Quantifying performance of a diagnostic test as the expected information for discrimination: Relation to the C-statistic.

Although the C-statistic is widely used for evaluating the performance of diagnostic tests, its limitations for evaluating the predictive performance of biomarker panels have been widely discussed. The increment in C obtained by adding a new biomarker to a predictive model has no direct interpretation, and the relevance of the C-statistic to risk stratification is not obvious. This paper proposes that the C-statistic should be replaced by the expected information for discriminating between cases and non-cases (expected weight of evidence, denoted as Λ), and that the strength of evidence favouring one model over another should be evaluated by cross-validation as the difference in test log-likelihoods. Contributions of independent variables to predictive performance are additive on the scale of Λ. Where the effective number of independent predictors is large, the value of Λ is sufficient to characterize fully how the predictor will stratify risk in a population with given prior probability of disease, and the C-statistic can be interpreted as a mapping of Λ to the interval from 0.5 to 1. Even where this asymptotic relationship does not hold, there is a one-to-one mapping between the distributions in cases and non-cases of the weight of evidence favouring case over non-case status, and the quantiles of these distributions can be used to calculate how the predictor will stratify risk. This proposed approach to reporting predictive performance is demonstrated by analysis of a dataset on the contribution of microbiome profile to diagnosis of colorectal cancer.