A menu-driven facility for sample-size calculation in novel multiarm, multistage randomized controlled trials with a time-to-event outcome
A menu-driven facility for sample-size calculation in novel multiarm, multistage randomized controlled trials with a time-to-event outcome
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DOI：
10.1177/1536867x0900900401
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发表时间：
2009-01-01
期刊：
影响因子：
4.8
通讯作者：
Parmar, Mahesh K. B.
中科院分区：
文献类型：
--
作者：
Barthel, Friederike M-S.;Royston, Patrick;Parmar, Mahesh K. B.
我们提出了菜单和命令驱动的 Stata 程序，用于计算新型临床试验设计的样本量、事件数量和试验持续时间，该设计具有事件发生时间结果和两个或多个实验组。该方法的基础是终止患者接受较差的实验性治疗；在试验的所有早期阶段都进行手臂治疗，只允许进入下一阶段，而这些治疗相对于对照治疗显示出预定程度的优势。测试的第一阶段使用中间结果测量来衡量最终（主要）结果，而不是主要结果本身。根据中间结果测量，将实验组与对照组进行成对比较。在比较中幸存下来的组进入患者应计的下一阶段，最终与主要结局指标的控制进行比较。支持的功能包括不平等的患者分配、考虑假设下可能不同于 1 的目标风险比，以及在试验开始后指定时间停止患者招募的能力。样本量和功效的计算基于原假设和备择假设下对数风险比的渐近均值和方差。总体操作特征是根据中间和最终阶段的显着性水平和功效以及不同阶段的中间和主要结果测量的对数风险比之间的相关性计算的。我们通过英国医学研究委员会六组前列腺癌试验的设计来说明该方法，其中中间结果是无失败生存，主要结果是总体生存。
We present menu- and command-driven Stata programs for the calculation of sample size, number of events, and trial duration for a novel type of clinical trial design with a time-to-event outcome and two or more experimental arms. The approach is based oil terminating accrual of patients to inferior experimental treatment; arms at all early stage in the trial, allowing through to the next stage only treatments that show a predefined degree of advantage against the control treatment. The first stage of testing uses an intermediate outcome measure for the definitive (primary) outcome rather than with the primary outcome itself. The experimental arms are compared pairwise with the control arm according to the intermediate outcome measure. Arms that survive the comparison enter the next stage of patient accrual, culminating in comparisons against control on the primary outcome measure.The features supported include unequal patient allocation, target hazard ratios that may differ from 1 under the mull hypothesis, and the ability to stop patient recruitment at a specified time after trial initiation. The computations of sample size and power are based on the asymptotic mean and variance of the log hazard-ratio under the null and alternative hypotheses. The overall operating characteristics are computed from the intermediate and final stage significance levels and power, and the correlation between the log hazard-ratios oil the intermediate and primary outcome measures at the different stages. We illustrate the approach with the design of a United Kingdom Medical Research Council six-arm trial ill prostate cancer in which the intermediate outcome is failure-free survival and the primary outcome is overall survival.