Confidence interval estimation of the difference between two sensitivities to the early disease stage

Biom J. 2014 Mar;56(2):270-86. doi: 10.1002/bimj.201200012. Epub 2013 Nov 22.


Although most of the statistical methods for diagnostic studies focus on disease processes with binary disease status, many diseases can be naturally classified into three ordinal diagnostic categories, that is normal, early stage, and fully diseased. For such diseases, the volume under the ROC surface (VUS) is the most commonly used index of diagnostic accuracy. Because the early disease stage is most likely the optimal time window for therapeutic intervention, the sensitivity to the early diseased stage has been suggested as another diagnostic measure. For the purpose of comparing the diagnostic abilities on early disease detection between two markers, it is of interest to estimate the confidence interval of the difference between sensitivities to the early diseased stage. In this paper, we present both parametric and non-parametric methods for this purpose. An extensive simulation study is carried out for a variety of settings for the purpose of evaluating and comparing the performance of the proposed methods. A real example of Alzheimer's disease (AD) is analyzed using the proposed approaches.

Keywords: Box-Cox transformation; Diagnostic studies; Disease with three ordinal stages; Generalized inference; Sensitivity to the early diseased stage.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Alzheimer Disease / diagnosis*
  • Biometry / methods*
  • Confidence Intervals
  • Humans
  • Models, Statistical
  • Sensitivity and Specificity
  • Statistics, Nonparametric