Economic Analysis Comparing Dalteparin to Vitamin K Antagonists to Prevent Recurrent Venous Thromboembolism in Patients With Cancer Having Renal Impairment.

BACKGROUND: In a randomized trial (ie, Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [CLOT]) that evaluated secondary prophylaxis of recurrent venous thromboembolism (VTE) in patients with cancer, dalteparin reduced the relative risk by 52% compared to oral vitamin K antagonists (VKAs; hazard ratio = 0.48, P = .002). A recent subgroup analysis in patients with moderate to severe renal impairment also revealed lower absolute VTE rates with dalteparin (3% vs 17%; P = .011). To measure the economic value of dalteparin in these populations, a pharmacoeconomic analysis was conducted from the Dutch health-care system perspective. METHODS: Resource utilization data contained within the CLOT trial database were extracted and converted into direct cost estimates. Univariate analysis was then conducted to compare the total cost of therapy between patients randomized to dalteparin or VKA therapy. Health state utilities were then measured in 24 members of the general public using the time trade-off technique. RESULTS: When all of the cost components were combined for the entire population (n = 676), the dalteparin group had significantly higher overall costs than the VKA control group (dalteparin = €2375 vs VKA = €1724; P < .001). However, dalteparin was associated with a gain of 0.14 (95% confidence interval [CI]: 0.10-0.18) quality-adjusted life years (QALYs) over VKA. When the incremental cost was combined with the utility gain, dalteparin had a cost of €4,697 (95% CI: €3824-€4951) per QALY gained. CONCLUSION: Secondary prophylaxis with dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer.

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.

Using meta-regression analyses in addition to conventional systematic review methods to examine the variation in cost-effectiveness results - a case study.

BACKGROUND: Systematic reviews of cost-effectiveness analyses summarize results and describe study characteristics. Variability in the study results is often explained qualitatively or based on sensitivity analyses of individual studies. However, variability due to input parameters and study characteristics (e.g., funding or study quality) is often not statistically explained. As a case study, a systematic review on the cost-effectiveness of drug-eluting stents (DES) versus bare-metal stents (BMS) using meta-regression analyses is performed to explore the usefulness of such methods compared with conventional review methods. METHODS: We attempted to identify and review all modelling studies published until January 2012 that compared costs and consequences of DES versus BMS. We extracted general study information (e.g., funding), modelling methods, values of input parameters, and quality of the model using the Philips et al. checklist. Associations between study characteristics and the incremental costs and effectiveness of individual analyses were explored using regression analyses corrected for study ID. RESULTS: Sixteen eligible studies were identified, with a combined total of 508 analyses. The overall quality of the models was moderate (59% ± 15%). This study showed associations (e.g., type of lesion) that were expected (based on individual studies), however the meta-regression analyses revealed also unpredicted associations: e.g., model quality was negatively associated with repeat revascularizations avoided. CONCLUSIONS: Meta-regressions can be of added value, identifying significant associations that could not be identified using conventional review methods or by sensitivity analyses of individual studies. Furthermore, this study underlines the need to examine input parameters and perform a quality check of studies when interpreting the results.

Cost-Effectiveness of Disease Management Programs for Cardiovascular Risk and COPD in The Netherlands.

BACKGROUND: Disease management programs (DMPs) for cardiovascular risk (CVR) and chronic obstructive pulmonary disease (COPD) are increasingly implemented in The Netherlands to improve care and patient's health behavior. OBJECTIVE: The aim of this study was to provide evidence about the (cost-) effectiveness of Dutch DMPs as implemented in daily practice. METHODS: We compared the physical activity, smoking status, quality-adjusted life-years, and yearly costs per patient between the most and the least comprehensive DMPs in four disease categories: primary CVR prevention, secondary CVR prevention, both types of CVR prevention, and COPD (N = 1034). Propensity score matching increased comparability between DMPs. A 2-year cost-utility analysis was performed from the health care and societal perspectives. Sensitivity analysis was performed to estimate the impact of DMP development and implementation costs on cost-effectiveness. RESULTS: Patients in the most comprehensive DMPs increased their physical activity more (except for primary CVR prevention) and had higher smoking cessation rates. The incremental QALYs ranged from -0.032 to 0.038 across all diseases. From a societal perspective, the most comprehensive DMPs decreased costs in primary CVR prevention (certainty 57%), secondary CVR prevention (certainty 88%), and both types of CVR prevention (certainty 98%). Moreover, the implementation of comprehensive DMPs led to QALY gains in secondary CVR prevention (certainty 92%) and COPD (certainty 69%). CONCLUSIONS: The most comprehensive DMPs for CVR and COPD have the potential to be cost saving, effective, or cost-effective compared with the least comprehensive DMPs. The challenge for Dutch stakeholders is to find the optimal mixture of interventions that is most suited for each target group.

The use of fenestrated and branched endovascular aneurysm repair for juxtarenal and thoracoabdominal aneurysms: a systematic review and cost-effectiveness analysis.

BACKGROUND: Patients with large abdominal aortic aneurysms (AAAs) are usually offered reparative treatment given the high mortality risk. There is uncertainty about how to treat juxtarenal AAAs (JRAAAs) or thoracoabdominal aortic aneurysms (TAAAs). Endovascular repair of an abdominal aortic aneurysm (EVAR) is often seen as safer and easier than open surgical repair (OSR). However, endovascular treatment of JRAAAs or TAAAs requires specially manufactured stent grafts, with openings to allow blood to reach branches of the aorta. Commissioners are receiving increasing requests for fenestrated EVAR (fEVAR) and branched EVAR (bEVAR), but it is unclear whether or not the extra cost of fEVAR or bEVAR is justified by advantages for patients. OBJECTIVE(S): To assess the clinical effectiveness, safety and cost-effectiveness of fEVAR and bEVAR in comparison with conventional treatment (i.e. no surgery) or OSR for two populations: JRAAAs and TAAAs. DATA SOURCES: Resources were searched from inception to October 2013, including MEDLINE (OvidSP), EMBASE (OvidSP) and the Cochrane Central Register of Controlled Trials (Wiley) and, additionally, for cost-effectiveness, NHS Economic Evaluation Database (NHS EED; Wiley) and EconLit (EBSCOhost). Conference abstracts were also searched. REVIEW METHODS: Studies were included based on an intervention of either fEVAR or bEVAR and a comparator of either OSR or no surgery. For clinical effectiveness, observational studies were excluded only if they were not comparative, i.e. explicitly selected on the basis of prognosis. RESULTS: For clinical effectiveness, searches retrieved 5253 records before deduplication. Owing to overlap between the databases, 1985 duplicate records were removed. Of the remaining 3268 records, based on titles and abstracts, 3244 records were excluded, leaving 24 publications to be ordered. All 24 studies were excluded as none of them satisfied the inclusion criteria. Sixteen studies were excluded on study design, six on intervention and two on comparator. Five out of 16 studies excluded on study design reported a comparison. However, all of the studies acknowledged that they had groups that were not comparable at baseline given that they had selectively assigned younger, fitter patients to OSR. Therefore, these studies were considered 'non-comparative'. For cost-effectiveness, searches identified 104 references before deduplication. Owing to overlap between the databases, 34 duplicate records were removed. Of the remaining 70 records, seven were included for the full assessment based on initial screening. After a full-text review, no studies were included. Because of the lack of clinical effectiveness evidence and difficulty in estimating costs given the rapidly changing and variable technology, a cost-effectiveness analysis (CEA) was not performed. Instead a detailed description of modelling methods was provided. CONCLUSIONS: Despite a thorough search, no studies could be found that met the inclusion criteria. All studies that compared either fEVAR or bEVAR with either OSR or no surgery explicitly selected patients based on prognosis, i.e. essentially the populations for each comparator were not the same. Despite not being able to conduct a CEA, we have provided detailed methods for the conduct if data becomes available. FUTURE WORK: We recommend at least one clinical trial to provide an unbiased estimate of effect for fEVAR/bEVAR compared with OSR or no surgery. This trial should also collect data for a CEA. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013006051. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Challenges in modelling the cost effectiveness of various interventions for cardiovascular disease.

OBJECTIVES: Decision 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. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: This 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.

Ivacaftor for the treatment of patients with cystic fibrosis and the G551D mutation: a systematic review and cost-effectiveness analysis.

BACKGROUND: Ivacaftor (Kalydeco(®), Vertex Pharmaceuticals) is the first of a new class of drugs that target the underlying protein defect in cystic fibrosis (CF). It is aimed at patients with the G551D (glycine to aspartate change in nucleotide 1784 in exon 11) mutation; 5.7% of patients with CF in the UK have this mutation. OBJECTIVES: To review the clinical effectiveness and cost-effectiveness of ivacaftor for the treatment of CF in patients aged ≥ 6 years who have the G551D mutation. METHODS: Ten databases, including MEDLINE and EMBASE, were searched from inception to July 2012. Studies that evaluated ivacaftor for the treatment of adults and children (≥ 6 years) with at least one G551D mutation were eligible. There were insufficient data to conduct a formal meta-analysis. The manufacturer of ivacaftor, Vertex Pharmaceuticals, submitted a deterministic patient-level simulation model for the assessment of the lifetime cost-effectiveness of ivacaftor. We modified the model where values were not UK-specific or not recent, or where better estimates could be found. The only change to the model structure was the addition of lung transplantations. We changed utility values, annual decline in percentage predicted forced expiratory volume in 1 second (FEV1), and the baseline exacerbation rate, and used data from the CF Registry to estimate the relation between costs, age and percentage predicted FEV1. Estimates of treatment effect of ivacaftor came from the clinical effectiveness review. We modelled three scenarios for the longer-term effects of ivacaftor. We also modelled an 'optimistic' scenario for patients aged < 12 years with little lung damage. We conducted a budget impact analysis to estimate the total cost to the NHS of introducing ivacaftor in England. RESULTS: Three studies were included: a randomised controlled trial (RCT) in adults (n = 167) (≥ 12 years), a RCT in children (n = 26) (6-11 years), and an open-label extension study of the two RCTs. Both RCTs reported significantly greater changes from baseline in all measures of lung function in patients receiving ivacaftor than in those receiving placebo. The mean difference in change in percentage predicted FEV1 was 10.5 [95% confidence interval (CI) 8.5 to 12.5] percentage points in the adults' study and 10.0 (95% CI 4.5 to 15.5) percentage points in the children's study at 48 weeks. Improvements in lung function were seen across all subgroups investigated (age, sex, study region and lung function). There were significantly greater improvements in the ivacaftor group than in the placebo group for all outcomes assessed (exacerbations, quality of life, sweat chloride and weight) with the exception of quality of life in children. Improvements were maintained in the open-label trial. Adverse events were mainly minor and comparable across treatment groups. Both RCTs reported more withdrawals in the placebo group than in the ivacaftor group. The incremental cost-effectiveness ratio varied between £335,000 and £1,274,000 per quality-adjusted life-year gained. The total additional lifetime costs for all eligible CF patients in England ranged from £438M to £479M; the lifetime cost for standard care only was £72M. CONCLUSIONS: The available evidence suggests that ivacaftor is a clinically effective treatment for patients with CF and the G551D mutation; the high cost of ivacaftor may prove an obstacle in the uptake of this treatment. The main priority for further research is the long-term effectiveness of ivacaftor. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002516. SOURCE OF FUNDING: The National Institute for Health Research Health Technology Assessment programme.

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.