Nonparametric methods for analysing the accuracy of diagnostic tests with multiple readers.

The evaluation of diagnostic agents or imaging procedures is governed by the same scientific and regulatory rules as that of other medical products. Receiver operating characteristic (ROC) curves, and especially the area under these ROC curves, are indices for the accuracy of a diagnostic test for continuous as well as ordinal data. The methodology of multivariate rank statistics for the nonparametric Behrens-Fisher problem is used to evaluate the accuracy of a diagnostic test in a complex factorial design with repeated measurements. Hypotheses are formulated by means of relative treatment effects and are tested by a multivariate extension of the Mann-Whitney statistic in a heteroscedastic model. The application of this method is demonstrated by the analysis of a data set from a diagnostic clinical trial.