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

Assessment of cost-effectiveness evidenceFor the secondary analysis evaluating the cost-effectiveness of adding other biomarkers to troponin atpresentation we used estimates of sensitivity and specificity from primary studies that compared thecombination of the biomarker and troponin (i.e. test positive if either troponin or biomarker is positive)with troponin alone (see Chapter 3, Diagnostic studies of biomarkers in combination with troponin). Weused primary studies to estimate the sensitivity and specificity of troponin alone rather than meta-analysisestimates because there was substantial heterogeneity between the studies with resulting heterogeneityin estimates of troponin sensitivity. Using estimates from the primary studies allowed us to evaluate therelative effect of adding another biomarker. Table 35 shows the sensitivity and specificity of troponin aloneand the biomarker plus troponin combination for each analysis. These strategies were only tested in thepopulation without known CAD in the twice-daily ward round scenario.OutcomesWe assumed that after the strategy had been applied and any treatments given the subsequent progressof each patient would depend on whether or not they had MI, and if they had MI whether or not it wasidentified and treated. Patients with MI risked reinfarction or death dependent on whether or not theyreceived treatment. The risk of reinfarction and death (with and without treatment) was determined usingdata from a study by Mills. 155 This cohort of patients with suspected ACS allows comparison betweenthose with recognised and treated MI, and those with untreated MI, because the threshold for reportingpositive results was changed after an initial validation phase when low positive results were recorded butnot reported. We selected patients from this study who matched our inclusion criteria of having a nondiagnosticECG. Table 36 shows the estimates of the risk of reinfarction and death among relevant patientsin the Mills 155 cohort.After this we assumed that survivors accrued QALYs according to their age and sex, whether or notthey had MI, and whether or not they suffered reinfarction. The lifetime QALYs are estimated basedon patients’ life expectancy and their corresponding annual utilities. The discounted life expectancy ofpatients with MI, and MI with reinfarction was captured from Polanczyk et al., 156 whereas the utility of MIpatients was estimated from Ward et al. 157 The utility of patients with reinfarction was estimated by usinga multiplicative factor of 0.8 for patients with MI based on the input from clinicians. Life expectancy ofTABLE 35 Strategy diagnostic accuracy for combination strategiesTroponin aloneCombinationStudyCombinationSensitivity(95% CI)Specificity(95% CI)Sensitivity(95% CI)Specificity(95% CI)Body 2011 57 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)Haltern 2010 67 TnT or H-FABP 0.74 (0.66 to 0.74) 1.00 (0.96 to 1.00) 0.97 (0.86 to 0.99) 0.65 (0.60 to 0.66)McCann TnT or H-FABP 0.75 (0.69 to 0.81) 0.94 (0.90 to 0.96) 0.93 (0.89 to 0.96) 0.93 (0.89 to 0.96)2008 76Mion 2007 77 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)Keller 2010 71 TnT or copeptin 0.62 (0.56 to 0.67) 0.97 (0.96 to 0.98) 0.88 (0.83 to 0.91) 0.76 (0.73 to 0.79)Reichlin 2009 80 TnT or copeptin 0.75 (0.65 to 0.83) 0.94 (0.91 to 0.96) 0.99 (0.92 to 1.00) 0.77 (0.73 to 0.81)Keller 2010 20Mion 2007 77TnT ormyoglobinTnI ormyoglobin0.62 (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 (0.80 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 2006 70 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)86NIHR Journals Library