Nhacolo Arsénio, Brannath Werner
Competence Centre for Clinical Trials, University of Bremen, Bremen, Germany.
Stat Methods Med Res. 2019 Sep;28(9):2635-2648. doi: 10.1177/0962280218781411. Epub 2018 Jun 19.
Phase II clinical trials are concerned with making decision of whether a treatment is sufficiently efficacious to be worth further investigations in late large scale Phase III trials. In oncology Phase II trials, frequentist single-arm two-stage group-sequential designs with a binary endpoint are commonly used. To allow for more flexibility, adaptive versions of these designs have been proposed. In this paper, we propose point and interval estimation for adaptive designs in which the second stage sample size is a pre-specified function of first stage's number of responses. Our approach is based on sample space orderings, from which we derive -values, and point and interval estimates. Simulation studies show that our proposed methods perform better, in terms of bias and root mean square error, than the fixed-sample maximum likelihood estimator.
II期临床试验关注的是确定一种治疗方法是否具有足够的疗效，值得在后期大规模III期试验中进一步研究。在肿瘤学II期试验中，常使用具有二元终点的频率主义单臂两阶段组序贯设计。为了增加灵活性，已提出了这些设计的自适应版本。在本文中，我们针对自适应设计提出了点估计和区间估计，其中第二阶段样本量是第一阶段反应数量的预先指定函数。我们的方法基于样本空间排序，从中得出p值以及点估计和区间估计。模拟研究表明，就偏差和均方根误差而言，我们提出的方法比固定样本最大似然估计器表现更好。
