Shan Guogen, Hutson Alan D, Wilding Gregory E
Department of Biostatistics, University at Buffalo, Buffalo, NY, USA.
Pharm Stat. 2012 Jul-Aug;11(4):287-94. doi: 10.1002/pst.1499. Epub 2012 Mar 9.
In preclinical studies and clinical dose-ranging trials, the Jonckheere-Terpstra test is widely used in the assessment of dose-response relationships. Hewett and Spurrier (1979) presented a two-stage analog of the test in the context of large sample sizes. In this paper, we propose an exact test based on Simon's minimax and optimal design criteria originally used in one-arm phase II designs based on binary endpoints. The convergence rate of the joint distribution of the first and second stage test statistics to the limiting distribution is studied, and design parameters are provided for a variety of assumed alternatives. The behavior of the test is also examined in the presence of ties, and the proposed designs are illustrated through application in the planning of a hypercholesterolemia clinical trial. The minimax and optimal two-stage procedures are shown to be preferable as compared with the one-stage procedure because of the associated reduction in expected sample size for given error constraints.
在临床前研究和临床剂量范围试验中，琼克尔-特普斯特拉检验被广泛用于评估剂量反应关系。休伊特和斯普里尔（1979年）在大样本量的背景下提出了该检验的两阶段类似方法。在本文中，我们基于最初用于基于二元终点的单臂II期设计的西蒙极小极大和最优设计标准，提出了一种精确检验。研究了第一阶段和第二阶段检验统计量的联合分布向极限分布的收敛速度，并针对各种假定的备择假设提供了设计参数。还研究了存在平局时检验的行为，并通过在高胆固醇血症临床试验规划中的应用来说明所提出的设计。结果表明，与单阶段程序相比，极小极大和最优两阶段程序更可取，因为在给定的误差约束下，预期样本量会相应减少。
