Exact sequential single-arm trial design with curtailment for binary endpoint
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Due to ethical and economical reasons, sequential single-arm trial designs are used for assessing the therapeutic efficacy of new treatments in phase II trials. Simon's 2-stage design and Lan-DeMets' α-spending function method with O'Brien-Fleming type are widely recognized as the traditional methods for futility stopping and efficacy stopping, respectively. These methods have two practical problems, which are the difficulty of interpretation for stopping under staggered entry and the inflation of error rate due to a small-sample trial. In this research, we propose the exact sequential design making the threshold value for efficacy fixed, and compare with traditional designs in sample size. Since the maximum sample size and average sample number of the proposed design are generally smaller than those of traditional designs containing fixed design, the proposed design is expected to be enrolled fewer subjects. In addition, we evaluate several kinds of point estimators and confidence intervals at the end of trials in the proposed design. If one is concerned with bias, the bias-adjusted estimator may be better. As for a confidence interval, the mid-p approach will be a good choice.
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