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.
What You Need to Know? 👇
What constitutes an unanticipated problem requiring IRB reporting in medical device trials?
An unanticipated adverse device effect (UADE) is any serious adverse effect, life-threatening problem, or death caused by a device that wasn’t previously identified in the investigational plan regarding nature, severity, or incidence degree.
How quickly must investigators report UADEs to sponsors and IRBs?
Investigators must submit UADE reports to both the sponsor and reviewing IRB as soon as possible, but no later than 10 working days after first learning of the event.
Can sponsors report directly to IRBs instead of investigators in multicenter studies?
Yes, investigators may rely on sponsor-prepared reports for IRB notification. If explicit agreements exist for direct sponsor-to-IRB reporting and investigators are copied, duplicate reporting isn’t required under FDA enforcement discretion.
What adverse events in drug trials require IRB reporting as unanticipated problems?
Single occurrences of serious, unexpected events strongly associated with drug exposure (like anaphylaxis), multiple occurrences showing increased rates through aggregate analysis, or events with unexpected severity/specificity compared to investigator’s brochure.
How do IDE regulations differ from IND regulations for adverse event reporting?
IDE regulations specifically define UADEs and require both investigators and sponsors to report to IRBs within 10 working days, while IND regulations focus on “unanticipated problems” with less specific timing requirements.
What information should accompany IRB reports of unanticipated problems?
Reports should include aggregate analyses supporting the determination, discussions of divergence from expected specificity/severity, explanations of rate increases compared to baseline, and rationale for any protocol or safety document modifications required.
What You Need to Do 👇
Recommended Actions
- Establish clear criteria for determining which AEs constitute unanticipated problems requiring IRB reporting
- Implement a process to analyze aggregate AE data before reporting to IRBs
- For multicenter studies, develop agreements between sponsors and investigators regarding AE reporting responsibilities
- Create templates for meaningful AE reports including analysis of significance
- Set up tracking systems for timing requirements, especially for device UADEs
- Review and update IRB reporting procedures to align with guidance recommendations
- Train investigators and study staff on proper AE assessment and reporting requirements
- Document agreements if sponsor will report directly to IRBs to avoid duplication
- Establish process for prompt sponsor evaluation of potential unanticipated problems
- 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