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

DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1AbstractSystematic review, meta-analysis and economicmodelling of diagnostic strategies for suspectedacute coronary syndromeS Goodacre,* P Thokala, C Carroll, JW Stevens, J Leaviss,M Al Khalaf, P Collinson, F Morris, P Evans and J WangSchool of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK*Corresponding authorBackground: Current practice for suspected acute coronary syndrome (ACS) involves troponin testing10–12 hours after symptom onset to diagnose myocardial infarction (MI). Patients with a negativetroponin can be investigated further with computed tomographic coronary angiography (CTCA) or exerciseelectrocardiography (ECG).Objectives: We aimed to estimate the diagnostic accuracy of early biomarkers for MI, the prognosticaccuracy of biomarkers for major adverse cardiac adverse events (MACEs) in troponin-negative patients,the diagnostic accuracy of CTCA and exercise ECG for coronary artery disease (CAD) and the prognosticaccuracy of CTCA and exercise ECG for MACEs in patients with suspected ACS. We then aimed to estimatethe cost-effectiveness of using alternative biomarker strategies to diagnose MI, and using biomarkers,CTCA and exercise ECG to risk-stratify troponin-negative patients.Data sources: We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations; CumulativeIndex of Nursing and Allied Health Literature (CINAHL), EMBASE, Web of Science, Cochrane CentralDatabase of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), NHS Databaseof Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment database from 1985(CTCA review) or 1995 (biomarkers review) to November 2010, reviewed citation lists and contactedexperts to identify relevant studies.Review methods: Diagnostic studies were assessed using the Quality Assessment of Diagnostic AccuracyStudies (QUADAS) tool and prognostic studies using a framework adapted for the project. Meta-analysiswas conducted using Bayesian Markov chain Monte Carlo simulation. We developed a decision-analysismodel to evaluate the cost-effectiveness of alternative biomarker strategies to diagnose MI, and the costeffectivenessof biomarkers, CTCA or exercise ECG to risk-stratify patients with a negative troponin.Strategies were applied to a theoretical cohort of patients with suspected ACS. Cost-effectiveness wasestimated as the incremental cost per quality-adjusted life-year (QALY) of each strategy compared with thenext most effective, taking a health-service perspective and a lifetime horizon.Results: Sensitivity and specificity (95% predictive interval) were 77% (29–96%) and 93% (46–100%) fortroponin I, 80% (33–97%) and 91% (53–99%) for troponin T (99th percentile threshold), 81% (50–95%)and 80% (26–98%) for quantitative heart-type fatty acid-binding protein (H-FABP), 68% (11–97%) and92% (20–100%) for qualitative H-FABP, 77% (19–98%) and 39% (2–95%) for ischaemia-modified albuminand 62% (35–83%) and 83% (35–98%) for myoglobin. CTCA had 94% (61–99%) sensitivity and 87%(16–100%) specificity for CAD. Positive CTCA and positive-exercise ECG had relative risks of 5.8 (0.6–24.5)© 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.v