6.3 IRB/IEC Composition and Independent Review
Key Takeaways
E6(R3) recommends at least five committee members with suitable collective expertise.
Only members independent of the investigator and sponsor should vote or provide an opinion.
Quorum is defined in the committee’s documented procedures and applicable requirements.
IRB/IEC Composition and Independent Review
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Payment Schedule & Accounting Verification: Review site payment logs and financial records against the IRB-approved Informed Consent Form (ICF) and protocol schedule. Verify that payments are prorated according to completed visits and that subjects who withdrew early received their earned prorated amounts.
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Vulnerable Population Enrollment Audits: Review source documentation for any enrolled vulnerable subjects. Ensure that pediatric assent forms match the participant's age at enrollment, that LAR documentation satisfies jurisdictional applicable requirements, and that no clinic or university subordinates were enrolled under coercive conditions.
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Withdrawal Documentation: Confirm that when a participant chooses to withdraw, the site honors their decision immediately, documents the withdrawal in medical source records without badgering the subject, and offers standard medical follow-up for safety without prejudice.
Institutional Review Boards & Independent Ethics Committees (IRB/IEC)
Note
In the regulatory architecture of clinical research, the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) serves as the primary independent entity responsible for prospective and ongoing human subject protections. Required ethics approval must precede trial participation. Protocol changes follow the applicable review process, with provisions for immediate hazards and permitted purely administrative/logistical changes under applicable requirements.
An Institutional Review Board (IRB) and an Independent Ethics Committee (IEC) share the identical core mandate: safeguarding the rights, safety, and well-being of trial subjects. For the Clinical Research Associate (CRA), verifying that valid, current, and unambiguous ethics committee approvals are maintained throughout the trial lifecycle is one of the most critical monitoring obligations.
Definition and Primary Responsibilities (ICH E6(R3))
Under ICH E6(R3), an IEC is defined as an independent body (a review board or a committee, institutional, regional, national, or supranational), constituted of medical professionals and non-medical members, whose responsibility it is to ensure the protection of the rights, safety, and well-being of human subjects involved in a trial and to provide public assurance of that protection.
According to ICH E6(R3), the IRB/IEC should review the following information as applicable when evaluating the trial:
- The clinical trial protocol and any amendments
- Written informed consent forms and consent form updates
- Subject recruitment procedures and advertisements
- Written information to be provided to subjects (e.g., patient diaries, instruction sheets)
- The Investigator's Brochure (IB) and available safety information
- Information about payments and compensation available to subjects
- The investigator's current curriculum vitae (CV) and other documentation evidencing qualifications
- Any other documents the IRB/IEC may require to fulfill its responsibilities
The committee must pay special attention to reviewing trials that involve vulnerable subjects (such as children, prisoners, pregnant women, or cognitively impaired individuals) to ensure adequate supplemental safeguards are established.
Membership Composition and Governance Rules
To ensure diverse perspectives, balanced ethical judgment, and protection against institutional bias, E6(R3) recommends a multidisciplinary composition and documented procedures:
Independent decisions and documented review procedures
Under E6(R3) Annex 1, membership should collectively cover scientific, medical and ethical expertise. ICH recommends at least five members, including a member outside medical sciences and one independent of the institution/site. Only members independent of the investigator and sponsor should vote or provide an opinion. Investigators and sponsor personnel may answer questions but should not take part in the decision.
The committee's documented procedures specify quorum. Do not substitute a universal national quorum formula for the international guideline. Decisions should identify the trial, documents reviewed, dates and outcome: approval, modifications required before approval, negative opinion, or suspension/termination. A request for modifications is not permission to start while the conditions remain unresolved.
Expedited review of minor changes follows applicable requirements and committee procedures. Country-specific exemption categories and limits on expedited disapproval are not a universal ICH examination rule. Verify the actual review determination rather than accepting an investigator's self-declared exemption.
Central IRB vs. Local / Institutional IRB
- Institutional (Local) IRB: Based within a specific university, academic medical center, or hospital. Local IRBs possess deep familiarity with institutional infrastructure, local clinical practice, community values, and state laws.
- Central IRB (Single IRB / sIRB): An independent or central review board that provides ethical oversight across multiple trial sites participating in a multi-center study under a formal reliance agreement (IRB authorization agreement). The sIRB model harmonizes review decisions, reduces redundant paperwork across sites, accelerates study activation, and provides centralized safety oversight.
Ongoing Oversight: Protocol Amendments and Continuing Review
IRB oversight does not conclude with initial study approval; it persists throughout the entire duration of the trial:
Official sources
Checked October 18, 2026: ICH E6(R3), Principles and Annex 1, WMA Declaration of Helsinki, 2024, ICH E11(R1).
An investigator is also a committee member reviewing their own trial. What role is appropriate?
Let the coordinator vote on the investigator’s behalf.
Sign the ethics approval before the meeting.
Provide requested information without participating in the decision or vote.
Vote after merely declaring the conflict.
Sections you finish are checked off in the contents.