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.     

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.     

The cost-effectiveness of levodopa/carbidopa intestinal gel compared to standard care in advanced Parkinson’s disease

Background: Parkinson’s disease (PD) is an incurable, progressive neurological condition, with symptoms impacting movement, walking, and posture that eventually become severely disabling. Advanced PD (aPD) has a significant impact on quality-of-life (QoL) for patients and their caregivers/families. Levodopa/carbidopa intestinal gel (LCIG) is indicated for the treatment of advanced levodopa-responsive PD with severe motor fluctuations and hyper-/dyskinesia when available combinations of therapy have not given satisfactory results.

Aims: To determine the cost-effectiveness of LCIG vs standard of care (SoC) for the treatment of aPD patients.

Methods: A Markov model was used to evaluate LCIG vs SoC in a hypothetical cohort of 100 aPD patients with severe motor fluctuations from an Irish healthcare perspective. Model health states were defined by Hoehn &; Yahr (H&;Y) scale—combined with amount of time in OFF-time—and death. SoC comprised of standard oral therapy?±?subcutaneous apomorphine infusion and standard follow-up visits. Clinical efficacy, utilities, and transition probabilities were derived from published studies. Resource use was estimated from individual patient-level data from Adelphi 2012 UK dataset, using Irish costs, where possible. Time horizon was 20 years. Costs and outcomes were discounted at 4%. Both one-way and probabilistic sensitivity analyses were conducted.

Results: The incremental cost-effectiveness ratio for LCIG vs SOC was €26,944/quality adjusted life year (QALY) (total costs and QALYs for LCIG vs SoC: €537,687 vs €514,037 and 4.37 vs 3.49, respectively). LCIG is cost-effective at a payer threshold of €45,000. The model was most sensitive to health state costs.

Conclusion: LCIG is a cost-effective treatment option compared with SoC in patients with aPD.     

司来吉兰联合多奈哌齐治疗帕金森病患者的临床疗效

目的 探讨司来吉兰联合多奈哌齐治疗帕金森病患者的临床疗效.方法 选取2018年1月至2020年3月辽宁省健康产业集团阜新矿总院收治的帕金森病患者92例为研究对象,随机分为对照组与观察组,各46例.对照组患者给予司来吉兰治疗,观察组患者采用多奈哌齐与司来吉兰联合治疗.比较两组患者治疗效果、氧化应激水平、简易智能精神状态检...     

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.     

The effect of functional status impairment on nursing home admission risk among patients with advanced Parkinson’s disease

Abstract

Aims: To estimate the relationship between functional status (FS) impairment and nursing home admission (NHA) risk in Parkinson’s disease (PD) patients, and quantify the effect of advanced PD (APD) treatment on NHA risk relative to standard of care (SoC).

Materials and methods: PD patients were identified in the Medicare Current Beneficiary Survey (MCBS) (1992–2010). A working definition based on the literature and clinical expert input determined APD status. A logit model estimated the relationship between FS impairment and NHA risk. The effect of levodopa-carbidopa intestinal gel (LCIG) on NHA risk relative to SoC was simulated using clinical trial data (control: optimized oral levodopa-carbidopa IR, ClinicalTrials.gov NCT00660387 and NCT0357994).

Results: Non-advanced PD and APD significantly increased NHA risk when controlling for demographics (p?<?0.01). APD status was no longer significant after controlling for FS limitations, implying that FS limitations explain the increased NHA risk in APD patients. Reduced impairment in FS in patients with APD treated with LCIG reduced risk of NHA by 13.5% relative to SoC.

Limitations: This study applies clinical trial results to real-world data. LCIG treatment might have a different effect on NHA risk for the nationally representative population than the effect measured in the trial. Both data sources employ different instruments to measure FS, instrument wording and study follow-up differed, which might bias our estimates. Finally, there lacks consensus on a definition of APD. The prevalence of APD in this study is high, perhaps due to the specific definition used.

Conclusions: Patients with APD experience a higher risk in NHA than those with non-advanced disease. This increased risk in NHA in patients with APD is explained by greater limitations in FS. The relative reduction in risk of NHA for the APD population treated with LCIG is quantitatively similar to doubling Medicaid home care services.     

The economic burden of advanced Parkinson’s disease: an analysis of a UK patient dataset

Abstract

Background:

To evaluate the cost burden of patients with advanced Parkinson’s disease (PD) according to the waking hours per day spent in OFF state. An analysis of resource use comprising medical services, professional care and informal care data from an observational, cross-sectional study was conducted.

Methods:

A total of 60 physicians comprising 40 neurologists and 20 geriatricians across the UK participating in the Adelphi PD Disease Specific Programme took part. There were 302 PD patients at H&Y stages 3–5. Patients were characterised according to the percentage of time per day spent in OFF state (<25%, 26–50%, 51–75%, >75%).

Results:

Average 12-monthly total costs increased according to the time spent in OFF state from £25,630 in patients spending less than 25% of their waking hours in OFF to £62,147 for patients spending more than 75% of their time in OFF. Overall, 7% of costs were attributed to direct medical care, while 93% were split between direct non-medical professional care (50%) and indirect informal care (43%).

Limitations:

Low patient numbers in the more advanced disease stages of PD led to very little or no data to directly inform some of the severe health states of the analysis. Data gaps were filled in with data derived from a regression analysis which may affect the robustness of the analysis.

Conclusion:

This study illustrates the increasing costs of advancing PD, in particular related to the time spent in OFF state, and identifies that the foremost cost burden is associated with the care needs of the patient rather than medical services.     

普拉克索联合左旋多巴治疗帕金森病患者的临床效果

目的 探讨普拉克索联合左旋多巴治疗帕金森病患者的临床效果.方法 选取2017年3月至2020年3月辽宁省健康产业集团阜新矿总院收治的帕金森患者82例作为研究对象,随机分为对照组与观察组,各41例.对照组采取单一药物疗法(口服左旋多巴片),观察组采取联合用药方案(口服左旋多巴、普拉克索),比较两组治疗效果.结果 用药后,...     

Cost-utility analysis of levodopa carbidopa intestinal gel (Duodopa) in the treatment of advanced Parkinson’s disease in patients in Scotland and Wales

Aims: To carry out a cost-utility analysis comparing the cost-effectiveness of levodopa carbidopa intestinal gel (LCIG) with standard of care (SOC) in patients with advanced Parkinson’s Disease (aPD) unsuitable for apomorphine or deep brain stimulation (DBS). LCIG is the only treatment option in this small, but clinically important, population.

Methods: A Markov model with 25 disease states based on disease stage and off-time status plus death. Patients enter the model with aPD spending >50% of their waking day in the off-state. Patients progress through the model in 6-monthly cycles for 20 years to approximate lifetime treatment and capture long-term costs and effects of therapy. Inputs are based on LCIG clinical trials for clinical outcomes and health state utilities, the literature for health state transitions and use UK-based input data wherever possible (drug costs, disease/adverse event management costs, discontinuation rates, mortality rates).

Limitations: Data collection can be challenging in this small, elderly population with advanced disease, therefore some model inputs were estimated, rather than collected directly. It was assumed that a reduction in off-time was the only benefit after the first year of treatment with LCIG; this is a conservative approach, since there may be additional clinical benefits.

Results: There is a considerable incremental gain in quality adjusted life years (QALYs) for patients treated with LCIG of 1.26 QALY with an associated incremental cost-effectiveness ratio (ICER) of £52,110. If the impact on caregivers is included, the ICER reduces to £47,266.

Conclusions: In cases where there is an orphan population, with no alternative treatment options, HTA assessments have a broader decision-making framework and the ICER is interpreted in this context. In the setting of a very small population, with considerable unmet need, LCIG represents value for money, as reflected by funding approval across the UK.     

盐酸普拉克索联合多巴丝肼片对帕金森病患者治疗效果、不良反应及生命质量的影响

目的探讨盐酸普拉克索联合多巴丝肼片对帕金森病患者治疗效果、不良反应及生命质量的影响。方法选取2016年2月至2019年2月大连市中心医院神经内二科收治的帕金森病患者60例作为研究对象,依据治疗方法不同分为盐酸普拉克索联合多巴丝肼片治疗组(联合治疗组,n=30)和单独多巴丝肼片治疗组(单独治疗组,n=30),比较两组患者的帕金森病评定量表(UPDRS)评分、临床疗效、不良反应发生情况、生命质量。结果治疗前,两组患者UPDRSⅠ、UPDRSⅡ、UPDRSⅢ、UPDRSⅣ、总UPDRS评分比较,差异无统计学意义(P>0.05);治疗后,两组患者的UPDRSⅠ、UPDRSⅡ、UPDRSⅢ、UPDRSⅣ、总UPDRS评分均显著降低,且联合治疗组患者的UPDRSⅠ、UPDRSⅡ、UPDRSⅢ、UPDRSⅣ、总UPDRS评分均显著低于单独治疗组,差异有统计学意义(P<0.05)。联合治疗组患者治疗有效率90.0%(27/30)显著高于单独治疗组70.0%(21/30)(P<0.05),不良反应发生率13.3%(4/30)显著低于单独治疗组26.7%(8/30)(P<0.05)。联合治疗组患者生命质量高比例63.3%(19/30)显著高于单独治疗组26.7%(8/30)(P<0.05),生命质量低比例6.7%(2/30)显著低于单独治疗组40.0%(12/30)(P<0.05),但两组患者生命质量中比例30.0%(9/30)、33.3%(10/30)比较,差异无统计学意义(P>0.05)。结论盐酸普拉克索联合多巴丝肼片对帕金森病患者治疗效果较单独使用多巴丝肼片好,不良反应少,生命质量高。     

Cost analysis of the treatments for patients with advanced Parkinson's disease: SCOPE study

Abstract

Objective:

To perform a comparative long-term analysis of the associated healthcare costs for the therapeutic options in advanced Parkinson’s Disease (PD): deep brain stimulation (DBS), continuous duodenal levodopa-carbidopa infusion (CDLCI), and continuous subcutaneous apomorphine infusion (CSAI).     

竞争优势基本形式理论及其对环境责任竞争力的解释

突破现有竞争优势理论关于竞争优势基本形式的成说具有理论和现实意义。文章在分析、总结竞争优势理论的基础上认为,现有竞争优势理论中竞争优势基本形式均呈现出产品低成本、差异化的二维理念,然而二维理念对企业环境责任竞争力不能做出较完好的解释。在分析原因后,提出了竞争优势基本形式的三维理念,并用该三维理念来解释企业环境责任竞争力的形成。     

The influence of Taiwan’s stock market on Bitcoin’s price under Taiwan’s monetary policy threshold

ABSTRACT

This study uses a smooth transition autoregressive model with exogenous variables (STARX) to investigate whether there is a nonlinear relationship between Bitcoin and Taiwan’s stock market taking into account Taiwan’s monetary policy threshold during 2 February 2012 to 31 August 2019. The statistical results show there is a threshold effect and confirm a nonlinear relationship between Taiwan’s stock market and Bitcoin, with variations over time and across Bitcoin and Taiwan’s stock market. Specifically, we find that Bitcoin responds asymmetrically to Taiwan’s stock market according to the threshold value. Furthermore, the return on the closing price of TAIEX with a lag of two periods under Taiwan’s monetary policy threshold has a nonlinear impact on the return on the closing price of Bitcoin.     

Constructing the Monetary Conditions Index for China

How can we fit different monetary transmission channels together to understand the effect of China’s monetary policy? This paper focuses on China’s monetary conditions and aggregate demand in terms of the monetary conditions index (MCI), which has been widely used as an important indicator for central banks, financial institutions, and scholars. To construct an MCI in the context of China over 1987Q1–2010Q2, we consider three channels through which monetary conditions might influence aggregate demand: the primary lending rate, the real effective exchange rate, and the bank credit. The weights of the component variables are obtained by estimating both the IS equation and the vector autoregressive model (VAR), which yield somewhat similar results. Further empirical tests show that the MCIs we derived contain useful information about future output growth and inflation in China over the short and medium term. From a historical perspective, the MCI we derived is more informative than individual monetary variables for the understanding of the development of China’s monetary conditions between 1987 and 2010.     

Validity of sustainability framework for China’s mining cities – a structural equation modelling approach

Many studies developed their framework for sustainability through indicator systems, but the interactions and relationships within these indicators have not been studied yet. In this article, based on indicator systems, we use a sample of 78 mining cities in China and employ structural equation modelling (SEM) method to explore the validity of sustainability framework. Our empirical results show that resources abundance positively affects urbanization level significantly but negatively affects cleaner production level and environmental protection level significantly; economic strength positively affects urbanization level significantly; cleaner production level has a significant effect on economic strength and non-mineral resources conversion efficiency. We also find that when economic strength is low, resources abundance might weaken the positive effect of economy on urbanization.     

Does China’s emissions trading system foster corporate green innovation? Evidence from regulating listed companies

Carbon emissions trading system is expected to be both efficient and flexible in carbon reduction through green innovation. As the world’s largest CO₂ emitter, China has launched the emissions trading system (CN-ETS) since 2013 in 7 pilot areas and vowed to build a nation-wide system in the second half of 2017. This study provides preliminary evidence on the impact of the CN-ETS on green innovation and the moderating role of market competition on this relationship at the firm level. Based on data of regulating listed companies in seven pilots, the results show that CN-ETS is significantly positively correlated with green innovation, and market competition weakens the positive relationship, indicating that CN-ETS is effective in the aspect of green innovation, and the effect would be better in less competitive markets.     

State Capitalism Revisited: A Review of Emergent Forms and Developments

Even when the neoliberal ideology of the free market was more dominant than it now is, the state was involved in economic activities that could be undertaken by private firms. State capitalism takes increasingly diverse forms, including beyond direct, partial or even indirect ownership. This paper briefly reviews some of these forms without claiming to be exhaustive as the shape state capitalism takes differs widely across the institutionalized contexts of countries. We assess state capitalism using Polanyi’s double movement framework and argue that this framework needs adaptation to novel forms of state capitalism that include, e.g., state-owned multinationals and sovereign wealth funds.     

比利时微电子研究中心30年发展概析及其启示

比利时微电子研究中心(IMEC)用30年时间,从一个地方性微电子研究中心发展成为欧洲最大、世界领先的产业共性技术研发组织,探索走出了一条独特的可持续发展道路。在系统梳理IMEC发展历程的基础上,重点研究了IMEC研究方向、组织结构、研究模式、经费收支、人员构成、成果转化和地区作用,分析了IMEC发展成功的主要经验,包括:选择产业共性技术研究方向,构建稳定开放式研发平台,获得政府长期持续资助,开展广泛国际合作,采用利益共享的商业模式及坚持中立性原则等。借鉴IMEC的成功经验,我国半导体产业需要像IMEC这种组织来聚合产业力量,增强产业活力;应采取IMEC典型的经济实惠模式;应构建类似于IMEC的开放式产业共性技术研发平台,以实现符合产业与市场规律的可持续发展的效果。