第三阶段癌症临床试验中的比例危险违规行为:试验误解的潜在来源
Timothy A Lin1,2, Zachary R McCaw3,4, Alex Koong1
1Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
概括
在癌症试验中,比例危险违规 (PHV) 是常见的,影响了23.8%的分析. 这些违规行为可能导致对生存数据的误解,突出需要更好的统计规划.
科学领域:
- 临床试验 临床试验
- 生物统计学 生物统计学
- 瘤学研究研究
背景情况:
- 瘤学中的生存分析通常涉及具有长期反应者的新药.
- 随着时间的推移,可能会发生不同的危险率,称为比例危险违规 (PHV).
- PHVs可能会降低日志等级测试的统计能力,并导致对临床试验结果的误解.
研究的目的:
- 为了确定PHVs在III期瘤学试验中的发病率.
- 确定与PHV相关的研究属性.
- 评估限制平均存活时间和最大组合试验作为替代分析的实用性.
主要方法:
- 搜索了clinicaltrials.gov和pubmed的第三阶段随机癌症试验,时间到事件终点发布到2020年.
- 从已发表的卡普兰-梅尔曲线中重建患者级数据.
- 通过使用Schoenfeld残留物评估PHV.
主要成果:
- 分析了来自341个试验的357个卡普兰-梅尔比较 (292,831名患者).
- 在23.8%的比较中确定了PHV.
- 非总生存终点 (OR,2.16) 和免疫疗法比较 (OR,1.94) 与PHVs的更高几率有关. 只有29.4%的PHV试验预先指定了解决它们的计划.
结论:
- 在各种癌症治疗类型中,PHVs很普遍.
- 在试验设计中缺乏PHV的统计规划,可能导致对结果的误解.
- 像限制平均存活时间这样的替代分析可能会在PHV试验中揭示不一致的信号.
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