Exploring sources of heterogeneity in systematic reviews of diagnostic tests

TLDR

Heterogeneity in diagnostic test reviews arises from differences in positivity cutpoints, patient selection, clinical setting, test type, reference standard, and study design flaws. This paper critically examines potential reasons for heterogeneity and the methods to explore them. The authors review empirical evidence for varied sources of variation, demonstrate incorporating these sources into systematic reviews, and discuss regression techniques to extract additional information. Analyses of variability help clarify transferability of diagnostic tests, identify flaws in primary studies, and guide the design of future research.

Abstract

It is indispensable for any meta-analysis that potential sources of heterogeneity are examined, before one considers pooling the results of primary studies into summary estimates with enhanced precision. In reviews of studies on the diagnostic accuracy of tests, variability beyond chance can be attributed to between-study differences in the selected cutpoint for positivity, in patient selection and clinical setting, in the type of test used, in the type of reference standard, or any combination of these factors. In addition, heterogeneity in study results can also be caused by flaws in study design. This paper critically examines some of the potential reasons for heterogeneity and the methods to explore them. Empirical support for the existence of different sources of variation is reviewed. Incorporation of sources of variability explicitly into systematic reviews on diagnostic accuracy is demonstrated with data from a recent review. Application of regression techniques in meta-analysis of diagnostic tests can provide relevant additional information. Results of such analyses will help understand problems with the transferability of diagnostic tests and to point out flaws in primary studies. As such, they can guide the design of future studies.