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

DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1TABLE 18 Sensitivity and specificity of combinations of biomarkers with troponin vs troponin aloneTroponin aloneCombinationStudyCombinationSensitivity(95% CI)Specificity(95% CI)Sensitivity(95% CI)Specificity(95% CI)Body TnI or H-FABP 0.42 (0.33 to 0.51) 0.96 (0.94 to 0.97) 0.82 (0.74 to 0.88) 0.88 (0.83 to 0.88)2011 57Haltern TnT or H-FABP 0.74 (0.66 to 0.74) 1.00 (0.96 to 1.0) 0.97 (0.86 to 0.99) 0.65 (0.60 to 0.66)2010 67McCann TnT or H-FABP 0.75 (0.69 to 0.81) 0.94 (0.9 to 0.96) 0.93 (0.89 to 0.96) 0.93 (0.89 to 0.96)2008 76Mion TnI or H-FABP 0.55 (0.39 to 0.70) 0.98 (0.92 to 1.00) 0.76 (0.60 to 0.87) 0.93 (0.86 to 0.97)2007 77Keller TnT or2010 71 copeptinReichlin TnT or2009 80 copeptinKeller TnT or2010 71 myoglobinMion TnI or2007 77 myoglobin0.62 (0.56 to 0.67) 0.97 (0.96 to 0.98) 0.88 (0.83 to 0.91) a 0.76 (0.73 to 0.79) a0.75 (0.65 to 0.83) 0.94 (0.91 to 0.96) 0.99 (0.92 to 1.00) b 0.77 (0.73 to 0.81) b0.62 (0.56 to 0.67) 0.97 (0.96 to 0.98) 0.81 (0.76 to 0.85) 0.85 (0.82 to 0.87)0.55 (0.39 to 0.70) 0.98 (0.92 to 1.00) 0.83 (0.68 to 0.92) 0.92 (0.84 to 0.97)Collinson TnT or IMA 0.95 (0.8 to 0.99) 0.95 (0.92 to 0.97) 1.00 (0.88 to 1.00) 0.35 (0.31 to 0.40)2006 48Keating TnI or IMA 0.74 (0.58 to 0.86) 0.99 (0.97 to 1.00) 0.98 (0.86 to 1.00) 0.14 (0.10 to 0.19)2006 70Apple TnI and CRP 0.72 (0.51 to 0.88) 0.89 (0.85 to 0.92) 0.56 (0.35 to 0.76) 0.95 (0.92 to 0.97)2009 55Apple TnI and MMP9 0.72 (0.51 to 0.88) 0.89 (0.85 to 0.92) 0.68 (0.47 to 0.85) 0.91 (0.88 to 0.94)2009 55a Results for copeptin threshold 13 pmol/l (97.5th percentile); 95th and 99th were also reported.b Results for copeptin threshold 14 pmol/l; 9, 20 and 24 pmol/l were also reported.can achieve sensitivity at presentation close to, or exceeding, 90%. However, maximising early sensitivityinvolves some loss of specificity. Only one study 60 compared presentation testing with a high-sensitivityassay with a reference standard based on a high-sensitivity assay and showed that the loss of specificity didnot seem to be explained by using a standard troponin assay in the reference standard.Many other biomarkers have been tested for their ability to detect MI at presentation but of those weset out to investigate only myoglobin and H-FABP have been evaluated against an acceptable referencestandard in a large number of studies. In general, the alternative biomarkers had inadequate diagnosticaccuracy to act as a single diagnostic test for MI at presentation. When used in combination withtroponin a number of biomarkers (H-FABP, copeptin, IMA and myoglobin) improved sensitivity for MI atpresentation, but at the expense of loss of specificity. Similar changes in sensitivity and specificity can beachieved with troponin as a single test by using a high-sensitivity assay.Overview of biomarker studies included in the prognostic reviewWe identified 44 studies 46–51,85–122 for inclusion in the prognostic accuracy review. These are listed alongwith the relevant biomarkers in Table 19. We have only listed the biomarkers identified for our review.Some studies evaluated additional biomarkers. Five studies 46,48–51 reported both prognostic and diagnostic© 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.55