Expected versus observed effect sizes for survival endpoints in phase 3 oncology trials.

Sophia J Lamp,Gina L Mazza
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Abstract

More than half of randomized phase 3 oncology trials fail to meet their primary endpoints, often despite favorable results from phase 1 and phase 2 trials. One potential reason for this high failure rate is effect size selection practices for powering these trials. In a systematic review of phase 3 oncology trials published in ten top medical journals in 2023, we identified a pattern of effect size overestimation for survival endpoints, where the expected hazard ratios (average HR = 0.66) were stronger than those observed in the primary analyses (average HR = 0.72; two-sided signed-rank test p = .0035). Across 111 trials, 82 of 143 observed hazard ratios for primary survival endpoints (57.3%) were weaker-than-expected; among five journals with 2023 impact factors between 9.9-56.7 (vs 58.7-98.4 for the top five journals), this ratio was 70.2% (59/84). These results suggest that phase 3 oncology trials are likely underpowered, contributing to the high failure rates in oncology research.
3期肿瘤试验中生存终点的预期效应量与观察效应量。
超过一半的随机3期肿瘤学试验未能达到其主要终点,尽管1期和2期试验结果良好。这种高失败率的一个潜在原因是为这些试验提供动力的效应大小选择实践。在对2023年发表在10个顶级医学期刊上的3期肿瘤试验的系统回顾中,我们发现了生存终点效应大小高估的模式,其中预期风险比(平均HR = 0.66)强于主要分析中观察到的结果(平均HR = 0.72;双侧有符号秩检验p = .0035)。在111项试验中,143项试验中有82项观察到主要生存终点的风险比(57.3%)低于预期;在影响因子在9.9 ~ 56.7之间的5种期刊中(前5种期刊为58.7 ~ 98.4),该比值为70.2%(59/84)。这些结果表明,3期肿瘤试验可能动力不足,导致肿瘤研究的高失败率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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