Unbiased estimation in seamless phase II/III trials with unequal treatment effect variances and hypothesis-driven selection rules.
Unbiased estimation in seamless phase II/III trials with unequal treatment effect variances and hypothesis-driven selection rules.
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DOI：
10.1002/sim.6974
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发表时间：
2016-09-30
影响因子：
2
通讯作者：
Bowden, Jack
中科院分区：
文献类型：
--
作者：
Robertson, David S.;Prevost, A. Toby;Bowden, Jack
关键词：
无缝II/III期临床试验提供了一种有效的方法来选择实验性治疗，并在一次试验中进行验证性分析。然而，在最后的分析中结合两个阶段的数据可能会导致对治疗效果的估计存在偏差。迄今为止发展的偏倚调整方法对所遵循的设计和选择规则作出了限制性假设。为了解决这些缺点，我们应用最新的方法学进展，推导出两阶段无缝II/III期试验的一致最小方差条件无偏估计量。我们的框架允许治疗组估计的精度取任意值，可用于所有进入III期的治疗，并且适用于选择或放弃治疗组的决定是由多重调整的假设检验程序驱动的。©2016作者。医学统计由约翰威利和儿子有限公司出版。
Seamless phase II/III clinical trials offer an efficient way to select an experimental treatment and perform confirmatory analysis within a single trial. However, combining the data from both stages in the final analysis can induce bias into the estimates of treatment effects. Methods for bias adjustment developed thus far have made restrictive assumptions about the design and selection rules followed. In order to address these shortcomings, we apply recent methodological advances to derive the uniformly minimum variance conditionally unbiased estimator for two‐stage seamless phase II/III trials. Our framework allows for the precision of the treatment arm estimates to take arbitrary values, can be utilised for all treatments that are taken forward to phase III and is applicable when the decision to select or drop treatment arms is driven by a multiplicity‐adjusted hypothesis testing procedure. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
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