The incidence and risks of adverse events in randomized controlled trials (RCTs) of cancer drugs downplaying the harms.

Abstract

e14036 Background: Proper assessment of harms of cancer treatment is essential to make risk-benefit trade off decisions in oncology clinic. CONSORT guidelines require the authors of RCTs to provide exact data for adverse events (AEs) grade 3 or higher (severe AEs), serious AEs (SAEs) and fatal AEs (FAEs) and avoid using general terms (such as well-tolerated) that downplay the harms. We aimed to assess the incidence and risks of severe AEs, SAEs and FAEs in such RCTs of cancer drugs that downplayed the harms. Methods: We extracted all the phase 2 and 3 RCTs of cancer drugs from the five major journals (NEJM, Lancet, Lancet Oncology, JAMA, JCO) from 2016 January to 2016 December. The abstracts/full texts of the papers were studied to assess if the harms of the experimental arm were downplayed. Use of any of the following terms while describing toxicities or AEs or safety was assumed to downplay the harms: acceptable, feasible, tolerable (or well-tolerated) , favorable, safe, manageable. Data on severe AEs, SAEs and FAEs for both the experimental and control cohorts were extracted from these RCTs and pooled using random-effects model to determine the overall incidence and risk. Results: Of 122 phase 2/3 RCTs of cancer drugs identified, 53 (43.4%) reports used terms downplaying the toxicities of the experimental arm and were included in this analysis. The overall incidence of severe AEs, SAEs and FAEs with these cancer drugs were 50.6% (95% CI: 41.5%-59.7%), 21.9% (95% CI: 16.3%-28.7%) and 1.6% (95% CI: 1.2%-2.2%) respectively. Compared with control, the risk of severe AEs and SAEs were significantly increased with the use of these cancer drugs: severe AEs (RR 1.15, 95% CI: 1.04-1.27, p = 0.005) and SAEs ( RR 1.49, 95% CI: 1.26-1.77, p < 0.001) . However, the risk of FAEs was similar across the experimental and control arms ( RR 0.89, 95% CI: 0.72-1.11, p = 0.306) Conclusions: Our analysis shows that considerable proportions of patients suffer severe AEs, SAEs and FAEs and significantly increased risk of severe AEs and SAEs in the trials that downplay the toxicities of cancer drugs. Terms that falsely downplay the toxicities of cancer drugs should be avoided in the reporting of RCTs to encourage accurate risk-benefit assessment.