Significance tests for covariates in the diagnostic accuracy index of a biomarker against a continuous gold standard.

Receiver operating characteristic (ROC) curve is a popular tool to describe and compare the diagnostic accuracy of biomarkers when a binary-scale gold standard is available. However, there are many examples of diagnostic tests whose gold standards are continuous. Hence, Several extensions of receiver operating characteristic (ROC) curve are proposed to evaluate the diagnostic potential of biomarkers when the gold standard is continuous-scale. Moreover, in evaluating these biomarkers, it is often necessary to consider the effects of covariates on the diagnostic accuracy of the biomarker of interest. Covariates may include subject characteristics, expertise of the test operator, test procedures or aspects of specimen handling. Applying the covariate adjustment to the case that the gold standard is continuous is challenging and has not been addressed in the literature. To fill the gap, we propose two general testing frameworks to account for the covariates effect on diagnostic accuracy. Simulation studies are conducted to compare the proposed tests. Data from a study that assessed three types of imaging modalities with the purpose of detecting neoplastic colon polyps and cancers are used to illustrate the proposed methods.