QRTI Newsline --- Wednesday September 8, 2010

FDA Guidance for Clinical Investigators, Sponsors and IRBs Regarding Adverse Event Reporting

By Phyllis B. Kent

FDA has issued a Draft "Guidance for Clinical Investigators, Sponsors and IRBs Adverse Event Reporting- Improving Human Subject Protection." When this guideline is finalized, it will represent FDA's current thinking regarding Adverse Event Reporting. FDA has issued this guidance in response to the IRB community reports of large volume of individual adverse experience reports inhibiting their ability to protect human subjects. It provides help interpreting the requirements for reporting unanticipated problems to the IRB and provides recommendations for improving the quality of the information provided to IRBs.

FDA has made specific recommendations to address the IRB's concerns. The guideline provides an explanation of how to determine if an Adverse Event is an unanticipated problem. FDA specifically states that an individual report should be evaluated with respect to the relevance and significance to the study and other adverse events before concluding that it is an unanticipated problem, even if it is not in the investigational brochure. Reports of unanticipated problems that are judged to be reportable to the IRB, should contain information to enable the IRB to determine how it might impact the safety of human subjects. An explanation of why the event is considered unanticipated and why it is a problem should be included in the report.

FDA indicates that only the following adverse experiences should be reported to the IRB as "unanticipated problems".

• "Any adverse experience that, even without detailed analysis, represents a serious unexpected adverse event that is rare in the absence of drug exposure (such as agranulocytosis, hepatic necrosis, Stevens-Johnson syndrome)."
  
• "A series of adverse events that, on analysis, is both unanticipated and a problem for the study. There would be a determination that the series of adverse events represents a signal that the adverse events were not just isolated occurrences and were significant to the rights and welfare of subjects. We recommend that a summary and analyses supporting the conclusion accompany the report."
  
• "An adverse event that is described or addressed in the investigator's brochure, protocol, or informed consent documents, or expected to occur in study subjects at an anticipated rate (e.g., expected progression of disease, occurrence of events consistent with background rate in subject population), but that occurs at a greater frequency or at greater severity than expected. We recommend that a discussion of the divergence from expected rates accompany the report."
  
• "Any other adverse event that would cause the sponsor to modify the investigator's brochure, study protocol, or informed consent documents, or would prompt other action by the IRB to assure the protection of human subjects. We recommend that an explanation of the conclusion accompany the report."

To review the complete guideline, please visit QRTI's Resources page or the FDA web page at http://www.fda.gov/cber/gdlns/advreport.htm

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