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

ConclusionsSuggested research prioritiesThe following suggested research priorities reflect the areas of uncertainty outlined in the previous chapter(see Chapter 5, Uncertainties) and are not listed in order of priority.1. A diagnostic cohort study is required to estimate the sensitivity and specificity of presentation and3-hour high-sensitivity troponin in patients presenting with suspected ACS compared with a 10-hourreference standard of MI based on high-sensitivity troponin.2. A cohort study of patients presenting with suspected ACS is required to determine the prognosticimportance of late troponin rises or troponin rises that are only detected by high-sensitivity assays.Alternatively a trial and economic evaluation could be used to evaluate the clinical effectiveness andcost-effectiveness of using high-sensitivity troponin compared with standard troponin, although thesample size required for such a trial may render it unfeasible.3. A diagnostic cohort study is required to estimate the effect on sensitivity and specificity of addingalternative biomarkers to high-sensitivity troponin at presentation.4. A cohort study is required to estimate the additional prognostic value of alternative biomarkersin suspected ACS. This study should measure all routinely available predictors (i.e. clinicalassessment, ECG and troponin) to determine whether or not alternative biomarkers add worthwhilepredictive information.5. A cohort study is required to estimate the prognostic value of CTCA in patients with suspectedACS but negative troponin. As with biomarkers, this study should measure all routinely availableclinical predictors to determine whether or not CTCA adds useful prognostic information. This studycould be combined with the cohort study of biomarkers to determine whether biomarkers andCTCA are independent predictors, and thus whether biomarkers could be used to select patients forCTCA. Alternatively, a trial and economic evaluation could be undertaken to determine the clinicaleffectiveness and cost-effectiveness of early CTCA for all patients to selective delayed CTCA for thosewith persistent symptoms.A single cohort study could be used to address many of these priorities. This would allow investigation ofthe interaction between different tests, investigation of the prognostic importance of different diagnosticreferences standards and ensure that the additional diagnostic or prognostic value of tests were estimatedtaking into account all available diagnostic and prognostic information. Thus the research priorities couldbe stated as follows:1. A large multicentre cohort study of patients presenting with suspected ACS in which all receivemultiple biomarker testing at presentation, 3 hours and 10 hours, CTCA and follow-up for at least6 months. This study could potentially address all five research priorities above.2. A clinical trial and economic evaluation comparing high-sensitivity troponin to standard troponin inthe diagnostic assessment of suspected ACS, to determine the effect of using high-sensitivity troponinon event rates and health-care costs.3. A clinical trial and economic evaluation comparing early CTCA for all patients to current standardpractice (selective CTCA for those with persistent symptoms) for patients with troponin-negative ACS,to determine the effect of early CTCA on event rates and health-care costs. The value of informationanalysis undertaken for this project suggests that such a trial would represent a cost-effective use ofNHS resources.118NIHR Journals Library