UM investigators participating in multi-site trials and those using sponsored agents routinely receive a large volume of reports of external adverse events. The HHS Office of Human Research Protections (OHRP) has released guidance urging sponsors that individual adverse events should only be reported to investigators at all institutions when a determination has been made by the sponsor that the events meet the criteria for an unanticipated problem.
OHRP recommends that any distributed reports include: (1) a clear explanation of why the adverse event or series of adverse events has been determined to be an unanticipated problem; and (2) a description of any proposed protocol changes or other corrective actions to be taken by the investigators in response to the unanticipated problem.
Nonetheless, investigators may continue to receive reports that have not been assessed by the sponsor. When a UM investigator receives a report of an adverse event that is unexpected and related to an agent or procedure used in the UM study, the UM investigator should review the report and assess whether it meets the criteria above for an unanticipated problem. If it does, then it should be reported to the IRB. Note that many reports labeled ‘unexpected' will not meet the criteria above. It is possible for an external adverse event report from a different study, or use of the agent or procedure in a different population or route of administration to constitute an unanticipated problem for a UM study. The UM investigator should assess whether or not the information in the report indicates a problem that affects the rights and welfare of UM subjects. If in the judgment of the UM investigator it does, then the report should be submitted.
If the report does not contain sufficient information for the UM investigator to make the needed assessment AND the source of the report (e.g. the sponsor) did not state the event is an “unanticipated problem” or an “unanticipated adverse device effect”, then a submission to the IRB is not required. Both FDA and the HHS Office of Human Research Protections have stated their expectation that an individual external adverse event will rarely meet these criteria for an unanticipated problem.