IRB Determinations
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AAHRPP Site Visit Results
• Site visitors observed a real commitment to
human subject protections
• Investigator and research staff opinions of
the IRB and OPHS are markedly positive
• Identified 8 areas of concern
o
All were addressed in a response sent to
AAHRPP January 3, 2014
• AAHRPP Accreditation Council meets on
March 17, 2014
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Areas of Concern
1. Technical resources for IRBear platform
2. Quality improvement activities to assess HRPP
compliance and quality, efficiency, and effectiveness
3. IRB determinations of serious and/or continuing
noncompliance; reports to regulatory agencies
4. Conflicts of interest – Organizational and individual
5. Control of investigational medical devices
6. Clinical trials agreements (contracts) with sponsors
7. Qualifications and knowledge of IRB chair, vice chairs, and
members -- Evaluations and feedback
8. Contingent approvals and deferrals of protocols
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IRB Approval
The IRB must determine that all of the approval criteria are
satisfied in accordance with the Common Rule and FDA regulations:
1. Risks are minimized
2. Risks are reasonable in relation to anticipated benefits and the
importance of the knowledge to be gained
3. Selection of subjects is equitable
4. Informed consent will be sought
5. Informed consent will be appropriately documented
6. Adequate provision for monitoring the data collected to
ensure subject safety
7. Adequate provisions to protect subject privacy and maintain
confidentiality of the data
8. Additional safeguards for subjects who are vulnerable to
coercion or undue influence
and relevant subparts (children, pregnant women, prisoners)
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IRB Approval of Research with Conditions
“Contingent Approval”
The IRB requests that the investigator either:
• Make specified changes to the research protocol or
consent documents;
• Confirm specific assumptions or understandings on the
part of the IRB regarding how the research will be
conducted; or
• Submit additional documents such that, based on the
assumption that the conditions are satisfied, the IRB is
able to make all of the determinations required for
approval.
The IRB chair or her qualified designee may determine by
expedited review that the investigator’s response satisfies the
IRB’s conditions, i.e., further review by the convened IRB is
unnecessary.
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IRB Deferral
The IRB cannot make one or more of the determinations
required for approval under the regulations.
• Information in the research protocol is insufficient for the
IRB to determine if one or more approval criteria have
been adequately met; and
• The IRB is unable to specify changes to the research
protocol that would allow the IRB to make the required
determinations
The IRB requires that the investigator either:
• Make changes to the protocol or consent documents; or
• Submit clarifications or additional documents
The convened IRB must review and approve the revised
research project.
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Contingent Approval or Deferral?
What’s your determination?
1. The convened IRB requires the investigator to do the
following:
• Re-locate in the informed consent document the
statement ,“You will receive $500 for participating in
this study,” from the Benefits section of the form to
a separate section titled Compensation.
Should the IRB “approve with contingencies” or
“defer” final review?
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Contingent Approval or Deferral?
2. The convened IRB requires the investigator to do the
following:
• Provide a justification for using a placebo and
withholding currently available treatment for a serious
medical condition for subjects assigned to the control
group.
Should the IRB “approve with contingencies” or “defer”
final review?
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Contingent Approval or Deferral?
3. The convened IRB requires the investigator to do the
following:
• Clarify whether individuals who have taken aspirin
within 14 days prior to enrollment will be excluded
from the study because of concerns about the risks
of bleeding.
Should the IRB “approve with contingencies” or
“defer” final review?
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Contingent Approval or Deferral?
4. The convened IRB requires the investigator to do the
following:
• Add “a history of aspirin use in the past 14 days” to
the exclusion criteria for subject enrollment in the
research protocol.
Should the IRB “approve with contingencies” or
“defer” final review?
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Serious and Continuing Noncompliance
Noncompliance – Failure to abide by the regulations,
institutional policies and procedures, or IRB
requirements or determinations.
Serious noncompliance – Noncompliance that may
impact subject safety, increase risks to subjects, affect
integrity of the data, violate a subject’s rights or welfare,
or affect subjects’ willingness to participate in the study.
Continuing noncompliance – Series of noncompliant
actions or omissions taken by an investigator or study
staff, in reasonably close proximity, which indicates the
need for evaluation of the methods and systems used to
protect human subjects.
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Examples of Serious Noncompliance
• Failure to notify the IRB of changes in approved
procedures
• Continuation of research activities following
protocol expiration
• Failure to adequately protect participant
privacy and confidentiality of data
• Failure to conduct research according to the
IRB approved protocol
• Failure to follow proper accountability
procedures for an investigational drug
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IRB Review of Investigator Noncompliance
• The fully convened IRB must make a formal
determination whether an event constitutes
serious and/or continuing noncompliance
• A motion should be made and a vote taken on
the determination
• The meeting minutes should include the
motion and outcome of the vote.
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Mandatory Reporting to External Agencies
• Serious or continuing noncompliance must be
reported to the appropriate Federal
Department or Agency head if the research is
federally funded or involves FDA-regulated
products.
• Other events that must be reported are:
o Unanticipated problems that involve risks
to subjects or others
o Suspension or termination of IRB approval
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Guidance for IRB Motions:
Noncompliance Determinations
• Acknowledge or Defer (see handout)
• If a final determination of serious and/or
continuing noncompliance is made, the IRB
must specify whether the noncompliance
requires reporting to an external agency such
as the study sponsor, OHRP, or the FDA
• The IRB also may defer its final determination
and require an additional response or action
on the part of the investigator to resolve the
issue
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