Laura Burgers

A systematic review and economic evaluation of new-generation computed tomography scanners for imaging in coronary artery disease and congenital heart disease: Somatom Definition Flash, Aquilion ONE, Brilliance iCT and Discovery CT750 HD

BACKGROUND Computed tomography (CT) is important in diagnosing and managing many conditions, including coronary artery disease (CAD) and congenital heart disease. Current CT scanners can very accurately diagnose CAD requiring revascularisation in most patients. However, imaging technologies have developed rapidly and new-generation computed tomography (NGCCT) scanners may benefit patients who are difficult to image (e.g. obese patients, patients with high or irregular heart beats and patients who have high levels of coronary calcium or a previous stent or bypass graft). OBJECTIVE To assess the clinical effectiveness and cost-effectiveness of NGCCT for diagnosing clinically significant CAD in patients who are difficult to image using 64-slice computed tomography and treatment planning in complex congenital heart disease. DATA SOURCES Bibliographic databases were searched from 2000 to February/March 2011, including MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED), Health Technology Assessment (HTA) database and Science Citation Index (SCI). Trial registers and conference proceedings were searched. REVIEW METHODS Systematic review methods followed published guidance. Risk of bias was assessed using QUADAS-2. Results were stratified by patient group. Summary sensitivity and specificity were calculated using a bivariate summary receiver operating characteristic, or random effects model. Heterogeneity was assessed using the chi-squared statistic and I(2)-statistic. Cost-effectiveness of NGCCT was modelled separately for suspected and known CAD, evaluating invasive coronary angiography (ICA) only, ICA after positive NGCCT (NGCCT-ICA), and NGCCT only. The cost-effectiveness of NGCCT, compared with 64-slice CT, in reducing imaging-associated radiation in congenital heart disease was assessed. RESULTS Twenty-four studies reported accuracy of NGCCT for diagnosing CAD in difficult-to-image patients. No clinical effectiveness studies of NGCCT in congenital heart disease were identified. The pooled per-patient estimates of sensitivity were 97.7% [95% confidence interval (CI) 88.0% to 99.9%], 97.7% (95% CI 93.2% to 99.3%) and 96.0% (95% CI 88.8% to 99.2%) for patients with arrhythmias, high heart rates and previous stent, respectively. The corresponding estimates of specificity were 81.7% (95% CI 71.6% to 89.4%), 86.3% (95% CI 80.2% to 90.7%) and 81.6% (95% CI 74.7% to 87.3%), respectively. In patients with high coronary calcium scores, previous bypass grafts or obesity, only per-segment or per-artery data were available. Sensitivity estimates remained high (> 90% in all but one study). In patients with suspected CAD, the NGCCT-only strategy appeared most cost-effective; the incremental cost-effectiveness ratio (ICER) of NGCCT-ICA compared with NGCCT only was £71,000. In patients with known CAD, the most cost-effective strategy was NGCCT-ICA (highest cost saving, dominates ICA only). The ICER of NGCCT only compared with NGCCT-ICA was £726,230. For radiation exposure only, the ICER for NGCCT compared with 64-slice CT in congenital heart disease ranged from £521,000 for the youngest patients to £90,000 for adults. LIMITATIONS Available data were limited, particularly for obese patients and patients with previous bypass grafts. All studies of the accuracy of NGCCT assume that the reference standard (ICA) is 100% sensitive and specific; however, there is some evidence that ICA may sometimes underestimate the extent and severity of stenosis. Patients with more than one criterion that could contribute to difficulty in imaging were often excluded from studies; the effect on test accuracy of multiple difficult to image criteria remains uncertain. CONCLUSIONS NGCCT may be sufficiently accurate to diagnose clinically significant CAD in some or all difficult-to-image patient groups. Economic analyses suggest that NGCCT is likely to be considered cost-effective for difficult-to-image patients with CAD, at current levels of willingness to pay in the NHS. For patients with suspected CAD, NGCCT only would be most favourable; for patients with known CAD, NGCCT-ICA would be most favourable. No studies assessing the effects of NGCCT on therapeutic decision making, or subsequent patient outcomes, were identified. The ideal study to address these questions would be a large multi-centre RCT. However, one possible alternative might be to establish a multicentre tracker study. High-quality test accuracy studies, particularly in obese patients, patients with high coronary calcium, and those with previous bypass grafts are needed to confirm the findings of our systematic review. These studies should include patients with multiple difficult to image criteria. FUNDING The National Institute for Health Research Health Technology Assessment programme. This project was funded by the HTA programme, on behalf of NICE, as project number 10/107/01.

Systematic Review of the Accuracy of Dual-Source Cardiac CT for Detection of Arterial Stenosis in Difficult to Image Patient Groups

PURPOSE To assess the diagnostic performance of dual-source cardiac (DSC) computed tomography (CT) newer-generation CT instruments for identifying anatomically significant coronary artery disease (CAD) in patients who are difficult to image by using 64-section CT. MATERIALS AND METHODS A literature search comprised bibliographic databases (January 1, 2000, to March 22, 2011, with a pragmatic update on September 6, 2012), trial registries, and conference proceedings. Only studies using invasive coronary angiography as reference standard were included. Risk of bias was assessed (QUADAS-2). Results were stratified according to patient group on the basis of clinical characteristics. Summary estimates of sensitivity and specificity of DSC CT for detecting 50% or greater arterial stenosis were calculated by using a bivariate summary receiver operating characteristic or random-effects model. RESULTS Twenty-five studies reported accuracy of DSC CT for diagnosing CAD in difficult to image patients; in 22 studies, one of two CT units of the same manufacturer (Somatom Definition or Somatom Definition Flash) was used, and in the remaining three, a different CT unit of another manufacturer (Aquilion One) was used. The pooled, per-patient estimates of sensitivity were 97.7% (95% confidence interval [CI]: 88.0%, 99.9%) and 97.7% (95% CI: 93.2%, 99.3%) for patients with arrhythmias and high heart rates, respectively. The corresponding pooled estimates of specificity were 81.7% (95% CI: 71.6%, 89.4%) and 86.3% (95% CI: 80.2%, 90.7%), respectively. All data were acquired by using Somatom Definition. In two studies with Somatom and one study with Aquilion One, sensitivity estimates of 90% or greater were reported in patients with previous stent implantations; specificities were 81.7% and 89.5% for Somatom and 81.0% for Aquilion One. In patients with high coronary calcium scores, previous bypass grafts, or obesity, only per-segment or per-artery data were available. Sensitivity estimates remained high (>90% in all but one study), and specificities ranged from 79.1% to 100%. All data were acquired by using Somatom Definition. CONCLUSION DSC CT may be sufficiently accurate to diagnose clinically significant CAD in some or all difficult to image patients. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13121136/-/DC1.

Cost-effectiveness of open versus endovascular repair of abdominal aortic aneurysm

BACKGROUND Patients with a large unruptured abdominal aortic aneurysm with a diameter >5.0 cm are treated with open surgical repair (OSR) or endovascular aneurysm repair (EVAR). Because many studies have assessed the cost-effectiveness of these treatments with conflicting results, this systematic review examined published cost-effectiveness analyses of elective EVAR vs OSR in patients with abdominal aortic aneurysm. METHODS A systematic search strategy using three databases was conducted to find all relevant studies. Characteristics extracted from these studies included study characteristics (eg, age of the population), input parameters (eg, costs of the EVAR procedure), general results, and sensitivity analyses. The quality of each study was assessed using the Drummond checklist. RESULTS The search identified 1141 potentially relevant studies, of which 13 studies met inclusion criteria. Most studies found that EVAR was more expensive and more effective than OSR. However, most studies concluded that the health gained from EVAR did not offset the higher total costs, leading to an unacceptably high incremental cost-effectiveness ratio. EVAR was considered more cost-effective in patient groups with a high surgical risk. The quality of most studies was judged as reasonably good. CONCLUSIONS Overall, published cost-effectiveness analyses of EVAR do not provide a clear answer about whether elective EVAR is a cost-effective solution because the incremental cost-effectiveness ratio varies considerably among the studies. This answer can best be provided through a cost-effectiveness analysis of EVAR that incorporates more recent technologic advances and the improved experience that clinicians have with EVAR.

How to prepare a systematic review of economic evaluations for clinical practice guidelines: database selection and search strategy development (part 2/3)

ABSTRACT Introduction: This article is part of the series “How to prepare a systematic review of economic evaluations (EES) for informing evidence-based healthcare decisions”, in which a five-step approach is proposed. Areas covered: This paper focuses on the selection of relevant databases and developing a search strategy for detecting EEs, as well as on how to perform the search and how to extract relevant data from retrieved records. Expert commentary: Thus far, little has been published on how to conduct systematic review EEs. Moreover, reliable sources of information, such as the Health Economic Evaluation Database, have ceased to publish updates. Researchers are thus left without authoritative guidance on how to conduct SR-EEs. Together with van Mastrigt et al. we seek to fill this gap.

Treatment variation in stent choice in patients with stable or unstable coronary artery disease

AimVariations in treatment are the result of differences in demographic and clinical factors (e.g. anatomy), but physician and hospital factors may also contribute to treatment variation. The choice of treatment is considered important since it could lead to differences in long-term outcomes. This study explores the associations with stent choice: i.e. drug-eluting stent (DES) versus bare-metal stents (BMS) for Dutch patients diagnosed with stable or unstable coronary artery disease (CAD).Methods & resultsAssociations with treatment decisions were based on a prospective cohort of 692 patients with stable or unstable CAD. Of those patients, 442 patients were treated with BMS or DES. Multiple logistic regression analyses were performed to identify variables associated with stent choice. Bivariate analyses showed that NYHA class, number of diseased vessels, previous percutaneous coronary intervention, smoking, diabetes, and the treating hospital were associated with stent type. After correcting for other associations the treating hospital remained significantly associated with stent type in the stable CAD population.ConclusionsThis study showed that several factors were associated with stent choice. While patients generally appear to receive the most optimal stent given their clinical characteristics, stent choice seems partially determined by the treating hospital, which may lead to differences in long-term outcomes.

Challenges in Modelling the Cost Effectiveness of Various Interventions for Cardiovascular Disease

ObjectivesDecision analytic modelling is essential in performing cost-effectiveness analyses (CEAs) of interventions in cardiovascular disease (CVD). However, modelling inherently poses challenges that need to be dealt with since models always represent a simplification of reality. The aim of this study was to identify and explore the challenges in modelling CVD interventions.MethodsA document analysis was performed of 40 model-based CEAs of CVD interventions published in high-impact journals. We analysed the systematically selected papers to identify challenges per type of intervention (test, non-drug, drug, disease management programme, and public health intervention), and a questionnaire was sent to the corresponding authors to obtain a more thorough overview. Ideas for possible solutions for the challenges were based on the papers, responses, modelling guidelines, and other sources.ResultsThe systematic literature search identified 1,720 potentially relevant articles. Forty authors were identified after screening the most recent 294 papers. Besides the challenge of lack of data, the challenges encountered in the review suggest that it was difficult to obtain a sufficiently valid and accurate cost-effectiveness estimate, mainly due to lack of data or extrapolating from intermediate outcomes. Despite the low response rate of the questionnaire, it confirmed our results.ConclusionsThis combination of a review and a survey showed examples of CVD modelling challenges found in studies published in high-impact journals. Modelling guidelines do not provide sufficient guidance in resolving all challenges. Some of the reported challenges are specific to the type of intervention and disease, while some are independent of intervention and disease.

Is it cost-effective to use a test to decide which individuals with an intermediate cardiovascular disease risk would benefit from statin treatment?

BACKGROUND The 2012 European guidelines recommend statins for intermediate-risk individuals with elevated cholesterol levels. Improved discrimination of intermediate-risk individuals is needed to prevent both cardiovascular disease (CVD) and statin side-effects (e.g. myopathy) efficiently since only 3-15 in every 100 individuals actually experience a cardiovascular event in the next 10 years. We estimated the potential cost-effectiveness of a hypothetical test which helps to determine which individuals will benefit from statins. METHODS AND RESULTS Prognosis of different age- and gender-specific cohorts with an intermediate risk was simulated with a Markov model to estimate the potential costs and quality-adjusted life-years for four strategies: treat all with statins, treat none with statins, treat according to the European guidelines, or use a test to select individuals for statin treatment. The test-first strategy dominated the other strategies if the hypothetical test was 100% accurate and cost no more than €237. This strategy and the treat-all strategy were equally effective but the test generated lower costs by reducing statin usage and side-effects. The treat-none strategy was the least effective strategy. Threshold analyses show that the test must be highly accurate (especially sensitive) and inexpensive to be the most cost-effective strategy, since myopathy has a negligible impact on cost-effectiveness and statin costs are low. CONCLUSION Use of a highly accurate prognostic test could reduce overall CVD risk, frequency of drug side-effects and lifetime costs. However, no additional test would add usefully to risk prediction over SCORE when it does not satisfy the costs and accuracy requirements.