Historical clinical and economic consequences of anemia management in patients with end-stage renal disease on dialysis using erythropoietin stimulating agents versus routine blood transfusions: a retrospective cost-effectiveness analysis

Abstract

Objective:

To determine whether Medicare’s decision to cover routine administration of erythropoietin stimulating agents (ESAs) to treat anemia of end-stage renal disease (ESRD) has been a cost-effective policy relative to standard of care at the time.

Methods:

The authors used summary statistics from the actual cohort of ESRD patients receiving ESAs between 1995 and 2004 to create a simulated patient cohort, which was compared with a comparable simulated cohort assumed to rely solely on blood transfusions. Outcomes modeled from the Medicare perspective included estimated treatment costs, life-years gained, and quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratio (ICER) was calculated relative to the hypothetical reference case of no ESA use in the transfusion cohort. Sensitivity of the results to model assumptions was tested using one-way and probabilistic sensitivity analyses.

Results:

Estimated total costs incurred by the ESRD population were $155.47B for the cohort receiving ESAs and $155.22B for the cohort receiving routine blood transfusions. Estimated QALYs were 2.56M and 2.29M, respectively, for the two groups. The ICER of ESAs compared to routine blood transfusions was estimated as $873 per QALY gained. The model was sensitive to a number of parameters according to one-way and probabilistic sensitivity analyses.

Limitations:

This model was counter-factual as the actual comparison group, whose anemia was managed via transfusion and iron supplements, rapidly disappeared following introduction of ESAs. In addition, a large number of model parameters were obtained from observational studies due to the lack of randomized trial evidence in the literature.

Conclusions:

This study indicates that Medicare’s coverage of ESAs appears to have been cost effective based on commonly accepted levels of willingness-to-pay. The ESRD population achieved substantial clinical benefit at a reasonable cost to society.     

Posaconazole vs fluconazole/itraconazole in the prophylaxis of invasive fungal infections in immunocompromised patients: A cost-effectiveness analysis in Greece

Abstract

Background:

Invasive fungal infections (IFIs) present a major issue in clinical practice, due to their high morbidity and mortality rates. In a pivotal multi-centre, randomized clinical trial, posaconazole prophylaxis prevented IFIs more effectively than did either fluconazole or itraconazole, and improved overall survival.

Objective:

The aim of this study was to perform an economic evaluation of the aforementioned therapeutic strategies for IFI prophylaxis in neutropenic patients, in the Greek healthcare setting.

Method:

A decision analytic model was developed, which described the course of neutropenic patients under posaconazole or standard azole (fluconazole or itraconazole) treatment. Effectiveness data for each treatment regimen were derived from published results of a pivotal, multi-centre, randomized clinical trial. Cost and healthcare resources utilization data depict Greek clinical practice and are derived from official Greek sources, from a third party payer perspective.

Results:

Prophylaxis with posaconazole resulted in fewer IFIs (0.05 vs 0.11 per patient) compared to treatment with fluconazole or itraconazole, during the first 100 days from initiation of prophylaxis treatment. The cost per avoided IFI with posaconazole was €6455, while the incremental cost per life year gained (LYG) was estimated at €24,196. Extensive sensitivity analyses corroborated the base-case results. Possible limitations of the study are the exclusion of indirect and outpatient costs from the analysis and the inherent uncertainty with regards to the transferability of the clinical efficacy results of the clinical trial to the Greek healthcare setting.

Conclusions:

The utilization of posaconazole for prophylaxis of IFIs neutropenic patients is a therapeutic strategy that provides superior clinical efficacy, while being cost-effective compared to alternative therapies.     

A systematic review of cost-effectiveness modeling of pharmaceutical therapies in neuropathic pain: variation in practice,key challenges,and recommendations for the future

Objectives: Complexities in the neuropathic-pain care pathway make the condition difficult to manage and difficult to capture in cost-effectiveness models. The aim of this study is to understand, through a systematic review of previous cost-effectiveness studies, some of the key strengths and limitations in data and modeling practices in neuropathic pain. Thus, the aim is to guide future research and practice to improve resource allocation decisions and encourage continued investment to find novel and effective treatments for patients with neuropathic pain.

Methods: The search strategy was designed to identify peer-reviewed cost-effectiveness evaluations of non-surgical, pharmaceutical therapies for neuropathic pain published since January 2000, accessing five key databases. All identified publications were reviewed and screened according to pre-defined eligibility criteria. Data extraction was designed to reflect key data challenges and approaches to modeling in neuropathic pain and based on published guidelines.

Results: The search strategy identified 20 cost-effectiveness analyses meeting the inclusion criteria, of which 14 had original model structures. Cost-effectiveness modeling in neuropathic pain is established and increasing across multiple jurisdictions; however, amongst these studies, there is substantial variation in modeling approach, and there are common limitations. Capturing the effect of treatments upon health outcomes, particularly health-related quality-of-life, is challenging, and the health effects of multiple lines of ineffective treatment, common for patients with neuropathic pain, have not been consistently or robustly modeled.

Conclusions: To improve future economic modeling in neuropathic pain, further research is suggested into the effect of multiple lines of treatment and treatment failure upon patient outcomes and subsequent treatment effectiveness; the impact of treatment-emergent adverse events upon patient outcomes; and consistent and appropriate pain measures to inform models. The authors further encourage transparent reporting of inputs used to inform cost-effectiveness models, with robust, comprehensive and clear uncertainty analysis and, where feasible, open-source modeling is encouraged.     

A cost-effectiveness analysis of denosumab for the prevention of skeletal-related events in patients with multiple myeloma in four European countries: Austria,Belgium, Greece,and Italy

Aim: The approved indication for denosumab (120?mg) was expanded in 2018 to include skeletal-related event (SRE) prevention in patients with multiple myeloma (MM). Therefore, a cost-effectiveness analysis was conducted comparing denosumab with zoledronic acid (ZA) for SRE prevention in patients with MM from the national healthcare system perspective in a representative sample of European countries: Austria, Belgium, Greece, and Italy.

Methods: The XGEVA global economic model for patients with MM was used to calculate incremental cost-effectiveness ratios (ICERs) for denosumab vs ZA over a lifetime horizon. Clinical inputs were derived from the denosumab vs ZA randomized, phase 3 study (“20090482”) in patients newly-diagnosed with MM, and comprised real-world adjusted SRE rates, serious adverse event (SAE) rates, treatment duration, dose intensity, progression-free survival (PFS), and overall survival (OS). Economic inputs comprised country-specific denosumab and ZA acquisition and administration costs, SRE and SAE management costs, and discount rates. Health utility decrements associated with MM disease progression, SRE and SAE occurrence, and route of administration were included.

Results: Estimated ICERs (cost per quality-adjusted life-year [QALY] gained) for denosumab vs ZA in Austria, Belgium, Greece, and Italy were €26,294, €17,737, €6,982, and €27,228, respectively. Using 1–3 times gross domestic product (GDP) per capita per QALY as willingness to pay thresholds, denosumab was 69–94%, 84–96%, 79–96%, and 50–92% likely to be cost-effective vs ZA, respectively.

Limitations: Economic inputs were derived from various sources, and time to event inputs were extrapolated from 20090482 study data.

Conclusions: Denosumab is cost-effective vs ZA for SRE prevention in patients with MM in Austria, Belgium, Greece, and Italy, based on often-adopted World Health Organization thresholds. This conclusion is robust to changes in model parameters and assumptions. Cost-effectiveness estimates varied across the four countries, reflecting differences in healthcare costs and national economic evaluation guidelines.     

元分析方法综述：从基础到高阶

作为一项重要的研究工具,元分析已广泛应用于心理学、管理学、教育学和医学等科学领域。随着统计技术的发展,传统元分析已逐渐衍生出大量高阶研究方法。为使研究者和从业者及时捕捉其发展现状,本文全面探讨了元分析的原理、应用及最新进展。首先,详细阐述了传统元分析的基本原理、历史发展及操作步骤。其次,归纳了传统元分析衍生出的高阶研究方法,包括：跨层次元分析、元分析结构方程模型及其他应用(如可复制性研究与大数据分析)等。最后,讨论了元分析在科学研究中的意义及局限性。本文为研究者提供了一个全面的元分析方法概述,帮助研究者识别其发展趋势和潜在问题,并有助于进一步改进该方法以适应不断变化的研究需求。     

Oil consumption and economic efficiency: A comparative analysis of advanced, developing and emerging economies

This paper investigates the economic efficiency-oil consumption relationship in 42 countries during the period 1986-2006. In a first stage by using DEA window analysis countries' economic efficiencies are obtained. In a second stage an econometric analysis based on robust GMM estimators reveals an inverted ‘U’-shape relationship between oil consumption and economic efficiency. In order to capture heterogeneities among countries' development stages the analysis has been separated into two groups (advanced economies and developing/emerging economies). The results show that advanced economies have much higher turning points compared to emerging and developing economies. It appears that oil consumption increases countries' economic efficiency. In addition the consumption patterns of oil products and its derivatives have changed through years and among countries. The different turning points from the econometric analysis indicate the dependence of oil consumption in advanced economies (higher turning points) is driven mainly by household purchasing activities and their standards of living (transport, housing and water, food, etc.). Finally, it appears that oil consumption is the main driver behind the progress of industrialization and urbanization regardless of the country's development stage.     

Complementarity between water pricing, water rights and local water governance: A Bayesian analysis of choice behaviour of farmers in the Krishna river basin, India

To ensure efficient water allocation and use, policy designers have adopted various strategies, including price setting, decentralising irrigation water management or improving water rights. Most of these strategies have been applied individually, without considering the complementary relationships between them. This paper uses a discrete choice model to analyse the scope for combinations of tools for irrigation water demand management and farmers' acceptance of these. In terms of local irrigation water governance, the presence or absence of collective irrigation water management, in the form of a Water Users Association, is considered. Water rights are specified in terms of the duration and quality of the entitlement and its transferability. Finally, four types of water pricing methods (area, crop, block and volumetric pricing) are considered. Using a choice experiment, we elicit the most preferred water pricing method, under different water rights situations, at different price levels and under various contexts for local irrigation water governance. Our results indicated that under conditions of improved water rights, preference for volumetric pricing increases, whilst the presence of a Water Users Association reduces this preference. Furthermore, it was found that using an appropriate combination of water demand management tools considerably increases the willingness to pay for a change in scenario.     

经济发展中的地方官员行为研究——基于政治晋升、财政分权与腐败的视角

本文同时考虑财政分权、政治晋升和腐败三个因素对地方官员行为的影响,进而构建了理论模型。从中得到的主要结论是,在基本模型中,地方官员对政治晋升的偏好程度越高,则其努力程度越高、腐败程度越低。而财政分权程度越高,官员的努力也越高,但对腐败水平影响却是不确定的。在进一步假设腐败会被惩罚的拓展模型中,基本模型的大部分结论都没有发生太大变化,只是分权程度的对努力的影响也变得不确定了。除此之外,我们进一步研究了,对官员腐败惩罚的力度和对官员腐败的惩罚准确程度的影响,相关命题表明,如果对官员腐败惩罚的越严厉,并且对官员腐败的惩罚越准确,官员努力水平和官员腐败程度都会变低。通过对研究结论的分析,我们还对以往文献的结果进行了重新解释。     

The state of research on technological uncertainties, social uncertainties and emerging markets: A multidisciplinary literature review

The objective of this research work is to study the progress of research on technological uncertainties, social uncertainties and emerging markets and outline and identify the key disciplines, journals, articles and authors. For this the author studied the existing literature from the various fields in which technological uncertainties, social uncertainties and emerging markets research work have been published using ISI Web of Knowledge database. The paper finds that there is increasing research work on technological uncertainties, social uncertainties and emerging markets and the bibliographical search resulted in ninety-one documents written by one-hundred-sixty-one authors in eighty-four journals in seventy-two disciplines. The five major disciplines and their underlying journals are business and economics, agriculture, psychology, public administration, and environmental sciences and ecology accounting for majority of publications. In journals the most prolific, measured by number of articles published are Harvard Business Review, Social Science and Medicine, World Development, and Higher Education; and most influential, measured by the global citation received, are Harvard Business Review, Social Science and Medicine and Sociological Review. The top 10% of the journals are responsible for 23% of all publications but 85% of all global citations received. This highlights that despite the high, diverse and increasing number of journals; only few are dominating and shaping the research arena of technological uncertainties, social uncertainties and emerging markets. Further, in the ten most cited articles, no author appears more than once.     

不同污染类型工业行业的环境污染分解分析——基于1998～2005年间中国工业行业数据分析

在利用数据包络分析(DEA)方法测算1998～2005年中国污染密集型和中、低污染型行业的全要素生产率的基础上,实证分析了各种因素对不同污染类型工业行业的污染排放的影响。结果表明:经济规模的扩大增加了污染排放,恶化了中国环境;工业内部的产业结构变化对污染密集型行业和中、低污染行业的污染排放均有显著的影响;全要素生产率的提高对控制污染密集型工业行业的污染排放有显著的作用;污染密集型行业出口商品结构变化对其行业污染排放有显著影响,进口商品结构变化对各污染类型工业行业污染排放均没有显著影响。     

揭示"制度与增长关系之谜"的一个研究视角——基于中国经济转型与经济增长关系的实证研究(1978-2004)

本文通过对中国经济转型与经济增长之间的实证研究,发现经济增长是直接推动经济体制转型深化的内在动力,而经济转型虽然对经济增长有长期的影响作用,但这种作用却不是决定性的.在制度与增长二者关系中,制度虽然是影响增长的长期重要因素,但这种影响却不是决定性的;而恰恰相反,增长对制度的影响却是决定性的.这说明制度创新在增长的大背景中更易达到,而中国改革成功的经验也充分证明了这一点.     

Engel’s curve and product differentiation: A dynamic analysis of the effects of quality on consumer’s choice

The application of Engel’s Curve in a single-product perspective may dramatically change the role of quality in affecting the dynamics of economic performance. This paper introduces a specification of preferences that regards quality as luxury, and quantity as necessary. The analysis is carried out by using a framework similar to Grossman’s and Helpman ’s (1991), while quality is defined as in Stokey (1988). The resulting consumer’s demand crucially depends on quality. Quality is potentially able to prevent the process, implied by neoclassical models, that leads the value of consumption goods to decline over time. By doing so, quality also affects the consumption bundle shares and the variety-specific consumption growth rates, thus influencing all dynamic quantitative variables of the economy. I thank Professor Beniamino Moro for his guidance and encouragement. I thank Stephen Wright for his comments and suggestions. I have benefited from the support of Alessio Moro, Dario Unali, Debora Fletcher, Emilio Merella, Esteban Jaimovich, Francesca Lamanna, Matteo Bellinzas, Mauro Merella and all my friends. I am also indebted to Professor Cuong Le Van and Professor Stephen Parente for their advice. I thank two anonymous Referees for their useful remarks.     

城郊结合部用地及生态环境问题研究——以四川达县城郊结合部为例

随着工业化、城市化进程的推进,城郊结合部处于动态迁移状态,其用地及生态环境问题凸显。化解这些问题已成为当务之急,并日益受到政府和学术界的广泛关注。文章以四川达县城郊结合部为例,揭示并分析了城郊结合部主要的用地及生态环境问题建,剖析了这些问题产生的根源,提出了解决这些问题的具体措施,其主要包括:(1)科学制订城郊结合部不同层次的规划;(2)加强农村建设用地监管;(3)改革现行的土地管理与经营体制;(4)强化城郊结合部生态环境管护措施。     

扭曲与矫正之成本权衡--汇率机制改革后人民币升值压力累积与释放效应分析

目前人民币仍面临由自身价值提高、篮子货币贬值和市场升值预期复合而成的多重升值压力.面对压力,有名义升值、实际升值和压力累积等三种政策方案可供选择.从成本收益量化比较来看,名义升值净成本最低.因此,应在不超过升值压力幅度的范围内允许人民币名义汇率继续缓升,以消除货币低估,实现内外均衡.     

Examining the global environmental impact of regional consumption activities — Part 1: A technical note on combining input-output and ecological footprint analysis

In recent years there have been a number of attempts to develop a more comprehensive approach to the issue of measuring resource use and/or pollution generation embodied in trade flows, including contributions that combine input-output techniques and Ecological Footprint analysis. In this two-part paper we describe how to enumerate the resource and/or pollution content of inter-regional and inter-national trade flows (Part 1) and we present a literature review of recent methodological and empirical developments (Part 2). It is straightforward in principle to extend the basic input-output approach to capture international trade flows. However, in practice, problems of data availability and compatibility, and of computability of extended input-output matrices, mean that simplifying assumptions are generally applied, but with the implications of these assumptions often not made fully explicit. What appears to be absent from previous applications is an account of the analytical method by which Ecological Footprints should ideally be estimated in an international input-output accounting analysis. This allows an explicit analysis of the problems that prevent the application of the full method and identification of the most appropriate short-cut methods in a transparent way. The objective of this paper is to provide such an account.