The Youden Index and the optimal cut-point corrected for measurement error

Biom J. 2005 Aug;47(4):428-41. doi: 10.1002/bimj.200410133.


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.

Publication types

  • Evaluation Study

MeSH terms

  • Biomarkers / blood
  • Computer Simulation
  • Confidence Intervals
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / diagnosis*
  • Data Interpretation, Statistical*
  • Diagnosis, Computer-Assisted / methods*
  • Humans
  • Models, Biological*
  • Models, Statistical*
  • ROC Curve*
  • Reproducibility of Results
  • Research Design
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Thiobarbituric Acid Reactive Substances / analysis*


  • Biomarkers
  • Thiobarbituric Acid Reactive Substances