Adjusting receiver operating characteristic curves and related indices for covariates

Continuous markers are often used to discriminate between diseased and healthy populations. In this context, the receiver operating characteristic (ROC) curve is a popular graphical visualization of the discriminatory effectiveness of the marker. Several indices which summarize the discriminatory power of the marker are used, the most common being the area under the ROC curve and the Youden index. We examine covariate effects on these indices, assuming that the marker, possibly transformed, follows the normal distribution. The ROC curve adjusted for covariates is estimated and approximate adjusted confidence intervals for the area under the ROC curve are provided. Further, we investigate bootstrap confidence intervals for both the Youden index and the corresponding critical threshold value, both adjusted for covariates. We motivate this methodology with an example of fingerstick post-prandial blood glucose as a marker for diabetes patients where age is known to be an important covariate for this marker, and we examine how age influences the discriminatory power of the marker.