title: LOGISTIC REGRESSION ANALYSIS WITH STANDARDIZED MARKERS.
abstract: Two different approaches to analysis of data from diagnostic biomarker studies are commonly employed. Logistic regression is used to fit models for probability of disease given marker values while ROC curves and risk distributions are used to evaluate classification performance. In this paper we present a method that simultaneously accomplishes both tasks. The key step is to standardize markers relative to the non-diseased population before including them in the logistic regression model. Among the advantages of this method are: (i) ensuring that results from regression and performance assessments are consistent with each other; (ii) allowing covariate adjustment and covariate effects on ROC curves to be handled in a familiar way, and (iii) providing a mechanism to incorporate important assumptions about structure in the ROC curve into the fitted risk model. We develop the method in detail for the problem of combining biomarker datasets derived from multiple studies, populations or biomarker measurement platforms, when ROC curves are similar across data sources. The methods are applicable to both cohort and case-control sampling designs. The dataset motivating this application concerns Prostate Cancer Antigen 3 (PCA3) for diagnosis of prostate cancer in patients with or without previous negative biopsy where the ROC curves for PCA3 are found to be the same in the two populations. Estimated constrained maximum likelihood and empirical likelihood estimators are derived. The estimators are compared in simulation studies and the methods are illustrated with the PCA3 dataset.
authors.affiliation: Fred Hutchinson Cancer Research Center Public Health Sciences 1100 Fairview Avenue N., Seattle, WA 98109 ; University of Washington, Department of Biostatistics, Seattle, WA, 98195.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Pepe
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
keywords: ROC curve; constrained likelihood; empirical likelihood; logistic regression; predictiveness curve