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

Discussionchanges in sensitivity and specificity resulting from adding another biomarker at presentation are similar tothe changes resulting from using a high-sensitivity troponin assay with a low threshold for positivity. If oneassay can provide the same result as a combination, then it is likely to be more cost-effective.We also used our economic model to produce estimates of 1-year rates of death and non-fatal MI among(1) all patients presenting with suspected ACS and (2) those discharged after negative assessment, for themain strategies tested. These estimates show how using more sensitive strategies decreases the expectedrisks of adverse outcome and could be used by clinicians attempting to weigh up the risks and benefits ofdifferent strategies for the individual patient. They could also be used, given a sufficiently interested andinformed patient, to explain the potential risks and benefits of different strategies to the individual patient,potentially allowing them to participate in shared decision-making.Cost-effectiveness of biomarkers, computed tomographic coronary angiographyand exercise electrocardiography in troponin-negative patientsWe developed a second (prognostic) decision-analysis model to evaluate the cost-effectiveness of usinga biomarker (H-FABP), exercise ECG or CTCA to select troponin-negative patients for further investigationwith ICA if positive or current standard care if negative. These strategies were compared with currentstandard care for all and ICA for all. We assumed that current standard care involved further investigationaccording to NICE guidance for stable chest pain 11 if symptoms persisted or recurred. The benefit ofinvestigation clearly depended on the subsequent risk of death and non-fatal MI, and we had two sourcesfor this with contrasting estimates and implicit assumptions. Data from an observational study of patientsadmitted to hospital with suspected ACS 155 produced an estimate of 1.0% for death and 3.9% for MI upto 1 year, whereas data from a randomised trial of ED chest pain assessment 12 produced correspondingestimates of 0.19% and 0.24%. The difference in these estimates reflects patient selection and duration offollow-up. In using either data source in the model we make an implicit assumption about the duration ofeffect of initial testing. Using the Mills data 155 we assumed that initial testing influences outcomes up to1 year, whereas the RATPAC data 12 assumes that initial testing only influences outcomes up to 3 months.There obviously is a limit to the effect of initial testing compared with current standard care as standardcare involves subsequent investigation if symptoms recur or persist. However, it is not clear when thislimit is.The analysis showed that the estimate of the adverse event rate and associated implicit assumptionregarding the duration of potential effect of initial testing on outcome were important in determiningcost-effectiveness. If the higher estimates of adverse outcome and 1-year duration of effect were used,then CTCA was likely to be the optimal strategy at the NICE threshold for willingness to pay. If the lowerestimates of adverse outcome and 3-month duration of effect were used, then the no-testing strategywas likely to be optimal. A threshold analysis suggested that CTCA was likely to be cost-effective if theestimated combined risk of death and non-fatal MI within the duration of effect of initial testing were> 2% or 3%, depending on the threshold used for willingness to pay (£20,000 or £30,000/QALY). It isimportant to note that this analysis was driven by the effectiveness of the strategies rather than costs, andoutcomes associated with a high rate of referral for ICA were little better than no testing. This emphasisesthe importance of specificity in prognostic testing and the need to ensure that diagnostic thresholds areset and tests interpreted in a way that does not result in a large number of FP cases being referred for ICA.The value of information analysis associated with this model showed that around the NICE threshold,assumed to be between £20,000/QALY and £30,000/QALY, the EVPPIs associated with the baselinerisk of MI and the relative reduction in risk with treatment were relatively high, suggesting that furtherexperimental research of these parameters will potentially be cost-effective. Research estimating theeffect of treatment on patients identified as being at increased risk by CTCA is unlikely to be consideredethical, but research comparing a strategy of liberal compared with restrictive CTCA use (with treatmentbeing consequent on CTCA findings) would be more likely to be considered ethical and would provide anestimate of the effect of treatment.112NIHR Journals Library