E2A: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting - Reminder for Sponsors
August 21, 2012
Our file number: 12-113569-723
The Adverse Drug Reaction Division of the Office of Clinical Trials (OCT), Therapeutic Products Directorate (TPD) and the Office of Regulatory Affairs, Biologics and Genetic Therapies Directorate (BGTD) would like to remind the sponsors of clinical trials that Division 5 of the Food and Drug Regulations mandates sponsors to report Adverse Drug Reactions (ADRs) that are determined to be both serious and unexpected to the OCT and the Office of Regulatory Affairs, BGTD, as applicable. ADR reports that are expected or unexpected, but not serious, should not be reported to the OCT in Health Canada nor the BGTD, but rather monitored and tracked by the sponsor. Sponsors are to report to Health Canada "expected, serious" ADRs, where an increase in the rate of occurrence or severity, was judged to be clinically important.
In addition, when evaluating adverse event information, the Qualified Investigator's and sponsor's determination of causality is very valuable. As per International Conference on Harmonisation (ICH) E2A Guidance Document: "Clinical Safety Data Management: Definitions and Standards for Expedited Reporting" adopted by Health Canada, only serious and unexpected ADR reports that have been assessed by either the investigator or the sponsor as having a reasonable suspected causal relationship to the drug, should be reported to TPD or BGTD, as applicable. Both investigators' and sponsors' causality assessment should be reported on the Council for International Organizations of Medical Sciences (CIOMS) form.
Therefore, reporting causality is expected to be carried out by the sponsor before reporting a clinical investigation case. By extension, if Health Canada is receiving a large number of reports on a specific event/drug combination this will potentially prompt a correspondence to the sponsor to discuss whether this is, in fact, a true safety signal that would require the development of a risk mitigation plan.
In addition, in order to enhance the quality of the ADR reports, it is recommended that comments related to the causality assessment of the event be reported on the CIOMS form in a location that is easily identifiable and written in straight forward language. Wording describing information about a dechallenge/rechallenge experience (if any) and the temporal association between the event and the drug usage, when available, should also be indicated in clear, concise text.
If you have any questions or comments about the above messaging, please do not hesitate to contact TPD or BGTD for clarification.
Hoda Eid, M.Sc., Ph.D.
Adverse Drug Reactions Division
Office of Clinical Trials
Therapeutic Products Directorate
Holland Cross, Tower B,
5th floor, room 5065, 1600 Scott Street
Address Locator 3105A
Office of Regulatory Affairs
Biologics and Genetic Therapies Directorate
200 Tunney's Pasture Driveway
Address Locator 0701B
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