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

DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1standard based on HsTnT, as well as a standard TnT assay. The sensitivity and specificity of HsTnT were95.0% and 61.5%, respectively, compared with a reference standard based on the standard assay, andwere 94.3% and 69.6%, respectively, compared with a reference standard based on the high-sensitivitytroponin assay. These findings suggest that the higher sensitivity and lower specificity of high-sensitivityassays compared with standard troponin assays are not simply due to different assays being used for indextest and reference standard, but represent a genuine improvement in early sensitivity at the expense ofspecificity for a final diagnosis of MI. The lower specificity of high-sensitivity assays may be due to a greaterability to detect myocardial injury secondary to other clinical conditions. 83,84Description of diagnostic studies of heart-type fatty acid-binding proteinWe identified 17 diagnostic studies 49,50,57–59,63,64,67,68,72–78,82 of H-FABP for inclusion in the review. Table 9shows the population characteristics and Table 10 shows the index and reference standard testcharacteristics. As with the troponin studies, reporting of exclusion criteria were variable, with somestudies excluding patients with diagnostic ECG changes. The prevalence of MI varied from 15% to 73%and was relatively high, suggesting some selection of higher risk cases. The time from symptom onsetto sampling varied from 1.2 hours (mean) to 5.9 hours (median). Around half of the studies evaluatedqualitative assays, most specifying that this was the CardioDetect assay with a diagnostic threshold of7 µg/l. The threshold used by quantitative assay was variable. Most of the studies used reference standardsbased on a standard modern troponin assay, using the 10% CV or 99th percentile as a diagnosticthreshold, although not all gave details of the assay and threshold.Quality assessment of diagnostic studies of heart-type fatty acid-binding proteinFigure 14 shows the quality assessments for studies of H-FABP, while Figure 15 shows the methodologicalquality summary. The overall quality and the issues raised were similar to those for the studies of troponin.Analysis of diagnostic studies of heart-type fatty acid-binding proteinFigure 16 shows the meta-analysis of the studies of quantitative H-FABP and Figure 17 shows themeta-analysis of qualitative assays. The summary estimates of sensitivity and specificity were 81% (95%predictive interval 50–95%) and 80% (95% predictive interval 26–98%), respectively, for the quantitativeassays and 68% (95% predictive interval 11–97%) and 92% (95% predictive interval 20–100%),respectively, for the qualitative assays.Description of diagnostic studies of ischaemia-modified albuminWe identified four studies 48,61,68,70 that were eligible for inclusion in the review (Tables 11 and 12). Anumber of other studies of IMA were excluded because the reference standard was ACS, based on clinicalcriteria, and cases with MI were not reported separately. Two studies restricted recruitment to patientspresenting within 3 70 and 8 hours 61 of symptom onset. Only one study 48 reported the median time delayfrom symptom onset. Thresholds of between 75 and 91 were used for IMA. Three studies used a modernstandard troponin assay for the reference standard, whereas the older study from Christensen et al. 61inevitably used an older troponin reference standard with a higher threshold for positivity.Quality assessment of diagnostic studies of ischaemia-modified albuminFigure 18 shows the quality assessments for studies of IMA, whereas Figure 19 shows the methodologicalquality summary.Analysis of diagnostic studies of ischaemia-modified albuminFigure 20 shows the results of meta-analysis of studies of IMA. The summary estimates of sensitivityand specificity were 77% (95% predictive interval 19–98%) and 39% (95% predictive interval 2–95%),respectively.Description of diagnostic studies of myoglobinWe identified 13 diagnostic studies 18,49,52,57,58,63,64,68,69,71,74,77,79 of myoglobin for inclusion in the review.Table 13 shows the population characteristics and Table 14 shows the index and reference standard© 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.35