Population Health Sciences Institute, Newcastle University, Baddiley-Clark Building, Richardson Road, Newcastle upon Tyne, NE2 4AX, UK.
Population Health Sciences Institute, Newcastle University, Baddiley-Clark Building, Newcastle upon Tyne, UK and MRC Biostatistics Unit, University of Cambridge, East Forvie Building, Forvie Site, Robinson Way, Cambridge Biomedical Campus, Cambridge, CB2 0SR, UK.
Biostatistics. 2023 Apr 14;24(2):327-344. doi: 10.1093/biostatistics/kxaa055.
The existing cross-validated risk scores (CVRS) design has been proposed for developing and testing the efficacy of a treatment in a high-efficacy patient group (the sensitive group) using high-dimensional data (such as genetic data). The design is based on computing a risk score for each patient and dividing them into clusters using a nonparametric clustering procedure. In some settings, it is desirable to consider the tradeoff between two outcomes, such as efficacy and toxicity, or cost and effectiveness. With this motivation, we extend the CVRS design (CVRS2) to consider two outcomes. The design employs bivariate risk scores that are divided into clusters. We assess the properties of the CVRS2 using simulated data and illustrate its application on a randomized psychiatry trial. We show that CVRS2 is able to reliably identify the sensitive group (the group for which the new treatment provides benefit on both outcomes) in the simulated data. We apply the CVRS2 design to a psychology clinical trial that had offender status and substance use status as two outcomes and collected a large number of baseline covariates. The CVRS2 design yields a significant treatment effect for both outcomes, while the CVRS approach identified a significant effect for the offender status only after prefiltering the covariates.
现有的交叉验证风险评分（CVRS）设计旨在使用高维数据（如遗传数据），在高疗效患者群体（敏感群体）中开发和测试治疗效果。该设计基于为每个患者计算风险评分，并使用非参数聚类程序将它们分为聚类。在某些情况下，需要考虑两种结果（如疗效和毒性，或成本和效果）之间的权衡。基于这种动机，我们扩展了 CVRS 设计（CVRS2）以考虑两种结果。该设计采用双变量风险评分，将其分为聚类。我们使用模拟数据评估 CVRS2 的特性，并在随机精神病学试验上说明其应用。我们表明，CVRS2 能够在模拟数据中可靠地识别敏感群体（新治疗在两种结果上都有获益的群体）。我们将 CVRS2 设计应用于一项有罪犯身份和物质使用状况作为两种结果的心理学临床试验，并收集了大量的基线协变量。CVRS2 设计对两种结果都产生了显著的治疗效果，而 CVRS 方法在对协变量进行预过滤后，仅对罪犯身份识别出了显著的效果。
