Identifying effective and/or safe doses by stepwise confidence intervals for ratios
Identifying effective and/or safe doses by stepwise confidence intervals for ratios
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DOI：
10.1002/sim.1449
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发表时间：
2003-03-30
影响因子：
2
通讯作者：
Hsu, JC
中科院分区：
文献类型：
--
作者：
Bretz, F;Hothorn, LA;Hsu, JC
典型的随机临床剂量探索研究包括比较几种剂量的药物与安慰剂。感兴趣的是估计正在研究的有效性和安全性变量的相关剂量，如最小有效剂量或最大安全剂量（或同时估计两种剂量）。已提出逐步下降程序来比较剂量组与安慰剂组的标准化差异。在本文中，我们认为人口的比率，并提出逐步置信区间这些比率。这些置信区间不需要多重性调整，并产生与相关测试程序相同的决策。此外，在本框架内，几个权力的概念进行了研究。结果允许在研究设计阶段确定样本量，以确定正确估计目标剂量的概率。数值研究的辅助结果显示了这些方法的应用范围。版权所有（C）2003约翰威利父子有限公司。
Typical randomized clinical dose-finding studies consist of the comparison of several doses of a drug versus a placebo. Interest lies in estimating relevant doses among those under investigation for efficacy and safety variables, such as the minimum effective dose or the maximum safe dose (or estimating both doses simultaneously). Step-down procedures have been proposed for comparing the standardized differences of the dose groups against placebo. In this paper we consider the ratio of population means and propose stepwise confidence intervals for these ratios. These confidence intervals do not require multiplicity adjustments and yield the same decisions as the associated test procedures. In addition, several power concepts are investigated within the present framework. The results allow sample size determination in the design phase of a study for the probability of estimating correctly the dose of interest. Auxiliary results of a numerical study show the range of application of these methods. Copyright (C) 2003 John Wiley Sons, Ltd.