论文标题
在小组顺序试验中考虑不一致的协变量调整不一致
Accounting for Inconsistent Use of Covariate Adjustment in Group Sequential Trials
论文作者
论文摘要
临床试验中的小组顺序设计允许进行临时功效和徒劳监测。基线协变量的调整可以增加估计效应的功率和精度。但是，在整个组顺序试验的整个阶段，不一致地应用协变量调整会导致I型误差，偏置点估计和抗保守置信区间的通胀。我们建议在这种情况下执行正确的临时监视，估计和推断的方法，以避免这些问题。我们专注于简单，平衡的随机化和连续结果的两臂试验。我们研究模拟研究中边界，估计和推理调整的性能。我们以有关在组顺序设计中应用协变量调整的建议结束。
Group sequential designs in clinical trials allow for interim efficacy and futility monitoring. Adjustment for baseline covariates can increase power and precision of estimated effects. However, inconsistently applying covariate adjustment throughout the stages of a group sequential trial can result in inflation of type I error, biased point estimates, and anti-conservative confidence intervals. We propose methods for performing correct interim monitoring, estimation, and inference in this setting that avoid these issues. We focus on two-arm trials with simple, balanced randomization and continuous outcomes. We study the performance of our boundary, estimation, and inference adjustments in simulation studies. We end with recommendations about the application of covariate adjustment in group sequential designs.
