One of the central aims in randomized clinical trials is to find well-validated surrogate endpoints to reduce the sample size and/or duration of trials. Clinical researchers and practitioners have proposed various surrogacy measures for assessing candidate surrogate endpoints. However, most existing surrogacy measures have the following shortcomings: (i) they often fall outside the range [0,1], (ii) they are imprecisely estimated, and (iii) they ignore the interaction associations between a treatment and candidate surrogate endpoints in the evaluation of the surrogacy level. To overcome these difficulties, we propose a new surrogacy measure, the proportion of treatment effect mediated by candidate surrogate endpoints (PMS), based on the decomposition of the treatment effect into direct, indirect, and interaction associations mediated by candidate surrogate endpoints. In addition, we validate the advantages of PMS through Monte Carlo simulations and the application to empirical data from ORIENT (the Olmesartan Reducing Incidence of Endstage Renal Disease in Diabetic Nephropathy Trial).

中文翻译：

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替代终点介导的治疗效果比例

随机临床试验的中心目标之一是找到经过充分验证的替代终点，以减少样本量和/或试验持续时间。临床研究人员和从业者提出了各种替代措施来评估候选替代终点。然而，大多数现有的代孕措施具有以下缺点：（i）它们通常超出范围 [0,1]，（ii）它们的估计不准确，以及（iii）它们忽略了治疗和候选替代终点之间的相互作用关联在代孕水平的评估中。为了克服这些困难，我们提出了一种新的替代指标，即候选替代终点（PMS）介导的治疗效果比例，基于将治疗效果分解为直接、间接、和由候选替代端点介导的交互关联。此外，我们通过 Monte Carlo 模拟验证 PMS 的优势，并将其应用于 ORIENT（奥美沙坦降低糖尿病肾病终末期肾病发病率试验）的经验数据。