Wu Yuan, Simmons Ryan A, Zhang Baoshan, Troy Jesse D
Department of Biostatistics and Bioinformatics, Duke University, Durham NC, USA.
PPD, Thermo Fisher Scientific, Durham NC, USA.
Stat Med. 2025 Mar 15;44(6):e70053. doi: 10.1002/sim.70053.
Group sequential trials include interim monitoring points to potentially reach futility or efficacy decisions early. This approach to trial design can safeguard patients, provide efficacious treatments for patients early, and save money and time. Group sequential methods are well developed for bell-shaped continuous, binary, and time-to-event outcomes. In this paper, we propose a group sequential design using the Mann-Whitney-Wilcoxon test for general two-sample ordinal data. We establish that the proposed test statistic has asymptotic normality and that sequential statistics satisfy the assumptions of Brownian motion. We also include results of finite sample simulation studies that show our proposed approach has the advantage over existing methods for controlling Type I errors while maintaining power for small sample sizes. A real data set is used to illustrate the proposed method and a sample size calculation approach is proposed for designing new studies.
序贯分组试验包括中期监测点，以便有可能尽早得出无效或有效结论。这种试验设计方法可以保护患者，尽早为患者提供有效治疗，并节省金钱和时间。对于钟形连续、二元和事件发生时间结局，序贯分组方法已经得到了很好的发展。在本文中，我们针对一般两样本有序数据，提出了一种使用曼-惠特尼-威尔科克森检验的序贯分组设计。我们证明了所提出的检验统计量具有渐近正态性，并且序贯统计量满足布朗运动的假设。我们还给出了有限样本模拟研究的结果，这些结果表明，我们提出的方法在控制I型错误的同时，对于小样本量保持检验功效方面优于现有方法。使用一个真实数据集来说明所提出的方法，并提出了一种样本量计算方法来设计新的研究。
