Point estimation and p-values in phase II adaptive two-stage designs with a binary endpoint

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• 作者：K. Kunzmann and M. Kieser
• 刊名：Statistics in Medicine
• 出版年：2017
• 出版时间：15 March 2017
• 年：2017
• 卷：36
• 期：6
• 页码：971-984
• 全文大小：746K
• ISSN：1097-0258

文摘

Clinical trials in phase II of drug development are frequently conducted as single-arm two-stage studies with a binary endpoint. Recently, adaptive designs have been proposed for this setting that enable a midcourse modification of the sample size. While these designs are elaborated with respect to hypothesis testing by assuring control of the type I error rate, the topic of point estimation has up to now not been addressed. For adaptive designs with a prespecified sample size recalculation rule, we propose a new point estimator that both assures compatibility of estimation and test decision and minimizes average mean squared error. This estimator can be interpreted as a constrained posterior mean estimate based on the non-informative Jeffreys prior. A comparative investigation of the operating characteristics demonstrates the favorable properties of the proposed approach. Copyright