1. The Core of IRB Review William L. Freeman, MD, MPH, CIP [with material by Jeff Cohen & Moira Keane] FALCON Meeting, Las Vegas, NV December 6, 2008 Director of Tribal Community Health Programs, & Human Protections Administrator Northwest Indian College wfreeman@nwic.edu

2. Hy’shqe siam - Thank you, respected teachers Community members, & community IRB members –Sam Deloria, Lisa Preston, and others IRB members –Dr. Francine Romero, and others IRB staff –Helen McGough, Moira Keane, and others Researchers Participants Carolyn Robbins - Wife

3. Overview What is the core of IRB review in regulations 45 CFR 46 ? Why is knowing the core important? What is the rationale of the core? –sequence or order of components –relationship to The Belmont Report What are the details of the core?

4. Criteria for IRB approval of research 45 CFR 46.111 REQUIRED CRITERIA: 1.Risks to subjects are minimized - avoid unnecessary risks - use existing procedures 2. Risks are reasonable in relation to anticipated benefits 3. Selection of participants or subjects is equitable 4. Informed consent is sought from all potential participants – 46.116 5. Informed consent is documented – 46.117 and, when appropriate 6. data collection is monitored to ensure subject safety 7. privacy and confidentiality of subjects is protected ADDITIONAL SAFEGUARDS: for people vulnerable to coercion or undue influence [“children, prisoners, pregnant women, mentally disabled..., or economically or educationally disadvantaged”]

5. Importance of knowing and observing 46.111 as the “core” of what IRBs do OHRP in its on-site reviews of IRBs has been faulting IRBs that do not consider explicitly every component of 46.111 –IRB self-interest suggests pro-active compliance Most important, 46.111 expresses what is the core of the meaning and substance of human research protection

6. Sequence of components The sequence of 46.111 is: 1. Minimize risks 2. Benefit:Risk Ratio is reasonable 3. Equitable selection of subjects / participants 4. Seek informed consent 5. Document informed consent appropriately 6. Monitor research if appropriate 7. Protect privacy & maintain confidentiality if appropriate ALSO additional safeguards for vulnerable subjects / partipants Why are 1, 2, and 3, listed before 4 and 5?

7. Relationship of.111(a) to Belmont Report BENEFICENCEJUSTICE RESPECT FOR PERSONS Privacy & Confidentiality (7) Informed consent (4,5) Surrogate consent Assent Experimental Design (1) Benefit:Risk Analysis (2) Data Safety (6) Subject selection (3) Inclusion/exclusion Recruitment modified from J. Cooper, AAHRPP Additional safeguards for vulnerable populations [.111(b)] ALL THREE PRINCIPLES

8. 46.111(a)(1) Minimize risks [“potential harm X chance of happening”] IRB’s responsibilities: Identify risks –intrinsic to the research itself -- not the disease, for instance Determine if risks are minimized –severity & number of potential harms are minimized –chance of the harms happening are minimized If harms are not yet fully minimized, require changes in the protocol to achieve full minimization Examples of minimization [from regs] –“sound research design” and least risk –use “procedures already being performed” for diagnosis or treatment purposes What are examples you know of?

9. Identifying & assessing potential risks People – e.g., researchers – may not be fully objective about their own work, and often underestimate the potential risks of things they are quite familiar with People – e.g., researchers & IRBers – often do not know the potential risks to people with a different culture, lifestyle, or personal & community history If unfamiliar with research, IRB may ask expert consultant(s) to help review protocol. If unfamiliar with population, researchers & IRBs may do or ask for a community consultation

10. 46.111(a)(2) Reasonable Benefit:Risk IRB’s responsibilities: Identify potential benefits [to participant, to society] –not benefits of the context of the research, e.g., general care –usually most potential benefits are to society – knowledge gained “risks to subjects are reasonable in relation to anticipated benefits” –compare / “balance” potential benefits and potential risks –both risks & benefits are intrinsic to the research itself Do “not consider possible long-range effects of applying knowledge gained in the research” –e.g., “possible effects of the research on public policy” knowledge may lead to policies decreasing or increasing abortions –May consider longer-range group harms of the research itself e.g., stigmatization of entire groups – real harms to group members

11. Identifying & assessing potential benefits People – e.g., researchers – may not be fully objective about their own work, and often overestimate the potential benefits of things they are quite familiar with People – e.g., researchers & IRBers – often do not know the potential benefits to people with different culture, lifestyle, or personal & community history If unfamiliar with research, IRB may ask expert consultant(s) to help review protocol. If unfamiliar with population, researchers & IRBs may do or ask for a community consultation