title: Nonparametric Bayesian covariate-adjusted estimation of the Youden index.
abstract: A novel nonparametric regression model is developed for evaluating the covariate-specific accuracy of a continuous biological marker. Accurately screening diseased from nondiseased individuals and correctly diagnosing disease stage are critically important to health care on several fronts, including guiding recommendations about combinations of treatments and their intensities. The accuracy of a continuous medical test or biomarker varies by the cutoff threshold (c) used to infer disease status. Accuracy can be measured by the probability of testing positive for diseased individuals (the true positive probability or sensitivity, Se(c), of the test), and the true negative probability (specificity, Sp(c)) of the test. A commonly used summary measure of test accuracy is the Youden index, YI=max{Se(c)+Sp(c)-1:c∈ℝ}, which is popular due in part to its ease of interpretation and relevance to population health research. In addition, clinical practitioners benefit from having an estimate of the optimal cutoff that maximizes sensitivity plus specificity available as a byproduct of estimating YI. We develop a highly flexible nonparametric model to estimate YI and its associated optimal cutoff that can respond to unanticipated skewness, multimodality, and other complexities because data distributions are modeled using dependent Dirichlet process mixtures. Important theoretical results on the support properties of the model are detailed. Inferences are available for the covariate-specific Youden index and its corresponding optimal cutoff threshold. The value of our nonparametric regression model is illustrated using multiple simulation studies and data on the age-specific accuracy of glucose as a biomarker of diabetes.
authors.affiliation: School of Mathematics, University of Edinburgh, Scotland, U.K.
authors.forename: Vanda
authors.initials: V
authors.lastname: Inácio de Carvalho
authors.affiliation: School of Mathematics, University of Edinburgh, Scotland, U.K.
authors.forename: Miguel
authors.identifier: 0000-0003-3248-6984
authors.initials: M
authors.lastname: de Carvalho
authors.affiliation: College of Public Health and Human Sciences, Oregon State University, Oregon, U.S.A.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Branscum
mesh_terms: D001499:Bayes Theorem; D015415:Biomarkers; D001786:Blood Glucose / Q000032:analysis; D003198:Computer Simulation; D003920:Diabetes Mellitus / Q000175:diagnosis; D006801:Humans; D015233:Models, Statistical; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D001786:Blood Glucose
keywords: Diagnostic test; Dirichlet process mixtures; Optimal cutoff; Sensitivity; Specificity