Conditionally unbiased estimation in phase II/III clinical trials with early stopping for futility.
Conditionally unbiased estimation in phase II/III clinical trials with early stopping for futility.
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DOI：
10.1002/sim.5757
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发表时间：
2013-07-30
影响因子：
2
通讯作者：
Stallard, Nigel
中科院分区：
文献类型：
--
作者：
Kimani, Peter K.;Todd, Susan;Stallard, Nigel
无缝 II/III 期临床试验将传统的 II 期和 III 期临床试验合并为一个试验，分两个阶段进行，第 1 阶段用于回答 II 期目标，例如治疗选择，第 2 阶段用于验证性分析，这是 III 期目标。尽管无缝 II/III 期临床试验非常有效，因为验证性分析包括来自第一阶段的 II 期数据，但推断可能会带来统计挑战。在本文中，我们考虑无缝 II/III 期临床试验后的点估计，其中第 1 阶段用于选择最有效的实验治疗，并决定与对照相比，试验是否应在第 1 阶段因无效而停止。如果试验没有停止，则试验的 III 期验证部分包括评估所选最有效的实验治疗和对照。我们针对这两种治疗之间的治疗差异开发了两种新的估计量，目的是减少以治疗选择和试验继续到第二阶段为条件的偏差。我们已经使用模拟证明了这些估计量的属性。版权所有 © 2013 约翰·威利父子有限公司
Seamless phase II/III clinical trials combine traditional phases II and III into a single trial that is conducted in two stages, with stage 1 used to answer phase II objectives such as treatment selection and stage 2 used for the confirmatory analysis, which is a phase III objective. Although seamless phase II/III clinical trials are efficient because the confirmatory analysis includes phase II data from stage 1, inference can pose statistical challenges. In this paper, we consider point estimation following seamless phase II/III clinical trials in which stage 1 is used to select the most effective experimental treatment and to decide if, compared with a control, the trial should stop at stage 1 for futility. If the trial is not stopped, then the phase III confirmatory part of the trial involves evaluation of the selected most effective experimental treatment and the control. We have developed two new estimators for the treatment difference between these two treatments with the aim of reducing bias conditional on the treatment selection made and on the fact that the trial continues to stage 2. We have demonstrated the properties of these estimators using simulations. Copyright © 2013 John Wiley & Sons, Ltd.
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