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A semiparametric method for comparing the discriminatory ability of biomarkers subject to limit of detection

机译:一种半参数方法用于比较受检测限限制的生物标志物的区分能力

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摘要

Receiver operating characteristic curves and the area under the curves (AUC) are often used to compare the discriminatory ability of potentially correlated biomarkers. Many biomarkers are subject to limit of detection due to the instrumental limitation in measurements and may not be normally distributed. Standard parametric methods assuming normality can lead to biased results when the normality assumption is violated. We propose new estimation and inference procedures for the AUCs of biomarkers subject to limit of detection by using the semiparametric transformation model allowing for heteroscedasticity. We obtain the nonparametric maximum likelihood estimators by maximizing the likelihood for the observed data with limit of detection. The proposed estimators are shown to be consistent, asymptotically normal, and asymptotically efficient. Additionally, we propose a Wald type test statistic to compare the AUCs of 2 potentially correlated biomarkers with limit of detection. Extensive simulation studies demonstrate that the proposed method is robust to non-normality while performing as well as its parametric counterpart when the normality assumption is true. An application to an autism study is provided.
机译:接收器工作特性曲线和曲线下面积(AUC)通常用于比较潜在相关生物标记物的区分能力。由于测量中仪器的局限性,许多生物标志物都受到检测的限制,因此可能无法正常分布。当违反正态性假设时,假设正态性的标准参数方法可能导致结果有偏差。我们通过使用允许异方差性的半参数转换模型,为受检测限的生物标志物的AUC提出了新的估计和推断程序。我们通过在检测限范围内最大化观测数据的似然性来获得非参数最大似然估计器。所提出的估计量被证明是一致的,渐近正态的和渐近有效的。此外,我们提出了Wald型检验统计量,以比较2种潜在相关生物标记物的AUC与检测限。大量的仿真研究表明,所提出的方法对非正态性具有鲁棒性,同时在正态性假设成立的情况下其参数对应性也很好。提供了对自闭症研究的应用。

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