Equity in national healthcare economic evaluation guidelines: Essential or extraneous?

BACKGROUND: The focus on health maximisation in a healthcare economic evaluation (HEE) - that is health gains are of equal value regardless of the recipient- has significant implications as health systems attempt to address persistent and growing health inequities. This study aimed to systematically compare and contrast the equity principles of different health technology assessment (HTA) agencies and how equity is addressed in HEE guidelines. METHODS: HTA agencies were identified through the ISPOR, GEAR, iDSI, HTAi, INAHTA, HTAsiaLink, and RedETSA websites in June 2021 and updated in August 2023. Agencies websites were then searched to retrieve HEE guidelines. The guidelines were grouped into two categories: well-established and newly-developed agency guidelines, based on whether or not they published their first guidelines before 2009. Data extracted summarised the methodological details in the reference cases, including specifics on how equity featured and in what role. In those agencies where equity did not feature explicitly in the HEE guidelines, an additional search of the agency website was undertaken to understand if equity featured in those agencies' decision-making frameworks. RESULTS: The study included 46 guidelines from 51 countries. Only 30% of the guidelines were explicit about the equity assumptions. Health equity (using a broad definition) was mentioned in 29 guidelines and 14 included a specific definition while only seven recommended specific methods to incorporate inequalities. Addressing equity concerns was usually suggested as an additional analyses rather than a key part of the assessment. It was unclear how equity was incorporated into decision-making processes. In addition, equity was mentioned in other guidance - such as decision-making frameworks - provided by five agencies that did not mention it in the HEE guidelines, and 7 of 14 topic selection criteria that were identified. CONCLUSION: Equity is given less attention than efficiency in HEE guidelines. This indicates that HTA agencies while subscribing to an extra-welfarist approach have a narrow evaluative space - focusing on maximising health and not considering the opportunity cost of the equity constraint. The omission of equity and the lack of systematic approaches in guidelines poses a threat to the international endeavours to reduce inequities. It is timely for HTA agencies to reconsider their positions on equity explicitly.

Are Medical Device Characteristics Included in HTA Methods Guidelines and Reports? A Brief Review.

It is well accepted that medical devices (MDs) and procedures have several unique characteristics compared with pharmaceuticals, such as learning curve (LC), incremental innovation (II), dynamic pricing (DP), and organizational impact (OI). The objective of this study was to determine the extent to which these MD characteristics are routinely assessed by health technology assessment (HTA) agencies and incorporated in their guidelines and reports. Three approaches were taken. First, a review of the most recent HTA methods guidelines from 14 selected HTA agencies and 5 HTA networks was undertaken. Next, HTA reports from these agencies were reviewed for inclusion of MD-specific characteristics for 16 selected MDs. Finally, a narrative literature review on this topic was conducted. A total of 13 of the included HTA organizations, and some HTA networks (2/5), have published either general or MD-specific method guidelines, whilst several addressed MD-specific characteristics. NICE included all four MD characteristics in their guidelines, but this did not equate to their inclusion in published HTA evaluations. European Network HTA (EUnetHTA) described the inclusion of LC (within patient safety) and OI within their guidance. The results highlight a lack of consistency. For the narrative review, 10/149 articles identified were reviewed. Most provided recommendations on challenges faced by HTAs, proposed steps to address uncertainties around MD characteristics and reported a lack of methodological guidance for evaluating MDs. A lack of inclusion of MD characteristics in HTA is a complex interplay of several important factors. For these characteristics to become a formal part of HTA of MDs in the future, clear guidance and frameworks are required to enable manufacturers to develop appropriate evidence, and HTA practitioners to assess their impact more broadly.

Consensus-Based Recommendations for the Implementation of Health Technology Assessment in the United Arab Emirates.

OBJECTIVES: Healthcare research and development have accelerated at an unprecedented rate creating a challenge even for high-income countries to finance all new technologies. Health technology assessment (HTA) aims to maximize health gains out of available resources. Our study aimed to provide tailor-made recommendations for HTA implementation in the United Arab Emirates (UAE). METHODS: We conducted a policy survey to explore the gap between the current and preferred future environment of HTA implementation in the UAE. The survey was distributed in 2 workshops discussing the importance of HTA implementation, and results were further aggregated to yield a list of draft recommendations. Recommendations were then assessed for their feasibility in a round table discussion with experts in the field to generate actions for HTA implementation. RESULTS: Survey results and round table discussion indicated the need to leverage HTA for value-based decision making. Experts confirmed the unmet need for broader coverage of graduate and postgraduate HTA training with the aim of specific PhD programs in the UAE. Public funding for HTA appraisals and expanding the scope of HTA to nonpharmaceuticals was recommended. Furthermore, experts recommended that several HTA bodies should be coordinated centrally and highlighted the importance of having an explicit soft cost-effectiveness threshold for common technologies and a higher threshold for orphan drugs. CONCLUSIONS: Although HTA in the UAE is still in its early stages, strong initiatives are being taken for its implementation. Our survey results served as a step in developing a detailed action plan for HTA implementation that will enhance the sustainability of the healthcare system.

Assessing medical devices: a qualitative study from the validate perspective.

OBJECTIVES: Our objective was to explore procedures and methods used at health technology assessment (HTA) agencies for assessing medical devices and the underlying views of HTA practitioners about appropriate methodology to identify challenges in adopting new methodologies for assessing devices. We focused on the role of normative commitments of HTA practitioners in the adoption of new methods. METHODS: An online survey, including questions on procedures, scoping, and assessments of medical devices, was sent to members of the International Network of Agencies for Health Technology Assessment. Interviews were conducted with survey respondents and HTA practitioners involved in assessments of transcatheter aortic valve implantation to gain an in-depth understanding of choices made and views about assessing medical devices. Survey and interview questions were inspired by the "values in doing assessments of health technologies" approach towards HTA, which states that HTA addresses value-laden questions and information. RESULTS: The current practice of assessing medical devices at HTA agencies is predominantly based on procedures, methods, and epistemological principles developed for assessments of drugs. Both practical factors (available time, demands of decision-makers, existing legal frameworks, and HTA guidelines), as well as commitments of HTA practitioners to principles of evidence-based medicine, make the adoption of a new methodology difficult. CONCLUSIONS: There is a broad recognition that assessments of medical devices may need changes in HTA methodology. In order to realize this, the HTA community may require both a discussion on the role, responsibility, and goals of HTA, and resulting changes in institutional context to adopt new methodologies.

Which value aspects are relevant for the evaluation of medical devices? Exploring stakeholders' views through a Web-Delphi process.

BACKGROUND: Implementation and uptake of health technology assessment for evaluating medical devices require including aspects that different stakeholders consider relevant, beyond cost and effectiveness. However, the involvement of stakeholders in sharing their views still needs to be improved. OBJECTIVE: This article explores the relevance of distinct value aspects for evaluating different types of medical devices according to stakeholders' views. METHODS: Thirty-four value aspects collected through literature review and expert validation were the input for a 2-round Web-Delphi process. In the Web-Delphi, a panel of participants from five stakeholders' groups (healthcare professionals, buyers and policymakers, academics, industry, and patients and citizens) judged the relevance of each aspect, by assigning a relevance-level ('Critical', 'Fundamental', 'Complementary', or 'Irrelevant'), for two types of medical devices separately: 'Implantable' and 'In vitro tests based on biomarkers'. Opinions were analysed at the panel and group level, and similarities across devices were identified. RESULTS: One hundred thirty-four participants completed the process. No aspects were considered 'Irrelevant', neither for the panel nor for stakeholder groups, in both types of devices. The panel considered effectiveness and safety-related aspects 'Critical' (e.g., 'Adverse events for the patient'), and costs-related aspects 'Fundamental' (e.g., 'Cost of the medical device'). Several additional aspects not included in existing frameworks' literature, e.g., related to environmental impact and devices' usage by the healthcare professional, were deemed as relevant by the panel. A moderate to substantial agreement across and within groups was observed. CONCLUSION: Different stakeholders agree on the relevance of including multiple aspects in medical devices' evaluation. This study produces key information to inform the development of frameworks for valuing medical devices, and to guide evidence collection.

Systematic Review of Health Economic Evaluations Focused on Artificial Intelligence in Healthcare: The Tortoise and the Cheetah.

OBJECTIVES: This study aimed to systematically review recent health economic evaluations (HEEs) of artificial intelligence (AI) applications in healthcare. The aim was to discuss pertinent methods, reporting quality and challenges for future implementation of AI in healthcare, and additionally advise future HEEs. METHODS: A systematic literature review was conducted in 2 databases (PubMed and Scopus) for articles published in the last 5 years. Two reviewers performed independent screening, full-text inclusion, data extraction, and appraisal. The Consolidated Health Economic Evaluation Reporting Standards and Philips checklist were used for the quality assessment of included studies. RESULTS: A total of 884 unique studies were identified; 20 were included for full-text review, covering a wide range of medical specialties and care pathway phases. The most commonly evaluated type of AI was automated medical image analysis models (n = 9, 45%). The prevailing health economic analysis was cost minimization (n = 8, 40%) with the costs saved per case as preferred outcome measure. A total of 9 studies (45%) reported model-based HEEs, 4 of which applied a time horizon >1 year. The evidence supporting the chosen analytical methods, assessment of uncertainty, and model structures was underreported. The reporting quality of the articles was moderate as on average studies reported on 66% of Consolidated Health Economic Evaluation Reporting Standards items. CONCLUSIONS: HEEs of AI in healthcare are limited and often focus on costs rather than health impact. Surprisingly, model-based long-term evaluations are just as uncommon as model-based short-term evaluations. Consequently, insight into the actual benefits offered by AI is lagging behind current technological developments.

Do Cost-Effectiveness Analyses Account for Drug Genericization? A Literature Review and Assessment of Implications.

OBJECTIVES: We investigated how health technology assessment (HTA) organizations around the world have handled drug genericization (an allowance for future generic drug entry and subsequent drug price declines) in their guidelines for cost-effectiveness analyses (CEAs). We also analyzed a large sample of published CEAs to examine prevailing practices in the field. METHODS: We reviewed 43 HTA guidelines to determine whether and how they addressed drug genericization in their CEAs. We also selected a sample of 270 US-based CEAs from the Tufts Medical Center's CEA Registry, restricting the sample to studies on pharmaceuticals published from 1991 to 2019 and to analyses taking a lifetime time horizon. We determined whether each CEA examined genericization (and if so, whether in base case or sensitivity analyses), and how inclusion of genericization influenced the estimated incremental cost-effectiveness ratios. RESULTS: Fourteen (33%) of the 43 HTA guidelines mention genericization for CEAs and 4 (9%) recommend that base case analyses include assumptions about future drug price changes due to genericization. Most published CEAs (95%) do not include assumptions about future generic prices for intervention drugs. Only 2% include such assumptions about comparator drugs. Most studies (72%) conduct sensitivity analyses on drug prices unrelated to genericization. CONCLUSIONS: The omission of assumptions about genericization means that CEAs may misrepresent the long run opportunity costs for drugs. The field needs clearer guidance for when CEAs should account for genericization, and for the inclusion of other price dynamics that might influence a drug's cost-effectiveness.

Systematic review automation tools improve efficiency but lack of knowledge impedes their adoption: a survey.

OBJECTIVE: We investigated systematic review automation tool use by systematic reviewers, health technology assessors and clinical guideline developerst. STUDY DESIGN AND SETTING: An online, 16-question survey was distributed across several evidence synthesis, health technology assessment and guideline development organizations. We asked the respondents what tools they use and abandon, how often and when do they use the tools, their perceived time savings and accuracy, and desired new tools. Descriptive statistics were used to report the results. RESULTS: A total of 253 respondents completed the survey; 89% have used systematic review automation tools - most frequently whilst screening (79%). Respondents' "top 3" tools included: Covidence (45%), RevMan (35%), Rayyan and GRADEPro (both 22%); most commonly abandoned were Rayyan (19%), Covidence (15%), DistillerSR (14%) and RevMan (13%). Tools saved time (80%) and increased accuracy (54%). Respondents taught themselves to how to use the tools (72%); lack of knowledge was the most frequent barrier to tool adoption (51%). New tool development was suggested for the searching and data extraction stages. CONCLUSION: Automation tools will likely have an increasingly important role in high-quality and timely reviews. Further work is required in training and dissemination of automation tools and ensuring they meet the desirable features of those conducting systematic reviews.

10 Years of End-of-Life Criteria in the United Kingdom.

OBJECTIVES: In January 2009, the National Institute for Health and Care Excellence introduced supplementary guidance for end-of-life (EoL) treatments, which allowed treatments with an incremental cost-effectiveness ratio over the regular threshold (£20 000-£30 000) to be recommended, if they satisfied the EoL criteria. The aims of this study were (1) to systematically review 10 years of EoL supplementary guidance implementation and explore how it could be improved, and (2) to create a framework for incorporating the uncertainty relating to EoL criteria satisfaction into model-based cost-effectiveness analyses for decision making. METHODS: All appraisals between January 2009 and 2019 were screened for EoL discussions. Data were extracted on the EoL criteria and cost-effectiveness assessment details. Additionally, a quantitative method was developed to include the EoL criteria satisfaction uncertainty into model-based cost-effectiveness analyses. A stylized example was created to provide a case study for the inclusion of EoL criteria satisfaction uncertainty. RESULTS: An EoL discussion was identified in 35% of appraisals, 57% of which led to a positive EoL decision. Only 5.7% of technologies with positive EoL decisions were not recommended, versus 43.8% of technologies with negative EoL decisions. EoL criteria assessment was often reported insufficiently and evaluated inconsistently and nontransparently. A total of 54.9% of EoL decisions were made while at least 1 criterion was surrounded by considerable uncertainty. By applying the proposed quantitative method, this EoL criteria satisfaction uncertainty was accounted for in decision making. The stylized example demonstrated that the impact of EoL criteria satisfaction uncertainty can be substantial enough to reverse the reimbursement decision. CONCLUSIONS: To improve consistency/transparency and correct reimbursement decisions' likelihood, new guidelines on the implementation of the EoL criteria are needed.

Associations between uncertainties identified by the European Medicines Agency and national decision making on reimbursement by HTA agencies.

We aimed to determine whether uncertainties identified by the European Medicines Agency (EMA) were associated with negative relative effectiveness assessments (REAs) and negative overall reimbursement recommendations by national health technology assessment (HTA) agencies. Therefore, we identified all HTA reports from Haute Autorité de Santé (HAS; France), National Institute for Health and Care Excellence (NICE; England/Wales), Scottish Medicine Consortium (SMC; Scotland), and Zorginstituut Nederland (ZIN; The Netherlands) for a cohort of innovative medicines that the EMA had approved in 2009 to 2010 (excluding vaccines). Uncertainty regarding pivotal trial methodology, clinical outcomes, and their clinical relevance were combined to reflect a low, medium, or high level of uncertainty. We assessed associations by calculating risk ratios (RRs) and 95% confidence intervals (CIs), and agreement between REA and overall reimbursement recommendation outcomes. We identified 36 medicines for which 121 reimbursement recommendations had been issued by the HTA agencies between September 2009 and July 2018. High versus low uncertainty was associated with an increased risk for negative REAs and negative overall reimbursement recommendations: RRs 1.9 (95% CI 0.9-3.9) and 1.6 (95% CI 0.7-3.5), respectively, which was supported by further sensitivity analyses. We identified a lack of agreement between 33 (27%) REA and overall reimbursement recommendation outcomes, which were mostly restricted recommendations that followed on negative REAs in case of low or medium uncertainty. In conclusion, high uncertainty identified by the EMA was associated with negative REAs and negative overall reimbursement recommendations. To reduce uncertainty and ultimately facilitate efficient patient access, regulators, HTA agencies, and other stakeholders should discuss how uncertainties should be weighed and addressed early in the drug life cycle of innovative treatments.

Bridging the gap: Can International Consortium of Health Outcomes Measurement standard sets align outcomes accepted for regulatory and health technology assessment decision-making of oncology medicines.

Standard outcome sets developed by the International Consortium for Health Outcomes Measurement (ICHOM) facilitate value-based health care in healthcare practice and have gained traction from regulators and Health Technology Assessment (HTA) agencies that regularly assess the value of new medicines. We aimed to assess the extent to which the outcomes used by regulators and HTA agencies are patient-relevant, by comparing these to ICHOM standard sets. We conducted a cross-sectional comparative analysis of ICHOM standard sets, and publicly available regulatory and HTA assessment guidelines. We focused on oncology due to many new medicines being developed, which are accompanied by substantial uncertainty regarding the relevance of these treatments for patients. A comparison of regulatory and HTA assessment guidelines, and ICHOM standard sets showed that both ICHOM and regulators stress the importance of disease-specific outcomes. On the other hand, HTA agencies have a stronger focus on generic outcomes in order to allow comparisons across disease areas. Overall, similar outcomes are relevant for market access, reimbursement, and in ICHOM standard sets. However, some differences are apparent, such as the acceptability of intermediate outcomes. These are recommended in ICHOM standard sets, but regulators are more likely to accept intermediate outcomes than HTA agencies. A greater level of alignment in outcomes accepted may enhance the efficiency of regulatory and HTA processes, and increase timely access to new medicines. ICHOM standard sets may help align these outcomes. However, some differences in outcomes used may remain due to the different purposes of regulatory and HTA decision-making.

Qualitative comparative analysis of health economic evaluation guidelines for health technology assessment in European countries.

OBJECTIVE: To classify, analyze, and compare published guidelines for economic evaluation within health technology assessment (HTA) in European countries and highlight differences and similarities. METHODS: We performed a literature review to identify published guidance for the conduct and assessment of economic evaluation studies that are undertaken within the context of HTA processes in European countries. Organizations and working groups were identified via the ISPOR, INAHTA, and EUnetHTA databases. Following the identification of official documents, we performed a qualitative content analysis to highlight discrepancies or common practices under the following categories: comparator, perspective on costs/benefits, time horizon, economic evaluation method, instrument used for utility measurement, outcome measure, source for efficacy, modeling, sensitivity analysis, discounting, and incremental cost-effectiveness ratio. RESULTS: A total of nineteen guidance documents were identified (in English) providing data for the analysis in nineteen countries. The comparative content analysis identified common practices in most countries regarding the approaches to the choice of comparator, source of data, the preferred economic evaluation method, the option for a lifetime analytical horizon, discounting, and the choice of key outcome measure-for which, most countries recommend the use of the EQ-5D instrument. Differences were mainly found in the choice of perspective, dealing with uncertainty and sensitivity analysis, the use of end points, and the required use of modeling. CONCLUSIONS: The use of economic evaluation constitutes one of the key pillars of the HTA process in Europe. Although a methodological convergence has occurred during the last few years, notable differences still remain.

Demonstrating the influence of HTA: INAHTA member stories of HTA impact.

A central function of health technology assessment (HTA) agencies is the production of HTA reports to support evidence-informed policy and decision making. HTA agencies are interested in understanding the mechanisms of HTA impact, which can be understood as the influence or impact of HTA report findings on decision making at various levels of the health system. The members of the International Network of Agencies for HTA (INAHTA) meet at their annual Congress where impact story sharing is one important activity. This paper summarizes four stories of HTA impact that were finalists for the David Hailey Award for Best Impact Story.The methods to measure impact include: document review; claims analysis and review of reimbursement status; citation analysis; qualitative evaluation of stakeholders' views; and review of media response. HTA agency staff also observed changes in government activities and priorities based on the HTA. Impact assessment can provide information to improve the HTA process, for example, the value of patient and clinician engagement in the HTA process to better define the assessment question and literature reviews in a more holistic and balanced way.HTA reports produced by publicly funded HTA agencies are valued by health systems around the globe as they support decision making regarding the appropriate use, pricing, reimbursement, and disinvestment of health technologies. HTAs can also have a positive impact on information sharing between different levels of government and across stakeholder groups. These stories show how HTA can have a significant impact, irrespective of the health system and health technology being assessed.

Evaluation of the National Institute for Health and Care Excellence Diagnostics Assessment Program Decisions: Incremental Cost-Effectiveness Ratio Thresholds and Decision-Modifying Factors.

OBJECTIVES: The National Institute for Health and Care Excellence (NICE) Diagnostics Assessment Programme (DAP) evaluates the cost-effectiveness of diagnostic technologies. A decision-making process benchmarking the incremental cost-effectiveness ratio (ICER) against a threshold while considering decision-modifying factors is common to NICE evaluations. This study investigated whether DAP decisions are consistent with the ICER thresholds described in the DAP manual, and to assess the impact of decision-modifying factors. METHODS: DAP evaluations published before March 2018 were reviewed, and the following items were extracted: diagnostic technologies evaluated, decision problems assessed, Diagnostics Advisory Committee (DAC) decisions, incremental quality-adjusted life years (QALYs), incremental costs, ICERs considered to be most plausible by the DAC, and decision justifications. RESULTS: All 30 evaluations were reviewed; 8 were excluded because the DAC concluded there was "insufficient evidence" for decision making. In the remaining 22 evaluations, 91 decision problems were identified for further analysis, of which 52, 15, and 24 received "recommended," "not recommended," and "not recommended-only in research" guidance, respectively. The overall consistency rate of the DAC decisions with the £20 000/QALY threshold was 73.6%. Diagnostic technologies that were not recommended, despite an ICER less than £20 000/QALY, were associated with a larger number of decision-modifying factors favoring the comparator, versus recommended diagnostic technologies with ICERs less than £20 000/QALY. For technologies with ICERs greater than £20 000/QALY, the number of decision-modifying factors was comparable for positive and negative recommendations. CONCLUSIONS: Most DAP decisions were consistent with the ICER threshold. However, cost-effectiveness was not the only determining factor in decision making; recommendations also considered patient- and healthcare-centric factors and uncertainty.

Inclusion of Carer Health-Related Quality of Life in National Institute for Health and Care Excellence Appraisals.

OBJECTIVES: Health interventions for patients can have effects on their carers too. For consistency, decision makers may wish to specify whether carer outcomes should be included. One example is the National Institute for Health and Care Excellence (NICE), whose reference case specifies that economic evaluations should include direct health effects for patients and carers where relevant. We aimed to review the methods used in including carer health-related quality of life (HRQL) in NICE appraisals. METHODS: We reviewed all published technology appraisals (TAs) and highly specialized technologies (HSTs) to identify those that included carer HRQL and discussed the methods and data sources. RESULTS: Twelve of 414 TAs (3%) and 4 of 8 HSTs (50%) included carer HRQL in cost-utility analyses. Eight were for multiple sclerosis, the remainder were each in a unique disease area. Twelve of the 16 appraisals modeled carer HRQL as a function of the patient's health state, 3 modeled carer HRQL as a function of the patient's treatment, and 1 included family quality-adjusted life year (QALY) loss. They used 5 source studies: 2 compared carer EQ-5D scores with controls, 2 measured carer utility only (1 health utilities index and 1 EQ-5D), and 1 estimated family QALY loss from a child's death. Two used disutility estimates not from the literature. Including carer HRQL increased the incremental QALYs and decreased incremental cost-effectiveness ratios in all cases. CONCLUSIONS: The inclusion of carer HRQL in NICE appraisals is relatively uncommon and has been limited by data availability.