Summary of FDA new draft guidance on safety reporting obligations for investigators

Most of the information about the safety of a drug prior to marketing comes from clinical trials. Adverse event reports from investigators are therefore critically important, given that it is the investigators who observe subjects responses to an investigational drug. 

The investigator must immediately report to the sponsor any SAEs, regardless of whether the investigator believes the SAEs are related to the drug. 

This requirement includes those:

• SAEs listed in the safety surveillance plan as anticipated to occur in the study population independent of drug exposure or 
• listed in the investigator brochure as predicted to occur with the drug. 
• study endpoints that are also SAEs (e.g., myocardial infarction, stroke, or death in trials evaluating drugs intended to treat cardiovascular conditions), which must be reported in accordance with the protocol not as SAE unless there is evidence suggesting a causal relationship between the drug and the event. In that case, the investigator must immediately report the event to the sponsor.
• Non-serious AEs must be reported according to the timetable for reporting specified in the protocol

Reporting timeline:

FDA recommends that this time frame for submitting such initial information also be specified in the protocol and anticipates that it will generally be no longer than 1 calendar day.

Causality Assessment:

Investigators are not required to determine whether an event is unexpected this determination is a sponsor’s responsibility.

Sponsor is responsible for causality assessment of the case than the individual investigator, hence except for most study endpoints, investigators must immediately report any SAE to the sponsor, whether or not the investigator considers the event to be drug related but investigator must also include in the report to the sponsor an assessment of whether there is a reasonable possibility that the drug caused the event.

Investigators are required to promptly report to the IRB – all unanticipated problems involving risk to human subjects or others, including adverse events that represent unanticipated problems.

For Medical device trials:

For device studies, investigators are required to submit a report of a UADE to the sponsor and the reviewing IRB as soon as possible, but in no event later than 10 working days after the investigator first learns of the effect.

Sponsors must immediately conduct an evaluation of a UADE and must report the results of the evaluation to FDA, all reviewing IRBs, and all participating investigators within 10 working days after the sponsor first receives notice of the effect.

Reference:

Investigator Responsibilities — Safety Reporting for Investigational Drugs and Devices