We address a multistage clinical trial to assess a sequence of hypotheses in the noninferiority and also rare events setting. Three successive hypotheses are used to evaluate whether the new treatment meets the criteria for new drug approval. Sample sizes for a five stage trial for all hypotheses are calculated using Poisson and Logrank sample size methods. Three strategies and corresponding analysis plans are developed to evaluate the sequential hypotheses. Simulations show the design is satisfactory with respect to controlled Type I error, sufficient power, and early success at interim analyses.



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