Safety Reporting Requirements for Clinical Investigators in IND and IDE Studies (DRAFT)
This guidance clarifies safety reporting requirements and responsibilities for clinical investigators conducting studies under Investigational New Drug Applications (INDs) and Investigational Device Exemptions (IDEs). It provides recommendations to help investigators identify and report safety information that requires prompt reporting to sponsors and Institutional Review Boards (IRBs).
This is a draft guidance. Not for implementation.
What You Need to Know? 👇
What are the key differences between adverse event reporting requirements for IND studies versus IDE studies?
For IND studies, investigators must immediately report all serious adverse events (SAEs) to sponsors regardless of causality, while for IDE studies, investigators report unanticipated adverse device effects (UADEs) to both sponsors and IRBs within 10 working days.
How quickly must investigators report serious adverse events to sponsors in drug studies?
Investigators must report SAEs “immediately” to sponsors, which FDA interprets as soon as feasible after recognizing an SAE. The guidance recommends this timeframe be specified in protocols, generally no longer than 1 calendar day.
When must investigators report safety information to IRBs for investigational drug studies?
Investigators must promptly report to IRBs all unanticipated problems involving risk to human subjects, including serious and unexpected adverse events that meet IND safety reporting criteria, plus other unanticipated problems like medication errors or privacy breaches.
What constitutes a “reasonable possibility” for drug causality assessment in adverse event reporting?
Reasonable possibility means there is evidence suggesting a causal relationship between the drug and adverse event. Factors include temporal relationship, biological plausibility, mechanism of action, nonclinical evidence, and dechallenge-rechallenge information.
Are study endpoints that are also serious adverse events reportable to sponsors?
Study endpoints that are SAEs must be reported according to protocol, not as SAEs to sponsors, unless there’s evidence suggesting a causal relationship between the drug and the event, in which case immediate reporting is required.
What safety information must be included in initial adverse event reports to sponsors?
Initial reports must include a specified subject, suspected drug (if any), reporting source, clinical description of the event, and an assessment of whether reasonable possibility exists that the drug caused the event.
What You Need to Do 👇
Recommended Actions
- Establish procedures to immediately report SAEs to sponsors (within 1 calendar day recommended)
- Implement a process to assess causality between adverse events and investigational products
- Create a system to track and report non-serious adverse events according to protocol timelines
- Develop procedures to identify and report unanticipated problems to IRBs
- For IDE studies:
- Set up UADE reporting process within 10 working days
- Prepare annual progress reports
- Document agreements with sponsors regarding IND safety report submissions to IRBs
- Review and maintain familiarity with IRB procedures for safety reporting
- Maintain records of all safety reports and communications with sponsors and IRBs
- Establish training for study team members on safety reporting requirements and procedures
- Implement quality control measures to ensure compliance with reporting timelines and requirements
Key Considerations
Clinical testing
- Investigators must immediately report any Serious Adverse Events (SAEs) to sponsors, regardless of causality assessment
- Study endpoints that are SAEs must be reported according to protocol unless there is evidence suggesting causal relationship with the drug
- For IDE studies, investigators must report Unanticipated Adverse Device Effects (UADEs) within 10 working days
Safety
- Investigators must assess causality between adverse events and investigational product
- Non-serious adverse events must be reported according to protocol timelines
- Investigators must report unanticipated problems involving risk to human subjects to IRBs
- For IDE studies, progress reports must be provided at least yearly
Other considerations
- Investigators must review all IND safety reports received from sponsors
- Many protocols specify that sponsors will submit IND safety reports to IRBs on investigators’ behalf
- Investigators should be familiar with IRB procedures for reporting unanticipated problems
Relevant Guidances đź”—
- Investigator Responsibilities - Protecting Human Subjects and Ensuring Data Integrity in Clinical Research
- IRB Responsibilities for Reviewing Investigator Qualifications, Research Sites, and IND/IDE Requirements
- IDE Clinical Investigation Decision Process and Requirements
Related references and norms đź“‚
- 21 CFR 312: Investigational New Drug Application
- 21 CFR 812: Investigational Device Exemptions
- 21 CFR 56: Institutional Review Boards