Cost-effectiveness of left atrial appendage closure with Watchman for non-valvular atrial fibrillation patients in Japan.

AIMS: Left atrial appendage closure (LAAC) has been demonstrated to be cost-saving relative to oral anticoagulants for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF) in the United States and Europe. This study assessed the cost-effectiveness of LAAC with the Watchman device relative to warfarin and direct oral anticoagulants (DOACs) for stroke risk reduction in NVAF from a Japanese public healthcare payer perspective. METHODS: A Markov model was developed with 70-year-old patients using a lifetime time horizon. LAAC clinical inputs were from pooled, 5-year PROTECT AF and PREVAIL trials; warfarin and DOAC inputs were from published meta-analyses. Baseline stroke and bleeding risks were from the SALUTE trial on LAAC. Cost inputs were from the Japanese Medical Data Vision database. Probabilistic and one-way sensitivity analyses were performed. RESULTS: Over the lifetime time horizon, LAAC was less costly than warfarin (savings of JPY 1,878,335, equivalent to US $17,600) and DOACs (savings of JPY 1,198,096, equivalent to US $11,226). LAAC also provided 1.500 more incremental quality-adjusted life years (QALYs) than warfarin and 0.996 more than DOACs. In probabilistic sensitivity analysis, LAAC was cost-effective relative to warfarin and DOACs in 99.98% and 99.73% of simulations, respectively. LAAC dominated (had higher cumulative QALYs and was less costly than) warfarin and DOACs in 89.94% and 83.35% of simulations, respectively. CONCLUSIONS: Over a lifetime time horizon, LAAC is cost-saving relative to warfarin and DOACs for stroke risk reduction in NVAF patients in Japan and is associated with improved quality-of-life.

This study examined the cost-effectiveness of left atrial appendage closure (LAAC) compared to oral anticoagulants for stroke risk reduction among individuals with a specific type of irregular heart rhythm called non-valvular atrial fibrillation (NVAF). This study evaluated the cost-effectiveness of LAAC using the Watchman device in comparison to warfarin and direct oral anticoagulants (DOACs) from the perspective of Japan's public healthcare system. To investigate this, a computer-based model was developed involving 70-year-old patients over their lifetime. Data from notable studies such as the PROTECT AF and PREVAIL trials (covering 5 years) for LAAC and published meta-analyses for warfarin and DOACs were incorporated into the model. Baseline stroke and bleeding risks were derived from the SALUTE trial on LAAC. Cost inputs were based on data from the Japanese Medical Data Vision database. Additionally, we performed thorough cost-effectiveness analyses, including probabilistic and one-way sensitivity assessments. Our findings revealed that, over a lifetime, LAAC was more cost-effective than both warfarin and DOACs. Further, LAAC contributed an additional 1.500 quality-adjusted life years (QALYs) compared to warfarin and 0.996 QALYs compared to DOACs. In the long-term, adopting LAAC as an alternative to warfarin and DOACs is a cost-effective strategy for reducing stroke risk in NVAF patients in Japan. Moreover, it is associated with enhanced quality-of-life. These findings hold significant implications for informing decision-making in healthcare policies and clinical practices for NVAF patients.

Cost-Effectiveness of Left Atrial Appendage Closure for Stroke Reduction in Atrial Fibrillation: Analysis of Pooled, 5-Year, Long-Term Data.

Background Recent publications reached conflicting conclusions about the cost-effectiveness of left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, Marlborough, MA) for stroke risk reduction in nonvalvular atrial fibrillation (AF). This analysis sought to assess the cost-effectiveness of LAAC relative to both warfarin and nonwarfarin oral anticoagulants (NOACs) using pooled, long-term data from the randomized PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) and PREVAIL (Prospective Randomized Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin) trials. Methods and Results A Markov model was constructed from a US payer perspective with a lifetime (20-year) horizon. LAAC clinical event rates and stroke outcomes were from pooled PROTECT AF and PREVAIL trial 5-year data. Warfarin and NOAC inputs were derived from published meta-analyses. The model was populated with a cohort of 10 000 patients, aged 70 years, at moderate stroke and bleeding risk. Sensitivity analyses were performed. LAAC was cost-effective relative to warfarin by year 7 ($48 674/quality-adjusted life-year) and dominant (more effective and less costly) by year 10. LAAC became cost-effective and dominant compared with NOACs by year 5. Over a lifetime, LAAC provided 0.60 more quality-adjusted life-years than warfarin and 0.29 more than NOACs. In sensitivity analyses, LAAC was cost-effective relative to warfarin and NOACs in 98% and 95% of simulations, respectively. Conclusions Using pooled, 5-year PROTECT AF and PREVAIL trial data, LAAC proved to be not only cost-effective, but cost saving relative to warfarin and NOACs. LAAC with the Watchman device is an economically viable stroke risk reduction strategy for patients with AF seeking an alternative to lifelong anticoagulation.

Cost-Effectiveness of Left Atrial Appendage Closure With the WATCHMAN Device Compared With Warfarin or Non-Vitamin K Antagonist Oral Anticoagulants for Secondary Prevention in Nonvalvular Atrial Fibrillation.

BACKGROUND AND PURPOSE: Once a patient with atrial fibrillation experiences an embolic event, the risk of a recurrent event increases 2.6-fold. New treatments have emerged as viable treatment alternatives to warfarin for stroke risk reduction in secondary prevention populations. This analysis sought to assess the cost-effectiveness of left atrial appendage closure (LAAC) compared with warfarin and the non-vitamin K antagonist oral anticoagulants dabigatran 150 mg, apixaban and rivaroxaban in the prevention of stroke in nonvalvular atrial fibrillation patients with a prior stroke or transient ischemic attack. METHODS: A Markov model was constructed using data from the secondary prevention subgroup analyses of the non-vitamin K antagonist oral anticoagulant and LAAC pivotal trials. Costs were from 2016 US Medicare reimbursement rates and the literature. The cost-effectiveness analysis was conducted from a US Medicare perspective over a lifetime (20 years) horizon. The model was populated with a cohort of 10 000 patients aged 70 years with a CHA2DS2-VASc score of 7 (annual stroke risk=9.60%) and HAS-BLED score of 3 (annual bleeding risk=3.74%). RESULTS: LAAC achieved cost-effectiveness relative to dabigatran at year 5 and warfarin and apixaban at year 6. At 10 years, LAAC had more quality-adjusted life years (4.986 versus 4.769, 4.869, 4.888, and 4.810) and lower costs ($42 616 versus $53 770, $58 774, $55 656, and $58 655) than warfarin, dabigatran, apixaban, and rivaroxaban, respectively, making LAAC the dominant (more effective and less costly) stroke risk reduction strategy. LAAC remained the dominant strategy over the lifetime analysis. CONCLUSIONS: Upfront procedure costs initially make LAAC higher cost than warfarin and the non-vitamin K antagonist oral anticoagulants, but within 10 years, LAAC delivers more quality-adjusted life years and has lower total costs, making LAAC the most cost-effective treatment strategy for secondary prevention of stroke in atrial fibrillation.

Variation in Health Technology Assessment and Reimbursement Processes in Europe.

BACKGROUND: It has been suggested that differences in health technology assessment (HTA) processes among countries, particularly within Europe, have led to inequity in patient access to new medicines. OBJECTIVES: To provide an up-to-date snapshot analysis of the present status of HTA and reimbursement systems in select European countries, and to investigate the implications of these processes, especially with regard to delays in market and patient access. METHODS: HTA and reimbursement processes were assessed through a review of published and gray literature, and through a series of interviews with HTA experts. To quantify the impact of differences among countries, we conducted case studies of 12 products introduced since 2009, including 10 cancer drugs. RESULTS: In addition to the differences in HTA and reimbursement processes among countries, the influence of particular sources of information differs among HTA bodies. The variation in the time from the authorization by the European Medicines Agency to the publication of HTA decisions was considerable, both within and among countries, with a general lack of transparency as to why some assessments take longer than others. In most countries, market access for oncology products can occur outside the HTA process, with sales often preceding HTA decisions. CONCLUSIONS: It is challenging even for those with considerable personal experience in European HTA processes to establish what is really happening in market access for new drugs. We recommend that efforts should be directed toward improving transparency in HTA, which should, in turn, lead to more effective processes.

A Framework for Developing the Structure of Public Health Economic Models.

BACKGROUND: A conceptual modeling framework is a methodology that assists modelers through the process of developing a model structure. Public health interventions tend to operate in dynamically complex systems. Modeling public health interventions requires broader considerations than clinical ones. Inappropriately simple models may lead to poor validity and credibility, resulting in suboptimal allocation of resources. OBJECTIVE: This article presents the first conceptual modeling framework for public health economic evaluation. METHODS: The framework presented here was informed by literature reviews of the key challenges in public health economic modeling and existing conceptual modeling frameworks; qualitative research to understand the experiences of modelers when developing public health economic models; and piloting a draft version of the framework. RESULTS: The conceptual modeling framework comprises four key principles of good practice and a proposed methodology. The key principles are that 1) a systems approach to modeling should be taken; 2) a documented understanding of the problem is imperative before and alongside developing and justifying the model structure; 3) strong communication with stakeholders and members of the team throughout model development is essential; and 4) a systematic consideration of the determinants of health is central to identifying the key impacts of public health interventions. The methodology consists of four phases: phase A, aligning the framework with the decision-making process; phase B, identifying relevant stakeholders; phase C, understanding the problem; and phase D, developing and justifying the model structure. Key areas for further research involve evaluation of the framework in diverse case studies and the development of methods for modeling individual and social behavior. CONCLUSIONS: This approach could improve the quality of Public Health economic models, supporting efficient allocation of scarce resources.

Cost effectiveness of left atrial appendage closure with the Watchman device for atrial fibrillation patients with absolute contraindications to warfarin.

AIMS: Atrial fibrillation (AF) patients with contraindications to oral anticoagulation have had few options for stroke prevention. Recently, a novel oral anticoagulant, apixaban, and percutaneous left atrial appendage closure (LAAC) have emerged as safe and effective therapies for stroke risk reduction in these patients. This analysis assessed the cost effectiveness of LAAC with the Watchman device relative to apixaban and aspirin therapy in patients with non-valvular AF and contraindications to warfarin therapy. METHODS AND RESULTS: A cost-effectiveness model was constructed using data from three studies on stroke prevention in patients with contraindications: the ASAP study evaluating the Watchman device, the ACTIVE A trial of aspirin and clopidogrel, and the AVERROES trial evaluating apixaban. The cost-effectiveness analysis was conducted from a German healthcare payer perspective over a 20-year time horizon. Left atrial appendage closure yielded more quality-adjusted life years (QALYs) than aspirin and apixaban by 2 and 4 years, respectively. At 5 years, LAAC was cost effective compared with aspirin with an incremental cost-effectiveness ratio (ICER) of €16 971. Left atrial appendage closure was cost effective compared with apixaban at 7 years with an ICER of €9040. Left atrial appendage closure was cost saving and more effective than aspirin and apixaban at 8 years and remained so throughout the 20-year time horizon. CONCLUSIONS: This analysis demonstrates that LAAC with the Watchman device is a cost-effective and cost-saving solution for stroke risk reduction in patients with non-valvular AF who are at risk for stroke but have contraindications to warfarin.

A systematic literature review of the key challenges for developing the structure of public health economic models.

OBJECTIVES: To identify the key methodological challenges for public health economic modelling and set an agenda for future research. METHODS: An iterative literature search identified papers describing methodological challenges for developing the structure of public health economic models. Additional multidisciplinary literature searches helped expand upon important ideas raised within the review. RESULTS: Fifteen articles were identified within the formal literature search, highlighting three key challenges: inclusion of non-healthcare costs and outcomes; inclusion of equity; and modelling complex systems and multi-component interventions. Based upon these and multidisciplinary searches about dynamic complexity, the social determinants of health, and models of human behaviour, six areas for future research were specified. CONCLUSIONS: Future research should focus on: the use of systems approaches within health economic modelling; approaches to assist the systematic consideration of the social determinants of health; methods for incorporating models of behaviour and social interactions; consideration of equity; and methodology to help modellers develop valid, credible and transparent public health economic model structures.

Time to Cost-Effectiveness Following Stroke Reduction Strategies in AF: Warfarin Versus NOACs Versus LAA Closure.

BACKGROUND: Left atrial appendage closure (LAAC) and nonwarfarin oral anticoagulants (NOACs) have emerged as safe and effective alternatives to warfarin for stroke prophylaxis in patients with nonvalvular atrial fibrillation (AF). OBJECTIVES: This analysis assessed the cost-effectiveness of warfarin, NOACs, and LAAC with the Watchman device (Boston Scientific, Marlborough, Massachusetts) for stroke risk reduction in patients with nonvalvular AF at multiple time points over a lifetime horizon. METHODS: A Markov model was developed to assess the cost-effectiveness of LAAC, NOACs, and warfarin from the perspective of the Centers for Medicare & Medicaid Services over a lifetime (20-year) horizon. Patients were 70 years of age and at moderate risk for stroke and bleeding. Clinical event rates, stroke outcomes, and quality of life information were drawn predominantly from PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) 4-year data and meta-analyses of warfarin and NOACs. Costs for stroke risk reduction therapies, treatment of associated acute events, and long-term care following disabling stroke were presented in 2015 U.S. dollars. RESULTS: Relative to warfarin, LAAC was cost-effective at 7 years ($42,994/quality-adjusted life-years [QALY]), and NOACs were cost-effective at 16 years ($48,446/QALY). LAAC was dominant over NOACs by year 5 and warfarin by year 10. At 10 years, LAAC provided more QALYs than warfarin and NOACs (5.855 vs. 5.601 vs. 5.751, respectively). In sensitivity analyses, LAAC remained cost-effective relative to warfarin ($41,470/QALY at 11 years) and NOACs ($21,964/QALY at 10 years), even if procedure costs were doubled. CONCLUSIONS: Both NOACs and LAAC with the Watchman device were cost-effective relative to warfarin, but LAAC was also found to be cost-effective and to offer better value relative to NOACs. The results of this analysis should be considered when formulating policy and practice guidelines for stroke prevention in AF.

A cost-effectiveness analysis of celecoxib compared with diclofenac in the treatment of pain in osteoarthritis (OA) within the Swedish health system using an adaptation of the NICE OA model.

OBJECTIVES: Celecoxib for the treatment of pain resulting from osteoarthritis (OA) was reviewed by the Tandvårds- och läkemedelsförmånsverket-Dental and Pharmaceutical Benefits Board (TLV) in Sweden in late 2010. This study aimed to evaluate the incremental cost-effectiveness ratio (ICER) of celecoxib plus a proton pump inhibitor (PPI) compared to diclofenac plus a PPI in a Swedish setting. METHODS: The National Institute for Health and Care Excellence (NICE) in the UK developed a health economic model as part of their 2008 assessment of treatments for OA. In this analysis, the model was reconstructed and adapted to a Swedish perspective. Drug costs were updated using the TLV database. Adverse event costs were calculated using the regional price list of Southern Sweden and the standard treatment guidelines from the county council of Stockholm. Costs for treating cardiovascular (CV) events were taken from the Swedish DRG codes and the literature. RESULTS: Over a patient's lifetime treatment with celecoxib plus a PPI was associated with a quality-adjusted life year (QALY) gain of 0.006 per patient when compared to diclofenac plus a PPI. There was an increase in discounted costs of 529 kr per patient, which resulted in an incremental cost-effectiveness ratio (ICER) of 82,313 kr ($12,141). Sensitivity analysis showed that treatment was more cost effective in patients with an increased risk of bleeding or gastrointestinal (GI) complications. CONCLUSIONS: The results suggest that celecoxib plus a PPI is a cost effective treatment for OA when compared to diclofenac plus a PPI. Treatment is shown to be more cost effective in Sweden for patients with a high risk of bleeding or GI complications. It was in this population that the TLV gave a positive recommendation. There are known limitations on efficacy in the original NICE model.

Cost-effectiveness and clinical effectiveness of catheter-based renal denervation for resistant hypertension.

OBJECTIVES: The purpose of this study was to assess cost-effectiveness and long-term clinical benefits of renal denervation in resistant hypertensive patients. BACKGROUND: Resistant hypertension affects 12% of hypertensive persons. In the Symplicity HTN-2 randomized controlled trial, catheter-based renal denervation (RDN) lowered systolic blood pressure by 32 ± 23 mm Hg from 178 ± 18 mm Hg at baseline. METHODS: A state-transition model was used to predict the effect of RDN and standard of care on 10-year and lifetime probabilities of stroke, myocardial infarction, all coronary heart disease, heart failure, end-stage renal disease, and median survival. We adopted a societal perspective and estimated an incremental cost-effectiveness ratio in U.S. dollars per quality-adjusted life-year, both discounted at 3% per year. Robustness and uncertainty were evaluated using deterministic and probabilistic sensitivity analyses. RESULTS: Renal denervation substantially reduced event probabilities (10-year/lifetime relative risks: stroke 0.70/0.83; myocardial infarction 0.68/0.85; all coronary heart disease 0.78/0.90; heart failure 0.79/0.92; end-stage renal disease 0.72/0.81). Median survival was 18.4 years for RDN versus 17.1 years for standard of care. The discounted lifetime incremental cost-effectiveness ratio was $3,071 per quality-adjusted life-year. Findings were relatively insensitive to variations in input parameters except for systolic blood pressure reduction, baseline systolic blood pressure, and effect duration. The 95% credible interval for incremental cost-effectiveness ratio was cost-saving to $31,460 per quality-adjusted life-year. CONCLUSIONS: The model suggests that catheter-based renal denervation, over a wide range of assumptions, is a cost-effective strategy for resistant hypertension that might result in lower cardiovascular morbidity and mortality.

A qualitative study of manufacturers' submissions to the UK NICE single technology appraisal process.

OBJECTIVES: As part of the National Institute for Health and Clinical Excellence (NICE) Single Technology Appraisal (STA) process, manufacturers present submissions outlining the clinical and cost-effectiveness of new technologies. These submissions are critically appraised by Evidence Review Groups (ERGs), who produce a report, which forms part of the evidence considered by the NICE Appraisal Committees. The purpose of this research was first to identify common issues and concerns identified by the ERGs in their analyses of manufacturers' submissions (MS). The aim was then to use these as a basis to develop feedback for manufacturers. DESIGN: A qualitative study using a content analysis approach to examine two sources of evidence, the first 30 ERG reports and 21 clarification letters associated with these STAs. SETTING: UK HTA programme. PRIMARY AND SECONDARY OUTCOME MEASURES: Common issues and concerns in MS. RESULTS: There were positive comments regarding the quality of the MS, many of which were clearly written. The majority, however, were generally of poor quality and issues and concerns identified across the ERG reports and clarification letters included: criticisms related to the data being used especially data employed in the cost-effectiveness model, failure to perform a necessary analysis and poor reporting of processes used in the MS. Aspects of the decision problem were also often poorly or inadequately addressed by manufacturers. The majority of points raised for clarification related to the economic data analysis. Internal inconsistencies between the clinical and economic sections of the submission were frequently highlighted. These were used as the basis for the development of 12 suggestions for manufacturers. CONCLUSIONS: Much can be done to improve the quality of MS in the NICE STA process. Suggestions include the need for clear and transparent reporting of methods and analyses.

Economic implications of the use of basiliximab in addition to triple immunosuppressive therapy in renal allograft recipients: a UK perspective.

OBJECTIVE: To compare resource use and costs in renal transplant recipients treated with basiliximab or placebo plus triple immunosuppressive therapy. DESIGN: International randomised, double-blind, placebo-controlled trial; economic evaluation undertaken alongside the efficacy trial. The economic evaluation was performed from a UK National Health Service hospital perspective. SETTING: 31 centres in 12 countries. PARTICIPANTS: 345 renal transplant recipients were enrolled; 340 were randomised (basiliximab 168; placebo 172) and included in the intention-to-treat analysis. INTERVENTION: Treatment with placebo or basiliximab (20mg intravenous bolus) on day 0 and day 4 after transplantation. MAIN OUTCOME MEASURES: Resource utilisation in multiple categories and treatment costs for basiliximab and placebo-treated patients during the 6-month post-transplantation period. RESULTS: No statistically significant differences were found in any of the economically important categories of resource use or in the mean cost of treatment per person across the whole trial. The mean cost of treatment, including the cost of basiliximab, was pound 16 095 for basiliximab recipients and pound 15 864 (1997/1998 costs) for placebo recipients, a mean difference of pound 231 (95% CI: - pound 1983 to pound 2446), which was not significant. Basiliximab treatment led to a significant reduction in acute rejection episodes (basiliximab 20.8%; placebo 34.9%; p = 0.005). CONCLUSIONS: Basiliximab therapy confers a significant clinical benefit to renal transplant recipients without increasing overall treatment costs.

The economics of basiliximab (Simulect) in preventing acute rejection in renal transplantation.

An economic evaluation was undertaken alongside a multicentre international trial of basiliximab. Resource usage within the trial was assessed, and the cost implications of using basiliximab evaluated. Recipients of a primary cadaveric kidney transplant were recruited into a double-blind trial and received either placebo ( n=186) or basiliximab ( n=190). Clinical outcomes and resource usage were monitored in the 12 months following transplantation. Local unit costs were obtained, and global analysis was undertaken using health sector purchasing-power parity rates. No statistically significant differences were found in the mean cost of treatment per patient. The mean cost of treatment was US$47,940 for basiliximab patients and US$46,280 for placebo patients, a mean difference of US$1,660 (95% confidence interval (CI): -US$4,150, US$7,360; P=0.58). Basiliximab produces clinical benefit in terms of preventing episodes of acute rejection, whilst the difference in the total resource usage and cost of treatment is not statistically significant.