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Abstract

Title: A model free approach to combining biomarkers.
Author: Pfeiffer RM,Bur E
Journal: Biom J 50(4):558-70
Year: 2008
Month: August

Abstract: For most diseases, single biomarkers do not have adequate sensitivity or specificity for practical purposes. We present an approach to combine several biomarkers into a composite marker score without assuming a model for the distribution of the predictors. Using sufficient dimension reduction techniques, we replace the original markers with a lower-dimensional version, obtained through linear transformations of markers that contain sufficient information for regression of the predictors on the outcome. We combine the linear transformations using their asymptotic properties into a scalar diagnostic score via the likelihood ratio statistic. The performance of this score is assessed by the area under the receiver-operator characteristics curve (ROC), a popular summary measure of the discriminatory ability of a single continuous diagnostic marker for binary disease outcomes. An asymptotic chi-squared test for assessing individual biomarker contribution to the diagnostic score is also derived.