Assessment <strong>of</strong> diagnostic <strong>and</strong> prognostic accuracyStudy TP FP FN TN Sensitivity Specificity Sensitivity SpecificityApple 2008 54 36 52 13 270 0.76 (0.63 to 0.86) 0.84 (0.80 to 0.88)Keller 2009 20 375 138 38 1267 0.91 (0.88 to 0.93) 0.90 (0.89 to 0.92)Reichlin 2009 19 109 48 14 547 0.89 (0.83 to 0.93) 0.92 (0.90 to 0.94)Pooled effect 0.86 (0.60 to 0.96) 0.89 (0.70 to 0.97)Predictive effect 0.86 (0.26 to 0.99) 0.89 (0.40 to 0.99)0 0.2 0.4 0.6 0.8 1.00 0.2 0.4 0.6 0.8 1.0FIGURE 11 Meta-<strong>analysis</strong> <strong>of</strong> studies <strong>of</strong> ADVIA Centaur Ultra TnI.Study TP FP FN TN Sensitivity Specificity Sensitivity SpecificityIlva 2009 50 105 0 29 158 0.79 (0.72 to 0.85) 0.99 (0.96 to 1.00)Reichlin 2009 19 105 42 18 553 0.85 (0.79 to 0.90) 0.93 (0.91 to 0.95)Rudolph 2010 81 86 17 14 157 0.86 (0.79 to 0.91) 0.91 (0.86 to 0.95)Pooled effect 0.84 (0.72 to 0.91) 0.95 (0.86 to 0.99)Predictive effect 0.84 (0.58 to 0.95) 0.95 (0.67 to 1.00)0 0.2 0.4 0.6 0.8 1.00 0.2 0.4 0.6 0.8 1.0FIGURE 12 Meta-<strong>analysis</strong> <strong>of</strong> studies <strong>of</strong> Abbott Architect TnI.Study TP FP FN TN Sensitivity Specificity Sensitivity SpecificityChrist 2010 60 19 45 1 72 0.96 (0.84 to 0.99) 0.62 (0.53 to 0.71)Reichlin 2009 19 117 119 6 476 0.95 (0.91 to 0.98) 0.80 (0.77 to 0.83)Pooled effect 0.96 (0.66 to 1.00) 0.72 (0.16 to 0.96)Predictive effect 0.96 (0.27 to 1.00) 0.72 (0.03 to 0.99)0 0.2 0.4 0.6 0.8 1.00 0.2 0.4 0.6 0.8 1.0FIGURE 13 Meta-<strong>analysis</strong> <strong>of</strong> studies <strong>of</strong> Roche HsTnT.34NIHR Journals Library
DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1st<strong>and</strong>ard based on HsTnT, as well as a st<strong>and</strong>ard TnT assay. The sensitivity <strong>and</strong> specificity <strong>of</strong> HsTnT were95.0% <strong>and</strong> 61.5%, respectively, compared with a reference st<strong>and</strong>ard based on the st<strong>and</strong>ard assay, <strong>and</strong>were 94.3% <strong>and</strong> 69.6%, respectively, compared with a reference st<strong>and</strong>ard based on the high-sensitivitytroponin assay. These findings suggest that the higher sensitivity <strong>and</strong> lower specificity <strong>of</strong> high-sensitivityassays compared with st<strong>and</strong>ard troponin assays are not simply due to different assays being used for indextest <strong>and</strong> reference st<strong>and</strong>ard, but represent a genuine improvement in early sensitivity at the expense <strong>of</strong>specificity for a final diagnosis <strong>of</strong> MI. The lower specificity <strong>of</strong> high-sensitivity assays may be due to a greaterability to detect myocardial injury secondary to other clinical conditions. 83,84Description <strong>of</strong> diagnostic studies <strong>of</strong> heart-type fatty acid-binding proteinWe identified 17 diagnostic studies 49,50,57–59,63,64,67,68,72–78,82 <strong>of</strong> H-FABP for inclusion in the <strong>review</strong>. Table 9shows the population characteristics <strong>and</strong> Table 10 shows the index <strong>and</strong> reference st<strong>and</strong>ard testcharacteristics. As with the troponin studies, reporting <strong>of</strong> exclusion criteria were variable, with somestudies excluding patients with diagnostic ECG changes. The prevalence <strong>of</strong> MI varied from 15% to 73%<strong>and</strong> was relatively high, suggesting some selection <strong>of</strong> higher risk cases. The time from symptom onsetto sampling varied from 1.2 hours (mean) to 5.9 hours (median). Around half <strong>of</strong> the studies evaluatedqualitative assays, most specifying that this was the CardioDetect assay with a diagnostic threshold <strong>of</strong>7 µg/l. The threshold used by quantitative assay was variable. Most <strong>of</strong> the studies used reference st<strong>and</strong>ardsbased on a st<strong>and</strong>ard modern troponin assay, using the 10% CV or 99th percentile as a diagnosticthreshold, although not all gave details <strong>of</strong> the assay <strong>and</strong> threshold.Quality assessment <strong>of</strong> diagnostic studies <strong>of</strong> heart-type fatty acid-binding proteinFigure 14 shows the quality assessments for studies <strong>of</strong> H-FABP, while Figure 15 shows the methodologicalquality summary. The overall quality <strong>and</strong> the issues raised were similar to those for the studies <strong>of</strong> troponin.Analysis <strong>of</strong> diagnostic studies <strong>of</strong> heart-type fatty acid-binding proteinFigure 16 shows the <strong>meta</strong>-<strong>analysis</strong> <strong>of</strong> the studies <strong>of</strong> quantitative H-FABP <strong>and</strong> Figure 17 shows the<strong>meta</strong>-<strong>analysis</strong> <strong>of</strong> qualitative assays. The summary estimates <strong>of</strong> sensitivity <strong>and</strong> specificity were 81% (95%predictive interval 50–95%) <strong>and</strong> 80% (95% predictive interval 26–98%), respectively, for the quantitativeassays <strong>and</strong> 68% (95% predictive interval 11–97%) <strong>and</strong> 92% (95% predictive interval 20–100%),respectively, for the qualitative assays.Description <strong>of</strong> diagnostic studies <strong>of</strong> ischaemia-modified albuminWe identified four studies 48,61,68,70 that were eligible for inclusion in the <strong>review</strong> (Tables 11 <strong>and</strong> 12). Anumber <strong>of</strong> other studies <strong>of</strong> IMA were excluded because the reference st<strong>and</strong>ard was ACS, based on clinicalcriteria, <strong>and</strong> cases with MI were not reported separately. Two studies restricted recruitment to patientspresenting within 3 70 <strong>and</strong> 8 hours 61 <strong>of</strong> symptom onset. Only one study 48 reported the median time delayfrom symptom onset. Thresholds <strong>of</strong> between 75 <strong>and</strong> 91 were used for IMA. Three studies used a modernst<strong>and</strong>ard troponin assay for the reference st<strong>and</strong>ard, whereas the older study from Christensen et al. 61inevitably used an older troponin reference st<strong>and</strong>ard with a higher threshold for positivity.Quality assessment <strong>of</strong> diagnostic studies <strong>of</strong> ischaemia-modified albuminFigure 18 shows the quality assessments for studies <strong>of</strong> IMA, whereas Figure 19 shows the methodologicalquality summary.Analysis <strong>of</strong> diagnostic studies <strong>of</strong> ischaemia-modified albuminFigure 20 shows the results <strong>of</strong> <strong>meta</strong>-<strong>analysis</strong> <strong>of</strong> studies <strong>of</strong> IMA. The summary estimates <strong>of</strong> sensitivity<strong>and</strong> specificity were 77% (95% predictive interval 19–98%) <strong>and</strong> 39% (95% predictive interval 2–95%),respectively.Description <strong>of</strong> diagnostic studies <strong>of</strong> myoglobinWe identified 13 diagnostic studies 18,49,52,57,58,63,64,68,69,71,74,77,79 <strong>of</strong> myoglobin for inclusion in the <strong>review</strong>.Table 13 shows the population characteristics <strong>and</strong> Table 14 shows the index <strong>and</strong> reference st<strong>and</strong>ard© Queen’s Printer <strong>and</strong> Controller <strong>of</strong> HMSO 2013. This work was produced by Goodacre et al. under the terms <strong>of</strong> a commissioning contract issued by the Secretary <strong>of</strong> Statefor Health. This issue may be freely reproduced for the purposes <strong>of</strong> private research <strong>and</strong> study <strong>and</strong> extracts (or indeed, the full report) may be included in pr<strong>of</strong>essional journalsprovided that suitable acknowledgement is made <strong>and</strong> the reproduction is not associated with any form <strong>of</strong> advertising. Applications for commercial reproduction should beaddressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials <strong>and</strong> Studies Coordinating Centre, Alpha House, University <strong>of</strong> Southampton SciencePark, Southampton SO16 7NS, UK.35
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