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

DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1at presentation and 3 hours later is the optimal strategy for MI diagnosis. However, this finding is basedon data from a single study. The CI for sensitivity derived from this single study is unlikely to reflect thetrue extent of uncertainty in the way that the predictive interval from our meta-analysis does. Furthermore,if the study population characteristics differ from the UK population, particularly in terms of time delaybefore presentation, then the findings may not be generalisable to the UK.We also assumed that the 10-hour troponin testing was diagnostically perfect (i.e. had 100% sensitivityand specificity). This assumption was necessary because the 10-hour troponin test is effectively thereference standard test for MI, so modelling outcomes following FN or FP 10-hour troponin testing wouldinvolve contentious and untestable assumptions. Although this assumption affects all the strategies,because they use the 10-hour troponin result to confirm MI, it favours the 10-hour strategy most.Another assumption in our model that favours the 10-hour troponin strategy is that a patient with a FNtroponin result at presentation was assumed to have the same prognosis (and thus the ability to benefitfrom treatment) as a patient with a TP troponin result at presentation. However, this assumption may nothold if those with a FN troponin result at presentation have a smaller infarct and better prognosis. Wewere unable to find adequate data to test this assumption.Having compared presentation high-sensitivity troponin to 10-hour standard troponin, the obvious nextquestion is whether or not the 10-hour troponin test should be of high sensitivity. We are unable toaddress this question because (1) our model assumes that the standard troponin assay at 10 hours isperfect for the reasons given above; (2) there are few data available to estimate presentation troponinaccuracy in comparison with a high-sensitivity reference standard; and (3) the prognostic and therapeuticimplications of a positive high-sensitivity troponin alongside a negative standard troponin are not clear.Our analysis only evaluated the role of high-sensitivity troponin in terms of an early biomarker rather thanas an alternative to a 10-hour standard troponin.Finally, our model assumes that patients awaiting troponin testing are cared for in hospital (even if notformally admitted) and therefore incur hospital costs. It could be argued that the benefits of delayedtroponin testing could be accrued without most of the costs if patients were discharged home and askedto return for delayed testing. However, the feasibility and acceptability of this practice has not been testedand it is not routinely used.The diagnostic decision-analysis model was also used to test the cost-effectiveness of H-FABP, copeptin,myoglobin and IMA measured at presentation alongside troponin, compared with troponin aloneat presentation or 10 hours. There was substantial variation in estimates of troponin sensitivity atpresentation in the sources studies for this analysis. This meant that we could not reasonably use ourmeta-analysis estimates of presentation troponin sensitivity and specificity in this particular analysis, as thiswould paradoxically result in the biomarker plus troponin sensitivity being lower than troponin alone insome analyses. We therefore used the individual studies to estimate the accuracy of troponin alone andundertook a separate analysis for each study. As a result, some of the analyses that were based on studieswith low estimates of troponin sensitivity at baseline produced results that were inconsistent with ourmain analysis and suggested that a 10-hour troponin test would be cost-effective at the £30,000/QALY oreven £20,000/QALY threshold. This is because we could not include the optimal strategy from the mainanalysis (high-sensitivity troponin at presentation) with our best estimate of sensitivity and specificity inthe analysis.The economic analysis of alternative biomarkers suggested that adding H-FABP, copeptin or myoglobinto troponin at presentation could be cost-effective, i.e. could improve sensitivity and thus QALYs at anacceptable cost per QALY. Adding IMA to troponin at presentation, in contrast, was unlikely to be costeffective.These findings are obviously limited by our inability to include the optimal strategy with bestestimates of sensitivity and specificity in the analysis. The findings of the meta-analyses suggest that the© 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.111