Sponsors Encouraged to Propose a Process
To comply with regulations, the pharmacovigilance team confirms whether or not the specific type of SAE is expected per the drug’s Reference Safety Information (RSI). Events which are not expected must be reported to regulatory agencies globally. Anticipated events that are not caused by study drug will never appear in RSI even if they occur frequently, and must be reported as expedited cases any time causality is unclear.
As single cases, these events are not informative for the safety profile of the drug. FDA has proposed in the current “Draft Guidance: Sponsor Responsibilities – Safety Reporting …” that expedited reporting of anticipated events only occur when the event is more frequent than predicted. Sponsors are encouraged to propose a process for making this prediction.
The Standard for an "Anticipated" Adverse Event
The standard for an 'anticipated' adverse event to be considered a Suspected Adverse Reaction may depend on the study design. Some sections in the Guidance seem to suggest that it is only applicable to studies with a comparator design; in others the assessment is described as relative to "expected background rates in the study population" or to "the rate of the same SAE in a similar population not exposed."
The Draft Guidance clarifies the distinction between anticipated events versus expected events. It explicitly states that "it is not expected that the list of anticipated events will cover all clinical events that may be background clinical events in the population...rather, such events should be carefully reviewed to determine if they meet the criteria for IND safety reporting when such a determination cannot be made based on a single case."