In pharmaceutical/clinical development, two-stage seamless adaptive designs are commonly considered. Such designs include a two-stage phase I/II or phase II/III adaptive trial that combines one phase IIb study for dose-finding or treatment selection and one phase III study for efficacy confirmation into a single study. At the end of stage 1, promising dose(s) will be selected based on pre-specified selection criteria. In practice, since there is little power with limited subjects available at interim, commonly considered selection criteria for critical decision-making include (i) conditional power, (ii) precision analysis, (iii) predictive probability of success, and (iv) probability of being the best dose or treatment. The selected promising dose(s) will then proceed to the next stage for efficacy confirmation. In this article, we introduce, compare, and evaluate these criteria. Simulation studies and a numeric example are given to illustrate those criteria. Besides, we attempt to address some concerns for the two-stage seamless adaptive clinical trial.

在药物/临床开发中，通常考虑两阶段无缝自适应设计。这样的设计包括一个分为两个阶段的I / II或II / III期适应性试验，该试验将一项IIb期研究（用于剂量确定或治疗选择）和一项III期研究（用于确认疗效）合并为一项研究。在第1阶段结束时，将根据预先指定的选择标准选择有希望的剂量。在实践中，由于在过渡时期可用的主题有限，因此权力很少，因此通常考虑的关键决策选择标准包括（i）有条件的权力，（ii）精确度分析，（iii）成功的预测概率和（iv）概率最好的剂量或治疗方法。选择的有希望的剂量然后将进入下一阶段以进行功效确认。在本文中，我们介绍 比较并评估这些标准。仿真研究和数值示例说明了这些标准。此外，我们尝试解决两阶段无缝适应性临床试验中的一些问题。