The Role of Noncomparative Evidence in Health Technology Assessment Decisions

Background

Many health technology assessment (HTA) agencies express a preference for randomized controlled trial evidence when appraising health technologies; nevertheless, it is not always feasible or ethical to conduct such comparative trials.

Challenges in Research and Health Technology Assessment of Rare Disease Technologies: Report of the ISPOR Rare Disease Special Interest Group

Background

Successful development of new treatments for rare diseases (RDs) and their sustainable patient access require overcoming a series of challenges related to research and health technology assessment (HTA). These impediments, which may be unique to RDs or also apply to common diseases but are particularly pertinent in RDs, are diverse and interrelated.

Reviewing the Evidence to Inform the Population of Cost-Effectiveness Models within Health Technology Assessments

ObjectivesHealth technology assessments (HTAs) typically require the development of a cost-effectiveness model, which necessitates the identification, selection, and use of other types of information beyond clinical effectiveness evidence to populate the model parameters. The reviewing activity associated with model development should be transparent and reproducible but can result in a tension between being both timely and systematic. Little procedural guidance exists in this area. The purpose of this article was to provide guidance, informed by focus groups, on what might constitute a systematic and transparent approach to reviewing information to populate model parameters.MethodsA focus group series was held with HTA experts in the United Kingdom including systematic reviewers, information specialists, and health economic modelers to explore these issues. Framework analysis was used to analyze the qualitative data elicited during focus groups.ResultsSuggestions included the use of rapid reviewing methods and the need to consider the trade-off between relevance and quality. The need for transparency in the reporting of review methods was emphasized. It was suggested that additional attention should be given to the reporting of parameters deemed to be more important to the model or where the preferred decision regarding the choice of evidence is equivocal.DiscussionThese recommendations form part of a Technical Support Document produced for the National Institute for Health and Clinical Excellence Decision Support Unit in the United Kingdom. It is intended that these recommendations will help to ensure a more systematic, transparent, and reproducible process for the review of model parameters within HTA.     

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.     

Challenges of Health Technology Assessment in Pluralistic Healthcare Systems: An ISPOR Council Report

Health technology assessment (HTA) has been growing in use over the past 40 years, especially in its impact on decisions regarding the reimbursement, adoption, and use of new drugs, devices, and procedures. In countries or jurisdictions with “pluralistic” healthcare systems, there are multiple payers or sectors, each of which could potentially benefit from HTA. Nevertheless, a single HTA, conducted centrally, may not meet the needs of these different actors, who may have different budgets, current standards of care, populations to serve, or decision-making processes.This article reports on the research conducted by an ISPOR Health Technology Assessment Council Working Group established to examine the specific challenges of conducting and using HTA in countries with pluralistic healthcare systems. The Group used its own knowledge and expertise, supplemented by a narrative literature review and survey of US payers, to identify existing challenges and any initiatives taken to address them. We recommend that countries with pluralistic healthcare systems establish a national focus for HTA, develop a uniform set of HTA methods guidelines, ensure that HTAs are produced in a timely fashion, facilitate the use of HTA in the local setting, and develop a framework to encourage transparency in HTA. These efforts can be enhanced by the development of good practice guidance from ISPOR or similar groups and increased training to facilitate local use of HTA.     

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.     

Formal Implementation of Cost-Effectiveness Evaluations in Japan: A Unique Health Technology Assessment System

In April 2019, Japan formally introduced health technology assessment (HTA) and, more specifically, a cost-effectiveness analysis, to inform healthcare decision making, mainly when it comes to the pricing of new technologies. This article provides an overview of this new policy, which was implemented formally after a pilot program. In the fiscal year (FY) 2012, discussions on cost-effectiveness assessments were initiated in Japan. After 7 years of deliberations, a cost-effectiveness assessment was implemented formally in April 2019. In Japan, the cost-effectiveness analysis has been used to inform price adjustments of healthcare technologies, although it has not yet been used for decision making on insurance coverage. Selection criteria were established because not all drugs and medical devices could be evaluated owing to a shortage of experts. Exclusion criteria have also been applied to prevent access restriction. The scope of the evaluation’s price adjustment target is limited to part of the product price. If the cost per quality-adjusted life-year (QALY) threshold falls below ¥5 million per QALY, the price adjustment rate changes stepwise according to the cost per QALY. In addition to price reduction, a price-raising scheme has also been implemented for scenarios where products are evaluated to be highly cost-effective and innovative. This article describes the first formally implemented HTA system in Japan. Although it is too early to make any conclusions about its effect, the Japan-specific context makes this system unique. To fully understand the opportunities and challenges of the new system, it is vital that Japan accumulates experience with this system and develops human resources in health economic evaluation.     

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.     

OECD国家的医学技术评估借鉴

医学技术评估作为一个新生事物，其重要性和实用性已越来越被各国所重视，成为一项国际性活动。主要以OECD国家为例，探计他们在利用干预机制影响医学技术的发展、传播及使用方面的一些经验教训。     

临床医生视角下新技术的转化应用与卫生技术评估

目的研究我国医学新技术临床应用中的卫生技术评估,分析卫生技术评估对临床医生新技术使用行为的关联性及影响。方法采用横断面设计和分层整群抽样方法,选取上海市、福建省、四川省18家医院患者进行调研,问卷为自主设计,应用logistic回归分析进行影响因素分析,此外通过相关文献检索进一步探究卫生技术评估在新技术使用过程中的作用。结果共调查了来自5城市的18家医院各临床科室的912名临床医生,临床医生层面,对于卫生技术评估证据的选择主要是根据证据的结果和结论在不同人群、地点的推广价值;医生对于新技术的有效性感知(P<0.01)及安全性感知(P<0.01)正向影响医生新技术的使用行为;药物涂层支架及高通量基因测序技术的医生使用人数与该项技术相关证据的强度具有一致性。结论医生对于新技术的有效性与安全性的感知越好,越倾向于使用新技术,此外虽然我国尚未建立完整的卫生技术评估体系,但是目前在临床医生的临床实践过程中还是存在卫生技术评估证据的使用模式。     

Distributional Cost-Effectiveness Analysis of Health Technologies: Data Requirements and Challenges

Governments and health technology assessment agencies are putting greater focus on and efforts in understanding and addressing health inequities. Cost-effectiveness analyses are used to evaluate the costs and health gains of different interventions to inform the decision-making process on funding of new treatments. Distributional cost-effectiveness analysis (DCEA) is an extension of cost-effectiveness analysis that quantifies the equity impact of funding new treatments. Key challenges for the routine and consistent implementation of DCEA are the lack of clearly defined equity concerns from decision makers and endorsed measures to define equity subgroups and the availability of evidence that allows analysis of differences in data inputs associated with the equity characteristics of interest. In this article, we detail the data gaps and challenges to build robust DCEA analysis routinely in health technology assessment and suggest actions to overcome these hurdles.     

Methods for Early Assessment of the Societal Value of Health Technologies: A Scoping Review and Proposal for Classification

ObjectivesEarly assessments of health technologies help to better align and integrate their development and assessment. Such assessments can take many forms and serve different purposes, hampering users in their selection of the most appropriate method for a specific goal. The aim of this scoping review was to structure the large set of methods according to their specific goal.MethodsA scoping review was conducted using PubMed and reference lists of retrieved articles, to identify review studies with a methodological focus. From the included reviews, all individual methods were listed. Based on additional literature and examples, we extracted the specific goal of each method. All goals were clustered to derive a set of subclasses and methods were grouped into these subclasses.ResultsOf the 404 screened, 5 reviews were included, and 1 was added when searching reference lists. The reviews described 56 methods, of which 43 (77%) were included and classified as methods to (1) explore the nature and magnitude of the problem, (2) estimate the nature and magnitude of the expected (societal) value, (3) identify conditions for the potential value to materialize, and (4) help develop and design the type of research that is needed.ConclusionsThe wide range of methods for exploring the societal value of health technologies at an early stage of development can be subdivided into a limited number of classes, distinguishing methods according to their specific objective. This facilitates selection of appropriate methods, depending on the specific needs and aims.     

Policies for Use of Real-World Data in Health Technology Assessment (HTA): A Comparative Study of Six HTA Agencies

Background

Randomized controlled trials provide robust data on the efficacy of interventions rather than on effectiveness. Health technology assessment (HTA) agencies worldwide are thus exploring whether real-world data (RWD) may provide alternative sources of data on effectiveness of interventions. Presently, an overview of HTA agencies’ policies for RWD use in relative effectiveness assessments (REA) is lacking.

How Are Incremental Cost-Effectiveness,Contextual Considerations,and Other Benefits Viewed in Health Technology Assessment Recommendations in the United States?

ObjectivesTo review assessments from the Institute for Clinical and Economic Review (ICER) and describe how cost-effectiveness, other benefits or disadvantages, and contextual considerations affect Council members’ assessments of value.MethodsAssessments published by the ICER between December 2014 and April 2019 were reviewed. Data on the assessment, intervention, results from cost-effectiveness analyses, and Council members’ votes were extracted. Voting data were examined using bar charts and radar plots. Spearman’s correlations between the number of votes for other benefits and contextual considerations were estimated. Two case studies (tisagenlecleucel and voretigene neparvovec) explored the relationship between different aspects of value and the vote.ResultsThirty-one ICER assessments were reviewed, which included 51 value votes and 17 votes on other benefits and contextual considerations. On average, interventions with lower cost-effectiveness ratios received a higher proportion of high and intermediate value votes; however, there was heterogeneity across assessments. Of other benefits or disadvantages, having a novel mechanism of action received the most votes (n = 138), and reducing health disparities received the fewest (n = 24). Of contextual considerations, treating a condition that has a severe impact on length and quality of life received the most votes (n = 164). There was a strong positive correlation between votes for reduced caregiver/family burden and improving return to work/productivity (ρ = 0.88, P < .05). Two case studies highlighted that factors beyond cost-effectiveness can lead to lower (tisagenlecleucel) or higher (voretigene neparvovec) assessments of value.ConclusionCouncil members’ judgments about the value of interventions are influenced by other benefits or disadvantages and contextual considerations but anchored by cost-effectiveness.     

广东省基层适宜卫生技术使用现状及筛选评价探讨

通过对广东省不同经济发展水平地区的基层医疗机构进行调查,了解其治疗常见病、多发病的卫生技术使用情况,探讨技术使用环境与卫生技术使用之间的关系,为开展适宜卫生技术遴选、推广和评估提供科学依据.     

Challenges and Opportunities of Health Care Supply Chain Management in the United States

This article explores current supply chain management challenges and initiatives and identifies problems that affect supply chain management success in the U.S. health-care industry. In addition, it investigates the impact of health care supply chain management (SCM) initiatives on the overall organizational effectiveness. The attitudinal results, as well as the performance results presented in this study support the claim of health care proponents that the SCM allows organizations to reduce cost, improve quality, and reduce cycle time, and leads to high performance.     

Emulating Target Trials With Real-World Data to Inform Health Technology Assessment: Findings and Lessons From an Application to Emergency Surgery

ObjectivesInternational health technology assessment (HTA) agencies recommend that real-world data (RWD) are used in some circumstances to add to the evidence base about the effectiveness and cost-effectiveness of health interventions. The target trial framework applies the design principles of randomized-controlled trials to RWD and can help alleviate inevitable concerns about bias and design flaws with nonrandomized studies. This article aimed to tackle the lack of guidance and exemplar applications on how this methodology can be applied to RWD to inform HTA decision making.MethodsWe use Hospital Episode Statistics data from England on emergency hospital admissions from 2010 to 2019 to evaluate the cost-effectiveness of emergency surgery for 2 acute gastrointestinal conditions. We draw on the case study to describe the main challenges in applying the target trial framework alongside RWD and provide recommendations for how these can be addressed in practice.ResultsThe 4 main challenges when applying the target trial framework to RWD are (1) defining the study population, (2) defining the treatment strategies, (3) establishing time zero (baseline), and (4) adjusting for unmeasured confounding. The recommendations for how to address these challenges, mainly around the incorporation of expert judgment and use of appropriate methods for handling unmeasured confounding, are illustrated within the case study.ConclusionsThe recommendations outlined in this study could help future studies seeking to inform HTA decision processes. These recommendations can complement checklists for economic evaluations and design tools for estimating treatment effectiveness in nonrandomized studies.