Generalized Confidence Interval Estimation for the Difference in Paired Areas Under the ROC Curves in the Absence of a Gold Standard

Receiver operating characteristic (ROC) curves can be used to assess the accuracy of tests measured on ordinal or continuous scales. The most commonly used measure for the overall diagnostic accuracy of diagnostic tests is the area under the ROC curve (AUC). A gold standard (GS) test on the true disease status is required to estimate the AUC. However, a GS test may be too expensive or infeasible. In many medical researches, the true disease status of the subjects may remain unknown. Under the normality assumption on test results from each disease group of subjects, we propose a heuristic method of estimating confidence intervals for the difference in paired AUCs of two diagnostic tests in the absence of a GS reference. This heuristic method is a three-stage method by combining the expectation-maximization (EM) algorithm, bootstrap method, and an estimation based on asymptotic generalized pivotal quantities (GPQs) to construct generalized confidence intervals for the difference in paired AUCs in the absence of a GS. Simulation results show that the proposed interval estimation procedure yields satisfactory coverage probabilities and expected interval lengths. The numerical example using a published dataset illustrates the proposed method.