Reporting of serious adverse events during cancer clinical trials to the institutional review board: an evaluation by the research on adverse drug events and reports (RADAR) project.

Global introspection is considered an unreliable method for attribution of causality of serious adverse events (SAEs), yet remains widely used for cancer drug clinical trials. Here, we compare structured case abstraction (SCA) to the routine method for detecting, evaluating, and reporting ADEs during cancer drug clinical trials to an Institutional Review Board (IRB). We obtained all SAE reports (2001-2008) received by one IRB for six clinical trials involving bevacizumab or oxaliplatin for treatment of gastrointestinal cancers. We compared the routine IRB SAE method to SCA for adverse event detection and causality attribution. Of 205 adverse events, 182 events (75%) were not reported; of these, 6 (20%) of 30 SAEs requiring an IRB report were unreported. For the 10 item Naranjo score, the amount of information useful for causality attribution was higher with SCA than the routine method (6.0 vs. 2.4 items, P < .0001). One-fifth of SAEs requiring an IRB report were unreported to the IRB via the routine method. SCA provided more useful information as to whether an SAE was caused by a cancer drug exposure. Our results suggest that SCA may improve SAE detection and the accuracy of attribution of causality during cancer drug clinical trials.

Quality of methods for assessing and reporting serious adverse events in clinical trials of cancer drugs.

The validity of information regarding drug toxicity in humans depends on the quality of the methods and instruments used to assess adverse drug events (ADEs). This study evaluates the quality of instruments used to assess and report ADEs to institutional review boards (IRBs) at US cancer centers. Forms from all 49 National Cancer Institute (NCI)-designated centers were assessed for utility in abstracting event type, severity, and causality; patient demographics; safety monitoring; and consequent changes in the conduct of the relevant study. Of the 55 items considered essential for ADE reporting, one item (event description) was present on all the forms. Seventy-eight percent of the instruments prompted for global introspection of the investigator, a method known to be unreliable. Of the 34 items that our panel of experts considered essential for event description, the median number of items present was four (domain = 1-11). The use of a validated tool to describe and assess event type, severity, and causality may lead to more timely, accurate identification of safety signals in cancer treatment.