Sample size re-estimation in Phase 2 dose-finding: Conditional power versus Bayesian predictive power |
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| Authors: | Qingyang Liu Guanyu Hu Binqi Ye Susan Wang Yaoshi Wu |
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| Affiliation: | 1. Department of Statistics, University of Connecticut, Storrs, Connecticut, USA;2. Department of Statistics, University of Missouri - Columbia, Columbia, Missouri, USA;3. Boehringer Ingelheim (China), Shanghai, China;4. Boehringer-Ingelheim Pharmaceutical Inc., Ridgefield, Connecticut, USA |
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| Abstract: | Unblinded sample size re-estimation (SSR) is often planned in a clinical trial when there is large uncertainty about the true treatment effect. For Proof-of Concept (PoC) in a Phase II dose finding study, contrast test can be adopted to leverage information from all treatment groups. In this article, we propose two-stage SSR designs using frequentist conditional power (CP) and Bayesian predictive power (PP) for both single and multiple contrast tests. The Bayesian SSR can be implemented under a wide range of prior settings to incorporate different prior knowledge. Taking the adaptivity into account, all type I errors of final analysis in this paper are rigorously protected. Simulation studies are carried out to demonstrate the advantages of unblinded SSR in multi-arm trials. |
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| Keywords: | adaptive design clinical trial contrast test prior information sample size re-estimation type I error |
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