Cost-effectiveness of sequential urate lowering therapies for the management of gout in Singapore

Abstract

Aims: Allopurinol is the most common urate lowering therapy (ULT) used to treat gout but may cause life-threatening severe cutaneous adverse reactions (SCAR) in a small number of patients. Risk of SCAR is increased for patients with the HLA-B*58:01 genotype. When alternative ULT is required, febuxostat or probenecid are recommended. The aim of this study was to conduct a cost-utility analysis of sequential ULT treatment strategies for gout, including strategies with and without HLA-B*58:01 genotyping prior to treatment initiation, with a view to inform optimal gout management in Singapore.

Materials and methods: A Markov model was developed from the Singapore healthcare payer perspective. Reflecting local practice, 12 different treatment strategies containing at least one ULT (allopurinol, febuxostat, probenecid) were evaluated in adults with gout. Response rates (SUA < 6mg/dL) were derived from an in-house network meta-analysis and from published literature. Incremental cost-effectiveness ratios (ICERs) were calculated over a 30-year time horizon, with costs and benefits discounted at 3% per annum. Sensitivity analyses were conducted to explore uncertainties.

Results: Sequential treatment of allopurinol 300?mg/day-allopurinol 600?mg/day-probenecid (“standard of care”) was cost-effective compared to no ULT, with an ICER of SGD1,584/QALY. Allopurinol300-allopurinol600-probenecid-febuxostat sequence compared to allopurinol300-allopurinol600-probenecid had an ICER of SGD11,400/QALY. All other treatment strategies were dominated by preceding strategies. Treatment strategies incorporating HLA-B*58:01 genotyping before ULT use were dominated by the corresponding non-genotyping strategy.

Conclusions: Current standard of care (allopurinol300-allopurinol 600-probenecid) for gout is cost-effective compared with no ULT in the local context. Febuxostat is unlikely to be cost-effective in Singapore at current prices unless it is used last-line.     

Cost-effectiveness achieved through changing the composition of renal replacement therapy in Japan

Abstract

Objective:

The cost-effectiveness of renal replacement therapy (RRT) is affected by the composition of treatment. This study aimed to estimate the costs and outcomes associated with changing the composition of RRT modality over time.

Methods:

By using clinical and cost data from a systematic review, a Markov model was developed to assess the costs and benefits of the four main treatments available for RRT in Japan. The model included direct health service costs and quality-adjusted life years (QALY). Sensitivity analyses were performed to assess the robustness of the results.

Results:

Over the 15-year period of the model, the current composition of RRT (i.e., the base composition of RRT) was $84,008/QALY. The most cost-effective treatment was when the likelihood of a living donor transplant was increased by 2.4-times ($70,581/QALY). Compared with the base composition of RRT, dominant treatments with respect to cost-effectiveness were when the likelihood of a deceased donor transplant was increased by 22-times and when the likelihood of a pre-emptive living donor transplant was increased by 2.4-times. Little difference was found between these two treatments. One-way sensitivity analysis did not change the cost effectiveness except for costs of chronic hemodialysis and a living donor transplant in subsequent years.

Limitations:

It is difficult to increase the rate of transplant overall in the shorter term nationally and internationally.

Conclusions:

Appropriate distribution of all transplant options and hemodialysis is necessary to achieve the most cost-effective solution.     

欧洲卫生技术评估网络发展概况

面对医疗技术更新、民众医疗服务需求提升和医疗投入有限等多重卫生系统压力,欧洲国家力图在其卫生政策制定、管理、报销或监管过程中利用卫生技术评估（Health Technology Assessment,HTA）方法,在充分进行医疗组织、经济、社会和伦理等方面论证的基础上,综合透明、科学和可靠的证据,确定卫生政策优先领域,推动卫生体系的健康可持续发展。欧洲在卫生技术评估方面的有益经验,对我国强化卫生技术评估理念和做法,支持卫生政策制定,具有积极的借鉴意义。     

Valuing Environmental Health Effects – An Economic Perspective

This paper provides an overview of some of the issues involved in comparing benefit-cost analysis and cost-effectiveness analysis based on quality-adjusted life-years as alternative approaches to assessing environmental policies that affect human health. It concludes that: (i) although QALYs have the advantage of reflecting policy impacts on both health status and longevity in a single scalar measure, they are not consistent with utility theory unless individuals’ preferences satisfy some restrictive conditions; (ii) they do not capture other important aspects of the valuation of changes in mortality and morbidity; (iii) cost-effectiveness analysis based on QALYs as a measure of effectiveness omits non-health related effects of environmental policy; and (iv) it leaves unanswered the important question of what level of environmental regulation is appropriate.     

Contribution of intangible costs to the economic burden of multiple sclerosis

Abstract

Background:

Multiple sclerosis (MS) is associated with a substantial economic burden resulting from direct medical costs associated with health and disability-related resource utilization and indirect costs relating to reduced productivity. However, reduced health-related quality of life (HR-QOL) may be associated with additional costs, often termed ‘intangible costs,’ that should be considered as part of the economic burden from the societal or patient perspectives.

Objectives:

To review the contribution of intangible costs to the overall economic burden of MS.

Methods:

Medline was searched through March 2010 for relevant articles that included the terms ‘multiple sclerosis’ in combination with ‘intangible costs,’ ‘QALY,’ ‘quality-adjusted life year,’ ‘willingness-to-pay,’ and ‘WTP.’ Other than the restriction that the articles were published in English, there were no other exclusionary criteria for the search. Identified references were hand-searched to determine if intangible costs were estimated.

Results:

Thirteen studies across ten countries were identified that estimated intangible costs based on the number of quality-adjusted life-years (QALYs) lost due to a reduction in HR-QOL multiplied by accepted willingness-to-pay (WTP) thresholds. Although absolute costs varied depending on thresholds used and year of evaluation, the intangible costs accounted for 17.5–47.8% of total costs of MS. Furthermore, evidence suggested intangible costs are positively correlated with worsening disability. The largest increase in intangible costs occurred at the transition between mild and moderate disability. However, since no value has been established as being acceptable to pay for a QALY, a limitation of these studies was their dependence on the definition of the WTP threshold.

Conclusions:

Intangible costs substantially add to the economic burden of MS. There is not only a need to further characterize these costs and incorporate them into economic studies, but also to determine how these costs can be reduced through appropriate management strategies.     

A cost-effectiveness analysis of levodopa/carbidopa intestinal gel compared to standard care in late stage Parkinson’s disease in the UK

Abstract

Objective:

Evaluation of cost-effectiveness of levodopa/carbidopa intestinal gel (LCIG), compared to standard care (SC) in patients with advanced Parkinson’s disease (aPD) in the UK.

Design:

Markov model to quantify costs and outcomes associated with LCIG versus SC in aPD patients at Hoehn and Yahr (H&Y) stages 3, 4 or 5 experiencing >50% OFF time per day. Time horizon was lifetime, LCIG treatment was assumed to last maximal 5 years after which patients revert to SC. Model comprised 12 aPD health states according to H&Y status and daily time spent in OFF state. Cost analyses are reported from a UK NHS and Personal Social Services perspective. Uncertainties were assessed through one-way sensitivity analyses.

Comparators:

LCIG, providing patients with continuous dopaminergic stimulation to maximise functional ON time during the day and SC, defined as medically determined best available oral medication.

Main outcome measures:

Cost-effectiveness, based on quality adjusted life years gained, presented as an incremental cost-effectiveness ratio.

Results:

Lifetime analysis yields an incremental cost per QALY of £36,024 for LCIG compared to SC (incremental cost £39,644, QALY gain 1.1). Results were sensitive to time on treatment, health state on treatment initiation, and estimates of long term benefit (OWSA results from £32,127 to £66,421 per QALY). Findings must be considered in the context of the study limitations which were mainly due to data availability constraints.

Conclusions:

LCIG is an effective treatment, reducing OFF time and improving quality of life in advanced PD. It provides value for money in levodopa-responsive aPD patients with severe motor fluctuations when no other treatment options are effective or suitable. Given LCIG is an orphan drug, it is reasonable to suggest that it may be considered cost-effective in the UK setting. However, further research is needed to complete current data gaps and increase robustness of the model.     

Economic Valuation of Health for Environmental Policy: Comparing Alternative Approaches. Introduction and Overview

Protecting human health is a primary goal of environmental policy and economic evaluation of health can help policy-makers judge the relative worth of alternative actions. Economists use two distinct approaches in normatively evaluating health. Whereas environmental economists use benefit-cost analysis supported by monetary valuation in terms of willingness-to-pay, health economists evaluate interventions based on cost-effectiveness or cost-utility analysis (CEA), using quality-adjusted life-years (QALY) or similar indexes. This paper provides background on the controversy about the relative merits of these approaches and introduces the remaining papers in the special issue. These papers (with one exception) were presented at a conference sponsored by the Department of Economics at the University of Central Florida with support from the US Environmental Protection Agency. Although CEA might not lead to substantially different implications for environmental policy than benefit-cost analysis, and QALY may provide a benefit transfer tool to fill gaps in the morbidity valuation literature, the papers in this issue raise serious concerns about the suitability of QALY-based CEA for environmental regulatory analysis. QALY does not in general appropriately represent individual preferences for health and CEA is neither independent of income distribution nor adequate to assess efficiency.     

The cost-effectiveness of dulaglutide versus insulin glargine for the treatment of type 2 diabetes mellitus in Japan

Aims: Dulaglutide is a new once weekly glucagon-like peptide-1 (GLP-1) receptor agonist administered via a disposable auto-injection pen for the management of type 2 diabetes mellitus (T2DM). The objective of this study was to estimate the cost-effectiveness of dulaglutide vs insulin glargine for the management of T2DM from a Japanese healthcare perspective, in accordance with recently approved Japanese Cost-Effectiveness Guidelines.

Methods: The IQVIA CORE Diabetes Model (version 9) was used to estimate the long-term costs and effects of treatment with dulaglutide and insulin glargine. Direct comparative data from the Araki 2015 trial (NCT01584232) was used to inform the analysis. Costs associated with treatment and complications were derived from Japanese sources wherever possible and inflated to 2015 Japanese Yen (JPY). Utilities were based upon a European systematic review of diabetes utilities and adjusted for use in a Japanese population. One-way and probabilistic sensitivity analyses (OWSA and PSA) were conducted on all inputs and key modeling assumptions.

Results: Dulaglutide 0.75?mg was associated with higher quality-adjusted life years (QALYs), life years (LYs), and total costs, compared to insulin glargine, resulting in an incremental cost-effectiveness ratio (ICER) of 416,280 JPY/QALY gained. Treatment with dulaglutide increased the time alive and free from diabetes-related complications by 4 months. OWSA and PSA indicated that results were robust to plausible variations in input parameters and modeling assumptions.

Limitations: Key limitations of this study are similar to other cost-utility analyses of diabetes, including the extrapolation of short-term clinical trial data into lifelong durations. In addition, due to the lack of robust published Japanese data, some values were derived from non-Japanese sources.

Conclusions: This analysis suggests that dulaglutide 0.75?mg may be a cost-effective treatment alternative to insulin glargine for patients with T2DM in Japan.     

Economic evaluation in health: saving money or improving care?

Summary

Economic evaluation, most commonly in the form of cost-effectiveness analysis, has now become an established tool of overall health financing policy. However, health policy makers choose to use or ignore the accumulated body of economic evidence for a variety of reasons. This policy review takes a step back and looks objectively at the appropriate role and use of cost-effectiveness analysis within the broader context of health system financing, and also discusses a series of technical limitations (and potential solutions) that impact on the generation of a genuinely comparable economic evidence base in health at the population level. While the explicit purpose of economic evaluation is to address the health financing objective of efficiency, the authors conclude that its application can be usefully extended to other health system goals, including financial protection (specification of core public healthcare packages for universal insurance) and equity in financing (assessment of intervention costs and effects by stakeholder or socioeconomic group). In order to contribute to these broader objectives, a sectoral or population-based approach to cost-effectiveness analysis is needed.     

Economic evaluation of healthcare technology improving the quality of social life: the case of assistive technology for the disabled and elderly

Public investments in healthcare technology for the disabled and elderly to improve the quality of social life have been vigorous, but the economic evaluation of the assistive technology is still lacking. Under this circumstance, the purpose of this study is to analyse the socio-economic value of developing assistive technologies with the potential to improve the quality of social life, especially for disabled and elderly individuals. Based on a survey of 400 respondents, the spike model, a special form of the contingent valuation method (CVM) is applied to assess the value of assistive technologies. In Korea, a household’s willingness-to-pay (WTP) for the development of assistive technologies is US$4.26 per year, on average, in the form of a government-levied tax; although many people express zero WTP for the development of these technologies, people with higher household savings, higher levels of education and higher levels of charity donations have a higher WTP for the development of assistive technology. We conclude that although assistive technologies have considerable economic value many people express zero WTP for the development of these technologies. Therefore, political and social educational efforts are necessary to reach social consensus on the government investment in such technologies.     

A review and validation of overall survival extrapolation in health technology assessments of cancer immunotherapy by the National Institute for Health and Care Excellence: how did the initial best estimate compare to trial data subsequently made available?

Background: Validation of overall survival (OS) extrapolations of immune-checkpoint inhibitors (ICIs) during the National Institute for Health and Care Excellence (NICE) Single Technology Assessment (STA) process is limited due to data still maturing at the time of submission. Inaccurate extrapolation may lead to inappropriate decision-making. The availability of more mature trial data facilitates a retrospective analysis of the plausibility and validity of initial extrapolations. This study compares these extrapolations to subsequently available longer-term data.

Methods: A systematic search of completed NICE appraisals of ICIs from March 2000 to December 2017 was performed. A targeted search was also undertaken to procure published OS data from the pivotal clinical trials for each identified STA made available post-submission to NICE. Initial Kaplan-Meier curves and associated extrapolations from NICE documentation were extracted to compare the accuracy of OS projections versus the most mature data.

Results: The review identified 11 STAs, of which 10 provided OS data upon submission to NICE. The extrapolations undertaken considered parametric or piecewise survival models. Additional data cut-offs provided a mean of 18 months of OS beyond the end of the original data. Initial extrapolations typically under-estimated OS from the most mature data cut-off by 0.4–2.7%, depending on the choice of assessment method and use of the manufacturer- or ERG-preferred extrapolation.

Conclusion: Long-term extrapolation of OS is required for NICE STAs based on initial immature OS data. The results of this study demonstrate that the initial OS extrapolations employed by manufacturers and ERGs generally predicted OS reasonably well when compared to more mature data (when available), although on average they appeared to underestimate OS. This review and validation shows that, while the choice of OS extrapolation is uncertain, the methods adopted are generally aligned with later-published follow-up data and appear appropriate for informing HTA decisions.