Luo Xiaolong, Wu Samuel S, Xiong Jie
Celgene Corporation, Summit, NJ 07901, USA.
Biom J. 2010 Dec;52(6):823-35. doi: 10.1002/bimj.200900134. Epub 2010 Nov 19.
Two-stage, drop-the-losers designs for adaptive treatment selection have been considered by many authors. The distributions of conditional sufficient statistics and the Rao-Blackwell technique were used to obtain an unbiased estimate and to construct an exact confidence interval for the parameter of interest. In this paper, we characterize the selection process from a binomial drop-the-losers design using a truncated binomial distribution. We propose a new estimator and show that it is asymptotically consistent with a large sample size in either the first stage or the second stage. Supported by simulation analyses, we recommend the new estimator over the naive estimator and the Rao-Blackwell-type estimator based on its robustness in the finite-sample setting. We frame the concept as a simple and easily implemented procedure for phase 2 oncology trial design that can be confirmatory in nature, and we use an example to illustrate its application.
许多作者都考虑过用于适应性治疗选择的两阶段淘汰失败者设计。利用条件充分统计量的分布和拉奥 - 布莱克韦尔技术来获得感兴趣参数的无偏估计并构建精确的置信区间。在本文中，我们使用截断二项分布来刻画二项淘汰失败者设计的选择过程。我们提出了一种新的估计量，并表明在第一阶段或第二阶段，随着样本量增大它是渐近一致的。在模拟分析的支持下，基于其在有限样本情况下的稳健性，我们推荐新的估计量优于朴素估计量和基于拉奥 - 布莱克韦尔型的估计量。我们将这个概念构建为一种简单且易于实施的用于二期肿瘤试验设计的程序，本质上它可以是确证性的，并且我们用一个例子来说明其应用。
