Continuing Review of Clinical Investigations by Institutional Review Boards (IRBs)

What You Need to Know? 👇

What are the key criteria IRBs must evaluate during continuing review of clinical investigations?

IRBs must determine that all criteria under 21 CFR 56.111 remain satisfied, including that risks are minimized, risks are reasonable relative to benefits, subject selection is equitable, informed consent is appropriate, and adequate safety monitoring provisions exist.

How often must IRBs conduct continuing review of FDA-regulated clinical studies?

Continuing review must occur at intervals appropriate to the degree of risk, but not less than once per year. Higher-risk studies may require more frequent review based on factors like subject vulnerability and investigator experience.

When can expedited review procedures be used for continuing review instead of convened meetings?

Expedited review may be used when research meets specific categories (8 or 9), such as when enrollment is closed and only long-term follow-up remains, or when no subjects are enrolled and no additional risks identified.

What information should investigators provide to IRBs for continuing review submissions?

Investigators should submit progress reports including subject accrual numbers, protocol amendments, new risk information, unanticipated problems summary, subject withdrawals, complaints, current protocol/consent documents, and relevant safety data from sponsors or monitoring committees.

How should IRBs handle lapses in approval when continuing review doesn’t occur before expiration?

When IRB approval lapses, all research activities must stop and new enrollment cannot occur. However, continuing interventions for enrolled subjects may be appropriate when they hold prospect of direct benefit or when withholding poses increased risk.

What are IRBs’ reporting obligations when suspending or terminating study approval?

IRBs must promptly report suspensions or terminations to the clinical investigator, institutional officials, and FDA, including the reasons for action. The report should contain study identifiers, investigator information, and corrective action plans.

---

What You Need to Do 👇

Recommended Actions

1. Establish written procedures for conducting continuing review that include:
   • Process for determining review frequency
   • Required documentation and materials
   • Methods for tracking approval periods
   • Procedures for expedited review when applicable
2. Implement a system to:
   • Track study approval periods
   • Notify investigators of upcoming continuing review deadlines
   • Document all continuing review activities
   • Report suspensions/terminations to FDA
3. For each continuing review:
   • Verify all required materials are received
   • Assess any new risk information
   • Review study progress and enrollment
   • Evaluate informed consent updates
   • Document determinations in minutes
4. For multi-site studies:
   • Obtain study-wide information
   • Review data monitoring committee reports
   • Consider using cooperative review agreements
   • Coordinate with other reviewing IRBs
5. Maintain clear communication with:
   • Investigators regarding requirements and deadlines
   • Sponsors regarding significant findings or concerns
   • FDA for reportable events
   • Study subjects when necessary for safety

Key Considerations

Clinical testing

• IRB must conduct continuing review at intervals appropriate to degree of risk, but not less than once per year
• For multi-site studies, IRBs should obtain study-wide information and data monitoring committee reports
• IRB should review trial progress including enrollment rates and subject withdrawals
• IRB should assess whether risks to subjects remain minimized and reasonable

Safety

• IRB must determine that criteria for approval under 21 CFR 56.111 continue to be satisfied
• IRB should review any new safety information since last review
• IRB must promptly report suspensions or terminations of approval to FDA
• IRB should consider need to inform subjects about suspensions/terminations

Other considerations

• IRB must follow written procedures for conducting continuing review
• IRB must document continuing review activities in meeting minutes
• IRB approval lapses require stopping all research activities except where necessary for subject safety
• IRB should maintain fixed anniversary dates for continuing review when possible
• Expedited review may be used in certain circumstances as defined in the regulations

---

Relevant Guidances 🔗

• IRB Responsibilities for Reviewing Investigator Qualifications, Research Sites, and IND/IDE Requirements
• Informed Consent in Clinical Investigations: Requirements, Documentation, and Procedures
• Minutes of Institutional Review Board (IRB) Meetings - Content and Documentation Requirements
• Written Procedures for Institutional Review Boards (IRBs): Content and Organization
• IRB Registration Requirements and Procedures
• Categories of Research Eligible for Expedited IRB Review

Related references and norms 📂

• 21 CFR 56: Institutional Review Boards
• 21 CFR 50: Protection of Human Subjects
• 21 CFR 312: Investigational New Drug Application
• 21 CFR 812: Investigational Device Exemptions

---

Original guidance

• Continuing Review of Clinical Investigations by Institutional Review Boards (IRBs)
• HTML / PDF
• Issue date: 2012-02-27
• Last changed date: 2020-04-24
• Status: FINAL
• Official FDA topics: Medical Devices, Good Clinical Practice (GCP), Drugs, Biologics, Administrative / Procedural
• ReguVirta ID: abb37d1ec06d1792276078253a6e3dbd