Department of Statistics and Data Sciences, The University of Texas at Austin, Austin, TX 78712, United States.
Biometrics. 2024 Oct 3;80(4). doi: 10.1093/biomtc/ujae108.
The identification of surrogate markers is motivated by their potential to make decisions sooner about a treatment effect. However, few methods have been developed to actually use a surrogate marker to test for a treatment effect in a future study. Most existing methods consider combining surrogate marker and primary outcome information to test for a treatment effect, rely on fully parametric methods where strict parametric assumptions are made about the relationship between the surrogate and the outcome, and/or assume the surrogate marker is measured at only a single time point. Recent work has proposed a nonparametric test for a treatment effect using only surrogate marker information measured at a single time point by borrowing information learned from a prior study where both the surrogate and primary outcome were measured. In this paper, we utilize this nonparametric test and propose group sequential procedures that allow for early stopping of treatment effect testing in a setting where the surrogate marker is measured repeatedly over time. We derive the properties of the correlated surrogate-based nonparametric test statistics at multiple time points and compute stopping boundaries that allow for early stopping for a significant treatment effect, or for futility. We examine the performance of our proposed test using a simulation study and illustrate the method using data from two distinct AIDS clinical trials.
替代标志物的鉴定是出于其能够更早地对治疗效果做出决策的潜力。然而，实际上很少有方法被开发出来，以实际使用替代标志物来检验未来研究中的治疗效果。大多数现有的方法考虑结合替代标志物和主要结局信息来检验治疗效果，依赖于充分的参数方法，对替代标志物和结局之间的关系做出严格的参数假设，并且/或者假设替代标志物仅在一个时间点进行测量。最近的工作提出了一种仅使用单一时间点的替代标志物信息的非参数治疗效果检验方法，通过借鉴先前研究中的信息，该研究同时测量了替代标志物和主要结局。在本文中，我们利用这种非参数检验方法，并提出了群组序贯程序，允许在替代标志物随着时间重复测量的情况下，提前停止治疗效果检验。我们在多个时间点推导了相关替代标志物的非参数检验统计量的性质，并计算了允许提前停止治疗效果有意义或无效的停止边界。我们使用模拟研究来检验我们提出的检验方法的性能，并使用来自两个不同的艾滋病临床试验的数据来说明该方法。
