Fang Fang, Tamura Roy N, Braun Thomas M, Kidwell Kelley M
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.
Health Informatics Institute, University of South Florida, Tampa, Florida, USA.
Pharm Stat. 2025 Jan-Feb;24(1):e2465. doi: 10.1002/pst.2465.
A recent study design for clinical trials with small sample sizes is the small n, sequential, multiple assignment, randomized trial (snSMART). An snSMART design has been previously proposed to compare the efficacy of two dose levels versus placebo. In such a trial, participants are initially randomized to receive either low dose, high dose or placebo in stage 1. In stage 2, participants are re-randomized to either dose level depending on their initial treatment and a dichotomous response. A Bayesian analytic approach borrowing information from both stages was proposed and shown to improve the efficiency of estimation. In this paper, we propose two sample size determination (SSD) methods for the proposed snSMART comparing two dose levels with placebo. Both methods adopt the average coverage criterion (ACC) approach. In the first approach, the sample size is calculated in one step, taking advantage of the explicit posterior variance of the treatment effect. In the other two step approach, we update the sample size needed for a single-stage parallel design with a proposed adjustment factor (AF). Through simulations, we demonstrate that the required sample sizes calculated using the two SSD approaches both provide the desired power. We also provide an applet to allow for convenient and fast sample size calculation in this snSMART setting.
最近针对小样本量临床试验的一种研究设计是小n序贯多分配随机试验（snSMART）。之前已经提出了一种snSMART设计来比较两种剂量水平与安慰剂的疗效。在这样的试验中，参与者在第1阶段最初被随机分配接受低剂量、高剂量或安慰剂。在第2阶段，参与者根据其初始治疗和二分反应重新随机分配到任一剂量水平。有人提出了一种从两个阶段借用信息的贝叶斯分析方法，并证明该方法可提高估计效率。在本文中，我们针对所提出的将两种剂量水平与安慰剂进行比较的snSMART提出了两种样本量确定（SSD）方法。两种方法均采用平均覆盖率标准（ACC）方法。在第一种方法中，利用治疗效果的显式后验方差一步计算样本量。在另一种两步法中，我们用一个提议的调整因子（AF）更新单阶段平行设计所需的样本量。通过模拟，我们证明使用两种SSD方法计算出的所需样本量都能提供所需的检验效能。我们还提供了一个小程序，以便在这种snSMART设置中方便快捷地计算样本量。
