Two Approaches to Incorporate Clinical Data Uncertainty into Multiple Criteria Decision Analysis for Benefit-Risk Assessment of Medicinal Products

BackgroundThe Problem formulation, Objectives, Alternatives, Consequences, Trade-offs, Uncertainties, Risk attitude, and Linked decisions (PrOACT-URL) framework and multiple criteria decision analysis (MCDA) have been recommended by the European Medicines Agency for structured benefit-risk assessment of medicinal products undergoing regulatory review.ObjectiveThe objective of this article was to provide solutions to incorporate the uncertainty from clinical data into the MCDA model when evaluating the overall benefit-risk profiles among different treatment options.MethodsTwo statistical approaches, the δ-method approach and the Monte-Carlo approach, were proposed to construct the confidence interval of the overall benefit-risk score from the MCDA model as well as other probabilistic measures for comparing the benefit-risk profiles between treatment options. Both approaches can incorporate the correlation structure between clinical parameters (criteria) in the MCDA model and are straightforward to implement.ResultsThe two proposed approaches were applied to a case study to evaluate the benefit-risk profile of an add-on therapy for rheumatoid arthritis (drug X) relative to placebo. It demonstrated a straightforward way to quantify the impact of the uncertainty from clinical data to the benefit-risk assessment and enabled statistical inference on evaluating the overall benefit-risk profiles among different treatment options.ConclusionsThe δ-method approach provides a closed form to quantify the variability of the overall benefit-risk score in the MCDA model, whereas the Monte-Carlo approach is more computationally intensive but can yield its true sampling distribution for statistical inference. The obtained confidence intervals and other probabilistic measures from the two approaches enhance the benefit-risk decision making of medicinal products.     

Treacle and Smallpox: Two Tests for Multicriteria Decision Analysis Models in Health Technology Assessment

Multicriteria decision analysis (MCDA) is rightly receiving increasing attention in health technology assessment. Nevertheless, a distinguishing feature of the health domain is that technologies must actually improve health, and good performance on other criteria cannot compensate for failure to do so. We argue for two reasonable tests for MCDA models: the treacle test (can a winning intervention be incompletely ineffective?) and the smallpox test (can a winning intervention be for a disease that no one suffers from?). We explore why models might fail such tests (as the models of some existing published studies would do) and offer some suggestions as to how practice should be improved.     

Towards Integrated Health Technology Assessment for Improving Decision Making in Selected Countries

Objectives

To assess the level of comprehensiveness of health technology assessment (HTA) practices around the globe and to formulate recommendations for enhancing legitimacy and fairness of related decision-making processes.

多维度决策分析在血友病预防性治疗中的应用

目的:比较影响血友病A治疗的主要疗效因素,评价不同治疗方案的优缺点,进而为治疗方案的决策提供参考。方法:采用多维度决策分析方法 (MDCA),通过组织专家组会议,对反映血友病治疗效果的10个特性因素及其标准剂量的预防治疗、中低剂量预防治疗和按需治疗这三种治疗方案进行评分;并获得不同特性指标的权重。结果:普遍认为标准预防治疗方案最好;对费用分析后发现,标准剂量的预防治疗费用高(34.5万元),但治疗效果远好于中低剂量预防治疗和按需治疗方案。结论:从长期的成本效果分析来看,预防性治疗可以减少并发症的发生,并且降低终生的医疗成本。但目前我国各地对血凝8因子医保报销政策不同,而且补偿水平不一,急需进一步提高。     

Strengthening the Interface of Evidence-Based Decision Making Across European Regulators and Health Technology Assessment Bodies

ObjectivesAccess to medicines in Europe depends on a benefit-risk decision taken by regulators and a relative effectiveness assessment performed by health technology assessment bodies (HTABs) to inform, as one element, a reimbursement decision. Although various similarities in evidence needs exist, understanding of their needs is currently suboptimal and therefore the evidence generated does not always meet their needs. Subsequently, delays in decision making can be expected, negatively affecting access. To overcome this, this study reviewed the evidentiary needs of European regulators and HTABs at European level and analyzed how their collaboration can further facilitate optimal evidence generation plans, evidence use, and evidence presentation.MethodsThrough systematic literature review, expert interviews, and pairwise comparison of assessment reports by the European Medicines Agency and European network for health technology assessment, respective clinical evidence requirements and impact of product-specific collaboration between European Medicines Agency and HTABs were established.ResultsClinical evidence needs are quite similar but differences exist in comparator choice, preferred efficacy endpoints, and target population. Results of the impact of collaboration to date were mixed: preapproval joint advice procedures were successful and highly valued by all stakeholders; information exchange at the time of regulatory decision is coming together, yet the European Public Assessment Report can be further optimized; and collaboration on postlicensing evidence generation requirements shows potential but needs solidifying.ConclusionsThese findings demonstrate the potential to further improve the evidence utilization across stakeholders to avoid duplication and streamline decision making, to ultimately improve access to medicines for European patients.     

A Conceptual Framework for Life-Cycle Health Technology Assessment

ObjectivesHealth technology assessment (HTA) uses evidence appraisal and synthesis with economic evaluation to inform adoption decisions. Standard HTA processes sometimes struggle to (1) support decisions that involve significant uncertainty and (2) encourage continued generation of and adaptation to new evidence. We propose the life-cycle (LC)-HTA framework, addressing these challenges by providing additional tools to decision makers and improving outcomes for all stakeholders.MethodsUnder the LC-HTA framework, HTA processes align to LC management. LC-HTA introduces changes in HTA methods to minimize analytic time while optimizing decision certainty. Where decision uncertainty exists, we recommend risk-based pricing and research-oriented managed access (ROMA). Contractual procurement agreements define the terms of reassessment and provide additional decision options to HTA agencies. LC-HTA extends value-of-information methods to inform ROMA agreements, leveraging routine, administrative data, and registries to reduce uncertainty.ResultsLC-HTA enables the adoption of high-value high-risk innovations while improving health system sustainability through risk-sharing and reducing uncertainty. Responsiveness to evolving evidence is improved through contractually embedded decision rules to simplify reassessment. ROMA allows conditional adoption to obtain additional information, with confidence that the net value of that adoption decision is positive.ConclusionsThe LC-HTA framework improves outcomes for patients, sponsors, and payers. Patients benefit through earlier access to new technologies. Payers increase the value of the technologies they invest in and gain mechanisms to review investments. Sponsors benefit through greater certainty in outcomes related to their investment, swifter access to markets, and greater opportunities to demonstrate value.     

荷兰卫生技术评估体系分析及对我国的启示*

目的：介绍荷兰卫生技术评估体系和政策转化现状，为完善我国价值医疗体系、提高卫生改革决策水平提供借鉴。方法：通过查阅国内外相关文献，描述荷兰的卫生技术评估体系，分析其常规应用的转化特点，综合评价其在新冠肺炎疫情中急性护理服务的网络构建特点。结果：荷兰卫生体系被称为“欧洲最佳医疗体系”，卫生技术评估在荷兰卫生系统决策中发挥了重要作用，特别是在降低医疗成本层面。相比荷兰，我国卫生技术评估政策转化成果相对较少。结论：我国需要完善卫生技术评估机构体系，加强研究人员与政策制定者的沟通，提升决策科学性及加快卫生技术评估转化效率。同时，筑牢分级诊疗体系，提升卫生技术评估综合性评价标准，进而推动实践价值医疗，促进我国卫生健康事业发展。     

英国NICE卫生技术评估流程的决策转化机制及启示

通过对英国国家健康与临床优化研究院(NICE)从2000年到2020年20年间针对卫生技术的评估方法、评估流程及评估结果及转化推广情况等进行详细梳理介绍.从加快建立我国独立的卫生技术评估机构、多元化HTA评估方法、完善评估主题遴选流程、建立健全评估委员会制度、评估流程的进一步优化、确保卫生技术评估证据来源的同步性和协调性等方面,为我国卫生技术的发展和进一步完善提供参考和借鉴.     

Dealing With Uncertainty in Early Health Technology Assessment: An Exploration of Methods for Decision Making Under Deep Uncertainty

ObjectivesIn early stages, the consequences of innovations are often unknown or deeply uncertain, which complicates early health economic modeling (EHEM). The field of decision making under deep uncertainty uses exploratory modeling (EM) in situations when the system model, input probabilities/distributions, and consequences are unknown or debated. Our aim was to evaluate the use of EM for early evaluation of health technologies.MethodsWe applied EM and EHEM to an early evaluation of minimally invasive endoscopy-guided surgery (MIS) for acute intracerebral hemorrhage and compared these models to derive differences, merits, and drawbacks of EM.ResultsEHEM and EM differ fundamentally in how uncertainty is handled. Where in EHEM the focus is on the value of technology, while accounting for the uncertainty, EM focuses on the uncertainty. EM aims to find robust strategies, which give relatively good outcomes over a wide range of plausible futures. This was reflected in our case study. EHEM provided cost-effectiveness thresholds for MIS effectiveness, assuming fixed MIS costs. EM showed that a policy with a population in which most patients had severe intracerebral hemorrhage was most robust, regardless of MIS effectiveness, complications, and costs.ConclusionsEHEM and EM were found to complement each other. EM seems most suited in the very early phases of innovation to explore existing uncertainty and many potential strategies. EHEM seems most useful to optimize promising strategies, yet EM methods are complex and might only add value when stakeholders are willing to consider multiple solutions to a problem and adopt flexible research and adoption strategies.     

Toward a sustainable European Network for Health Technology Assessment

EUnetHTA is a recently initiated EU network aiming at connecting national HTA agencies, research institutions, and health ministries to enable an effective exchange of information and to lend support to health policy decisions by the Member States. The article briefly discusses the policy background, the specific objectives, and the project structure of the network.     

人工晶体卫生技术评估方法学分析及启示

目的通过分析国际典型的人工晶体卫生技术评估(HTA)案例,为我国开展相关评估提供方法学参考。方法通过范围综述方法检索国际卫生技术评估网络成员HTA机构网站,对纳入的人工晶体HTA报告进行结构化信息提取和分析。结果共纳入3个国家5家HTA机构的15篇HTA报告,其中,rHTA 12篇,fHTA 3篇。HTA评估的核心维度为安全性和有效性,支持医保部门的研究需要纳入经济性维度。对现有研究证据开展系统分析是当前主流方法,但针对重大决策的HTA一般会进行本土化数据收集和分析。结论可为我国开展人工晶体HTA的总体设计、评估问题、评估维度、工具方法、具体指标等选择提供方法学参考,从而助力我国高值耗材治理决策制定。     

卫生技术评估的基本步骤

该文结合国际经验和目前国内开展卫生技术评估研究工作的实践 ,简要介绍了卫生技术评估的基本步骤 ,以促进评估工作在我国进一步系统化和科学化 ,更好地为合理利用卫生资源服务。     

多种赋权方法联合应用制定科技实力评价指标权重

目的 制定评价科技实力指标权重.方法 采用主观赋权(专家打分法、对比排序法、Saaty’s权重法)和客观赋权(标准离差法、熵权法、CRITIC法)相结合的方法制定科技实力指标权重.结果 主观赋权法得到的指标权重之间相关系数均大于0.7,客观赋权方法中,熵权法和标准离差法及CRITIC法得到的权重之间存在负相关；主观赋权方法中排序法和Satty,s权重法均与熵权法得到的权重存在正相关.权重较大的指标为科学著作总数、装备定型总数、军用标准总数、SCI/EI/ISTP数、第一等级科技获奖数等.结论 多种赋权方法联合应用制定评价指标权重较单一方法赋权更具有合理性.     

决策者视角的中国卫生技术评估决策转化情况分析

目的 从决策者的角度来研究中国卫生技术评估在决策中的转化和利用情况,探索其中可能存在的影响决策转化的因素,为促进卫生技术评估决策转化提供参考.方法 采用问卷调查法对国家和地方层面的卫生政策决策人员利用卫生技术评估研究结果情况进行调查,并进行描述性分析.结果 调查共回收有效问卷112份.结果显示,决策人员对卫生技术评估能够一定程度上参考借鉴,或进行决策采纳,但在促进行动方面有所欠缺.决策部门内部相关培训、资助方面尚十分有限.但决策者对未来卫生技术评估在决策中能够起到的作用给予了很高的信心.决策者重视研究的时效性和语言的通俗易懂程度,因此与研究方也会较多地交流报告提交的方式,他们更倾向于收到报告的概述.结论 卫生技术评估决策转化程度和水平有待提升,决策部门对卫生技术评估的资助力度有待加大,将卫生技术评估引入决策过程的相关机制有待构建.     

CT卫生技术评估报告分析及启示

目的为我国开展影像学诊断设备卫生技术评估（HTA）提供方法学参考。方法检索国际卫生技术评估机构网站,对纳入的CT HTA报告进行结构化信息提取和分析。结果共纳入4个国家6家机构的24篇HTA报告。其中,快速卫生技术评估12篇,全面卫生技术评估12篇。评估核心维度为有效性、经济性和安全性。纳入报告均采用了文献综述分析,部分针对重大决策的HTA进行了Meta分析、成本-效果分析和预算影响分析。 结论可为我国CT等影像学诊断设备技术评估提供参考,提高我国大型医疗设备治理决策的科学化水平。     

层次分析法分析医疗设备供应商评价指标权重系数

为了有效地管理供应链．非常有必要建立对供应商的评价系统，而对供应商的评价指标包括供货的质量、成本、服和和交货能力等诸多因素的非量化指标．根据各个指标的重要性应具有不同的评价权重，采用层次分析法来分析确定复杂评价体系中的各个指标的权重，进而形成一个完整的评价指标体系。