A Statistical Challenge: Developing Tests for Biomarker Utility Specific to the Intended Use
A partir d'une base de données portant sur 10 000 individus, cette étude analyse la validité statistique d'un indicateur appelé "Net Reclassification Index", couramment utilisé dans les études sur des biomarqueurs prédictifs d'un risque de cancer
Does my biomarker have clinical value? With the advent of -omics techniques, this important question now arises far more frequently in oncology research. In 1988, two statisticians and a gynecologic oncologist (1) collaborated to develop an omnibus answer: calculate the receiver operator curve with and without the biomarker and compare the areas under the curve (AUCs). Assessing the increase in the AUC’s statistical significance built on pioneering research by Hoeffding in the late 1940s (2). His statistical breakthrough showed that for a wide class of nonparametric “statistics” the standard Normal distribution was applicable for assessing statistical significance (P values) when the sample size was sufficiently large. DeLong et al. (1) showed that the increase in the AUC belonged to this general class of “statistics,” enabling the powerful theory of U statistics (U for unbiased) to gauge accurately its statistical significance with a simple Normal distribution z test. The appeal of the AUC was its general applicability because it was nonparametric; the power of U statistics was that the derived standard error accounted correctly for the implicit correlation between the two curves (with and without the biomarker) evaluated on the same patients. The oncologist made the vital contribution of defining a clear clinical indication for the biomarker—namely, “when to perform surgical correction of intestinal obstruction in patients known to have ovarian carcinoma.”(1)
However, the generality of the AUC results in a less powerful test than one constructed for a specific intended use. The AUC is the average sensitivity across all specificities from 0% to 100%, which dilutes the signal for a particular clinical question when the range of relevant specificities is narrow. For example, early detection of ovarian cancer in the general postmenopausal population with a blood test requires a biomarker …
Journal of the National Cancer Institute , éditorial, 2014