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Introduction: This paper summarizes the results from a forum of healthcare experts, academia representatives, and public agency officials from emerging and established market countries on Value-Based Healthcare (VBHC) and Health Technology Assessment (HTA). Presentations from experts provided insights into current developments and challenges, followed by interactive roundtable discussions. Emerging markets have unique healthcare systems, patient populations, resource constraints and needs., Areas Covered: Each roundtable explored specific topics including the role of HTA and Real-world evidence (RWE) in healthcare decision-making, challenges in biosimilar value assessment and incorporating non-price criteria reflecting context-related specifications of emerging markets such as the multifaceted nature of value in healthcare decision-making, emphasizing stakeholder perspectives and system complexities., Expert Opinion: RWE emerged as important in understanding biosimilar value recognition and decision-making processes, with insights into its applications and challenges. Recommendations were provided for utilizing Multi-Criteria Decision Analysis (MCDA) in pharmaceutical procurement, particularly for off-patent medicines, underscoring the importance of comprehensive evaluation frameworks and adherence to value-based principles. Overall findings suggest avenues for collaboration between industry, academia, and public agencies to address implementation barriers and promote equitable, efficient, and high-quality healthcare systems in emerging markets through public-private partnerships, joint capacity building and training initiatives, and knowledge transfers.

Objective: Inclusion of relevant effectiveness and safety outcomes in economic evaluation of health technologies is required to aid efficient healthcare decisions. Our objective was to identify the key issues related to the inclusion of adverse events (AEs) in economic evaluation and explore perspectives for good practice recommendations to handle these issues., Methods: We focused on the frequently encountered methodological issues related to the integration of AEs in economic evaluations of health technologies. We distinguished the following elements: the incorporation of AEs in decision models, the terminology of AEs, the estimation of AEs consequences in terms of quality of life (QoL) and costs, and the exploration of the uncertainty related to the impact of AEs on the economic results., Results: We illustrated and discussed each of the identified issues by giving health technology assessment examples. We focused on the extent to which the integration of AEs in decision models can be improved by dealing with the lack of relevant real-world safety data, estimating the consequences of AEs (eg, for costs and QoL loss), exploring the impacts of AEs that are not adequately captured in current measurement of health-related QoL, and identifying the need for development of a good terminology of relevant types of AEs to be incorporated in economic evaluation., Conclusion: Based on a reflection the key methodological issues related to the incorporation of adverse drug events in economic evaluations, we suggested several recommendations to serve a starting point for health technology assessment agencies and researchers to develop good research practices in this field., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Health technology assessment (HTA) decisions for pharmaceuticals are complex and evolving. New rare disease treatments are often approved more quickly through accelerated approval schemes, creating more uncertainties about clinical evidence and budget impact at the time of market entry. The use of real-world evidence (RWE), including early coverage with evidence development, has been suggested as a means to support HTA decisions for rare disease treatments. However, the collection and use of RWE poses substantial challenges. These challenges are compounded when considered in the context of treatments for rare diseases. In this paper, we describe the methodological challenges to developing and using prospective and retrospective RWE for HTA decisions, for rare diseases in particular. We focus attention on key elements of study design and analyses, including patient selection and recruitment, appropriate adjustment for confounding and other sources of bias, outcome selection, and data quality monitoring. We conclude by offering suggestions to help address some of the most vexing challenges. The role of RWE in coverage and pricing determination will grow. It is, therefore, necessary for researchers, manufacturers, HTA agencies, and payers to ensure that rigorous and appropriate scientific principles are followed when using RWE as part of decision-making., (© 2024. The Author(s).)

Background: The aims of this research were to provide a better understanding of the specific evidence needs for assessment of clinical and cost-effectiveness of cell and gene therapies, and to explore the extent that the relevant categories of evidence are considered in health technology assessment (HTA) processes., Methods: A targeted literature review was conducted to identify the specific categories of evidence relevant to the assessment of these therapies. Forty-six HTA reports for 9 products in 10 cell and gene therapy indications across 8 jurisdictions were analysed to determine the extent to which various items of evidence were considered., Results: The items to which the HTA bodies reacted positively were: treatment was for a rare disease or serious condition, lack of alternative therapies, evidence indicating substantial health gains, and when alternative payment models could be agreed. The items to which they reacted negatively were: use of unvalidated surrogate endpoints, single arm trials without an adequately matched alternative therapy, inadequate reporting of adverse consequences and risks, short length of follow-up in clinical trials, extrapolating to long-term outcomes, and uncertainty around the economic estimates., Conclusions: The consideration by HTA bodies of evidence relating to the particular features of cell and gene therapies is variable. Several suggestions are made for addressing the assessment challenges posed by these therapies. Jurisdictions conducting HTAs of these therapies can consider whether these suggestions could be incorporated within their existing approach through strengthening deliberative decision-making or performing additional analyses., (© 2023. The Author(s).)

Introduction: The new European Union (EU) Regulations for medical devices (MDs) and health technology assessment (HTA) are welcome developments that should increase the quality of clinical evidence for MDs and reduce fragmentation in the EU market access process. To fully exploit anticipated benefits, their respective assessment processes should be closely coordinated, particularly for promising, highly innovative MDs. Accelerated approval is worth exploring for certain categories of high-risk MDs to keep the EU regulatory process competitive compared to accelerated MD approval programs elsewhere (e.g. US)., Areas Covered: Problems observed in worldwide accelerated drug and MD regulatory approval programs are reviewed, including greater uncertainty in premarket clinical evidence generation and lack of oversight for post approval evidence requirements. Implications for MD approval, HTA and coverage are explored., Expert Opinion: Through analysis of two decades of drug and MD accelerated approval programs worldwide, recommendations for an Accelerated Access Pathway for select innovative, high-risk MDs are proposed to fit the EU context, leverage the two new regulations, increase opportunities for Expert Panels to provide timely advice regarding manufacturers' evidence generation plans along the MD lifecycle (pre, postmarket), and safely speed patient access while promoting increased collaboration among Member States on coverage decisions.

Rare diseases are often severe, debilitating, life-limiting conditions, many of which occur in childhood. These complex conditions have a wide range of clinical manifestations that have a substantial impact on the lives of patients, carers and families and often produce heterogeneous clinical outcomes. Therefore, the evaluation of quality-of-life (QoL) impacts is important. In health technology assessment (HTA), patient-reported outcome measures (PROMs) and/or health state utility values (HSUVs) are used to determine QoL impacts of new treatments, but their use in rare diseases is challenging due to small and heterogeneous populations and limited disease knowledge. This paper describes challenges associated with the use of patient-reported outcomes (PROs)/HSUVs to evaluate QoL in HTA of rare disease treatments (RDTs) and identifies five recommendations to ensure appropriate interpretation of QoL impacts. These were derived from mixed methods research (literature reviews, appraisal document analyses, appraisal committee observations and interviews) examining the use of PROs/HSUVs in HTA of RDTs. They highlight that HTAs of RDTs must (1) understand the QoL impacts of the disease and of treatments; (2) critically assess PRO data, recognising the nuances in development and administration of PROMs/HSUVs, considering what is feasible and what matters most to the patient population; (3) recognise that lack of significant effect on a PRO does not imply no QoL benefit; (4) use different forms of evidence to understand QoL impacts, such as patient input; and (5) provide methodological guidance to capture QoL impacts on patients/carers., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Health technology assessment (HTA) offers a set of analytical tools to support health systems' decisions about resource allocation. Although there is increasing interest in these tools across the world, including in some middle-income countries, they remain rarely used in low-income countries (LICs). In general, the focus of HTA is narrow, mostly limited to assessments of efficacy and cost-effectiveness. However, the principles of HTA can be used to support a broader series of decisions regarding new health technologies. We examine the potential for this broad use of HTA in LICs, with a focus on Malawi. We develop a framework to classify the main decisions on health technologies within health systems. The framework covers decisions on identifying and prioritizing technologies for detailed assessment, deciding whether to adopt an intervention, assessing alternative investments for implementation and scale-up, and undertaking further research activities. We consider the relevance of the framework to policymakers in Malawi and we use two health technologies as examples to investigate the main barriers and enablers to the use of HTA methods. Although the scarcity of local data, expertise, and other resources could risk limiting the operationalisation of HTA in LICs, we argue that even in highly resource constrained health systems, such as in Malawi, the use of HTA to support a broad range of decisions is feasible and desirable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ramponi, Twea, Chilima, Nkhoma, Kazanga Chiumia, Manthalu, Mfutso-Bengo, Revill, Drummond and Sculpher.)

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., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: Challenges with patient-reported outcome (PRO) evidence and health state utility values (HSUVs) in rare diseases exist due to small, heterogeneous populations, lack of disease knowledge and early onset. To better incorporate quality of life (QoL) into Health Technology Assessment, a clearer understanding of these challenges is needed., Methods: NICE appraisals of non-oncology treatments with an EMA orphan designation (n = 24), and corresponding appraisals in the Netherlands, France, and Germany were included. Document analysis of appraisal reports investigated how PROs/HSUVs influenced decision-making and was representative of QoL impact of condition and treatment., Results: PRO evidence was not included in 6/24 NICE appraisals. When included, it either failed to demonstrate change, capture domains important for patients, or was uncertain. In the other countries, little information was reported and evidence largely did not demonstrate change. In NICE appraisals, HSUVs were derived through the collection of EQ-5D data (7/24 cases), mapping (6/24), vignettes (5/24), and published literature or other techniques (6/24). The majority did not use data collected alongside clinical trials. Few measures demonstrated significant change due to lack of sensitivity or face validity, short-term data, or implausible health states. In 8/24 NICE appraisals, patient surveys or input during appraisal committee meetings supported the interpretation of uncertainty or provided evidence about QoL., Conclusions: This study sheds light on the nature of PRO evidence in rare diseases and associated challenges. Results emphasise the need for improved development and use of PRO/HSUVs. Other forms of evidence and expert input are crucial to support better appraisal of uncertain or missing evidence., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

New technologies, including pharmaceuticals and medical devices, can improve treatment options in healthcare but also bring concerns about rising healthcare costs. We undertake a narrative review of the United Kingdom's (UK) approach to appraising new health technologies. We find that the National Institute for Health and Care Excellence (NICE), Scottish Medicines Consortium (SMC) and All Wales Medicines Strategy Group (AWMSG) have contributed to the UK's robust and transparent approach towards the evaluation of new health technologies using the cost per QALY approach. However, there are limitations to this approach including several external benefits not captured, bias against less treatable diseases, and deciding the appropriate level of the threshold. NICE, SMC, and AWMSG have attempted to overcome some of these limitations by considering additional factors such as end-of-life criteria, highly specialised treatments, and populations that experience unmet need. Looking to the future, the advent of 'personalised' and 'genomic' medicine, will likely mean the UK has to accommodate an increasing number of 'step-change' and 'highly specialised' technologies as well as respond to changes in pharmaceutical licensing and increasing use of real-world evidence., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this manuscript to declare., (Copyright © 2022. Published by Elsevier B.V.)

Transformative cell and gene therapies have now launched worldwide, and many potentially curative cell and gene therapies are in development, offering the prospect of significant health gains for patients. Access to these therapies depend on decisions made by health technology assessment (HTA) and payer organizations. We sought to describe the emerging cell and gene therapies market access landscape by analyzing 17 US commercial payer medical policies, and HTA reports from five European countries and Canada. We found that some US health plans applied coverage restrictions more often than others (four plans applied restrictions in all decisions, while four plans applied restrictions in <30% of decisions). The European and Canadian HTA bodies recommend access to fewer therapies than US health plans, reflecting a more stringent approach in the context of limited evidence and high scientific uncertainty that is commonly associated with these treatments. Our findings suggest that patient access to approved cell and gene therapies is restricted in all regions studied, though the nature of these restrictions differs between US health plans and the European/Canada HTA recommendations. Payers, HTA groups, pharmaceutical companies, and other stakeholders should collaborate to more clearly define the "uncertainties" and develop market access policies that balance benefits of early access with ongoing data collection to close evidence gaps over time., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: Medical devices are potentially good candidates for coverage with evidence development (CED) schemes, as clinical data at market entry are often sparse and (cost-)effectiveness depends on real-world use. The objective of this research was to explore the diffusion of CED schemes for devices in Europe, and the factors that favour or hamper their utilization., Methods: We conducted structured interviews with 25 decision-makers from 22 European countries to explore the characteristics of existing CED programmes for devices, and how decision makers perceived 13 pre-identified challenges associated with initiating and operating CED schemes for devices. We also collected data on individual schemes that were either initiated or still ongoing in the last 5 years., Results: We identified seven countries with CED programmes for devices and 78 ongoing schemes. The characteristics of CED programmes varied across countries, including eligibility criteria, roles and responsibilities of stakeholders, funding arrangements, and type of decisions being contemplated at the outset of each scheme. We observed a high variability in how decision makers perceived CED-related challenges possibly reflecting country-specific arrangements and different experiences with CED. One general finding across all countries was that relatively little attention was paid to the evaluation of schemes, both during and at their completion., Conclusions: CED programmes for devices with different characteristics exist in Europe. Decision-makers' perceptions differ on the challenges associated with these schemes. More exchange of knowledge and experience will help decision makers anticipate the likely challenges in CED schemes for devices, and to learn from good practices existing elsewhere., (© 2021. The Author(s).)

Objectives: there are very few value frameworks (VFs) to assess health technologies that are focused on diagnostic tests; they usually do not reflect a multistakeholder process; and they are all developed in high-income countries. Our project performed a targeted systematic review, with the objective of proposing an evidence-based, up-to-date VF informed by a multinational multistakeholder group working in the health technology assessment (HTA) space., Methods: (1) A targeted systematic review, with the aim to identify existing VFs and their dimensions; and (2) generation a VF proposal through a mixed-methods, qualitative-quantitative approach., Results: From 73 citations identified, 20 met our inclusion criteria and served to provide the initial list of dimensions for our VF. An initial list of criteria and subcriteria for a preliminary VF was proposed. After a full-day deliberative face-to-face meeting with 30 relevant stakeholders from seven Latin American countries and the United Kingdom, the final VF was defined, consisting of 15 criteria: five "essential or core," six highly relevant, three moderately relevant, and one of low relevance. Barriers and facilitators of value assessment of diagnostic technologies were also discussed., Conclusions: We propose a VF oriented to diagnostic technologies based on a targeted systematic review and a participatory process with key HTA stakeholders. It is the first to be produced in a lower and middle income setting but can also be potentially useful in other contexts aimed to assist decision-making processes with these particularly complex health technologies., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objectives: Methodological challenges in the evaluation of medical devices (MDs) may be different for early and late technology adopter countries, as well as the potential health technology assessment (HTA) solutions to tackle them. This study aims to provide guidance to Central and Eastern European (CEE) countries on how to address key challenges of HTA for MDs with special focus on the transferability of scientific evidence. Methods: As part of the COMED Horizon 2020 project, a comprehensive list of issues related to MD HTA were identified based on a targeted literature review. Health technology assessment issues which pose a greater challenge or require different solutions in late technology adopter countries were selected. Draught recommendations to address these issues were developed and discussed in a focus group. The recommendations were then validated with a wider group of experts, including HTA and reimbursement decision makers from CEE countries in May and June 2020. Results: A consolidated list of 11 recommendations were developed in 3 major areas: (1) clinical value assessment, focusing on the use of joint EU work, relying on real-world evidence, use of coverage with evidence development schemes, transferring evidence from foreign countries and addressing the challenges of learning curve and centre effect; (2) economic value assessment, covering cost calculation of complex medical devices and transferability of economic evaluations of MDs; (3) HTA processes, related to the frequent product modifications and various indications of MDs. Conclusions: Central and Eastern European countries with limited resources for conducting HTA, can benefit from HTA methods and evidence generated in early technology adopter countries. Considering the appropriate reuse of international HTA materials, late technology adopter countries can still implement HTA, even for MDs, which have a more limited evidence base compared with pharmaceuticals., Competing Interests: RD-B, SK, AZ, and ZK were employed by Syreon Research Institute. MH is self-employed in HTA/EBM Consulting Centre and has not received any remuneration of funding from the COMED project, nor has any commercial or financial relationship that could be construed as a potential conflict of interest. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Daubner-Bendes, Kovács, Niewada, Huic, Drummond, Ciani, Blankart, Mandrik, Torbica, Yfantopoulos, Petrova, Holownia-Voloskova, Taylor, Al, Piniazhko, Lorenzovici, Tarricone, Zemplényi and Kaló.)

Objectives: To investigate whether the use of economic evaluation (EE) in healthcare decision making is influenced by the social values and institutional context in a given country., Methods: We developed and tested a conceptual framework for the 36 Organisation for Economic Co-operation and Development (OECD) countries. The countries were divided into two groups based on the extent of their use of EE in drug reimbursement. The key social values were efficiency, equity, and personal responsibility, measured in an international survey. Countries were classified based on their institutional context in terms of their general welfare paradigm/type of healthcare system and the administrative tradition to which they belong. We performed correlation tests and ran path analysis regression models to test our hypotheses., Results: EE high users included significantly more Beveridge-type systems (50% vs 31%) and fewer Bismarck-type (15% vs 56%). Napoleonic tradition countries seemed to reject personal responsibility in health (r = -0.511, P = .009), whereas Germanic tradition countries embraced it (r = 0.572, P = .003); Anglo-American tradition countries exhibited a significant association with efficiency (r = 0.444, P = .026), whereas Scandinavian tradition countries appeared to reject it as a criterion for rationing in healthcare (r = -0.454, P = .023). No significant direct association was found between social values and use of EE., Conclusion: Our exploratory analysis suggests that institutional context and, indirectly, social values may play a role in shaping the use of EE in healthcare decision making. Because of the differences among countries in terms of institutional context, which may in part be influenced by social values, it is unlikely that there will ever be a single, harmonious approach to the use of EE., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

The systematic use of evidence to inform healthcare decisions, particularly health technology assessment (HTA), has gained increased recognition. HTA has become a standard policy tool for informing decision makers who must manage the entry and use of pharmaceuticals, medical devices, and other technologies (including complex interventions) within health systems, for example, through reimbursement and pricing. Despite increasing attention to HTA activities, there has been no attempt to comprehensively synthesize good practices or emerging good practices to support population-based decision-making in recent years. After the identification of some good practices through the release of the ISPOR Guidelines Index in 2013, the ISPOR HTA Council identified a need to more thoroughly review existing guidance. The purpose of this effort was to create a basis for capacity building, education, and improved consistency in approaches to HTA-informed decision-making. Our findings suggest that although many good practices have been developed in areas of assessment and some other key aspects of defining HTA processes, there are also many areas where good practices are lacking. This includes good practices in defining the organizational aspects of HTA, the use of deliberative processes, and measuring the impact of HTA. The extent to which these good practices are used and applied by HTA bodies is beyond the scope of this report, but may be of interest to future researchers., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

The fifth section of our Special Task Force report identifies and discusses two aggregation issues: 1) aggregation of cost and benefit information across individuals to a population level for benefit plan decision making and 2) combining multiple elements of value into a single value metric for individuals. First, we argue that additional elements could be included in measures of value, but such elements have not generally been included in measures of quality-adjusted life-years. For example, we describe a recently developed extended cost-effectiveness analysis (ECEA) that provides a good example of how to use a broader concept of utility. ECEA adds two features-measures of financial risk protection and income distributional consequences. We then discuss a further option for expanding this approach-augmented CEA, which can introduce many value measures. Neither of these approaches, however, provide a comprehensive measure of value. To resolve this issue, we review a technique called multicriteria decision analysis that can provide a comprehensive measure of value. We then discuss budget-setting and prioritization using multicriteria decision analysis, issues not yet fully resolved. Next, we discuss deliberative processes, which represent another important approach for population- or plan-level decisions used by many health technology assessment bodies. These use quantitative information on CEA and other elements, but the group decisions are reached by a deliberative voting process. Finally, we briefly discuss the use of stated preference methods for developing "hedonic" value frameworks, and conclude with some recommendations in this area., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

This summary section first lists key points from each of the six sections of the report, followed by six key recommendations. The Special Task Force chose to take a health economics approach to the question of whether a health plan should cover and reimburse a specific technology, beginning with the view that the conventional cost-per-quality-adjusted life-year metric has both strengths as a starting point and recognized limitations. This report calls for the development of a more comprehensive economic evaluation that could include novel elements of value (e.g., insurance value and equity) as part of either an "augmented" cost-effectiveness analysis or a multicriteria decision analysis. Given an aggregation of elements to a measure of value, consistent use of a cost-effectiveness threshold can help ensure the maximization of health gain and well-being for a given budget. These decisions can benefit from the use of deliberative processes. The six recommendations are to: 1) be explicit about decision context and perspective in value assessment frameworks; 2) base health plan coverage and reimbursement decisions on an evaluation of the incremental costs and benefits of health care technologies as is provided by cost-effectiveness analysis; 3) develop value thresholds to serve as one important input to help guide coverage and reimbursement decisions; 4) manage budget constraints and affordability on the basis of cost-effectiveness principles; 5) test and consider using structured deliberative processes for health plan coverage and reimbursement decisions; and 6) explore and test novel elements of benefit to improve value measures that reflect the perspectives of both plan members and patients., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

The efficacy of medicines, medical devices, and other health technologies should be proved in trials that assess final patient-relevant outcomes such as survival or morbidity. Market access and coverage decisions are, however, often based on surrogate end points, biomarkers, or intermediate end points, which aim to substitute and predict patient-relevant outcomes that are unavailable because of methodological, financial, or practical constraints. We provide a summary of the present use of surrogate end points in health care policy, discussing the case for and against their adoption and reviewing validation methods. We introduce a three-step framework for policymakers to handle surrogates, which involves establishing the level of evidence, assessing the strength of the association, and quantifying relations between surrogates and final outcomes. Although the use of surrogates can be problematic, they can, when selected and validated appropriately, offer important opportunities for more efficient clinical trials and faster access to new health technologies that benefit patients and health care systems., (Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

There are particular characteristics of Medical Devices, such as the device-user interaction, the incremental nature of innovation and the broader organizational impact that lead to additional challenges for health technology assessment (HTA). The project explored key aspects of the conduct and methods of HTA for MDs. Systematic reviews and original research studies were conducted to determine improvements in processes and methods that could enhance the potential for HTA and optimize the diffusion of MDs. Regulatory processes for MDs should be more closely aligned, the HTA evaluative framework should be harmonized and processes for conditional coverage and evidence development should be used. The methods for HTA should consider MDs as complex interventions, require the establishment of high quality registries, consider an iterative approach to the evaluation over time, recognize and allow for the particular characteristics of devices and use appropriate approaches for confounder adjustment in comparative effectiveness studies. To optimize the diffusion, a common classification should be developed across countries in order to facilitate international comparisons, factors driving diffusion should be explored in HTA reports and physicians' personal goals and motivation should be better understood. The key recommendations of the MedtecHTA project should improve the conduct and use of HTA for MDs. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd., (© 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd.)

Assessing medical devices (MDs) raises challenges which require us to reflect on whether current methods are adequate. Major features of devices are: (i) device-operator interaction can generate learning curve effects; (ii) incremental nature of innovation needs to be addressed by careful identification of the alternatives for comparative and incremental cost-effectiveness analysis; and (iii) broader organizational impact in terms of training and infrastructure, coupled with dynamic pricing, requires a more flexible approach to costing. The objective of the MedtecHTA project was to investigate improvements in HTA methods to allow for more comprehensive evaluation of MDs. It consisted of several work packages concerning (i) the available evidence on the currently adopted approaches for regulation and HTA of medical devices; (ii) the geographical variation in access to MDs; (iii) the development of methodological frameworks for conducting comparative effectiveness research and economic evaluation of MDs; and (iv) the organizational impact of MDs. This introductory paper summarizes the main results of the project and draws out the main overarching themes. This supplement represents a comprehensive report of all the main findings of the MedtecHTA project, and it is intended to be the main source for researchers and policy makers wanting information on the project. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd., (© 2017 The Authors. Health Economics Published by John Wiley & Sons, Ltd.)

The National Institute for Health and Care Excellence (NICE) in the United Kingdom initiated its clinical guidelines program in 2001 and more than 200 guidelines have been produced to date. As with most of NICE's other programs, the clinical guidelines program also must take into account the relative costs and benefits of interventions when deciding whether to recommend them. The three main advantages of the program are that 1) it represents an important collaboration with the medical profession, thereby increasing the likelihood of recommendations being adopted; 2) the guidelines provide an opportunity to review all aspects of the clinical pathway, rather than focusing on only the adoption of a new technology; and 3) the guidelines offer the potential to discuss disinvestment as well as new investment. All the guidelines contain a systematic review of the relevant economic evaluation literature, and the 12 guidelines published from January 1 to August 31, 2015, contain 28 de novo economic analyses. The main challenges encountered in the guidelines program are that 1) there is an inevitable tension in advising on the quality of care that individual patients could expect while recognizing the broader public health objectives of equity, fairness, and efficiency; 2) the impact of economics is sometimes lessened because of the lack of time to conduct de novo analyses; and 3) unlike NICE's technology appraisal program, the adoption of recommendations is not mandatory for the UK National Health Service., (Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Decision makers in middle-income countries are using economic evaluations (EEs) in pricing and reimbursement decisions for pharmaceuticals. However, whilst many of these jurisdictions have local submission guidelines and local expertise, the studies themselves often use economic models developed elsewhere and elements of data from countries other than the jurisdiction concerned. The objectives of this study were to describe the current situation and to assess the challenges faced by decision makers in transferring data and analyses from other jurisdictions., Methods: Experienced health service researchers in each region conducted an interview survey of representatives of decision making bodies from jurisdictions in Asia, Central and Eastern Europe, and Latin America that had at least 1 year's experience of using EEs., Results: Representatives of the relevant organizations in twelve countries were interviewed. All twelve jurisdictions had developed official guidelines for the conduct of EEs. All but one of the organizations evaluated studies submitted to them, but 9 also conducted studies and 7 commissioned them. Nine of the organizations stated that, in evaluating EEs submitted to them, they had consulted a study performed in a different jurisdiction. Data on relevant treatment effect was generally considered more transferable than those on prices/unit costs. Views on the transferability of epidemiological data, data on resource use and health state preference values were more mixed. Eight of the respondents stated that analyses submitted to them had used models developed in other jurisdictions. Four of the organizations had a policy requiring models to be adapted to reflect local circumstances. The main obstacles to transferring EEs were the different patterns of care or wealth of the developed countries from which most economic evaluations originate., Conclusions: In middle-income countries it is commonplace to deal with the issue of transferring analyses or data from other jurisdictions. Decision makers in these countries face several challenges, mainly due to differences in current standard of care, practice patterns, or gross domestic product between the developed countries where the majority of the studies are conducted and their own jurisdiction.

Background: Regulatory approval and reimbursement are necessary to bring health technologies to market. As both are distinct processes, the lack of interaction between regulators and payers has been criticized for resulting in health system inefficiencies., Objectives: This study describes the experiences of health system stakeholders on the development and implementation of initiatives to better harmonize HTA-reimbursement and regulatory activities, as well as Canadian perceptions on such initiatives., Methods: Thematic analysis of semi-structured interviews was conducted. Participants represented those whom have published or worked actively in this area or who held positions in HTA and/or reimbursement agencies that gave them insight into the Canadian healthcare system. Interviews were recorded, transcribed and analyzed to identify emerging themes and relationships., Results: Fourteen individuals from twelve organizations participated, including representatives from Canada, US, UK and Netherlands. Harmonization was identified as either a means to: (i) develop economies of scale in the generation of clinical data; and/or (ii) align the lifecycle of a health technology. For such initiatives to be successfully implemented, the following key issues emerged: (i) fostering healthy relationships; (ii) promoting well-intentions; (iii) defining governance and leadership clearly; and (iv) securing organizational infrastructure., Conclusions: Attempts to harmonize reimbursement and regulatory activities is in its infancy; although, much can be learned from current Canadian and international experiences. Within Canada there is much interest, although concerns have been raised on the extent to which harmonization is possible. Successful policy implementation would require inter-agency collaborations, with particular attention towards capacity building and strong leadership.

A considerable degree of overlap exists between reimbursement and regulatory approval of health technologies, and harmonization of certain aspects is both possible and feasible. Various models to harmonization have been suggested in which a number of practical attempts have been drawn from. Based on a review of the literature, approaches can be categorized into those focused on reducing uncertainty and developing economies of scale in the evidentiary requirements; and/or aligning timeframes and logistical aspects of the review process. These strategies can further be classified based on the expected level of structural and organizational change required to implement them into the existing processes. Passive processes require less modification, whereas active processes are associated with greater restructuring. Attempts so far at harmonization have raised numerous legal and practical issues and these must be considered when introducing a more harmonized framework into the existing regulatory and reimbursement arrangements.

Providing universal access to innovative, high-cost technologies leads to tensions in today's health care systems. The tension becomes particularly evident in the context of scarce resources, where the risk of taking contentious coverage decisions increases rapidly. To ensure economic sustainability, the payers of health care think that the benefits from the use of the new technologies need to be commensurate with the costs. Therefore, many jurisdictions have programs of health technology assessment, which often results in restrictions of access to care, either through complete refusal to reimburse the technology or its restriction of use to only a subset of the eligible patient population. However, manufacturers feel that they should be adequately rewarded for their innovations and require sufficient funds to invest in further research. Finally, patients perceive these technologies to have added benefits, and so they are concerned when they are denied access. If sustainable access to health care is to be maintained in the future, approaches are needed to reconcile these different perspectives. This article explores the approaches, in both methods and policy, to help bring about this reconciliation. These include rethinking the notion of social value (on the part of payers), aligning manufacturers' research more closely with societal objectives, and increasing patient participation in health technology assessment., (Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Introduction: HTA agencies, especially in developing countries, are under resourced and unable to conduct the desired amount of assessments. Adapting HTA reports (HTAs) from other jurisdictions is an alternative for saving resources., Objectives: To explore HTA transferability experiences in Latin-America and Caribbean (LAC): are decision makers (DMs) using HTAs from other jurisdictions? Are researchers adapting HTAs when developing local reports? How useful is the information found in HTAs from other jurisdictions?, Methods: Web-based survey sent to 13031 HTA researchers and DMs., Results: We received 671 responses from 19 countries. DMs reported using HTAs from other jurisdictions to guide decisions in the majority of the situations: 52.6 percent HTAs from outside LAC (e.g., Europe), 23.1 percent from other LAC countries, and only 24.3 percent HTAs from their own countries. 63 percent of researchers reported using HTAs from other jurisdictions. Usefulness scored significantly higher for HTAs from other jurisdictions as compared to local HTAs (7.1 versus 6.0 in a 1-10 scale; p < .01). Both DMs and researchers considered the information regarding safety and effectiveness more applicable than the information on social aspects, or economic evaluation. Barriers that limit transferability had significantly different scores for HTAs from other LAC countries as compared to those from regions outside LAC (i.e., poor methodological quality 6.7 versus 5.3, different epidemiological context 6.0 versus 7.4; all p < .01)., Conclusions: HTAs from outside the region are commonly used. However, DMs and researchers agreed that HTAs from LAC had the greatest potential for transferability, provided that barriers such as poor methodological quality could be overcome.

Objectives: In recent years, there has been growth in the use of health technology assessment (HTA) for making decisions about the reimbursement, coverage, or guidance on the use of health technologies. Given this greater emphasis on the use of HTA, it is important to develop standards of good practice and to benchmark the various HTA organizations against these standards., Methods: This study discusses the conceptual and methodological challenges associated with benchmarking HTA organizations and proposes a series of audit questions based on a previously published set of principles of good practice., Results and Conclusions: It is concluded that a benchmarking exercise would be feasible and useful, although the question of who should do the benchmarking requires further discussion. Key issues for further research are the alternative methods for weighting the various principles and for generating an overall score, or summary statement of adherence to the principles. Any weighting system, if developed, would need to be explored in different jurisdictions to assess the extent to which the relative importance of the principles is perceived to vary. Finally, the development and precise wording of the audit questions requires further study, with a view to making the questions as unambiguous as possible, and the reproducibility of the assessments as high as possible.

Objectives: This article provides a detailed understanding of the differences in selected formulary submission guidelines supplied by various health technology assessment (HTA) agencies and indicates how these differences can impact the evidence base used to populate the HTA., Methods: Detailed summaries of the recommended methods for evidence generation, organized by topic areas relevant for clinical and economic data, for twelve countries in Europe, North America, and Australia where HTA processes are well developed were prepared. Using these summaries, we provide examples of the likely impact these differences in recommended methods could have on the evidence base used to evaluate new health technologies., Results: Areas where recommendations differed included methodologies for systematic literature reviews (e.g., preferred databases and study designs for inclusion); selection of appropriate comparators; guidance on critical appraisal and synthesis of clinical evidence; appropriate sources for health value measures, resource use, and cost data; and approaches to uncertainty analyses. Performing literature searches that capture all relevant studies and then creating subsets of the literature based on a listing of country-specific requirements could allow for direct comparison of the evidence bases associated with the different guidelines., Conclusions: If the formulary submission guidelines were followed as written, different (although overlapping) bodies of evidence likely would be generated for each country, which could contribute to disparate assessments and recommendations. This comparison of the formulary submission guidelines could contribute to an understanding of why clinical and reimbursement decisions vary across countries.

Reference pricing and health technology assessment are policies commonly applied in order to obtain more value for money from pharmaceuticals. This study focussed on decisions about the initial price and reimbursement status of innovative drugs and discussed the consequences for market access and cost. Four countries were studied: Germany, The Netherlands, Sweden and the United Kingdom. These countries have operated one, or both, of the two policies at certain points in time, sometimes in parallel. Drugs in four groups were considered: cholesterol-lowering agents, insulin analogues, biologic drugs for rheumatoid arthritis and "atypical" drugs for schizophrenia. Compared with HTA, reference pricing is a relatively blunt instrument for obtaining value for money from pharmaceuticals. Thus, its role in making reimbursement decisions should be limited to drugs which are therapeutically equivalent. HTA is a superior strategy for obtaining value for money because it addresses not only price but also the appropriate indications for the use of the drug and the relation between additional value and additional costs. However, given the relatively higher costs of conducting HTAs, the most efficient approach might be a combination of both policies.

It is common practice for developers of new health care technologies to engage in early dialogue with the major regulatory agencies; such discussions frequently center around the proposed clinical trial designs to support the registration of new interventions and suggestions on their improvement. Pricing and reimbursement agencies are increasingly using the results from health technology assessments to inform their decision making for new technologies. Such assessments are invariably underpinned by the phase 3 clinical trial evidence which may not provide answers to the key questions. Technology developers are beginning to realize that direct, early dialogue on the evidence requirements of the major pricing and reimbursement agencies, before phase 3 clinical trial designs for their key development compounds have been finalized, may be beneficial. This article reports on the pioneering efforts of one technology developer in seeking early dialogue with seven pricing and reimbursement agencies in five countries globally in 2007-2008 on their likely evidence requirements for a new oral treatment for patients with chronic plaque psoriasis. The pilot project demonstrated that a feasible process of early dialogue could be established, through a face-to-face meeting with prior circulation of a briefing book. Although there was some variation in the advice the similarities far outweighed the differences. More experience of early dialogue needs to be accumulated, involving a wider range of pricing and reimbursement agencies and compounds. The conclusion of this study, however, was that early dialogue can be a worthwhile process for all parties and can lead to a common understanding about evidence development for market access., (Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objectives: A set of fifteen key principles (KP) has been recently proposed to guide decisions on the structure of HTA programs, the methods of HTA, the processes for conducting HTA and the use of HTA findings in decision-making. The objective of this research is to explore whether these KPs are relevant and useful in Latin America (LA), and to what extent they are being applied., Methods: A Web-based survey was sent to 11,792 HTA researchers and users in LA to explore the perceived relevance of each KP, its current level of application and the gap between these two., Results: We received 1,142 responses from nineteen LA countries (9.7 percent response rate). The subgroup of KP related to Methods and to the Use of HTA received the higher mean scores in the relevance scale (9.00 and 8.94). Level of current application scored low in all KP (3.2 to 4.9). Higher gaps were observed in principles related to the use of HTA in decision making and to the processes for conducting HTA. Countries with more developed HTA showed higher scores in the degree of current application (5.3 versus 3.4, p < .01) and lower gaps (3.84 versus 5.21, p < .01). Researchers, compared with research users, scored the relevance of the KPs higher., Conclusions: KPs seem to be very relevant to most HTA researchers and users in LA. However, the current level of application was considered uniformly poor. Higher gaps were observed in KPs related to the link between HTA and decision making, highlighting one of the major challenges for the countries in the region.

Context: The terms evidence-based medicine (EBM), health technology assessment (HTA), comparative effectiveness research (CER), and other related terms lack clarity and so could lead to miscommunication, confusion, and poor decision making. The objective of this article is to clarify their definitions and the relationships among key terms and concepts., Methods: This article used the relevant methods and policy literature as well as the websites of organizations engaged in evidence-based activities to develop a framework to explain the relationships among the terms EBM, HTA, and CER., Findings: This article proposes an organizing framework and presents a graphic demonstrating the differences and relationships among these terms and concepts., Conclusions: More specific terminology and concepts are necessary for an informed and clear public policy debate. They are even more important to inform decision making at all levels and to engender more accountability by the organizations and individuals responsible for these decisions.

Previously, our group-the International Working Group for HTA Advancement-proposed a set of fifteen Key Principles that could be applied to health technology assessment (HTA) programs in different jurisdictions and across a range of organizations and perspectives. In this commentary, we investigate the extent to which these principles are supported and used by fourteen selected HTA organizations worldwide. We find that some principles are broadly supported: examples include being explicit about HTA goals and scope; considering a wide range of evidence and outcomes; and being unbiased and transparent. Other principles receive less widespread support: examples are addressing issues of generalizability and transferability; being transparent on the link between HTA findings and decision-making processes; considering a full societal perspective; and monitoring the implementation of HTA findings. The analysis also suggests a lack of consensus in the field about some principles--for example, considering a societal perspective. Our study highlights differences in the uptake of key principles for HTA and indicates considerable room for improvement for HTA organizations to adopt principles identified to reflect good HTA practices. Most HTA organizations espouse certain general concepts of good practice--for example, assessments should be unbiased and transparent. However, principles that require more intensive follow-up--for example, monitoring the implementation of HTA findings--have received little support and execution.

Objectives: The aim of this study was to describe generally the development and present situation with health technology assessment (HTA) in the United Kingdom., Methods: The methods used are a review of important materials that have described the development process and present situation, supplemented by some personal experiences., Results: The United Kingdom has been characterized historically as a country with a strong interest in evidence in health care, both clinical trials for efficacy and cost-effectiveness analyses. However, this evidence was not well-linked to the needs of the National Health Services (NHS) before formation of the NHS R&D Programme in 1991, The R&D Programme brought substantial resources into HTA and related activities, with the central aim of improving health care in Britain and increasing value for money. However, policy makers as well as staff of the R&D Programme were dissatisfied with the use of the HTA results in clinical and administrative practice. Therefore, the National Institute of Clinical Excellence (NICE) was formed in 1999. NICE issues guidance intended to influence practical decision making in health care at the national and local levels, based on efficacy information and, in some cases, economic analyses. NICE is now also seeking ways to maximize impacts on practice., Conclusions: The UK experience shows that information on clinical and cost-effectiveness may not be enough to change practice, at least in the short-run. Still, one may conclude that the United Kingdom now has one of the few most important and influential HTA programs in the world.

Health technology assessment (HTA) is a dynamic, rapidly evolving process, embracing different types of assessments that inform real-world decisions about the value (i.e., benefits, risks, and costs) of new and existing technologies. Historically, most HTA agencies have focused on producing high quality assessment reports that can be used by a range of decision makers. However, increasingly organizations are undertaking or commissioning HTAs to inform a particular resource allocation decision, such as listing a drug on a national or local formulary, defining the range of coverage under insurance plans, or issuing mandatory guidance on the use of health technologies in a particular healthcare system. A set of fifteen principles that can be used in assessing existing or establishing new HTA activities is proposed, providing examples from existing HTA programs. The principal focus is on those HTA activities that are linked to, or include, a particular resource allocation decision. In these HTAs, the consideration of both costs and benefits, in an economic evaluation, is critical. It is also important to consider the link between the HTA and the decision that will follow. The principles are organized into four sections: (i) "Structure" of HTA programs; (ii) "Methods" of HTA; (iii) "Processes for Conduct" of HTA; and (iv) "Use of HTAs in Decision Making."

Background: Decision analytic models, as used in economic evaluations, require data on several clinical parameters. The gold standard approach is to conduct a systematic review of the relevant clinical literature, although reviews of economic evaluations indicate that this is rarely done. Technology appraisals for the National Institute for Health and Clinical Excellence (NICE), which are fully funded, represent the best case scenario for the close integration of economic evaluations and systematic reviews. The objective of this study was to assess the extent to which the systematic review of the clinical literature informs the economic evaluation in NICE technology appraisals., Methods: All NICE technology assessment reports (TARs) published between January 2003 and July 2006 were considered. Data were abstracted on the TAR topics, the primary measure of clinical effectiveness, the approach to pooling in the clinical review, the measure of economic benefit and the use, or non-use, of the systematic review in the economic evaluation., Results: Forty-one TARs were published in the period studied, all of which contained a systematic review. Most of the economic evaluations (85 percent) were cost-utility analyses, reflecting NICE's guidelines for economic evaluation. In seventeen cases, the clinical data were not pooled in the review, owing to heterogeneity in the clinical data or the limited number of studies. In these cases, the economists used alternative approaches for estimating the key effectiveness parameter in the model. The results of the review (when pooled) were always used when the primary clinical effectiveness measure corresponded with the measure of economic benefit (e.g., survival). However, because preference-based quality of life measures are rarely included in clinical trials, the results of the systematic review were never directly used in the cost-utility analyses. Nevertheless, the outputs of the systematic review were used when the data were useful in estimating components of the quality-adjusted life-year (QALY) (e.g., the life-years gained, or the frequencies of health states to which QALYs could be assigned). Problems occurred mainly when the clinical data were not pooled, or when the measure of clinical benefit could not be converted into health states to which QALYs could be assigned., Conclusions: Economic evaluations can benefit from systematic reviews of the clinical literature. However, such reviews are not a panacea for conducting a good economic evaluation. Much of the relevant data for estimating QALYs are not contained in such reviews and the chosen method for summarizing the clinical data may inhibit the assessment of economic benefit. Problems would be reduced if those undertaking the technology assessments discussed the data requirements for the economic model at an early stage.

Objectives: Although the importance of economic evaluations is recognized, research suggests the ways in which studies are summarized may not be optimal for a busy decision maker with little training in economics methodology. Therefore, the objective of this study was to seek decision makers' views on different summary formats, including a score, short summary, and structured abstracts of different degrees of detail., Methods: We contacted 2,400 people, of which 84 decision makers volunteered and were presented, cumulatively, with different formats and asked whether these provided sufficient detail on the methodology and results of an economic study., Results: From the fifty decision makers who responded to the questionnaire, it was found that the preferred combination was a very short summary, plus a more detailed structured abstract. It was also found that decision makers with economics training preferred the most detailed format, partly reflecting their reasons for consulting economic evaluations., Conclusions: Decision makers require both an initial screen of study content, plus more detail should they find the study relevant or interesting.

Historically, patients with rare diseases have been underserved by commercial drug development. In several jurisdictions, specific legislation has been enacted to encourage the development of drugs for rare diseases (orphan drugs), which would otherwise not be commercially viable. However, because of the small market, these drugs are often very expensive. Under the standard methods of health technology assessment (HTA) incorporating economic evaluation, orphan drugs do not usually prove to be cost-effective and this, coupled with their high cost, means that funding and patient access may be limited. However, these restrictions may not be in line with societal preferences. Therefore, this study discusses whether the standard methods of HTA are adequate for assisting decisions on patient access to and funding of orphan drugs and outlines a research agenda to help understand the societal value of orphan drugs and issues surrounding their development, funding, and use.

Objectives: Health technology assessment (HTA) is increasingly an international activity, and HTA agencies collaborate to avoid unnecessary duplication of effort. However, the sharing of the results from HTAs raises questions about their generalizability; namely, are the results of an HTA undertaken in one country relevant to another?, Methods: This study presents recommendations for increasing the generalizability of economic evaluations. They represent an important component of HTAs and are commonly thought to have limited generalizability., Results: Recommendations are given for studies using patient-level data (i.e., evaluations conducted alongside clinical trials) and for studies using decision analytic modeling., Conclusions: If implemented, the recommendations would increase the value for investments in HTA.

Objectives: Health-care technology reviews now increasingly include outcome costs as well as clinical effects. This study reports the findings and implications of a survey to explore the usefulness of the National Health Service Economic Evaluation Database (NHS EED) within this process., Methods: Postal survey of lead authors of Technology Assessment Reviews (TARs) commissioned by the United Kingdom's National Institute for Clinical Excellence (NICE). The questionnaire investigated the usefulness of NHS EED in terms of (a) search strategy, (b) data extraction, (c) quality assessment, and (d) determining requirements for new modeling studies. Qualitative data were requested, including opinions regarding NHS EED., Results: NHS EED was used in 90 percent of all identified reviews (n = 46). The questionnaire response rate was 63 percent. The percentage of scores 3 or above (most useful), 2 or below (least useful), or N/A were, respectively, (a) search strategy= 62 percent, 23 percent, 15 percent; (b) data extraction = 23 percent, 27 percent, 50 percent, (c) quality assessment= 38 percent, 19 percent, 42 percent; (d) determining requirements for new modeling studies = 27 percent, 23 percent, 50 percent. The results were expanded further in the qualitative data from the respondents., Conclusions: NHS EED is a useful tool for a variety of tasks in the NICE/TAR process but not, unsurprisingly, as a replacement for understanding primary studies. There is, however, a need to reduce the impact of time lags between the publication of economic evaluations and the appearance of abstracts relating to them on NHS EED. The results will inform future developments of the NHS EED database, which should increase its usefulness to researchers.