Design-related bias in studies investigating diagnostic tests for venous thromboembolic diseases: a systematic review and meta-analysis

Background Early detection and diagnosis of venous thromboembolism are vital for effective treatment. To what extent methodological shortcomings exist in studies of diagnostic tests and whether this affects published test performance is unknown. Objectives We aimed to assess the methodological quality of studies evaluating diagnostic tests for venous thromboembolic diseases and quantify the direction and impact of design characteristics on diagnostic performance. Methods We conducted a literature search using Medline and Embase databases for systematic reviews summarizing diagnostic accuracy studies for five target disorders associated with venous thromboembolism. The following data were extracted for each primary study: methodological characteristics, the risk of bias scored by the QUADAS QUADAS-2 instrument, and numbers of true-positives, true-negatives, false-positives, and false-negatives. In a meta-analysis, we compared diagnostic accuracy measures from studies unlikely to be biased with those likely to be biased. Results Eighty-five systematic reviews comprising 1'818 primary studies were included. Adequate quality assessment tools were used in 43 systematic reviews only (51%). The risk of bias was estimated to be low for all items in 23% of the primary studies. A high or unclear risk of bias in particular domains of the QUADAS/QUADAS-2 tool was associated with marked differences in the reported sensitivity and specificity. Conclusions Significant limitations in the methodological quality of studies assessing diagnostic tests for venous thromboembolic disorders exist, and studies at risk of bias are unlikely to report valid estimates of test performance. Established guidelines for evaluation of diagnostic tests should be more systematically adopted. Systematic Review Registration PROSPERO (CRD 42021264912).