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