FAQ: Unanticipated Problems

  1. Do I have to report all internal (occurred at CHOP) SAE's to the IRB?

    Only SAEs that are unexpected and related. For example, hospitalization of children with Sickle Cell Disease for painful crisis is expected as would be death after cardiac surgery. These events do not have to be reported promptly because they do not represent unanticipated problems involving risks to subjects. Well-written protocols anticipate and delineate the likely serious events and list the ones that will not be reported as SAEs.

  2. Do I have to report every external SAE report that the sponsor sends me?

    The IRB does not want to see most of these reports; only events that are serious, unexpected and related to the research activity need to be reported. A single event, by itself, is usually insufficient to make a judgment about change in possible risks to subjects. If in the investigator's judgment, the event was expected as a result of the subject's age, existing condition, other treatment administered or another factor, there is no need to report the event. The report must be maintained in the study file.

  3. What about the external SAE follow-up reports?

    The IRB does not want to receive follow-up reports that add no additional information about possible risks to subjects.

  4. Why do sponsors send all of these reports if they aren't of any benefit?

    Sponsors believe that they are complying with the regulatory requirements. They are unwilling to classify SAEs as unrelated to the study drug or other intervention even when there are other plausible and much more likely explanations. From the IRB's perspective, a report is only useful if the sponsor believes that the event is of sufficient significance to modify the protocol, the consent form or the Investigators Brochure. Less than 1% of the SAE reports received by the IRB result in a change to the research. As a result, the IRB has issued a Memo clarifying its requirements for external SAE reports.

  5. My sponsor requires that I send all of the SAE reports to the IRB; what do I do?

    If the sponsor requires that they be sent, the IRB's memo should be provided to explain CHOP's policy. If these reports are sent to the IRB, an acknowledgement will be issued without review by the SAE subcommittee. This is not a productive use of the investigator's or the IRB's time. Hopefully, the new FDA Guidance on Adverse Event Reporting to IRBs will diminish the frequency of these reports.