Bayesian meta-analysis of the accuracy of a test for tuberculous pleuritis in the absence of a gold standard reference

Abstract

Absence of a perfect reference test is an acknowledged source of bias in diagnostic studies. In the case of tuberculous pleuritis, standard reference tests such as smear microscopy, culture and biopsy have poor sensitivity. Yet meta-analyses of new tests for this disease have always assumed the reference standard is perfect, leading to biased estimates of the new test's accuracy. We describe a method for joint meta-analysis of sensitivity and specificity of the diagnostic test under evaluation, while considering the imperfect nature of the reference standard. We use a Bayesian hierarchical model that takes into account within- and between-study variability. We show how to obtain pooled estimates of sensitivity and specificity, and how to plot a hierarchical summary receiver operating characteristic curve. We describe extensions of the model to situations where multiple reference tests are used, and where index and reference tests are conditionally dependent. The performance of the model is evaluated using simulations and illustrated using data from a meta-analysis of nucleic acid amplification tests (NAATs) for tuberculous pleuritis. The estimate of NAAT specificity was higher and the sensitivity lower compared to a model that assumed that the reference test was perfect.

Figure 1

Summary receiver operating characteristic curves for competing meta-analysis models of sensitivity and specificity of an in-house nucleic acid amplification test for tuberculous pleuritis (IS6110).