Measuring diagnostic accuracy for biomarkers under tree-ordering.

In the field of diagnostic studies for tree or umbrella ordering, under which the marker measurement for one class is lower or higher than those for the rest unordered classes, there exist a few diagnostic measures such as the naive AUC ( NAUC), the umbrella volume ( UV), and the recently proposed TAUC, i.e. area under a ROC curve for tree or umbrella ordering (TROC). However, an important characteristic about tree or umbrella ordering has been neglected. This paper mainly focuses on promoting the use of the integrated false negative rate under tree ordering ( ITFNR) as an additional diagnostic measure besides TAUC, and proposing the idea of using ( TAUC, ITFNR) instead of TAUC to evaluate the diagnostic accuracy of a biomarker under tree or umbrella ordering. Parametric and non-parametric approaches for constructing joint confidence region of ( TAUC, ITFNR) are proposed. Simulation studies under a variety of settings are carried out to assess and compare the performance of these methods. In the end, a published microarray data set is analyzed.