Biomarkers abound in many areas of clinical research, and often investigators are interested in combining them for diagnosis, prognosis, or screening. In many applications, the true positive rate (TPR) for a biomarker combination at a prespecified, clinically acceptable false positive rate (FPR) is the most relevant measure of predictive capacity. We propose a distribution-free method for constructing biomarker combinations by maximizing the TPR while constraining the FPR. Theoretical results demonstrate desirable properties of biomarker combinations produced by the new method. In simulations, the biomarker combination provided by our method demonstrated improved operating characteristics in a variety of scenarios when compared with alternative methods for constructing biomarker combinations. Thus, use of our method could lead to the development of better biomarker combinations, increasing the likelihood of clinical adoption.

中文翻译：

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通过最大化固定假阳性率的真阳性率来组合生物标志物

生物标志物在临床研究的许多领域比比皆是，研究人员通常有兴趣将它们结合起来用于诊断、预后或筛查。在许多应用中，生物标志物组合在预先指定的、临床上可接受的假阳性率 (FPR) 下的真阳性率 (TPR) 是预测能力最相关的衡量标准。我们提出了一种通过在限制 FPR 的同时最大化 TPR 来构建生物标志物组合的无分布方法。理论结果证明了新方法产生的生物标志物组合的理想特性。在模拟中，与构建生物标志物组合的替代方法相比，我们的方法提供的生物标志物组合在各种情况下表现出改进的操作特性。因此，