Exact Inference for Adaptive Group Sequential Designs
In this paper we present a method for estimating the treatment effect in a two-arm adaptive group sequential clinical trial that permits sample size re-estimation, alterations to the number and spacing of the interim looks, and changes to the error spending function based on an unblinded look at the accruing data. The method produces a median unbiased point estimate and a confidence interval having exact coverage of the parameter of interest. The procedure is based on mapping the final test statistic obtained in the modified trial into a corresponding backward image in the original trial. Methods that were developed for classical (non-adaptive) group sequential inference can then be applied to the backward image.
KeywordsEstimation in adaptive design Exact adaptive confidence intervals Adaptive median unbiased estimates Group sequential estimation
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