Testing hypotheses about medical test accuracy: considerations for design and inference

Developing new medical tests and identifying single biomarkers or panels of biomarkers with superior accuracy over existing classifiers promotes lifelong health of individuals and populations. Before a medical test can be routinely used in clinical practice, its accuracy within diseased and non-diseased populations must be rigorously evaluated. We introduce a method for sample size determination for studies designed to test hypotheses about medical test or biomarker sensitivity and specificity. We show how a sample size can be determined to guard against making type I and/or type II errors by calculating Bayes factors from multiple data sets simulated under null and/or alternative models. The approach can be implemented across a variety of study designs, including investigations into one test or two conditionally independent or dependent tests. We focus on a general setting that involves non-identifiable models for data when true disease status is unavailable due to the nonexistence of or undesirable side effects from a perfectly accurate (i.e. ‘gold standard’) test; special cases of the general method apply to identifiable models with or without gold-standard data. Calculation of Bayes factors is performed by incorporating prior information for model parameters (e.g. sensitivity, specificity, and disease prevalence) and augmenting the observed test-outcome data with unobserved latent data on disease status to facilitate Gibbs sampling from posterior distributions. We illustrate our methods using a thorough simulation study and an application to toxoplasmosis.