A SIMEX approach for meta-analysis of diagnostic accuracy studies with attention to ROC curves.

Bivariate random-effects models represent an established approach for meta-analysis of accuracy measures of a diagnostic test, which are typically given by sensitivity and specificity. A recent formulation of the classical model describes the test accuracy in terms of study-specific Receiver Operating Characteristics curves. In this way, the resulting summary curve can be thought of as an average of the study-specific Receiver Operating Characteristics curves. Within this framework, the paper shows that the standard likelihood approach for inference is prone to several issues. Small sample size can give rise to unreliable conclusions and convergence problems deeply affect the analysis. The proposed alternative is a simulation-extrapolation method, called SIMEX, developed within the measurement error literature. It suits the meta-analysis framework, as the accuracy measures provided by the studies are estimates rather than true values, and thus are prone to error. The methods are compared in a series of simulation studies, covering different scenarios of interest, including deviations from normality assumptions. SIMEX reveals a satisfactory strategy, providing more accurate inferential results if compared to the likelihood approach, while avoiding convergence failure. The approaches are applied to a meta-analysis of the accuracy of the ultrasound exam for diagnosing abdominal tuberculosis in HIV-positive subjects.