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

DOI: 10.3310/hta17010 Health Technology Assessment 2013 Vol. 17 No. 1MI diagnosis: biomarkersWe will test up to ten different biomarker strategies selected on the basis of the quality of supporting datafrom the literature review, the accuracy of the strategy for early MI diagnosis and/or the prognostic valueof the strategy. We will also include a ‘zero option’ of discharging all patients without testing and thecurrent recommended strategy of a 10–12 h troponin for all patients.Each strategy will be applied in the model to a theoretical cohort of patients attending hospital withsuspected ACS with a defined prevalence of MI and a defined prevalence of previously diagnosed andundiagnosed CAD. Estimates of diagnostic and prognostic accuracy from the systematic reviews willdetermine how many cases of MI are correctly identified, how many cases without MI require furthertesting and how many expected adverse events would be accurately predicted. We will assume thatpatients with positive biomarkers will receive hospital treatment while those with negative biomarkerswill be discharged home. Adverse outcomes up to six months in patients with MI at presentation will bedetermined by whether the patient receives appropriate treatment. Adverse outcomes up to six months inpatients without MI will be determined by whether the patient has CAD and whether a positive biomarkertest predicts their risk of adverse outcome.Initially we will assume that patients with negative biomarkers receive exercise ECG testing and subsequentcoronary angiography if positive, according to current guidelines. We will then explore interactionsbetween MI and CAD diagnosis.CAD diagnosis: exercise ECG or CT coronary angiographyInitially we will assume that all patients receive diagnostic testing for MI with a 10–12 h troponin, beforeexploring interactions between MI and CAD diagnosis.We will test strategies of using exercise ECG, CT coronary angiography and no CAD testing for biomarkernegative patients. We will also test strategies based on these approaches but using different decisionthresholds for undertaking coronary angiography and instituting secondary prevention on the basis offirst-line tests. For the baseline analysis the decision threshold will be ≥ 50% luminal diameter stenosis ina major epicardial vessel for CT coronary angiography and greater than 2-mm ST depression on exerciseECG. We will estimate long-term outcomes depending upon whether each patient has CAD or not andwhether they receive secondary prevention and/or percutaneous coronary intervention consequent uponpositive findings at coronary angiography.Long-term outcomes will be modelled as QALYs, determined by whether patients suffer death or adverseoutcome up to six months, and whether they suffer subsequent CAD-related mortality or morbidity. Cohortstudy and registry data identified by the literature review or used in previous models [32,33] will be usedto estimate QALYs after adverse events.A societal costing perspective will be used and the following costs estimated from literature reviewand expert panel assessment: clinical assessment, tests, hospital admission, outpatient review, generalpractitioner review, treatments for MI or CAD, treatments for adverse outcomes, long-term costs of careand productivity losses. Where possible the modelling will adhere to the NICE reference case [34] withsensitivity analyses conducted on including further aspects such as productivity losses.These costs, and the results of evidence synthesis, will be applied to the model and probabilistic modellingused to estimate the net benefit [35] of each strategy at varying thresholds of willingness to pay for healthgain. The optimum strategy will be the one with the maximum expected net benefit at the NICE thresholdof £20,000 per QALY gained. This will be the most appropriate strategy for the NHS. Modelling will be aniterative process with estimates of net benefit from the model being used to inform the development ofnew strategies until all potentially feasible alternatives have been explored.© 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.183