Research Ethics Board (REB)
The Rehabilitation Centre (TRC)
GUIDELINES FOR REPORTING ADVERSE EVENTS
Introduction
For the purpose of reporting to The Rehabilitation Centre Research Ethics Board (TRC-REB), adverse events fall into two main categories: (a) those occurring in a clinical trial of a pharmaceutical product, and (b) those occurring in a research project other than a clinical trial of a pharmaceutical product. TRC has two different reporting forms for these categories.
In the first category, the "sponsor" (the pharmaceutical company that is funding and directing the clinical trial) is obliged to prepare and disseminate a detailed report on every adverse event that (a) is considered serious and unexpected, and (b) has at least a reasonable possibility of being caused by the study drug. Such a report can come from any of the sites that are participating in a common multi-centre trial of an investigational new drug, or it might come from an unrelated clinical trial of the same drug.
Note that there is no obligation for the sponsor to report a non-serious adverse event. Nor are sponsors required to report a serious adverse event if it is already commonly known to be an expected side effect of the study drug. An exception to this would be if the serious adverse event occurred under unusual circumstances, e.g. at a much lower dose of the drug than has been previously reported, or as the result of a previously unsuspected interaction with a second drug.
Clinical trial of a pharmaceutical product:
The Principal Investigator at TRC is responsible for following all national guidelines as outlined in “Good Clinical Practice: Consolidated Guideline" (ICH Guidance Code E6); see http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/e6_e.html at the Health Canada website.
The following definitions of adverse events come from Canada Gazette Part 11, Vol. 135, No. 13, and will be used at TRC for reporting adverse events.
An “adverse event” (AE) means any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product. Note that this occurrence does not necessarily have a causal relationship with the treatment; the relationship need only be a reasonable possibility. Where the adverse event is not considered to be serious (see SADR, SAE, SUADR definitions below), the event is commonly referred to as a "non-serious adverse event" (NSAE).
An “adverse drug reaction”(ADR), means any noxious and unintended response to a drug that is caused by the administration of any dose of the drug. Note that the relationship to study drug need not be proved: it need only be a reasonable possibility ("cannot be ruled out").
A “serious adverse drug reaction”(SADR), also known as a "serious adverse event" (SAE), means an ADR (see above) that requires in-patient hospitalization, or prolongation of existing hospitalization, or that causes congenital malformation, or that results in persistent or significant disability or incapacity, or that is life threatening or results in death.
A “serious unexpected adverse drug reaction”(SUADR), means a serious adverse drug reaction that is not identified in nature, severity or frequency by the risk information provided in the clinical investigator’s brochure (CIB) or on the drug label.
Research involving Non-Pharmaceutical Products:
Some examples of adverse events in this category are:
· Physical injury, including falls
· Equipment failure
· Suicidal ideation or attempted suicide
· Aggressive behavior of the subject towards the researcher, staff or others.
Reporting Requirements at TRC:
The report is to be submitted using the appropriate TRC form - either the Adverse Event Report for Non-pharmaceutical Protocols or, for SAEs associated with a clinical trial of an investigational drug, the Cumulative Adverse Event Report. SAE reports received from a sponsor may often be submitted using the sponsor’s own forms, since they are standardized and quite thorough. Nevertheless, the REB would appreciate it if the Principal Investigator (or delegate) at TRC also appended a brief summary of the event in order to put each such report in perspective.
Unexpected adverse events occurring at TRC that are not considered "serious" (AEs, ADRs, NSAEs), but are considered (at least possibly) related to the study drug, device or intervention, should be reported to TRC-REB within 15 days of the event. Since these events are, according to the definitions given above, not considered serious, the Principal Investigator must decide whether or not a particular event is reportable. When in doubt, the PI should bring the event to the attention of the REB Chair, who will decide if it is necessary to file a formal report and whether it needs to be discussed at a Board meeting.
Serious unexpected adverse events (SAEs, SADRs, SUADRs) should be reported to TRC-REB within 7 days of either (a) the event, or (b) the investigator at TRC receiving notification of the event from the sponsor. Fatal or life-threatening events must be reported to TRC-REB as soon as possible after they occur.
\\C-gen-fp6\research\Common\Ethics\REB Administration\Adverse event definition.doc 4 June 2004