Post

Adverse Event Reporting to IRBs Under FDA-Regulated Research

This guidance aims to assist clinical investigators, sponsors, and IRBs in interpreting requirements for reporting unanticipated problems and adverse events (AEs) to IRBs under 21 CFR parts 56, 312, and 812. It focuses on helping differentiate between adverse events that must be reported as unanticipated problems and those that do not require reporting.

  1. Establish clear criteria for determining which AEs constitute unanticipated problems requiring IRB reporting
  2. Implement a process to analyze aggregate AE data before reporting to IRBs
  3. For multicenter studies, develop agreements between sponsors and investigators regarding AE reporting responsibilities
  4. Create templates for meaningful AE reports including analysis of significance
  5. Set up tracking systems for timing requirements, especially for device UADEs
  6. Review and update IRB reporting procedures to align with guidance recommendations
  7. Train investigators and study staff on proper AE assessment and reporting requirements
  8. Document agreements if sponsor will report directly to IRBs to avoid duplication
  9. Establish process for prompt sponsor evaluation of potential unanticipated problems
  10. Maintain records of all AE assessments and reporting decisions

Key Considerations

Clinical testing

  • Only specific AEs should be reported as unanticipated problems:
    • Single occurrence of serious, unexpected events strongly associated with drug exposure
    • Single/small number of serious, unexpected events uncommon in study population
    • Multiple occurrences showing higher rates in treatment vs control groups
    • Events with unexpected severity/specificity compared to investigator’s brochure
    • Events with clinically significant increase in expected occurrence rate
    • Safety findings requiring protocol modifications

Safety

  • For multicenter studies, sponsors should assess and analyze AE information
  • Investigators may rely on sponsor’s assessment for reporting to IRB
  • For device studies, UADEs must be reported within 10 working days
  • Sponsors must evaluate UADEs and report to FDA, IRBs and investigators within 10 working days

Other considerations

  • IRBs should receive meaningful AE information with proper analysis
  • Sponsors should provide analysis of event significance and previous similar events
  • Agreement can be made for sponsors to report directly to IRBs to avoid duplicate reporting

Original guidance

  • Adverse Event Reporting to IRBs Under FDA-Regulated Research
  • HTML / PDF
  • Issue date: 2009-01-14
  • Last changed date: 2020-05-06
  • Status: FINAL
  • Official FDA topics: Medical Devices, Good Clinical Practice (GCP), Drugs, Biologics, Administrative / Procedural
  • ReguVirta summary file ID: b769d17bbc624293c5f811b4a5b59cbd
This post is licensed under CC BY 4.0 by the author.