Analytic Considerations in Economic Evaluations of Multinational Cardiovascular Clinical Trials

OBJECTIVES: The growing number of economic evaluations that use data collected in multinational clinical trials raises numerous questions regarding their execution and interpretation. Although recommendations for conducting economic evaluations have been widely disseminated, relatively little guidance has been given for conducting economic evaluations alongside clinical trials, particularly multinational trials. METHODS: Building on a literature review that was conducted in preparation for an expert workshop, we evaluated a subset of methodological issues related to conducting economic evaluations alongside multinational clinical trials. RESULTS: We found wide variation in the types of costs included as part of the analyses and in the methods used to assign costs to hospitalization events. Furthermore, we found that the extrapolation of costs and survival outcomes beyond the trial period is an inconsistent practice and is often not dependent on whether a survival benefit was observed in the trial or on the epidemiology or practice patterns in the country to which the findings are directed. CONCLUSIONS: Although the limited sample size precluded a quantitative analysis of trial characteristics and their associations with the methodologies employed, our findings highlight the need for more guidance to analysts regarding the execution of economic evaluations using data from multinational clinical trials. As the research community grapples with the complexities of methodological and logistical issues involved in multinational economic evaluations, the development of a standardized format to report the basic methodological characteristics of such studies would help to improve transparency and comparability for other analysts and decision-makers.     

我国慢性病直接经济负担研究

目的:通过对1993年和2004年《中国卫生统计年鉴》和第一次及第三次国家卫生服务调查相关数据的分析,测算5类慢性疾病的直接医疗费用。方法:直接医疗费用由出院人数、出院患者平均住院医疗费用、门诊人次数和门诊病人次均医疗费用求得。结果:2003年5类慢性疾病的直接医疗费用为1209.42亿元,其中,住院医疗费用588.37亿元,门诊医疗费用为621.05亿元:5类慢性疾病的直接医疗费用构成了国家医疗总费用的重要组成部分(占21.05%),其中,各病种(类)的费用负担在门诊和住院中表现不一,并且在城市主要以住院费用为主,在农村则以门诊费用为主;自1993年以来,其年平均增长速度为14.37%,超过了同期国内生产总值(GDP)、卫生总费用和医疗总费用的增长速度,其中,门诊病人次均医疗费用和出院者平均住院医疗费用的增长速度大大超过了同期的门诊人次数和出院人次数的增长速度,提示我国医疗行业存在垄断现象。     

Economic evaluation and the postponement of health care costs

The inclusion of medical costs in life years gained in economic evaluations of health care technologies has long been controversial. Arguments in favour of the inclusion of such costs are gaining support, which shifts the question from whether to how to include these costs. This paper elaborates on the issue how to include cost in life years gained in cost effectiveness analysis given the current practice of economic evaluations in which costs of related diseases are included. We combine insights from the theoretical literature on the inclusion of unrelated medical costs in life years gained with insights from the so-called 'red herring' literature. It is argued that for most interventions it would be incorrect to simply add all medical costs in life years gained to an ICER, even when these are corrected for postponement of the expensive last year of life. This is the case since some of the postponement mechanism is already captured in the unadjusted ICER by modelling the costs of related diseases. Using the example of smoking cessation, we illustrate the differences and similarities between different approaches. The paper concludes with a discussion about the proper way to account for medical costs in life years gained in economic evaluations.     

部队卫生装备检修的经济效益分析

目的：评价药品仪器检验所年度巡回检修的经济效益，揭示卫生设备维修投资的经济作用。方法：根据药品仪器检验所2007年巡回检修的记录，用Excel2003建立数据库，对21种常用卫生设备维护所产生的经济效益进行分析。结果：总收益成本比（BCR）为5．32。结论：卫生装备维修投资具有显著的经济作用。     

Assessment of Total Economic Burden of Chronic Hepatitis B (CHB)-Related Diseases in Beijing and Guangzhou, China

Objective:  To estimate the total annual cost due to Chronic Hepatitis B (CHB)-related diseases imposed on each patient and his/her family in Beijing and Guangzhou, China.
Methods:  Economic burden of CHB-related diseases (CHB, compensated cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma) were examined. A retrospective cohort of 328 patients in Beijing and 271 in Guangzhou were identified to obtain their socioeconomic status, utilization and costs of treatment, and work loss days due to illness with a structured questionnaire. Costs of hospitalization were extracted from databases of two hospitals in Beijing and Guangzhou Social Insurance Information System, respectively. The outpatient expenditure per patient was measured through the rate of outpatient visits and average cost per visit reported by the patients, while the inpatient cost was calculated through annual rate of hospitalization and average expenditure for different types of hospitals. Self medication and direct nonmedical cost were also reported. The Human Capital Approach was employed to measure the work loss cost.
Results:  The total annual cost per patient for CHB, compensated cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma were US$1636, US$2722, US$4611, and US$6615 in Beijing, and US$1452, US$2065, US$4290 and US$6054 in Guangzhou, respectively.
Conclusion:  This study confirms that CHB-related diseases impose a substantial economic burden on patients, families, and the society in China urban areas. The study demonstrates increasing health-care costs related to disease progression and provides useful information on cost of treatment and work loss for different disease states, which can be further utilized in cost-effectiveness evaluation.     

Indirect Economic Burden of Sickle Cell Disease

ObjectiveThis study aimed to quantify the indirect costs of sickle cell disease in the United States.MethodsAdult patients from a sickle cell disease clinic at an urban academic healthcare system completed an adapted Institute for Medical Technology Assessment Productivity Cost Questionnaire related to the impact of their disorder on absenteeism, presenteeism, ability to contribute through unpaid work outside of employment, and other aspects of life. Additional data were collected from patient records about each participant’s genotype, total hemoglobin level, and pain level.ResultsOf the 192 individuals, 187 who completed the survey reported experiencing vaso-occlusive crisis pain events during the last year that negatively affected their productivity at work and in daily roles. Three-fourths of respondents reported impairment in their ability to complete everyday tasks, such as caring for children, running errands, doing housework, shopping for groceries, and volunteer (unpaid) work. Only 30% of respondents reported being employed or self-employed. Of those employed, estimated costs of absenteeism and presenteeism attributable to pain events averaged $15 103 per person annually. Estimated total annual losses in unpaid work productivity averaged $3 145 862 for the study respondents and another $2 870 652 for their caregivers.ConclusionsSickle cell disease affected the work productivity, nonwork productivity, and the daily lives of adults seen with the disorder in an academic medical center.     

Variability of Cost-Effectiveness Estimates for Pharmaceuticals in Western Europe: Lessons for Inferring Generalizability

OBJECTIVES: It has long been suggested that, whereas the results of clinical studies of pharmaceuticals are generalizable from one jurisdiction to another, the results of economic evaluations are location dependent. There has been, however, little study of the causes of variation, whether differences in study results among countries are systematic, or whether they are important for decision making. METHODS: A literature search was conducted to identify economic evaluations of pharmaceuticals conducted in two or more European countries. The studies identified were then classified by methodological type and analyzed to assess their level of variability and to identify the main causes of variation. Assessments were also made of the extent to which differences in study results among countries were systematic and whether they would lead to a different decision, assuming a range of values of the threshold willingness-to-pay for a life-year or quality-adjusted life-year (QALY). RESULTS: In total 46 intercountry drug comparisons were identified, 29 in multicountry studies and 17 in comparable single country studies that were considered to be sufficiently similar in terms of methodology. The type of study (i.e., trial-based or modeling study) had some impact on variability, but the most important factor was the extent of variation across countries in effectiveness, resource use or unit costs, allowed by the researcher's chosen methodology. There were few systematic differences in study results among countries, so a decision maker in country B, on seeing a recent economic evaluation of a new drug in country A, would have little basis on which to predict whether the drug, if evaluated, would be more or less cost-effective in his or her country. Given the extent of variation in cost-effectiveness estimates among countries, the importance of this for decision making depends on decision makers' thresholds in willingness-to-pay for a QALY or life-year. If a cost-effectiveness threshold (i.e., willingness-to-pay) for a life-year or QALY of dollar 50,000 were assumed, the same conclusion regarding cost-effectiveness would be reached in most cases. CONCLUSION: This review shows that cost-effectiveness results for pharmaceuticals vary from country to country in Western Europe and that these variations are not systematic. In addition, constraints imposed by analysts may reduce apparent variability in the estimates. The lessons for inferring generalizability are not straightforward, although the implications of variation for decision making depend critically on the cost-effectiveness thresholds applying in Western Europe.     

Evaluating and Valuing Drugs for Rare Conditions: No Easy Answers

We find ourselves in an era of unprecedented growth in the development and use of so-called “orphan” drugs to treat rare diseases, which are poised to represent more than one-fifth of pharmaceutical expenditures by 2022. This widespread use has been facilitated by legislative and regulatory incentives in both the United States and abroad, yet US payers and health systems have not yet made a concerted effort to understand whether and how rare diseases require special considerations on their part and how to adapt traditional methods of health technology assessment and economic evaluation to accommodate these situations. In this article, we explore the general ethical dilemmas that rare diseases present, steps taken by health technology assessment bodies worldwide to define the level of rarity that would necessitate special measures and the modifications to their assessment and valuation processes needed, and the contextual components for rare-disease evaluation that lie outside of the assessment framework as a guide to US decision makers on constructing a formal and relevant process stateside.     

Budgetary Impact and Cost Drivers of Drugs for Rare and Ultrarare Diseases

Objectives

To review recent studies reporting health care expenditures (budgetary impact) for orphan medicinal products (OMPs) in Europe and to contribute to our understanding of the cost drivers of nononcological OMPs by means of an empirical analysis in Germany.

In defence of societal sovereignty: a comment on Nyman 'the inclusion of survivor consumption in CUA'

Whether to include or exclude consumption costs and costs of unrelated illnesses in economic evaluation is not a technical issue which may be answered by reference to individuals alone and the consistency of the treatment of individual costs and benefits. In the context of a publicly funded health service the relevant costs and benefits may differ from those normally included in evaluation studies. Specifically, the social welfare function is likely to exclude benefits which would result in preferential care for wealthier members of society. But this conclusion must be established by analysis of social, not individual, values.     

Review of Rare Diseases Resources: National Organization for Rare Disorders (NORD) Rare Disease Database,NIH Genetic and Rare Diseases Information Center,and Orphanet

This column profiles three important online resources for rare disorder information. The National Organization for Rare Disorders (NORD) Rare Disease Database set the standard for thorough, detailed monographs on rare diseases starting in the 1990s. The NORD Database is complemented by the National Institutes of Health (NIH) Genetic and Rare Diseases Information Center online and the European resource, Orphanet, both of which provide much broader coverage, if less in depth than NORD’s. Reading level for all three information sources is high, and there are occasional issues with currency. However, consumer health librarians should find these organizations’ web-based databases to be reliable sources of information on health conditions that can be perplexing for both patient and health care providers alike.     

Economic evaluation and catheter-related bloodstream infections

Catheter-related bloodstream infections are a serious problem. Many interventions reduce risk, and some have been evaluated in cost-effectiveness studies. We review the usefulness and quality of these economic studies. Evidence is incomplete, and data required to inform a coherent policy are missing. The cost-effectiveness studies are characterized by a lack of transparency, short time-horizons, and narrow economic perspectives. Data quality is low for some important model parameters. Authors of future economic evaluations should aim to model the complete policy and not just single interventions. They should be rigorous in developing the structure of the economic model, include all relevant economic outcomes, use a systematic approach for selecting data sources for model parameters, and propagate the effect of uncertainty in model parameters on conclusions. This will inform future data collection and improve our understanding of the economics of preventing these infections.     

Practical Guidance for Including Future Costs in Economic Evaluations in The Netherlands: Introducing and Applying PAID 3.0

ObjectivesA consensus has been reached in The Netherlands that all future medical costs should be included in economic evaluations. Furthermore, internationally, there is the recognition that in countries that adopt a societal perspective estimates of future nonmedical consumption are relevant for decision makers as much as production gains are. The aims of this paper are twofold: (1) to update the tool Practical Application to Include Future Disease Costs (PAID 1.1), based on 2013 data, for the estimation of future unrelated medical costs and introduce future nonmedical consumption costs, further standardizing and facilitating the inclusion of future costs; and (2) to demonstrate how to use the tool in practice, showing the impact of including future unrelated medical costs and future nonmedical consumption in a case-study where a life is hypothetically saved at different ages and 2 additional cases where published studies are updated by including future costs.MethodsUsing the latest published cost of illness data from the year 2017, we model future unrelated medical costs as a function of age, sex, and time to death, which varies per disease. The Household Survey from Centraal Bureau Statistiek is used to estimate future nonmedical consumption by age.ResultsThe updated incremental cost-effectiveness ratios (ICERs) from the case studies show that including future costs can have a substantial effect on the ICER, possibly affecting choices made by decision makers.ConclusionThis article improves upon previous work and provides the first tool for the inclusion of future nonmedical consumption in The Netherlands.     

On future non-medical costs in economic evaluations

Economic evaluation in health care is still an evolving discipline. One of the current controversies in cost‐effectiveness analysis regards the inclusion or exclusion of future non‐medical costs (i.e. consumption net of production) due to increased survival. This paper examines the implications of a symmetry rule stating that there should be consistency between costs included in the numerator and utility aspects included in the denominator. While the observation that no quality‐adjusted life year (QALY) instruments explicitly include consumption and leisure seems to give support to the notion that future non‐medical costs should be excluded when QALYs are used as the outcome measure, a better understanding of what respondents actually consider when reporting QALY weights is required. However, the more fundamental question is whether QALYs can be interpreted as utilities. Or more precisely, what are the assumptions needed for a general utility model also including consumption and leisure to be consistent with QALYs? Once those assumptions are identified, they need to be experimentally tested to see whether they are at least approximately valid. Until we have answers to these areas for future research, it seems premature to include future non‐medical costs. Copyright © 2007 John Wiley & Sons, Ltd.     

我国常见病与罕见病住院患者医疗服务需求特点分析

目的:探索不同疾病类患者住院医疗服务需求的经济成本与治疗选择之间的关系。方法:通过计算家庭卫生筹资贡献率划分灾难性卫生支出疾病类型,应用需求函数模型预测常见病和罕见病患者住院需求的弹性系数。结果:罕见病成为灾难性疾病的比例更高;11种常见病和11种罕见病患者住院需求的价格弹性和收入弹性系数的估计值分别为-0.967、1.253和2.354、1.805。结论:我国常见病和罕见病患者的住院医疗服务均属奢侈性服务,罕见病患者的住院医疗服务需求短期呈现吉芬商品需求特点。     

Economic analysis model for inpatient parenteral nutrition: A pilot study

Aim: Parenteral nutrition is a high‐cost but essential support service in contemporary health care, yet no model exists to determine the total cost. This study aimed to create a cost analysis model identifying both direct and indirect costs of parenteral nutrition inpatient care. Methods: A health economics analysis model was constructed and used to create an audit tool for measuring parenteral nutrition costs in seven predefined categories. This tool was piloted on a cohort of 21 consecutive patients commencing parenteral nutrition at a large city hospital between March and April 2008. These patients were prospectively audited for a maximum 12 days or until parenteral nutrition cessation (192 patient days). Costs and adherence to evidence‐based guidelines were compared across the seven categories and between patient subgroups determined by ward locality upon commencement. Results: The mean total cost for all parenteral nutrition patients was $1579(NZD)/day, of which non‐parenteral hospital costs comprised 85%. For patients treated solely outside the intensive care unit, cost was $1045 per day, of which 24% was directly attributed to provision of parenteral nutrition. Formula accounted for nearly two‐thirds (63%) of parenteral nutrition direct costs and 8.5% of that prescribed was wasted. Return to oral or enteral nutrition was achieved in 57% patients within 12 days of commencing parenteral nutrition. Conclusions: Direct costs involved in providing parenteral nutrition appear to be less than previously reported, and represent a relatively small proportion of the total cost of care. This cost category analysis may have application in measuring and comparing parenteral nutrition service delivery in other institutions.     

肺癌的直接经济成本研究

目的:对国内外有关肺癌直接医疗费用的文献进行研究。数据来源:对Medline、PubMed、中国期刊网、维普资讯和万方数据资源系统进行搜索,1994-2004年之间对肺癌直接医疗费用进行研究的文献共10篇。研究方法:对文献中的研究方法和结论进行综合和评述。结论:国外对肺癌的直接医疗费用的研究一般基于初次诊断至几年之后的总成本。其结果相差较大,与各国的保险方式、治疗模式和研究方法均有关系。国内对肺癌直接医疗费用的研究绝大多数属于化疗方式的对比,并且均为1次住院费用的研究,原因可能是存在数据和方法学的缺陷。     

论医疗器械库房的经济效益管理

结合医院实际对医疗器械库房实行科学化的经济效益管理，在取得较好效果的基础上，对医院所有医疗器械的使用进行经济效益跟踪分析，加大监管力度，形成了一个适用于医院医疗器械库房的管理模式。