DOVER and QUVER -: New marker combinations to detect and monitor at-risk drinking

At-risk drinking is a common medical problem. "Objective" laboratory tests are widely used, especially in situations where it might be favorable for the patient to dissimulate the existing alcohol problem. In this study, we report a new approach to combine the biological markers % carbohydrate-deficient transferrin (%CDT) and gamma-glutamyltransferase (gamma GT) to increase diagnostic properties to identify patients with at-risk drinking behavior. Fifty-eight general practitioners (GPs) participated in the study at 2 study sites in South-West Germany. Patients filled in a questionnaire that included the Alcohol Use Disorders Identification Test (AUDIT) and gave a blood sample. The GP recorded his assessment about the presence of an alcohol-related disorder in the patient. Screening results of 1 test center were used as a calculation sample. The results at the other site were used to cross-validate the study outcomes. The markers were combined by 2 methods. The first approach used the AUDIT (QUestionnaire VERified; QUVER), and the second was performed using the clinical judgment of the treating GP (DOctor VERified; DOVER). The formulas were calculated using linear and logistic regression models, respectively. A total of 2,940 patients participated in the study, of whom 2,496 completed data sets that could be used for further analysis. In the receiver-operating characteristics (ROC) curves with the reference standard of an AUDIT >= 8, the area under the curve (AUC) of 78.8% for DOVER and 80.6% (QUVER) are in a higher range than the values for gamma-%CDT (75.4%) or gamma-GT (66.3%) and %CDT (74.3%) and suggest a clear superiority of the proposed marker combinations. Regarding the combinations DOVER and QUVER, the cross-validation results were almost identical, with 78.4/78.8% and 80.6/79.5%, respectively. Our study is to date the largest practice-based trial that examines the value of the markers CDT and gamma-GT and their combinations for the screening of at-risk drinking in general practice under routine conditions. Our ROC analysis clearly demonstrated that the combination of the markers gamma-GT and %CDT under routine conditions with a behaviorally oriented reference standard leads to an improvement of diagnostic performance, more so than the use of single markers.