How real can we get in generating real world evidence? Exploring the opportunities of routinely collected administrative data for evaluation of medical devices.

Real-world data are considered a potentially valuable source of evidence for assessing medical technologies in clinical practice, but their widespread use is hampered by numerous challenges. Using the case of coronary stents in Italy, we investigate the potential of administrative databases for estimating costs and health outcomes associated with the use of medical devices in real world conditions. An administrative dataset was created ad hoc by merging hospital records from patients admitted between 2013 and 2019 for stent implantations with ambulatory records, pharmaceutical use data and vital statistics. Health outcomes were multifold: all-cause and cardiac mortality and myocardial infarction, within 30 days, 1, 2, 5 years. Costs were estimated from the National Health System perspective. We used multivariable Cox models and propensity score (PS) methods (PS matching; stratification on PS; inverse probability of treatment weighting using PS; PS adjustment). 257,907 coronary stents were implanted in 113,912 patients. For all health outcomes and follow-up times, and across all methods, patients receiving drug-eluting stents (DES) presented lower risk. For all-cause mortality, the DES patient advantage over bare-metal stent (BMS) patients declined over time but remained significant even at 5 years. For myocardial infarction, results remained quite stable. The DES group presented lower cumulative total costs (ranging from 3264 to 2363 Euros less depending on methods). Our results confirm the consolidated evidence of the benefits of DES compared to BMS. The consistency of results across methods suggests internal validity of the study, while highlighting strengths and limitations of each depending on research context. Administrative data yield great potential to perform comparative effectiveness and cost-effectiveness analysis of medical devices provided certain conditions are met.

Antibiotic or silver versus standard ventriculoperitoneal shunts (BASICS): a multicentre, single-blinded, randomised trial and economic evaluation.

BACKGROUND: Insertion of a ventriculoperitoneal shunt for hydrocephalus is one of the commonest neurosurgical procedures worldwide. Infection of the implanted shunt affects up to 15% of these patients, resulting in prolonged hospital treatment, multiple surgeries, and reduced cognition and quality of life. Our aim was to determine the clinical and cost-effectiveness of antibiotic (rifampicin and clindamycin) or silver shunts compared with standard shunts at reducing infection. METHODS: In this parallel, multicentre, single-blind, randomised controlled trial, we included patients with hydrocephalus of any aetiology undergoing insertion of their first ventriculoperitoneal shunt irrespective of age at 21 regional adult and paediatric neurosurgery centres in the UK and Ireland. Patients were randomly assigned (1:1:1 in random permuted blocks of three or six) to receive standard shunts (standard shunt group), antibiotic-impregnated (0·15% clindamycin and 0·054% rifampicin; antibiotic shunt group), or silver-impregnated shunts (silver shunt group) through a randomisation sequence generated by an independent statistician. All patients and investigators who recorded and analysed the data were masked for group assignment, which was only disclosed to the neurosurgical staff at the time of operation. Participants receiving a shunt without evidence of infection at the time of insertion were followed up for at least 6 months and a maximum of 2 years. The primary outcome was time to shunt failure due the infection and was analysed with Fine and Gray survival regression models for competing risk by intention to treat. This trial is registered with ISRCTN 49474281. FINDINGS: Between June 26, 2013, and Oct 9, 2017, we assessed 3505 patients, of whom 1605 aged up to 91 years were randomly assigned to receive either a standard shunt (n=536), an antibiotic-impregnated shunt (n=538), or a silver shunt (n=531). 1594 had a shunt inserted without evidence of infection at the time of insertion (533 in the standard shunt group, 535 in the antibiotic shunt group, and 526 in the silver shunt group) and were followed up for a median of 22 months (IQR 10-24; 53 withdrew from follow-up). 32 (6%) of 533 evaluable patients in the standard shunt group had a shunt revision for infection, compared with 12 (2%) of 535 evaluable patients in the antibiotic shunt group (cause-specific hazard ratio [csHR] 0·38, 97·5% CI 0·18-0·80, p=0·0038) and 31 (6%) of 526 patients in the silver shunt group (0·99, 0·56-1·74, p=0·96). 135 (25%) patients in the standard shunt group, 127 (23%) in the antibiotic shunt group, and 134 (36%) in the silver shunt group had adverse events, which were not life-threatening and were mostly related to valve or catheter function. INTERPRETATION: The BASICS trial provides evidence to support the adoption of antibiotic shunts in UK patients who are having their first ventriculoperitoneal shunt insertion. This practice will benefit patients of all ages by reducing the risk and harm of shunt infection. FUNDING: UK National Institute for Health Research Health Technology Assessment programme.

Economic Analysis of Surgical and Interventional Treatments for Patients with Complex Coronary Artery Disease: Insights from a One-Year Single-Center Study.

BACKGROUND Surgical treatment methods for patients with complex coronary artery disease (CAD) who have undergone vascular reconstruction mainly include coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI). The purpose of the study aimed to compare a 1-year follow-up for the patient clinical outcomes and costs between PCI and CABG treatment. MATERIAL AND METHODS There were 840 patients enrolled in this study from July 2015 to September 2016. Among the study participants, 420 patients underwent PCI treatment and 420 patients underwent off-pump CABG. Patients costs were assessed from the perspective of the China healthcare and medical insurance system. EuroQOL 5-dimension 3 levels (EQ-5D-3L) questionnaire was used to evaluate the general health status, and the Seattle Angina Questionnaire (SAQ) was used to assess the disease-specific health status. RESULTS After a 1-year follow-up, the all-cause mortality (P=0.0337), the incidence of major adverse cardiac and cerebrovascular events (P<0.001), and additional revascularization (P<0.001) in PCI group were significantly higher than those in CABG group. Both groups have significant sustained benefits in the SAQ subscale. The CABG group had a higher score on the frequency of angina than the PCI group. In addition, the quality-adjusted life year value of PCI and CABG resulted was 0.8. The average total cost for PCI was $14 643 versus CABG cost of $13 842 (P=0.0492). CONCLUSIONS In the short-term, among the CAD patients with stable triple-vessel or left-main, costs and clinical outcomes are substantially higher for CABG than PCI. Long-term, economic, and health benefits analysis, is warranted.

Cost-Effectiveness of Drug-Eluting Stents in Elderly Patients With Coronary Artery Disease: The SENIOR Trial.

BACKGROUND: Elderly patients receive bare metal stents instead of drug-eluting stents (DES) to shorten the duration of dual antiplatelet therapy (DAPT). The SENIOR trial compared outcomes between these 2 types of stents combined with a short duration of DAPT. A significant decrease in the number of patients with at least 1 major adverse cardiac and cerebrovascular event (MACCE) was noted in the DES group. OBJECTIVES: The objective of this article was to perform an economic evaluation of the SENIOR trial. METHODS: This evaluation was performed separately in 5 participating countries using pooled patient-level data from all study patients and country-specific unit costs and utility values. Costs, MACCEs, and quality-adjusted life-years (QALYs) were calculated in both arms at 1 year, and an incremental cost-effectiveness ratio was estimated. Uncertainty was explored by probabilistic bootstrapping. RESULTS: A total of 1200 patients underwent randomization. The average total cost per patient was higher in the DES group. The number of MACCEs and average QALYs were not statistically different between the 2 groups. The 1-year incremental cost-effectiveness ratio for each country of reference ranged from €13 752 to €20 511/MACCE avoided and from €42 835 to €68 231/QALY gained. The scatter plots found a wide dispersion, reflecting a large uncertainty surrounding the results. But in each country studied, 90% of the bootstrap replications indicated a higher cost for greater effectiveness for the DES group. Assuming a willingness to pay of €50 000/QALY, there was between a 40% and 50% chance that the use of DES was cost-effective in 4 countries. CONCLUSION: The use of DES instead of bare metal stents combined with a short duration of DAPT in elderly patients induced higher cost for greater effectiveness in each of the 5 countries studied.

Comparison of the Cost of Drug-Eluting Stents versus Bare Metal Stents in the Treatment of Critical Limb Ischemia in the United States.

BACKGROUND: Despite significant technical advancement in the last decade, the durability of endovascular management of critical limb ischemia (CLI) remains highly debatable. Drug-eluting stents (DESs) are being popularized for the management of CLI after its precedent success in coronary intervention. Initial reports on the durability of DES are promising. However, little is known on the additional cost of this relatively newer technology. The aim of this study is to compare the cost of the traditional bare metal stents (BMSs) to the newly introduced DES in a large cohort of CLI patients. METHODS: Using the Premier database (2009-2015), we identified all patients with CLI undergoing DES and BMS. A multivariable generalized linear model was implemented to examine in-hospital cost adjusting for patients' characteristics, comorbidities, and regional characteristics. RESULTS: A total of 20,702 patients with CLI underwent peripheral artery revascularization using BMS (18,924 [91.41%]) or DES (1,778 [8.6%]). Majority of patients were males (53%) and whites (71%). Patients undergoing BMS were slightly younger (median age [interquartile range]: 70 [62-79] versus 71 [63-80]) and were more likely to be smokers (46% vs. 39%) and have a history of cerebrovascular disease (10% vs. 8%) and chronic pulmonary disease (24.5% vs. 20.9%) as compared with those undergoing DES (all P < 0.05). On the other hand, DES patients had a high prevalence of diabetes (4% vs. 3%) and renal disease (25% vs. 22%) (both P < 0.05). There was also a significant increase in the proportion of patients undergoing DES and a corresponding decrease in BMS (P < 0.001) over the study period. Median total in-hospitalization cost (BMS: $13,342 [8,574 to 21,166], DES: $13,243 [8,560-20,232], P = 0.76) was similar for both approaches. After adjusting for potential confounders, DES was associated with $407 higher cost than BMS (adjusted mean difference [95% confidence interval]: 407 [17 to 798], P = 0.04). In addition, the cost was $672 higher in teaching hospitals, $1,153 higher in Rural areas, and increased in all regions compared with the Midwest (adjusted mean difference [95% confidence interval]-South: $293 [31 to 555], Northeast: $2,006 [1,517 to 2,495], West: $3,312 [2,930 to 3,695], all P < 0.05). CONCLUSIONS: In this large cohort of CLI patients, after controlling for potential confounders, we demonstrated that the cost of endovascular revascularization is significantly higher in patients undergoing DES than those undergoing BMS. Regional disparities in cost were also observed. Further studies looking at the long-term durability and costs of DES versus BMS are needed.

Implementation of drug-eluting stents for the treatment of femoropopliteal disease provides significant cost-to-system savings in a single-state outpatient simulation.

OBJECTIVES: Initial data on drug-eluting stents (DES) shows that they may increase the durability of endovascular treatment of superficial femoral artery disease compared with traditional bare-metal stents (BMS). Observed decreased target lesion revascularization (TLR) rates have potential for cost savings despite an increased initial cost. The purpose of this study was to run a simulation model of progressive transition from BMS to DES over 5 years evaluating the overall cost impact of that transition. METHODS: Florida State Ambulatory Databases were searched for all patients undergoing superficial femoral artery stenting in 2013 using Current Procedural Terminology codes 37226 and 37227. A simulation model was developed to estimate the impact of a progressive transition from BMS to DES over a 5-year horizon in this patient population. Cost estimates were determined from available cost charge ratio data. For the 5-year model, 2013 served as the initial year with each subsequent year based on the expected number of interventions per year. Up to one TLR per patient was assumed for the model. The 5-year TLR rates for DES and other parameter estimates were based on pooled data from the literature. Institutional data were used to estimate that up to 48% of superficial femoral artery lesions would fit the instructions for use for the Zilver PTX (Cook Medical, Bloomington, Ind), which is currently the only DES approved by the U.S. Food and Drug Administration for peripheral interventions. The net budget impact was expressed as the difference in total costs (primary stenting and reinterventions) for a scenario where BMS is progressively replaced by Zilver PTX compared with a scenario of BMS only. Multiple sensitivity analyses were performed on the base scenario. RESULTS: We identified 4107 peripheral interventions in the first year that fit our study. The overall cost for these procedures in Florida database was $51,362,142.00. In the base case scenario, DES was introduced slowly into the population at a rate of 8% per year up to 48% at the end of the model. This strategy resulted in an overall cost savings of $1,688,953.72 compared with the model with BMS alone. Sensitivity analyses including slower adoption of DES up to only 24% at 5 years, a 20% increase in TLR rates per year for the DES, and a 10% reduction in TLR rates per year for BMS still resulted in a net savings. As long as the additional cost of a DES compared with BMS is less than $677, the DES model remains less expensive. CONCLUSIONS: The adoption of DES in lieu of traditional BMS can lead to significant cost savings in a single state model over a short time horizon.

Cost-effectiveness analysis of drug-coated therapies in the superficial femoral artery.

OBJECTIVE: Drug-coated balloons (DCBs) may increase durability of endovascular treatment of superficial femoral artery (SFA) disease while avoiding stent-related risks. The purpose of this study was to use meta-analytic data of DCB studies to compare the cost-effectiveness of potential SFA treatments: DCB, drug-eluting stent (DES), plain old balloon angioplasty (POBA), or bare-metal stent (BMS). METHODS: A search for randomized controlled trials comparing DCB with POBA for treatment of SFA disease was performed. Hazard ratios were extracted to account for the time-to-event primary outcome of target lesion revascularization. Odds ratios were calculated for the secondary outcomes of primary patency (PP) and major amputation. Incorporating pooled data from the meta-analysis, cost-effectiveness analysis, assuming a payer perspective, used a decision model to simulate patency at 1 year and 2 years for each index treatment modality: POBA, BMS, DCB, or DES. Costs were based on current Medicare outpatient reimbursement rates. RESULTS: Eight studies (1352 patients) met inclusion criteria for meta-analysis. DCB outperformed POBA with respect to target lesion revascularization over time (pooled hazard ratio, 0.41; P < .001). Risk of major amputation at 12 months was not significantly different between groups. There was significantly improved 1-year PP in the DCB group compared with POBA (pooled odds ratio, 3.30; P < .001). In the decision model, the highest PP at 1 year was seen in the DES index therapy strategy (79%), followed by DCB (74%), BMS (71%), and POBA (64%). With a baseline cost of $9259.39 per patent limb at 1 year in the POBA-first group, the incremental cost per patent limb for each other strategy compared with POBA was calculated: $14,136.10/additional patent limb for DCB, $38,549.80/limb for DES, and $59,748,85/limb for BMS. The primary BMS option is dominated by being more expensive and less effective than DCB. Compared directly with DCB, DES costs $87,377.20 per additional patent limb at 1 year. Based on the projected PP at 1 year in the decision model, the number needed to treat for DES compared with DCB is 20. At current reimbursement, the use of more than two DCBs per procedure would no longer be cost-effective compared with DES. At 2 years, DCB emerges as the most cost-effective index strategy with the lowest overall cost and highest patency rates over that time horizon. CONCLUSIONS: Current data and reimbursements support the use of DCB as a cost-effective strategy for endovascular intervention in the SFA; any additional effectiveness of DES comes at a high price. Use of more than one DCB per intervention significantly decreases cost-effectiveness.

Cost-effectiveness of percutaneous coronary intervention with cobalt-chromium everolimus eluting stents versus bare metal stents: Results from a patient level meta-analysis of randomized trials.

BACKGROUND: Second-generation drug eluting stents (DES) may reduce costs and improve clinical outcomes compared to first-generation DES with improved cost-effectiveness when compared to bare metal stents (BMS). We aimed to conduct an economic evaluation of a cobalt-chromium everolimus eluting stent (Co-Cr EES) compared with BMS in percutaneous coronary intervention (PCI). OBJECTIVE: To conduct a cost-effectiveness analysis (CEA) of a cobalt-chromium everolimus eluting stent (Co-Cr EES) versus BMS in PCI. METHODS: A Markov state transition model with a 2-year time horizon was applied from a US Medicare setting with patients undergoing PCI with Co-Cr EES or BMS. Baseline characteristics, treatment effects, and safety measures were taken from a patient level meta-analysis of 5 RCTs (n = 4,896). The base-case analysis evaluated stent-related outcomes; a secondary analysis considered the broader set of outcomes reported in the meta-analysis. RESULTS: The base-case and secondary analyses reported an additional 0.018 and 0.013 quality-adjusted life years (QALYs) and cost savings of $236 and $288, respectively with Co-Cr EES versus BMS. Results were robust to sensitivity analyses and were most sensitive to the price of clopidogrel. In the probabilistic sensitivity analysis, Co-Cr EES was associated with a greater than 99% chance of being cost saving or cost effective (at a cost per QALY threshold of $50,000) versus BMS. CONCLUSIONS: Using data from a recent patient level meta-analysis and contemporary cost data, this analysis found that PCI with Co-Cr EES is more effective and less costly than PCI with BMS. © 2016 The Authors. Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc.

Variability in utilization of drug eluting stents in United States: Insights from nationwide inpatient sample.

OBJECTIVES: We studied the trends and predictors of drug eluting stent (DES) utilization from 2006 to 2011 to further expound the inter-hospital variability in their utilization. BACKGROUND: We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (NIS) between 2006 and 2011 using ICD-9-CM procedure code, 36.06 (bare metal stent) or 36.07 (drug eluting stents) for Percutaneous Coronary Intervention (PCI). Annual hospital volume was calculated using unique identification numbers and divided into quartiles for analysis. METHODS AND RESULTS: We built a hierarchical two level model adjusted for multiple confounding factors, with hospital ID incorporated as random effects in the model. About 665,804 procedures (weighted n = 3,277,884) were analyzed. Safety concerns arising in 2006 reduced utilization DES from 90% of all PCIs performed in 2006 to a nadir of 69% in 2008 followed by increase (76% of all stents in 2009) and plateau (75% in 2011). Significant between-hospital variation was noted in DES utilization irrespective of patient or hospital characteristics. Independent patient level predictors of DES were (OR, 95% CI, P-value) age (0.99, 0.98-0.99, <0.001), female(1.12, 1.09-1.15, <0.001), acute myocardial infarction(0.75, 0.71-0.79, <0.001), shock (0.53, 0.49-0.58, <0.001), Charlson Co-morbidity index (0.81,0.77-0.86, <0.001), private insurance/HMO (1.27, 1.20-1.34, <0.001), and elective admission (1.16, 1.05-1.29, <0.001). Highest quartile hospital (1.64, 1.25-2.16, <0.001) volume was associated with higher DES placement. CONCLUSION: There is significant between-hospital variation in DES utilization and a higher annual hospital volume is associated with higher utilization rate of DES. © 2015 Wiley Periodicals, Inc.

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 percutaneous coronary intervention with drug-eluting stents versus bypass surgery for patients with 3-vessel or left main coronary artery disease: final results from the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial.

BACKGROUND: The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial demonstrated that in patients with 3-vessel or left main coronary artery disease, coronary artery bypass graft surgery (CABG) was associated with a lower rate of cardiovascular death, myocardial infarction, stroke, or repeat revascularization compared with percutaneous coronary revascularization with drug-eluting stents (DES-PCI)). The long-term cost-effectiveness of these strategies is unknown. METHODS AND RESULTS: Between 2005 and 2007, 1800 patients with left main or 3-vessel coronary artery disease were randomized to CABG (n=897) or DES-PCI (n=903). Costs were assessed from a US perspective, and health state utilities were evaluated with the EuroQOL questionnaire. A patient-level microsimulation model based on the 5-year in-trial data was used to extrapolate costs, life expectancy, and quality-adjusted life expectancy over a lifetime horizon. Although initial procedural costs were $3415 per patient lower with CABG, total hospitalization costs were $10 036 per patient higher. Over the next 5 years, follow-up costs were higher with DES-PCI as a result of more frequent hospitalizations, revascularization procedures, and higher medication costs. Over a lifetime horizon, CABG remained more costly than DES-PCI, but the incremental cost-effectiveness ratio was favorable ($16 537 per quality-adjusted life-year gained) and remained <$20 000 per quality-adjusted life-year in most bootstrap replicates. Results were consistent across a wide range of assumptions about the long-term effect of CABG versus DES-PCI on events and costs. In patients with left main disease or a SYNTAX score ≤22, however, DES-PCI was economically dominant compared with CABG, although these findings were less certain. CONCLUSIONS: For most patients with 3-vessel or left main coronary artery disease, CABG is a clinically and economically attractive revascularization strategy compared with DES-PCI. However, among patients with less complex disease, DES-PCI may be preferred on both clinical and economic grounds. CLINICAL TRIAL REGISTRATION URL: www.clinicaltrials.gov. Unique identifier: NCT00114972.

Human recombinant activated protein C-coated stent for the prevention of restenosis in porcine coronary arteries.

Activated protein C (APC), an endogenous protein, inhibits inflammation and thrombosis and interrupts the coagulation cascade. Here, we investigated the effect of human recombinant APC on the development of neointimal hyperplasia in porcine coronary arteries. Yukon Choice bare metal stents were coated with 2.6 µg APC/mm(2). Under general anesthesia, APC-coated and bare stents were implanted in the left anterior descending and circumflex coronary arteries of 10 domestic pigs. During the 4-week follow-up, animals were treated with dual antiplatelet therapy and neointimal hyperplasia was evaluated via histology. Scanning electron microscopy indicated successful but unequal coating of stents with APC; nearly complete drug release occurred within 4 h. Enzyme-linked immunosorbent assay revealed that intracoronary stent implantation rapidly increased the levels of monocyte chemoattractant protein-1, an effect that was inhibited by APC release from the coated stent. Fibrin deposition and adventitial inflammation were significantly decreased 1 month after implanting APC-coated stents versus bare stents, paralleled by significantly smaller neointimal area (0.98 ± 0.92 vs. 1.44 ± 0.91 mm(2), P = 0.028), higher lumen area (3.47 ± 0.94 vs. 3.06 ± 0.91 mm(2), P = 0.046), and lower stenosis area (22.2 ± 21.2% vs. 32.1 ± 20.1%, P = 0.034). Endothelialization was complete with APC-coated but not bare (90%) stents. P-selectin immunostaining revealed significantly fewer activated endothelial cells in the neointima in the APC group (4.6 ± 1.9 vs. 11.6 ± 4.1%, P < 0.001). Thus, short exposure of coronary arteries to APC reduced inflammatory responses, neointimal proliferation, and in-stent restenosis, offering a promising therapy to improve clinical outcomes of coronary stenting. However, coating stents with APC for prolonged, controlled drug release remains technically challenging.

Economic Evaluation of the Use of Drug-Eluting Stents versus Bare-Metal Stents in Adults with Ischemic Cardiomyopathy Requiring Angioplasty.

BACKGROUND: The value of drug-eluting stents in preventing cardiovascular events has not been investigated in Mexico. OBJECTIVE: To conduct a cost-effectiveness analysis of early and new-generation drug-eluting stents from the perspective of a healthcare provider. METHODS: We conducted a cost-effectiveness analysis of early and new-generation drug-eluting stents in patients with ischemic cardiomyopathy attending a Cardiology Hospital of the Mexican Social Security Institute. The health endpoint used was major acute cardiovascular events prevented. The effectiveness by stent type was obtained from the literature. A retrospective chart review study was conducted to collect cost data on cardiovascular events including seven cost categories. Average and incremental cost-effectiveness ratios were estimated. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of estimates. RESULTS: Incremental cost-effectiveness ratios in base-case were 28,910 and US$ 35,590 for early and new-generation stents, respectively. In an optimal scenario, incremental-cost effectiveness ratio was 24,776 and US$ 25,262 for early and new stents, respectively. Probabilistic sensitivity analysis suggested that 90% of cases were cost-effective when willingness-to-pay was 58,000 and US$ 66,000 for early and new-generation stents, respectively. CONCLUSIONS: The cost-effectiveness ratios of early and new-generation stents were significantly higher than corresponding bare-metal stents.

Cost-effectiveness of percutaneous coronary intervention with drug eluting stents versus bypass surgery for patients with diabetes mellitus and multivessel coronary artery disease: results from the FREEDOM trial.

BACKGROUND: Studies from the balloon angioplasty and bare metal stent eras have demonstrated that coronary artery bypass grafting (CABG) is cost-effective compared with percutaneous coronary intervention (PCI) for patients undergoing multivessel coronary revascularization-particularly among patients with complex coronary artery disease or diabetes mellitus. Whether these results apply in the drug-eluting stent (DES) era is unknown. METHODS AND RESULTS: Between 2005 and 2010, 1900 patients with diabetes mellitus and multivessel coronary artery disease were randomized to PCI with DES (DES-PCI; n=953) or CABG (n=947). Costs were assessed from the perspective of the U.S. health care system. Health state utilities were assessed using the EuroQOL 5 dimension 3 level questionnaire. A patient-level microsimulation model based on U.S. life-tables and in-trial results was used to estimate lifetime cost-effectiveness. Although initial procedural costs were lower for CABG, total costs for the index hospitalization were $8622 higher per patient. Over the next 5 years, follow-up costs were higher with PCI, owing to more frequent repeat revascularization and higher outpatient medication costs. Nonetheless, cumulative 5-year costs remained $3641 higher per patient with CABG. Although there were only modest gains in survival with CABG during the trial period, when the in-trial results were extended to a lifetime horizon, CABG was projected to be economically attractive relative to DES-PCI, with substantial gains in both life expectancy and quality-adjusted life expectancy and incremental cost-effectiveness ratios <$10 000 per life-year or quality-adjusted life-year gained across a broad range of assumptions regarding the effect of CABG on post-trial survival and costs. CONCLUSIONS: Despite higher initial costs, CABG is a highly cost-effective revascularization strategy compared with DES-PCI for patients with diabetes mellitus and multivessel coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: http://www.clinical-trials.gov. Unique identifier: NCT00086450.

Economic analysis of endovascular interventions for femoropopliteal arterial disease: a systematic review and budget impact model for the United States and Germany.

OBJECTIVES: To study the economic impact on payers and providers of the four main endovascular strategies for the treatment of infrainguinal peripheral artery disease. BACKGROUND: Bare metal stents (BMS), drug-eluting stents (DES), and drug-coated balloons (DCB) are associated with lower target lesion revascularization (TLR) probabilities than percutaneous transluminal angioplasty (PTA), but the economic impact is unknown. METHODS: In December 2012, PubMed and Embase were systematically searched for studies with TLR as an endpoint. The 24-month probability of TLR for each treatment was weighted by sample size. A decision-analytic Markov model was used to assess the budget impact from payers' and facility-providers' perspectives of the four index procedure strategies (BMS, DES, DCB, and PTA). Base cases were developed for U.S. Medicare and the German statutory sickness fund perspectives using current 2013 reimbursement rates. RESULTS: Thirteen studies with 2,406 subjects were included. The reported probability of TLR in the identified studies varied widely, particularly following treatment with PTA or BMS. The pooled 24-month probabilities were 14.3%, 19.3%, 28.1%, and 40.3% for DCB, DES, BMS, and PTA, respectively. The drug-eluting strategies had a lower projected budget impact over 24 months compared to BMS and PTA in both the U.S. Medicare (DCB: $10,214; DES: $12,904; uncoated balloons $13,114; BMS $13,802) and German public health care systems (DCB €3,619; DES €3,632; BMS €4,026; PTA €4,290). CONCLUSIONS: DCB and DES, compared to BMS and PTA, are associated with lower probabilities of target lesion revascularization and cost savings for U.S. and German payers.

Polymer-based drug-eluting stent treatment extends the time to reintervention for patients with symptomatic femoropopliteal artery disease: clinical evidence and potential economic value.

Aim: Use long-term follow-up data from the IMPERIAL study to determine whether drug-eluting polymer-based nitinol stent treatment can delay the time to repeat intervention for femoropopliteal artery disease and how such a delay may result in cost savings in a value-based episode of care. Patients & methods: The IMPERIAL randomized controlled trial was an international study of a paclitaxel-eluting polymer-coated stent (Eluvia, Boston Scientific, MA, USA) versus a polymer-free paclitaxel-coated stent (Zilver PTX, Cook Corporation, IN, USA) for treating lesions of the femoropopliteal arterial segment. Study patients (n = 465) had symptomatic lower limb ischemia. Safety and efficacy assessments were performed through 5 years. Mean time to first reintervention was calculated in post-hoc analysis for patients who underwent a clinically driven target lesion revascularization (CD-TLR) through 3 or 5 years following the index procedure. To simulate potential cost savings associated with differential CD-TLR burden over time, a cost-avoidance analysis using input parameters from IMPERIAL and US 100% Medicare standard analytical files was developed. Results: Among patients with a first CD-TLR through 3 years of follow-up, mean time to reintervention was 5.5 months longer (difference 166 days, 95% CI: 51, 282 days; p = 0.0058) for patients treated with Eluvia (n = 56) than for those treated with Zilver PTX (n = 30). Through the 5-year study follow-up period, CD-TLR rates were 29.3% (68/232) for Eluvia and 34.2% (39/114) for Zilver PTX (p = 0.3540) and mean time to first reintervention exceeded 2 years for patients treated with Eluvia at 737 days versus 645 days for the Zilver PTX group (difference 92 days, 95% CI: -85, 269 days; p = 0.3099). Simulated savings considering reinterventions occurring over 1 and 5 years following initial use of Eluvia over Zilver PTX were US $1,395,635 and US $1,531,795, respectively, when IMPERIAL CD-TLR rates were extrapolated to 1000 patients. Conclusion: IMPERIAL data suggest initial treatment with Eluvia extends the time patients spend without undergoing reintervention. This extension may be associated with cost savings in relevant time frames.

Cost-effectiveness analysis of enhancements to angioplasty for infrainguinal arterial disease.

BACKGROUND: The aim was to perform an economic evaluation of the cost-effectiveness of endovascular enhancements to percutaneous transluminal balloon angioplasty (PTA) with bail-out bare metal stents for infrainguinal peripheral arterial disease. METHODS: The following interventions were considered: PTA with no bail-out stenting, PTA with bail-out drug-eluting stents, drug-coated balloons, primary bare metal stents, primary drug-eluting stents, endovascular brachytherapy, stent-grafts and cryoplasty. A discrete-event simulation model was developed to assess the relative cost-effectiveness of the interventions from a health service perspective over a lifetime. Populations of patients with intermittent claudication (IC) and critical leg ischaemia (CLI) were modelled separately. Univariable and probabilistic sensitivity analyses were undertaken. Effectiveness was measured by quality-adjusted life-years (QALYs). RESULTS: For both patient populations, the use of drug-coated balloons dominated all other options by having both lower lifetime costs and greater effectiveness. For willingness-to-pay thresholds between £0 and £100,000 per additional QALY, the probability of drug-coated balloons being cost-effective was at least 58.3 per cent for patients with IC and at least 72.2 per cent for patients with CLI. Sensitivity analyses showed that the results were robust to different assumptions regarding the clinical benefits attributable to the interventions. CONCLUSION: The use of drug-coated balloons represents a cost-effective alternative to the use of PTA with bail-out bare metal stents.

Cost effectiveness of drug-eluting stents as compared with bare metal stents in patients with coronary artery disease.

The aim of this study was to estimate the incremental cost effectiveness of replacing bare metal stents (BMS) by drug-eluting stents (DES) when using trial data and registry data. We developed a Markov model (model of cost effectiveness of coronary artery disease) in which 60-year-old patients started by undergoing percutaneous coronary intervention for acute or subacute coronary artery disease. The patients are followed until death or 100 years of age. Data on the occurrence of events (revascularization, acute myocardial infarction, and death) were based on Scandinavian registry data. Separate analyses were conducted with data on effectiveness based on randomized controlled trials and patient registries. On using trial data, it was found that sirolimus-eluting stents (SES) yield 0.003 greater life expectancy and $3300 lower costs than do BMS (dominant strategy). Paclitaxel-eluting stents (PES) yield 0.148 more life years than do SES at additional lifetime costs of $2800 ($21,400 per life year gained). On using registry data, the cost per life year gained was found to be $4900 when replacing BMS with DES. Probabilistic sensitivity analyses, on the other hand, indicate that PES only has a 50%-75% probability of being cost effective, regardless of the type of effectiveness data. DESs are cost effective with current willingness to pay for life year gains. Whether PES or SES is the most effective DES remains uncertain.

Optimal decision rules for HTA under uncertainty: a wider, dynamic perspective.

We present a two-period framework, which combines real option and decision-theoretic approaches to health technology assessment under uncertainty. By viewing adoption, treatment and research decisions as a single economic project, we illustrate how their key dimensions affect optimal rules. We consider the results in relation to the existing literature and argue that developments in this direction could contribute substantially to efficiency gains in resource allocation.