Attwood Kristopher, Tian Lili, Xiong Chengjie
a Department of Biostatistics , University at Buffalo , Buffalo , New York , USA.
J Biopharm Stat. 2014;24(3):608-33. doi: 10.1080/10543406.2014.888437.
In practice, there exist many disease processes with three ordinal disease classes; for example, in the detection of Alzheimer's disease (AD) a patient can be classified as healthy (disease-free stage), mild cognitive impairment (early disease stage), or AD (full disease stage). The treatment interventions and effectiveness of such disease processes will depend on the disease stage. Therefore, it is important to develop diagnostic tests with the ability to discriminate between the three disease stages. Measuring the overall ability of diagnostic tests to discriminate between the three classes has been discussed extensively in the literature. However, there has been little proposed on how to select clinically meaningful thresholds for such diagnostic tests, except for a method based on the generalized Youden index by Nakas et al. (2010). In this article, we propose two new criteria for selecting diagnostic thresholds in the three-class setting. The numerical study demonstrated that the proposed methods may provide thresholds with less variability and more balance among the correct classification rates for the three stages. The proposed methods are applied to two real examples: the clinical diagnosis of AD from the Washington University Alzheimer's Disease Research Center and the detection of liver cancer (LC) using protein segments.
在实际应用中,存在许多具有三个有序疾病类别的疾病过程;例如,在阿尔茨海默病(AD)的检测中,患者可被分类为健康(无病阶段)、轻度认知障碍(疾病早期阶段)或AD(疾病完全阶段)。此类疾病过程的治疗干预措施和效果将取决于疾病阶段。因此,开发能够区分这三个疾病阶段的诊断测试非常重要。测量诊断测试区分这三个类别的总体能力在文献中已有广泛讨论。然而,除了Nakas等人(2010年)基于广义约登指数的方法外,关于如何为此类诊断测试选择具有临床意义的阈值的提议很少。在本文中,我们提出了两个在三类设置中选择诊断阈值的新标准。数值研究表明,所提出的方法可能会提供变异性较小且三个阶段正确分类率之间更平衡的阈值。所提出的方法应用于两个实际例子:来自华盛顿大学阿尔茨海默病研究中心的AD临床诊断以及使用蛋白质片段检测肝癌(LC)。