Adaptive designs for selecting drug combinations based on efficacy–toxicity response

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• 作者：Vladimir Dragalin ; Valerii Fedorov ; Yuehui Wu
• 关键词：Adaptive design ; Bivariate probit model ; Dose-finding ; Dose– ; response ; Drug combination ; Early phase clinical trials ; Information matrix ; Optimal experimental design ; Optimal safe dose
• 刊名：Journal of Statistical Planning and Inference
• 出版年：2008
• 期刊代码：36_03783758
• 类别：mt
• 出版时间：1 February 2008
• 卷：138
• 期：2
• 页码：352-373
• 文件大小：975 K

摘要

We propose a new adaptive procedure for dose-finding in clinical trials with combination of two drugs when both efficacy and toxicity responses are available. We model the distribution of this bivariate binary endpoint using the bivariate probit model. The analytic formulae for the Fisher information matrix are obtained, that form the basis for derivation of the locally optimal, minimax, Bayesian, and adaptive designs in the framework of optimal design theory.