Randomized Trials in Oncology Stopped Early for Benefit

atedwithimprovedsurvival(hazardratio[HR],0.55;95%CI,0.38 to0.80;P.002).Giventheimplausibilityoftheseresults(because ofthelargerthanexpectedeffectonmortalityanditsinconsistency with the reduction in the risk of relapse, the key postulated mechanism for improved survival), the investigators continued the trial despite the apparent difference in survival. After random assignment of more than 1,000 patients, a significant survival advantage for five courses of consolidation chemotherapy could not be demonstrated, with an HR of 1.09 (95% CI, 0.87 to 1.37; P .4). The apparently significant results observed after few end points (ie, deaths) had occurred may be explained by data analysis at a “random high,” when a disproportionate number of events had occurred in the experimental arm by chance. Had this trial been stopped early and its results used to justify an additional course of consolidation chemotherapy, subsequent patients with acute myeloid leukemia would have been exposed to a costly, potentially toxic and ineffective therapy. The extent to which medical oncology RCTs that are stopped early for benefit manifest problems of inadequate reporting and likely effect overestimations, remains uncertain. Therefore, we examinedindetailthemedicaloncologyRCTspreviouslyreportedin the larger systematic review. 1 We reviewed the study characteristics, features related to the decision to monitor and stop the study early (sample size, interim analyses, monitoring and stopping rules), the number of events, and the estimated treatment effects reportedinthe29RCTsinmedicaloncologythathadbeenstopped early for benefit (Appendix, online only).