Systematic review, meta-analysis and economic modelling of ...

DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1TABLE 2 Studies and biomarkers included in the diagnostic accuracy review (continued)StudyReichlin 2009 80Reichlin 2009 19Rudolf 2010 81Valle 2008 82Relevant index test biomarkers in studyCopeptinTnI, TnTTnI, MPOTnT, H-FABPCD4OL, CD4O ligand.Analysis of diagnostic accuracy studies of presentation troponinTables 7 and 8 show the reported sensitivity and specificity of each assay at key thresholds in each studyof TnI and TnT, respectively. The studies used a variety of different assays and thresholds for positivity. Inconsequence, there is a wide range of reported values for sensitivity and specificity.We did not undertake meta-analysis across all studies because of variation in the assays and thresholdsused, with some studies using high thresholds with no clear basis. Instead, we undertook separateanalyses for TnI and TnT using the 99th percentile or 10% CV threshold, when these data were reported(Figures 7–10). The studies by Christ and Popp 60 and Reichlin et al. 19 reported data for more than oneassay in each potential analysis, so we selected data from one assay in each analysis. We also analysed thefollowing high-sensitivity assays using the 99th percentile (Figures 11–13):1. ADVIA Centaur Ultra troponin I (Siemens Healthcare, Basel, Switzerland)2. Abbott Architect troponin I (Abbott Laboratories, IL, USA)3. Roche hsTnT. (Roche Diagnostics, Basel, Switzerland).The results show that sensitivity and specificity for TnI were 77% (95% predictive interval 29–96%) and93% (95% predictive interval 46–100%), respectively, when the 99th percentile was used and 82% (95%predictive interval 40–97%) and 93% (95% predictive interval 74–98%) when the 10% CV was used. Thisapparently counterintuitive finding (lower sensitivity at a lower diagnostic threshold) is probably explainedby either random error or differences in the study populations or assays included in the two analyses.The corresponding results for TnT were 80% (95% predictive interval 33–97%) and 91% (95% predictiveinterval 53–99%) when the 99th percentile was used and 74% (95% predictive interval 34–94%) and 96%(95% predictive interval 76–99%) when the 10% CV was used, suggesting that different thresholds providea trade-off between sensitivity and specificity. The differences between point estimates of sensitivity andspecificity for TnI and TnT probably reflect differences in the assays or thresholds evaluated, the constituentstudy populations or random error, rather than a systematic difference between TnI and TnT. The credibleranges for the estimates differed markedly depending upon whether the pooled effect or predictive effectwas estimated, reflecting the marked heterogeneity between the studies. The predictive distribution is likelyto provide the most appropriate reflection of uncertainty and is used in the cost-effectiveness modelling.The high-sensitivity assays unsurprisingly had higher sensitivity but lower specificity, although withconsiderable uncertainty reflected in the wide predictive intervals for their estimates. The Roche HsTnTassay had a sensitivity of 96% (95% predictive interval 27–100%) and a specificity of 72% (95% predictiveinterval 3–96%). The ADVIA Centaur Ultra-TnI assay had a sensitivity of 86% (95% predictive interval22–96%) and a specificity of 89% (95% predictive interval 40–97%). The Abbot Architect troponin I assayhad a sensitivity of 83% (95% predictive interval 58–95%) and a specificity of 95% (95% predictive interval67–100%).These analyses compared high-sensitivity troponin index tests with a reference standard based on astandard troponin assay. We identified one study 60 that compared HsTnT at presentation with a reference© Queen’s Printer and Controller of HMSO 2013. This work was produced by Goodacre et al. under the terms of a commissioning contract issued by the Secretary of Statefor Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journalsprovided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should beaddressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton SciencePark, Southampton SO16 7NS, UK.19