The Youden Index and the optimal cut-point corrected for measurement error.
Random measurement error can attenuate a biomarker's ability to discriminate between diseased and non-diseased populations. A global measure of biomarker effectiveness is the Youden index, the maximum difference between sensitivity, the probability of correctly classifying diseased individuals, and 1-specificity, the probability of incorrectly classifying health individuals. We present an approach for estimating the Youden index and associated optimal cut-point for a normally distributed biomarker that corrects for normally distributed random measurement error. We also provide confidence intervals for these corrected estimates using the delta method and coverage probability through simulation over a variety of situations. Applying these techniques to the biomarker thiobarbituric acid reaction substance (TBARS), a measure of sub-products of lipid peroxidation that has been proposed as a discriminating measurement for cardiovascular disease, yields a 50% increase in diagnostic effectiveness at the optimal cut-point. This result may lead to biomarkers that were once naively considered ineffective becoming useful diagnostic devices.
Perkins
Neil J
NJ
Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
Schisterman
Enrique F
EF
D015415:Biomarkers / Q000097:blood; D003198:Computer Simulation; D016001:Confidence Intervals; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis*; D003627:Data Interpretation, Statistical; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D012372:ROC Curve; D015203:Reproducibility of Results; D012107:Research Design; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis*
D015415:Biomarkers; D017392:Thiobarbituric Acid Reactive Substances