The investigator must report adverse events to the:
The sponsor. In FDA-regulated clinical research, the investigator must promptly report adverse events to the study sponsor, and must report unanticipated problems involving risks to subjects to the IRB. Among Subject/Sponsor/FDA/IRB, the sponsor is the correct answer.
The answer
The correct choice is the sponsor. In FDA-regulated clinical trials, the investigator sits at the point where the data are actually collected, but the investigator is not the party who talks to the FDA about individual adverse events. That job belongs to the sponsor. The regulatory chain is deliberate: the investigator reports adverse events to the sponsor, the sponsor evaluates them across every site in the study, and the sponsor then reports qualifying serious and unexpected events to the FDA. This mirrors the language of 21 CFR 312.64, which requires an investigator to report adverse effects to the sponsor.
The investigator also has a parallel duty to the IRB, but that duty is narrower and triggered differently. The investigator reports unanticipated problems involving risks to subjects or others to the IRB, not every routine adverse event. So the honest, complete picture is: adverse events flow to the sponsor, unanticipated problems flow to the IRB, and the FDA is reached through the sponsor.
Why the other options are wrong
The subject. Subjects are the people being protected, not a reporting authority. Telling the participant about a side effect is good clinical care, but it does not satisfy any regulatory reporting obligation and it does nothing to trigger review or trial-wide safety analysis.
The FDA. The investigator does not report individual adverse events directly to the FDA. Only the sponsor sees the full multi-site dataset, so only the sponsor can judge whether an event is serious, unexpected, and drug-related enough to warrant an IND safety report. If every investigator flooded the FDA independently, the agency would receive uncontextualized noise. The sponsor is the required filter.
The IRB. This is the tempting distractor because the IRB does receive reports from the investigator. But what the IRB receives is unanticipated problems, not the general stream of adverse events. Choosing the IRB confuses the two categories. On CITI-style exams, the specific stem 'report adverse events to the' maps to the sponsor.
The bigger picture: the reporting chain and its timelines
Think of safety reporting as a relay. The investigator observes an adverse event and reports it to the sponsor, promptly, following the protocol's definitions of serious and expected. The sponsor aggregates events from all sites, and when an event is serious, unexpected, and reasonably related to the drug, the sponsor files an IND safety report with the FDA — within 15 calendar days, or within 7 for fatal or life-threatening unexpected events. Separately, the investigator notifies the IRB of unanticipated problems, typically within the timeframe the IRB sets (often promptly, within days for serious events).
An unanticipated problem is an event that is unexpected given the protocol and subject population, related or possibly related to participation, and suggests a greater risk than previously known. Not every adverse event meets that bar, which is exactly why the sponsor — not the IRB or FDA — is the investigator's first stop for adverse events.
- 1
Investigator observes adverse event
At the study site, the investigator records the event and assesses seriousness, expectedness, and relatedness per the protocol.
- 2
Investigator reports to the Sponsor
Adverse events are reported promptly to the sponsor (21 CFR 312.64). The sponsor aggregates data across all sites.
- 3
Sponsor reports to the FDA
Serious, unexpected, drug-related events become IND safety reports filed with the FDA within 15 days (7 days if fatal/life-threatening and unexpected).
- 4
Investigator reports unanticipated problems to the IRB
Separately, events that are unexpected, related, and indicate greater risk go to the IRB as unanticipated problems, promptly.
Frequently asked
Who does an investigator report adverse events to?
To the study sponsor. Under 21 CFR 312.64, the investigator promptly reports adverse events to the sponsor, who then aggregates safety data across all sites and reports qualifying events to the FDA.
What is the difference between the sponsor and the IRB?
The sponsor funds and runs the trial and handles FDA safety reporting; it is the investigator's contact for adverse events. The IRB is an independent ethics board that protects subjects and receives reports of unanticipated problems, not routine adverse events.
When must adverse events be reported to the IRB?
The IRB receives reports of unanticipated problems involving risks to subjects or others, generally promptly and within the timeframe the IRB specifies. Routine, expected adverse events usually go to the sponsor, not the IRB.
What is an unanticipated problem in research?
It is an event or outcome that is unexpected given the protocol and population, at least possibly related to study participation, and suggests subjects face a greater risk than was previously known. All three criteria must be met.