Components-of-variance models for random-effects ROC analysis: The case of unequal variance structures across modalities

Rationale and Objectives. Several of the authors have previously published an analysis of multiple sources of uncertainty in the receiver operating characteristic (ROC) assessment and comparison of diagnostic modalities. The analysis assumed that the components of variance were the same for the modalities under comparison. The purpose of the present work is to obtain a generalization that does not require that assumption. Materials and Methods. The generalization is achieved by splitting three of the six components of variance in the previous model into modality-dependent contributions. Two distinct formulations of this approach can be obtained from alternative choices of the three components to be split; however, a one-to-one relationship exists between the magnitudes of the components estimated from these two formulations. Results, The method is applied to a study of multiple readers, with and without the aid of a computer-assist modality, performing the task of discriminating between benign and malignant clusters of microcalcifications. Analysis according to the first method of splitting shows large decreases in the reader and reader-by-case components of variance when the computer assist is used by the readers. Analysis in terms of the alternative splitting shows large decreases in the corresponding modality-interaction components. Conclusion. A solution to the problem of multivariate ROC analysis without the assumption of equal variance structure across modalities has been provided. Alternative formulations lead to consistent results related by a one-to-one mapping. A surprising result is that estimates of confidence intervals and numbers of cases and readers required for a specified confidence interval remain the same in the more general model as in the restricted model.