A SEQUENTIAL MULTIPLE COMPARISON PROCEDURE FOR DETECTING A LOWEST DOSE HAVING INTERACTION IN A DOSE-RESPONSE TEST

Tomohiro Nakamura, H. Douke
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Abstract

In this study, we propose a multiple comparison procedure for detecting sequentially a lowest dose level having interaction based on two dose sample means on two treatments with increasing dose levels in a dose-response test. We apply a group sequential procedure in order to realize our method that tests sequentially the null hypotheses of no interaction based on tetrad differences. If we can first detect a dose level having interaction at an early stage in the sequential test, since we can terminate the procedure with just the few observations up to that stage, the procedure is useful from an economical point of view. In the procedure, we present an integral formula to determine the repeated confidence boundaries for satisfying a predefined type I familywise error rate. Furthermore, we show how to decide a required sample size in each cell so as to guarantee the power of the test. In the simulation studies, we evaluate the superiority among the procedures based on three α spending functions in terms of the power of the test and the required sample size for various configurations of population means.
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用于检测剂量-反应试验中具有相互作用的最低剂量的顺序多重比较程序
在这项研究中,我们提出了一种多重比较程序,用于在剂量-反应试验中,根据两种剂量水平增加的治疗方法的两个剂量样本均值,依次检测具有相互作用的最低剂量水平。为了实现对基于四分体差异的无相互作用的零假设进行序贯检验的方法,我们采用了一组序贯过程。如果我们能够在顺序试验的早期阶段首先检测到具有相互作用的剂量水平,因为我们可以在该阶段之前仅进行少量观察就结束该程序,因此从经济的角度来看,该程序是有用的。在此过程中,我们提出了一个积分公式来确定满足预定义的I型家族错误率的重复置信边界。此外,我们展示了如何在每个单元中确定所需的样本量,以保证测试的功率。在仿真研究中,我们根据检验的威力和各种总体均值配置所需的样本量来评估基于三个α花费函数的程序之间的优越性。
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