title: 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.
abstract: 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.
authors.affiliation: Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Belknap
authors.forename: C H
authors.initials: CH
authors.lastname: Georgopoulos
authors.forename: J
authors.initials: J
authors.lastname: Lagman
authors.forename: S A
authors.initials: SA
authors.lastname: Weitzman
authors.forename: L
authors.initials: L
authors.lastname: Qualkenbush
authors.forename: P R
authors.initials: PR
authors.lastname: Yarnold
authors.forename: B J
authors.initials: BJ
authors.lastname: Edwards
authors.forename: J M
authors.initials: JM
authors.lastname: McKoy
authors.forename: S M
authors.initials: SM
authors.lastname: Trifilio
authors.forename: D P
authors.initials: DP
authors.lastname: West
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000068258:Bevacizumab; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D028744:Ethics Committees, Research; D006801:Humans; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D014481:United States
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab
keywords: clinical pharmacology; clinical trials; drug information; oncology; outcomes research; pharmacoepidemiology; pharmacovigilance; toxicology