a potential serious risk to health of subject and the device is An implant Used in supporting/sustaining life Important to diagnose, mitigate, or treat disease or prevent impairment of human health  Otherwise: Non-significant

23. Worth keeping in mind: IRB review of research is NOT an adversarial enterprise 1.With proper review, consideration of regulations, and inclusion of safeguards human subjects research relatively safe to participants 2.Human subjects research can be beneficial to improving health care at large and/or basic knowledge

24. All share the same mission The IRB should be working with investigators as part of a cooperative “Research Enterprise” whose goal is to advance society and its health Consideration of Risks and Benefits is part of the overall review of Hum Sub research focusing on subject safety and welfare

25. Consideration of Risks and Benefits