The idea of using measurements such as biomarkers, clinical data, or molecular biology assays for classification and prediction is popular in modern medicine. The scientific evaluation of such measures includes assessing the accuracy with which they predict the outcome of interest. Receiver operating characteristic curves are commonly used for evaluating the accuracy of diagnostic tests. They can be applied more broadly, indeed to any problem involving classification to two states or populations (D = 0 or D = 1). We show that the ROC curve can be interpreted as a cumulative distribution function for the discriminatory measure Y in the affected population (D = 1) after Y has been standardized to the distribution in the reference population (D = 0). The standardized values are called placement values. If the placement values have a uniform (0, 1) distribution, then Y is not discriminatory., because its distribution in the affected population is the same as that in the reference population. The degree to which the distribution of the standardized measure differs from uniform (0, 1) is a natural way to characterize the discriminatory capacity of Y and provides a non-traditional interpretation for the ROC curve. Statistical methods for making inference about distribution functions therefore motivate new approaches to making inference about ROC curves. We demonstrate this by considering the ROC-GLM regression model and observing that it is equivalent to a regression model for the distribution of placement values. The likelihood of the placement values provides a new approach to parameter estimation that appears to be more efficient than previously proposed methods. The methods are applied to two datatsets, one that involves comparing two biomarkers for pancreatic cancer and one that evaluates a pulmonary function measure in cystic fibrosis patients to predict the occurrence of sever acute pulmonary infection requiring hospitalization. Finally, we note the relationship between regression models for the mean placement value and recently proposed models for the area under the ROC curve, which is the classic summary index of discrimination.


Clinical Epidemiology | Epidemiology | Multivariate Analysis | Statistical Methodology | Statistical Theory