Covariate-specific ROC curve analysis can accommodate differences between covariate subgroups in the evaluation of diagnostic accuracy

Abstract

Objectives: We present an illustrative application of methods that account for covariates in receiver operating characteristic (ROC) curve analysis, using individual patient data on D-dimer testing for excluding pulmonary embolism.

Study design and setting: Bayesian nonparametric covariate-specific ROC curves were constructed to examine the performance/positivity thresholds in covariate subgroups. Standard ROC curves were constructed. Three scenarios were outlined based on comparison between subgroups and standard ROC curve conclusion: (1) identical distribution/identical performance, (2) different distribution/identical performance, and (3) different distribution/different performance. Scenarios were illustrated using clinical covariates. Covariate-adjusted ROC curves were also constructed.

Results: Age groups had prominent differences in D-dimer concentration, paired with differences in performance (Scenario 3). Different positivity thresholds were required to achieve the same level of sensitivity. D-dimer had identical performance, but different distributions for YEARS algorithm items (Scenario 2), and similar distributions for sex (Scenario 1). For the later covariates, comparable positivity thresholds achieved the same sensitivity. All covariate-adjusted models had AUCs comparable to the standard approach.

Conclusion: Subgroup differences in performance and distribution of results can indicate that the conventional ROC curve is not a fair representation of test performance. Estimating conditional ROC curves can improve the ability to select thresholds with greater applicability.

Keywords: Covariate-adjustment; D-dimer; Diagnostic accuracy study; Pulmonary embolism; ROC curve; Subgroup analysis.