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Conditionally unbiased estimation in phase II/III clinical trials with early stopping for futility

机译:II / III期临床试验中的有条件无偏估计,且因无效而提前停止

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摘要

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
机译:无缝的II / III期临床试验将传统的II期和III期合并为一个分为两个阶段的单一试验,其中第1阶段用于回答II期目标(例如治疗选择),第2阶段用于确认性分析,这是一个阶段第三目标。尽管无缝的II / III期临床试验是有效的,因为确认分析包括来自第1阶段的II期数据,推论可能会带来统计学上的挑战。在本文中,我们考虑在无缝的II / III期临床试验后进行点估计,在该试验中,第1阶段用于选择最有效的实验治疗方法,并确定与对照组相比,该试验是否应在第1阶段停止以徒劳无益。如果试验没有停止,则试验的III期验证部分将涉及对所选最有效的实验治疗方法和对照的评估。我们针对这两种疗法之间的差异开发了两个新的估算器,目的是根据所选择的疗法以及试验继续进行到第2步的事实来减少偏差。我们已经通过模拟展示了这些估算器的特性

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