成本效果可接受曲线与成本效果阈值

成本效果可接受曲线是药物经济学评价不确定性分析中的重要工具。成本效果阈值是药物经济学评价不可缺少的结果比照标准。二者之间有一定关联,但成本效果可接受曲线不能代替成本效果阈值,成本效果阈值的存在可以使成本效果可接受曲线的分析结果更加科学准确。     

成本-效果可支付曲线的理论与应用

目的:从理论和应用角度对一种新兴分析工具——成本-效果可支付曲线进行介绍,以期为我国药品决策研究与实践提供新思路。方法:通过分析成本-效果平面中成本-效果阈值线和可支付线的含义来引出和分析成本-效果可支付曲线,并借助已有实证研究对其含义进行分析和解释。结果:成本-效果可支付曲线结合了可支付线与阈值线二者提供的信息,是成本-效果阈值和预算限制的函数。结论:成本-效果可支付曲线可同时提供经济性与可支付性信息,在给定预算下随成本-效果阈值的变化而变化。     

从净收益视角探讨成本-效果阈值的意义

目的:旨在从净收益法视角出发,明确成本-效果阈值在药物经济学中的重要意义。方法:分类介绍净收益法的4种情况,从理论方法层面分析4种情况下成本-效果阈值与净收益法的内在联系。结果:净收益法4种情况中的任何一种都要受到成本-效果阈值的影响。结论:净收益法的4种情况均是成本-效果阈值的函数,成本-效果阈值的取值直接决定净收益计算结果。     

信息价值分析与成本效果阈值

本文介绍了信息价值分析,明确信息价值分析与成本效果阈值之间的关系,指出在我国医药领域引进信息价值分析的必要性,从而进一步论证确定成本效果阈值的理论与现实意义。本文另阐述了信息价值分析的含义、指标及方法,深入分析并举例说明其与成本效果阈值的关系。信息价值分析可视为对不确定性分析的深化,能够定量计算降低不确定性所带来的期望价值;成本效果阈值对信息价值分析意义重大,其取值对信息价值分析起着决定性作用。引进信息价值分析有助于提高行业整体效率。     

成本效果阈值确定方法分类研究进展(英文)

成本效果分析在卫生保健领域的决策制定当中所起的作用越来越重要。成本效果阈值是成本效果分析的重要决策标准。本文将对成本效果阈值的定义进行回顾,并对现有的成本效果阈值确定方法进行分类介绍,同时对这些现有方法各自的优缺点进行比较分析。在预算具有相对灵活性,即易于改变(增加)既定预算的情况下,成本效果阈值的确定方法主要包括:从过去的决策当中推测阈值、将特殊卫生保健项目的ICER值作为成本效果阈值或借鉴其他公共领域中生命/健康的价值、社会意愿支付法、借助人均GDP确定成本效果阈值法、以及经验确定法。在难以改变既定预算限制的情况下,即当预算具有相对固定性时,能够用于确定成本效果阈值的方法包括:影子价格法、机会成本法和阈值寻找者模型法。现有的八种方法具有其各自的优缺点和适用条件,本文对这些现有方法进行介绍和比较分析,以期能够为我国的成本效果阈值确定方法的选择提供信息储备和支持。     

对我国成本效果阈值确定方法的思考

目的:对成本效果阈值现有的主要确定方法进行分析,寻找适合我国的阈值确定方法,为我国成本效果阈值的确定及应用奠定基础。方法:通过文献综述的方法,对目前主要的成本效果阈值确定方法进行回顾分析和归纳总结,在此基础上找出适合我国的成本效果阈值确定方法。结果:社会意愿支付法、阈值寻找者模式、人均GDP法均对我国成本效果阈值的确定有重要的借鉴意义。结论:建议以阈值寻找者模式为主、以人均GDP法(社会意愿支付法)为参考来确定我国的成本效果阈值,在寻找我国的成本效果阈值期间,可暂时先借鉴人均GDP法确定的经济性评价标准。     

影响贴现率选择的关键要素:成本效果阈值

目的:明确成本效果阈值是成本与效果贴现率选择的关键性影响因素,为进一步完善我国的贴现率提供启示。方法:通过介绍贴现率计算的公式推导来分析成本效果阈值如何影响贴现率的选择。结果:当两个时期的成本效果阈值相同时,成本和效果应该使用相同的贴现率;当两个时期的成本效果阈值不同时,应对成本和效果分别选择不同的贴现率进行计算。结论:成本效果阈值是影响成本贴现率与结果贴现率是否同一的关键性因素。     

阿利西尤单抗联合他汀类药物治疗急性冠脉综合征的成本-效果分析

目的 分析阿利西尤单抗联合他汀类药物治疗急性冠脉综合征（ACS）的成本-效果。方法 从支付者角度,应用ODYSSEY OUTCOMES研究数据,结合目前我国ACS的医疗成本和心血管事件再发生概率等构建Markov模型,结果指标包括人均医疗成本、质量调整生命年（QALY）的健康指标和增量成本-效果比（ICER）。使用单因素敏感性分析和概率敏感性分析（PSA）探究模型潜在的不确定性。结果 在为期20年的模拟治疗中阿利西尤单抗联合他汀类药物较他汀类单药治疗的人均医疗成本高,分别为239 081和156 403元,但联合用药效果更佳,QALY分别为9.6和9.4,ICER为413 390元,大于预设的支付意愿阈值。结论 与他汀单药相比,阿利西尤单抗联合他汀类药物治疗ACS可降低心血管事件的发生,但目前尚不具备成本-效果优势。     

社会意愿支付法确定成本效果阈值的介绍与思考

目的:介绍并分析社会意愿支付法的基本理论,为我国成本效果阈值的确定提供一定的方法论基础。方法:总结社会意愿支付法的优缺点,并与我国实际情况相结合,明确其对我国成本效果阈值确定的借鉴意义。结果:社会意愿支付法有体现民众意愿、随经济发展水平变化等优点、同时在理论角度、实践角度、制度角度以及方法本身角度等方面均存在一定的争议。结论:社会意愿支付法是最常用的成本效果阈值确定方法之一,在理论与实践等方面均有着独特的优势,运用该方法将会对我国的成本效果阈值科学确定起到积极的推进作用。     

吸入制剂治疗慢性阻塞性肺疾病的Markov模型构建方法学研究

摘要：目的:采用系统评价方法对国内外吸入制剂治疗慢性阻塞性肺疾病（COPD）的Markov模型方法学进行研究。方法:计算机检索PubMed、the Cochrane Library、Embase、CNKI、WanFang Data、VIP、SinoMed等文献数据库,搜集吸入制剂治疗COPD的Markov模型研究,检索年限均为从建库至2020年12月31日。由两名评价员独立进行文献筛选、方法学质量评价,重点对模型构建方法及参数进行提取,并对结果进行汇总分析。结果:共纳入28篇中英文研究,大部分研究的方法学质量较高。在模型循环状态构建上以先按照疾病严重程度分级,再按COPD恶化程度划分为主。研究时间水平以1年以上为主,多项研究采用终身用药时间水平。循环周期为1个月～1年。建Markov模型的状态转化相关数据基本采用文献报道的数据。成本计算因研究角度或纳入内容不同,大部分研究仅纳入直接医疗成本。多数研究采用效用指标,主要来源于文献报道。研究多采用增量成本效果分析,并绘制成本效果可接受曲线对可接受阈值进行分析。部分研究对成本及效果指标进行贴现。敏感性分析多采用概率敏感性分析。采用的模拟软件以Treeage Pro及Excel为主。结论:吸入制剂治疗COPD的Markov模型构建应基于临床指南推荐的治疗路径下进行模拟,以获得短期及终身治疗获益数据,同时成本效果评价结果需考虑患者可接受阈值。     

Cost-effectiveness of computer-assisted training in cognitive-behavioral therapy as an adjunct to standard care for addiction

Aim

To determine the cost-effectiveness, from clinic and patient perspectives, of a computer-based version of cognitive-behavioral therapy (CBT4CBT) as an addition to regular clinical practice for substance dependence.

Participants, design and measurements

This cost-effectiveness study is based on a randomized clinical trial in which 77 individuals seeking treatment for substance dependence at an outpatient community setting were randomly assigned to treatment as usual (TAU) or TAU plus biweekly access to computer-based training in CBT (TAU plus CBT4CBT). The primary patient outcome measure was the total number of drug-free specimens provided during treatment. Incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves (CEACs) were used to determine the cost-effectiveness of TAU plus CBT4CBT relative to TAU alone. Results are presented from both the clinic and patient perspectives and are shown to be robust to (i) sensitivity analyses and (ii) a secondary objective patient outcome measure.

Findings

The per patient cost of adding CBT4CBT to standard care was $39 ($27) from the clinic (patient) perspective. From the clinic (patient) perspective, TAU plus CBT4CBT is likely to be cost-effective when the threshold value to decision makers of an additional drug-free specimen is greater than approximately $21 ($15), and TAU alone is likely to be cost-effective when the threshold value is less than approximately $21 ($15). The ICERs for TAU plus CBT4CBT also compare favorably to ICERs reported elsewhere for other empirically validated therapies, including contingency management.

Conclusions

TAU plus CBT4CBT appears to be a good value from both the clinic and patient perspectives.     

Cost-effectiveness acceptability curves and a reluctance to lose

Cost-effectiveness acceptability curves (CEACs) are a method used to present uncertainty surrounding incremental cost-effectiveness ratios (ICERs). Construction of the curves relies on the assumption that the willingness to pay (WTP) for health gain is identical to the willingness to accept (WTA) health loss. The objective of this paper is to explore the impact that differences between WTP and WTA health changes have on CEACs. Previous empirical evidence has shown that the relationship between WTP and WTA is not 1:1. The discrepancy between WTP and WTA for health changes can be expressed as a ratio: the accept/reject ratio (which can vary between 1 and infinity). Depending on this ratio, the area within the southwest quadrant of the cost-effectiveness plane in which any bootstrap cost-effect pairs will be considered to be cost effective will be smaller, resulting in a lower CEAC. We used data from two clinical trials to illustrate that relaxing the 1:1 WTP/WTA assumption has an impact on the CEACs. Given the difficulty in assessing the accept/reject ratio for every evaluation, we suggest presenting a series of CEACs for a range of values for the accept/reject ratio, including 1 and infinite. Although it is not possible to explain this phenomenon within the extra-welfarist framework, it has been shown empirically that individuals give a higher valuation to the removal of effective therapies than to the introduction of new therapies that are more costly and effective. In cost-effectiveness analyses where uncertainty of the ICER covers the southwest quadrant of the cost-effectiveness plane, the discrepancy between societies' WTP and WTA should be indicated by drawing multiple CEACs.     

从多国视角看成本效果阈值的应用现状

目的通过各国成本效果阈值的横向比较,为我国的成本效果阈值设定提供一定的经验与启示。方法归纳总结药物经济学利用程度较高的国家和地区成本效果阈值及其相关规定的现状。结果各国成本效果阈值都不尽相同,成本效果阈值的设定受很多因素的影响。结论不能简单地借鉴国外经验,必须在充分考虑我国具体情况的基础上设定科学合理的成本效果阈值。     

Cost-Effectiveness of Treating Upper Limb Spasticity Due to Stroke with Botulinum Toxin Type A: Results from the Botulinum Toxin for the Upper Limb after Stroke (BoTULS) Trial

Stroke imposes significant burdens on health services and society, and as such there is a growing need to assess the cost-effectiveness of stroke treatment to ensure maximum benefit is derived from limited resources. This study compared the cost-effectiveness of treating post-stroke upper limb spasticity with botulinum toxin type A plus an upper limb therapy programme against the therapy programme alone. Data on resource use and health outcomes were prospectively collected for 333 patients with post-stroke upper limb spasticity taking part in a randomized trial and combined to estimate the incremental cost per quality adjusted life year (QALY) gained of botulinum toxin type A plus therapy relative to therapy alone. The base case incremental cost-effectiveness ratio (ICER) of botulinum toxin type A plus therapy was £93,500 per QALY gained. The probability of botulinum toxin type A plus therapy being cost-effective at the England and Wales cost-effectiveness threshold value of £20,000 per QALY was 0.36. The point estimates of the ICER remained above £20,000 per QALY for a range of sensitivity analyses, and the probability of botulinum toxin type A plus therapy being cost-effective at the threshold value did not exceed 0.39, regardless of the assumptions made.     

Advantages of using the net-benefit approach for analysing uncertainty in economic evaluation studies

No consensus has yet been reached on how to analyse uncertainty in economic evaluation studies where individual patient data are available for costs and health effects. This paper summarises the available results regarding the analysis of uncertainty on the cost-effectiveness plane and argues for using the net-benefit approach when analysing uncertainty in cost-effectiveness studies. The net-benefit approach avoids the interpretation and statistical problems related to the incremental cost effectiveness ratio and implies several advantages. First, traditional statistical methods can be used for confidence-interval estimation and hypothesis testing. Second, calculation of the optimal sample size and the power of the study are facilitated allowing the correlation between costs and effects to vary within and between patient groups. Third, the use of a Bayesian approach to cost-effectiveness analysis is facilitated. Fourth, a formal relation between cost-effectiveness acceptability curves and statistical inference is provided. Finally, the net-benefit approach gives the Fieller's limits of the confidence interval for the incremental cost-effectiveness ratio in the cost-effectiveness plane. Based on these advantages the net-benefit approach should strongly be considered when analysing uncertainty in cost-effectiveness analyses.     

恩格列净治疗射血分数降低的心力衰竭的药物经济学评价

目的对恩格列净治疗射血分数降低的心力衰竭(HFrEF)进行药物经济学评价,为临床合理用药和医疗卫生决策提供循证依据。方法运用马尔可夫模型对恩格列净治疗HFrEF的方案进行成本-效果分析,评价标准治疗方案联合恩格列净(恩格列净组)与单用标准治疗方案(标准治疗组)的成本和效果。临床参数来自EMPEROR-Reduced研究,成本和健康效用值数据来自己发表的文献。模型的循环周期为1个月,模拟时间为20年。采用单因素敏感性分析和概率敏感性分析对成本-效果分析的结果进行验证。结果恩格列净组较标准治疗组每增加1个质量调整生命年要多花费37 995.94元,低于1倍2020年中国人均国内生产总值(GDP),即72 447元。单因素敏感性分析结果显示,两组患者的稳定状态住院率是对增量成本-效果比影响最大的因素。概率敏感性分析结果显示,当支付意愿阈值(WTP)取1倍2020年中国人均GDP(72 447元)时,恩格列净组有58.8%的概率具有成本-效果优势;当WTP取3倍2020年中国人均GDP(217 341元)时,恩格列净组有63.8%的概率具有成本-效果优势。结论采用标准治疗方案联合恩格列净治疗HFrEF较单纯采用标准治疗方案更具有成本-效果优势,但经济性概率不高。     

RESAMPLING AND MULTIPLICITY IN COST-EFFECTIVENESS INFERENCE

We compare published methods for placing statistical confidence limits around incremental cost-effectiveness ratio statistics and show that only a nonparametric, bootstrap approach using polar angles gives completely reasonable results when neither treatment has significant advantages in cost or effectiveness. We also discuss alternative ways to report analytical results using plots, confidence or tolerance limits, and quadrant acceptability fractions. Finally, we use simulation to study the multiplicity bias that can be introduced into ICER confidence limits when only the most favorable results are reported over several possible choices of numerator cost measure and denominator effectiveness measure.     

Presenting evidence and summary measures to best inform societal decisions when comparing multiple strategies

Multiple strategy comparisons in health technology assessment (HTA) are becoming increasingly important, with multiple alternative therapeutic actions, combinations of therapies and diagnostic and genetic testing alternatives. Comparison under uncertainty of incremental cost, effects and cost effectiveness across more than two strategies is conceptually and practically very different from that for two strategies, where all evidence can be summarized in a single bivariate distribution on the incremental cost-effectiveness plane. Alternative methods for comparing multiple strategies in HTA have been developed in (i) presenting cost and effects on the cost-disutility plane and (ii) summarizing evidence with multiple strategy cost-effectiveness acceptability (CEA) and expected net loss (ENL) curves and frontiers. However, critical questions remain for the analyst and decision maker of how these techniques can be best employed across multiple strategies to (i) inform clinical and cost inference in presenting evidence, and (ii) summarize evidence of cost effectiveness to inform societal reimbursement decisions where preferences may be risk neutral or somewhat risk averse under the Arrow-Lind theorem. We critically consider how evidence across multiple strategies can be best presented and summarized to inform inference and societal reimbursement decisions, given currently available methods. In the process, we make a number of important original findings. First, in presenting evidence for multiple strategies, the joint distribution of costs and effects on the cost-disutility plane with associated flexible comparators varying across replicates for cost and effect axes ensure full cost and effect inference. Such inference is usually confounded on the cost-effectiveness plane with comparison relative to a fixed origin and axes. Second, in summarizing evidence for risk-neutral societal decision making, ENL curves and frontiers are shown to have advantages over the CEA frontier in directly presenting differences in expected net benefit (ENB). The CEA frontier, while identifying strategies that maximize ENB, only presents their probability of maximizing net benefit (NB) and, hence, fails to explain why strategies maximize ENB at any given threshold value. Third, in summarizing evidence for somewhat risk-averse societal decision making, trade-offs between the strategy maximizing ENB and other potentially optimal strategies with higher probability of maximizing NB should be presented over discrete threshold values where they arise. However, the probabilities informing these trade-offs and associated discrete threshold value regions should be derived from bilateral CEA curves to prevent confounding by other strategies inherent in multiple strategy CEA curves. Based on these findings, a series of recommendations are made for best presenting and summarizing cost-effectiveness evidence for reimbursement decisions when comparing multiple strategies, which are contrasted with advice for comparing two strategies. Implications for joint research and reimbursement decisions are also discussed.     

基于Markov模型的肺动脉高压靶向治疗药物的成本-效果分析

目的：评价中国医疗环境下肺动脉高压一线靶向治疗药物的成本-效果。方法：从支付者角度,根据肺动脉高压的自然转归和现有的医疗成本构建Markov模型。结果指标包括人均总成本、总质量调整生命年和增量成本-效果比,应用一元敏感度和概率敏感度分析验证模型稳定性。结果：基线分析结果显示：在整个生命周期的模拟过程中安立生坦、马昔腾坦、波生坦、他达拉非、西地那非和姑息治疗的人均医疗成本分别为363 406.14,481 387.69,323 264.71,167 531.23,41 700.08和24 507.12元,人均可获得5.61,6.14,5.23,5.88,4.64和2.33个质量调整生命年,姑息治疗作为对照组的增量成本-效果比分别为103 410.74,120 034.97,103 079.80,40 351.36和7 438.14元/质量调整生命年,小于预设的意愿支付阈值,敏感度分析显示结果稳定。结论：在中国肺动脉高压患者使用安立生坦、马昔腾坦、波生坦、他达拉非和西地那非具有成本-效果性。