The reporting of adverse events in oncology phase III trials: a comparison of the current status versus the expectations of the EORTC members.
BACKGROUND
Determination of drug safety and tolerability is usually based on the frequency of certain key adverse events (AEs) rather than the frequency of all-grade toxicities. We assessed the reporting of key AEs in oncology randomized, controlled trials (RCTs) and compared that with the expectations of the European Organization for Research and Treatment of Cancer (EORTC) membership.


METHODS
RCTs reports published between 2007 and 2011 were reviewed regarding the reporting of key AEs, namely: grade 3/4 AEs, grade 5 AEs, and AEs resulting in study withdrawal or in dose reduction. Study characteristics associated with better reporting of key AEs were investigated. Finally, a survey was conducted among the EORTC membership to determine their expectations on key AEs reporting.


RESULTS
Although the frequency of grade 3/4 was reported in most reports (96%), only 17% of them described the reporting threshold above which grade 3/4 AEs were included for reporting, raising the possibility that important but less frequent grade 3/4 AEs might be underreported. Frequency and nature of grade 5 AEs were adequately reported in 161 (50%) of manuscripts; AEs leading to study withdrawal in 61 manuscripts (19%); and AEs leading to dose reduction in 43 manuscripts (13%). In contrast, most EORTC members expected a comprehensive reporting of grade 5 AEs (96% of EORTC member's responses), AEs leading to study withdrawal (86%) and AEs leading to dose reduction (70%). In multivariate analysis, frequencies of grade 5 AEs were less frequently reported in European trials (P = 0.004). Frequencies of AEs leading to withdrawals were more frequently reported in trials funded by industry (P = 0.005) and in trials including patients with breast or urological cancers (P = 0.006).


CONCLUSIONS
These findings suggest that current practice of key AEs reporting remains highly variable and sometimes inadequate in oncology RCTs reports. Current standards for safety reporting in RCTs should be revised to emphasize the importance of key AEs reporting.
Department of Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), Lyon.
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Maillet
Department of Medical Oncology, Centre Léon Bérard, Lyon, France EORTC, Bruxelles, Belgium.
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Blay
Department of Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), Lyon Department of Medical Oncology, Faculté de Médecine Lyon-Sud, EMR UCBL/HCL 3738, Lyon, France.
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You
Department of Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), Lyon.
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Rachdi
Medical Oncology Unit and Olivia Newton-John Cancer Research Institute, Austin Hospital, Melbourne School of Cancer Medicine, La Trobe University, Bundoora, Australia.
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Gan
Department of Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), Lyon Biostatistics Unit, Hospices Civils de Lyon, Lyon Biometry and Evolutionary Biology Laboratory, Health and Biostatistics Team, Villeurbanne, France julien.peron@chu-lyon.fr.
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D016907:Adverse Drug Reaction Reporting Systems; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D005060:Europe; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D017410:Practice Guidelines as Topic
D000970:Antineoplastic Agents
CONSORT statement; EORTC; adverse events; grade 5 adverse events; phase III trial reports