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This study maps the conceptual structure of health technology assessment (HTA) research with the aim of contributing to a better understanding of this research stream. A bibliometric analysis of 1,198 HTA articles retrieved from the Web of Science database was conducted. The analysis of descriptive performance indicators identified the main traits of the scientific debate about the HTA in terms of publications, productive countries, and sources. A co-word analysis was performed by adopting social network analysis tools to map the conceptual structure of the dataset. The results highlight the growing academic interest in the research topic, especially in recent years. The results revealed that HTA is a widely known term and represents the reference paradigm for assessment in healthcare technologies. This paper contributes to the field by providing an examination of the current state of the art of HTA research and identifying possible future research directions. This study differs from existing studies because it involved a conceptual analysis of the scientific literature using macro keywords.

Objectives A recent debate in health economics and outcomes research community identified option value as one of the elements warranting consideration in the assessment of medical technologies. To conduct a scoping review of contributions on option value in the healthcare sector and identify relevant conceptual aspects and methods used to incorporate it in standard economic evaluations. Methods A systematic search was conducted up to July 2020 to identify contributions from electronic bibliographic database and gray literature. Data on the proposed definitions of option value, theoretical implications of its use in economic evaluations, and methods used to estimate it were extracted and analyzed. Results We found 57 eligible studies. Three different definitions emerged: insurance value, real option value, and option value of survival. Focusing on the latter (24 studies), we analyzed in depth 8 empirical applications across 7 therapeutic areas. The most relevant methodological challenges were on the perspective used in economic evaluations and how to robustly manage forecasting uncertainty, update cost-effectiveness thresholds, and avoid double-counting issues. For empirical studies assessing the total value of the technology, including option value, estimates ranged from +7% to +469% of its conventional value. Conclusions This review synthesizes theoretical and empirical aspects on option value of healthcare technologies and proposes a terminology to distinguish 3 different concepts identified. Future work should focus primarily on agreeing on whether option value should be included in economic evaluations and, if so, on developing and validating reliable methods for its ex-ante estimation.

Differing contexts have greatly influenced HTA development in various countries, with considerable effort recently made by international HTA networks (e.g., EUnetHTA) and the European Union (EU) to make HTA a more coherent, equal, and efficient process. Medical devices (MDs) present particular challenges for HTA because of frequent, rapid innovation, outcomes influenced by end-user competence, dynamic pricing and often low-quality scientific evidence. Our objective is to describe the development, structure and governance of a National HTA Program for MDs (PNHTADM) in Italy, a highly participatory, stakeholder-engaged, evidence-based process to reform a fragmented system of appraisal and approval. Based largely on EUnetHTA methods, the resulting process delineates a standardized system for proposing MDs by any stakeholders, accrediting HTA producers, setting criteria for prioritization and appraisals, and innovatively linking recommendations with coverage, reimbursement and procurement of MDs. Expected benefits include reduced disparities in pricing and reimbursement policies and improved access to new technologies across 21 regional healthcare systems in Italy's decentralized, universal system, complete with provisions to require additional evidence collection and centrally monitor diffusion. Though devised for Italy, the design, resources and underlying analysis provide a framework for other nations seeking to consolidate HTA initiatives, particularly in light of new EU regulation.

Background Health Technology Assessment (HTA), which can support public drug reimbursement decisions will play a core function in the planned national Pharmacare program in Canada. To address existing barriers to the use of HTA, these must be ranked in order of priority. The goal of this study was to access the relative importance of known facilitators and barriers to the use of HTA in the context of the Canadian health care system, with attention to differences between regions and stakeholder groups. Methods We used the best-worst scaling object case approach to elicit a quantitative ranking of a list of 20 facilitators and 22 barriers. A sample of 68 Canadian HTA stakeholders, including members of expert committees, decision/policymakers, researchers/academics, and others participated in the study. Their task was to identify the most important and the least important item in 12 sub-sets of five facilitators and 14 sub-sets of five barriers. Findings Relative Importance Scores derived via hierarchical Bayes analysis revealed relations, engagement, and contact between stakeholders as most important on both the barrier and facilitator sides. Other top-ranked facilitators included the availably of credible and relevant research. Other top-ranked barriers included inconsistencies in the evidence and limited generalizability. The availability of HTA guidelines did not rank highly on either side. The main limitation of the study was the challenge with reaching the relevant respondents; this was mitigated by involving the national HTA agency in the research. Conclusion Canadian stakeholders consider the relationships within the HTA network among the most important. Policies should focus on strengthening these relationships. Future research should focus on the connectivity and distribution of knowledge and power within the HTA network.

Due to uncertainty regarding the potential impact of unmeasured confounding, health technology assessment (HTA) agencies often disregard evidence from nonrandomized studies when considering new technologies. Quantitative bias analysis (QBA) methods provide a means to quantify this uncertainty but have not been widely used in the HTA setting, particularly in the context of cost–effectiveness modelling (CEM). This study demonstrated the application of an aggregate and patient-level QBA approach to quantify and adjust for unmeasured confounding in a simulated nonrandomized comparison of survival outcomes. Application of the QBA output within a CEM through deterministic and probabilistic sensitivity analyses and under different scenarios of knowledge of an unmeasured confounder demonstrates the potential value of QBA in HTA.

Evidence generated from nonrandomized studies (NRS) is increasingly submitted to health technology assessment (HTA) agencies. Unmeasured confounding is a primary concern with this type of evidence, as it may result in biased treatment effect estimates, which has led to much criticism of NRS by HTA agencies. Quantitative bias analyses are a group of methods that have been developed in the epidemiological literature to quantify the impact of unmeasured confounding and adjust effect estimates from NRS. Key considerations for application in HTA proposed in this article reflect the need to balance methodological complexity with ease of application and interpretation, and the need to ensure the methods fit within the existing frameworks used to assess nonrandomized evidence by HTA bodies.

Orphan drugs have high acquisition costs and when standard health technology assessment (HTA) approaches are used to assess their cost-effectiveness, they often appear not cost-effective. The Canadian Patented Medicine Review Board (PMPRB), through new regulations, will apply HTA assessment results from the Canadian Agency for Drugs and Technologies in Health (CADTH) and Institut national d’excellence en santé et en services sociaux (INESSS) when setting the maximum price that can be charged for Category I patented medicines (treatments with an annual cost exceeding 150% of GDP per capita of Canada or with expected annual market size >$50M). Through these regulations, PMPRB has also established a willingness-to-pay threshold of CAD$200,000 or CAD$150,000 per quality adjusted life year (QALY) for medications with a prevalence of no more than 1 in 2000 across all approved indications. We reviewed the orphan drug submissions made to CADTH’s Common Drug Review (CDR) January 2015–May 2020 to understand how the methodology of assessing cost-effectiveness of orphan drugs has guided pricing in Canada. A total of 35 orphan drug submissions were assessed by CDR in this period, none of which met the willingness-to-pay threshold of CAD$50,000 per QALY. Only one drug met the CAD$200,000 per QALY for Therapeutic Criteria Level I, and two drugs met CAD$150,000 per QALY for other Therapeutic Criteria Levels proposed by PMPRB. Price reductions of 32–99% were recommended for treatments that were approved in order to be listed for reimbursement. This review showed that the new PMPRB regulations could be creating challenges for manufacturers of rare disease treatments to meet Canadian pricing regulations. These regulations may jeopardize the launch of new medicines and limit opportunities to add to the development of real-world evidence of orphan drugs, which can be used in reimbursement approaches such as pay-for-performance.

In the drive towards faster patient access to treatments, health technology assessment (HTA) agencies are increasingly faced with reliance on evidence from surrogate endpoints, leading to increased decision uncertainty. This study undertook an updated survey of methodological guidance for using surrogate endpoints across international HTA agencies. We reviewed HTA and economic evaluation methods guidance from European, Australian and Canadian HTA agencies. We considered how guidelines addressed the methods for handling surrogate endpoints, including (1) level of evidence, (2) methods of validation, and (3) thresholds of acceptability. Across the 73 HTA agencies surveyed, 29 (40%) had methodological guidelines that made specific reference to consideration of surrogate outcomes. Of the 45 methods documents analysed, the majority [27 (60%)] were non-technology specific, 15 (33%) focused on pharmaceuticals and three (7%) on medical devices. The principles of the European network for Health Technology Assessment (EUnetHTA) guidelines published in 2015 on the handling of surrogate endpoints appear to have been adopted by many European HTA agencies, i.e. preference for final patient-relevant outcomes and reliance on surrogate endpoints with biological plausibility and epidemiological evidence of the association between the surrogate and final endpoint. Only a small number of HTA agencies (UK National Institute for Care and Excellence; the German Institute for Medical Documentation and Information and Institute for Quality and Efficiency in Health Care; the Australian Pharmaceutical Benefits Advisory Committee; and the Canadian Agency for Drugs and Technologies in Health) have developed more detailed prescriptive criteria for the acceptance of surrogate endpoints, e.g. meta-analyses of randomised controlled trials showing strong association between the treatment effect on the surrogate and final outcomes. As the decision uncertainty associated with reliance on surrogate endpoints carries a risk to patients and society, there is a need for HTA agencies to develop more detailed methodological guidance for consistent selection and evaluation of health technologies that lack definitive final patient-relevant outcome evidence at the time of the assessment.

Digital health and mobile medical apps (MMAs) have shown great promise in transforming health care, but their adoption in clinical care has been unsatisfactory, and regulatory guidance and coverage decisions have been lacking or incomplete. A multidimensional assessment framework for regulatory, policymaking, health technology assessment, and coverage purposes based on the MMA lifecycle is needed. A targeted review of relevant policy documents from international sources was conducted to map current MMA assessment frameworks, to formulate 10 recommendations, subsequently shared amongst an expert panel of key stakeholders. Recommendations go beyond economic dimensions such as cost and economic evaluation and also include MMA development and update, classification and evidentiary requirements, performance and maintenance monitoring, usability testing, clinical evidence requirements, safety and security, equity considerations, organizational assessment, and additional outcome domains (patient empowerment and environmental impact). The COVID-19 pandemic greatly expanded the use of MMAs, but temporary policies governing their use and oversight need consolidation through well-developed frameworks to support decision-makers, producers and introduction into clinical care processes, especially in light of the strong international, cross-border character of MMAs, the new EU medical device and health technology assessment regulations, and the Next Generation EU funding earmarked for health digitalization.

Objectives To conduct a formative evaluation of applying the VALIDATE approach in practice by (i) assessing how students appreciated the e-learning course, (ii) exploring how, for what purposes and with what outcomes the acquired VALIDATE competences subsequently were used in internships in different institutional contexts, and how this was shaped by these contexts, and (iii) what this shows on real-world use of VALIDATE. Methods Comparative discussion of experiences of applying the VALIDATE approach via a semistructured survey and oral feedback from e-course students; final reports on internships in health technology assessment (HTA) practice, followed by semistructured interviews with interns and supervisors to complement and interpret results. Results All students considered the VALIDATE approach an enlightening and important addition to current HTA knowledge, especially regarding understanding the relation between empirical analysis and normative inquiry, identifying policy relevant questions and using the method of reconstructing interpretive frames for scoping. The latter appeared intellectually challenging and requiring some prior HTA knowledge. The use the VALIDATE approach in practice shows that interns productively redefined the HTA problem, based on appreciation of different stakeholders’ definition of the issue; they experienced constraints from retrieving all relevant perspectives from existing literature as well as from institutional rules and routines. Conclusions Some challenges in applying the VALIDATE approach deserve attention for its future use: currently used research approaches often assume a problem as “given”; and the data needed on different perspectives is often not reported in scientific literature. Finally, data gathering on and evaluation of value dimensions was experienced as challenging.

Introduction: Hereditary angioedema (HAE) is a rare genetic disease that impairs quality of life and could be life-threatening. The aim of this study was to apply a multicriteria decision analysis to assess the value of three long-term prophylactic (LIP) therapies for HAE in Spain. Methods: A multidisciplinary committee of 10 experts assessed the value of lanadelumab (subcutaneous use), C1-inhibitor (C1-INH; intravenous), and danazol (orally), using placebo as comparator. We followed the EVIDEM methodology that considers a set of 13 quantitative criteria. The overall estimated value of each intervention was obtained combining the weighting of each criterion with the scoring of each intervention in each criterion. We used two alternative weighting methods: hierarchical point allocation (HPA) and direct rating scale (DRS). A reevaluation of weightings and scores was performed. Results: Lanadelumab obtained higher mean scores than C1-INH and danazol in all criteria, except for the cost of the intervention and clinical practice guidelines. Under the HPA method, the estimated values were 0.51 (95% confidence interval [CI]: 0.44-0.58) for lanadelumab, 0.47 (95%CI: 0.41-0.53) for C1-INH, and 0.31 (95%CI: 0.240.39) for danazol. Similar results were obtained with the DRS method: 0.51 (95%CI: 0.42-0.60), 0.47 (95%CI: 0.40-0.54), and 0.27 (95%CI: 0.18-0.37), respectively. The comparative cost of the intervention was the only criterion that contributed negatively to the values of lanadelumab and C1-INH. For danazol, four criteria contributed negatively, mainly comparative safety. Conclusion: Lanadelumab was assessed as a high-value intervention, better than C1-INH and substantially better than danazol for LTP treatment of HAE.

Adequate methods are urgently needed to guarantee the good practice of health technology assessment (HTA) for technologies with novel properties. The aim of the study was to construct a conceptual framework to help understand the innovation of HTA methods (IHTAM). The construction of the IHTAM framework was based on two scoping reviews, one on the current practice of innovating methods, that is existing HTA frameworks, and one on theoretical foundations for innovating methods outside the HTA discipline. Both aimed to identify and synthesize concepts of innovation (i.e., innovation processes and roles of stakeholders in innovation). Using these concepts, the framework was developed in iterative brainstorming sessions and subsequent discussions with representatives from various stakeholder groups. The framework was constructed based on twenty documents on innovating HTA frameworks and fourteen guidelines from three scientific disciplines. It includes a generic innovation process consisting of three phases (“Identification,” “Development,” and “Implementation”) and nine subphases. In the framework, three roles that HTA stakeholders can play in innovation (“Developers,” “Practitioners,” and “Beneficiaries”) are defined, and a process on how the stakeholders innovate HTA methods is included. The IHTAM framework visualizes systematically which elements and stakeholders are important to the development and implementation of novel HTA methods. The framework could be used by all stakeholders involved in HTA innovation to learn how to engage dynamically and collaborate effectively throughout the innovation process. HTA stakeholders in practice have welcomed the framework, though additional testing of its applicability and acceptance is essential.

Introduction Drug reimbursement decisions are often made based on a price set by the manufacturer. In some cases, this price leads to public and scientific debates about whether its level can be justified in relation to its costs, including those related to research and development (R&D) and manufacturing. Such considerations could enter the decision process in collectively financed health care systems. This paper investigates whether manufacturers’ costs in relation to drug prices, or profit margins, are explicitly mentioned and considered by health technology assessment (HTA) organisations. Method An analysis of reimbursement reports for cancer drugs was performed. All relevant Dutch HTA-reports, published between 2017 and 2019, were selected and matched with HTA-reports from three other jurisdictions (England, Canada, Australia). Information was extracted. Additionally, reimbursement reports for three cases of expensive non-oncolytic orphan drugs prominent in pricing debates in the Netherlands were investigated in depth to examine consideration of profit margins. Results A total of 66 HTA-reports concerning 15 cancer drugs were included. None of these reports contained information on manufacturer’s costs or profit margins. Some reports contained general considerations of the HTA organisation which related prices to manufacturers’ costs: six contained a statement on the lack of price setting transparency, one mentioned recouping R&D costs as a potential argument to justify a high price. For the case studies, 21 HTA-reports were selected. One contained a cost-based price justification provided by the manufacturer. None of the other reports contained information on manufacturer’s costs or profit margins. Six reports contained a discussion about lack of transparency. Reports from two jurisdictions contained invitations to justify high prices by demonstrating high costs. Conclusion Despite the attention given to manufacturers’ costs in relation to price in public debates and in the literature, this issue does not seem to get explicit systematic consideration in the reimbursement reports of expensive drugs.

Background Health care coverage decisions deal with health care technology provision or reimbursement at a national level. The coverage decision report, i.e., the publicly available document giving reasons for the decision, may contain various elements: quantitative calculations like cost and clinical effectiveness analyses and formalised and non-formalised qualitative considerations. We know little about the process of combining these heterogeneous elements into robust decisions. Methods This study describes a model for combining different elements in coverage decisions. We build on two qualitative cases of coverage appraisals at the Dutch National Health Care Institute, for which we analysed observations at committee meetings (n = 2, with field notes taken) and the corresponding audio files (n = 3), interviews with appraisal committee members (n = 10 in seven interviews) and with Institute employees (n = 5 in three interviews), and relevant documents (n = 4). Results We conceptualise decisions as combinations of elements, specifically (quantitative) findings and (qualitative) arguments and values. Our model contains three steps: 1) identifying elements; 2) designing the combinations of elements, which entails articulating links, broadening the scope of designed combinations, and black-boxing links; and 3) testing these combinations and choosing one as the final decision. Conclusions Based on the proposed model, we suggest actively identifying a wider variety of elements and stepping up in terms of engaging patients and the public, including facilitating appeals. Future research could explore how different actors perceive the robustness of decisions and how this relates to their perceived legitimacy.

Aim : analyze the structure and funding of health technology assessment (HTA) agencies abroad. Materials and methods . Here, we review the organizational structure and funding of HTA agencies in Europe (Austria, Belgium, Germany, Ireland, the Netherlands, the United Kingdom, France, and Sweden), Canada and Australia. The relevant information was found on web-sites of HTA agencies, in the Medline database, and via the searching engines Yandex and Google; the search was conducted using the specific descriptors: «organizational structure of HTA agency», «funding of HTA agency», «pharmaceutical», «reimbursement», «healthcare decision-making», and «funding». Results. The identified HTA-agencies may have a status of either government-funded or nonprofit organization or a structural element of a governmental body. These hTa agencies are funded mainly from the national budget. The funding varies from €550 000 for Ireland to £63.1 mln (€70 million) for the National Institute for Clinical Excellence (NICE) in the UK. The number of employees in the reviewed HTA agencies varies from 6.8 full time employees (FTE) in the Health Information and Quality Authority (HIQA) in Ireland to 604 FTEs in the NICE.

Introduction: The unparalleled surge in digital health adoption during the COVID-19 pandemic has emphasized the potential of mHealth apps. However, the quality of available evidence is generally low, and regulatory frameworks have focused on apps with medical purposes only, overlooking apps with significant interactions with patients that may require stronger oversight. Areas covered: To support this expanded evidence generation process, we identified the reasons that distinguish mHealth apps compared to medical devices at large and that should differentially feature their assessment. mHealth apps are characterized by the iterative nature of the corresponding interventions, frequent user interactions with a non-linear relationship between technology usage, engagement and outcomes, significant organizational implications, as well as challenges associated with genericization, their broad diagnostic potential, and price setting. Expert Opinion: The renewed reliance experienced during the pandemic and the unprecedented injection of resources through recovery instruments can further boost the development of apps. Only robust evidence of the benefits of mHealth apps will persuade health-care professionals and beneficiaries to systematically deploy them. Regulatory bodies will need to question their current approaches by adopting comprehensive evaluation processes that adequately consider the specific features of mHealth apps.

Executive summary: Aim: The aim of this project was to provide insight into the range of options for topic identification, selection and prioritisation (TISP) for health technology assessment (HTA) in low- and middleincome countries (LMICs). Background: HTA is an internationally accepted multidisciplinary approach to analysing and assessing evidence to inform health policy. HTA is recommended by the World Health Organization (WHO) to support universal health coverage (UHC). According to WHO, HTA should ideally be implemented in a formalised decision-support process or system. Deciding what topic(s) to assess represents the first step of this process. In the TISP approach, Topic Identification describes the step where topics potentially suitable for HTA are identified. Selection describes the step where details on the topics are collected and the identified topics are checked for conformity with the aims of the HTA process. Prioritisation describes the step where a decision is made to either initiate, reject or postpone the commencement of an assessment, taking into account the best use of limited resources and context-dependent values. This first step in the HTA process is very important as it has implications for subsequent steps. If TISP fails to work efficiently, this may jeopardise the value of the entire HTA process. In engaging in capacity building for strengthening HTA in LMICs, we (i.e. the Norwegian Institute of Public Health) emphasize approaches to TISP based on experiences from our own country. However, the concept of HTA is relatively new to most LMICs and, with limited institutional mechanisms, adapting complex TISP approaches may be difficult to operationalise. By describing a range of options to choose from, and by providing examples of TISP approaches adopted by countries with a formalised HTA process in Africa, Asia, Latin America and Eastern Europe, our aim in this report is to provide grounds for informed decisions on how best to proceed when planning to implement TISP. Methods: This report uses a systematic scoping review, a country survey and a stakeholder webinar as its methods. The systematic scoping review was guided by established scoping review methodology. A protocol of this review is published on our website. Articles from 2015 onwards were included, and the predefined elements analysed were: the TISP processes, criteria, methods or tools, collaborative networks or initiatives, governance and evaluation. In addition, we conducted a country survey to identify details of TISP approaches in selected African, Asian, Latin-American and Eastern European countries. We anticipated that survey results would supplement (or confirm) findings from the literature. Survey results would also be valuable, considering the paucity of research on LMICs in this field. Finally, we hosted a webinar to present preliminary findings of the scoping search and survey and to gather stakeholder feedback. Take-home messages from the webinar were noted. This report has been subject to internal and external peer review. Results: In presenting the results, we do not structure the narrative in accordance with our methodological chronology (i.e., scoping review, survey, and webinar feedback) but rather use the information from these sources to discuss i) the existing recommendations for TISP implementation guidance, ii) Topic Identification, Selection and Prioritisation, and lastly iii) selected country examples and other aspects of TISP. i)We identified and included five recent (2015 and later) guides on HTA implementation that included information on TISP. Findings suggest that TISP practices could not be translated to a set of common recommendations. In low resourced settings, the TISP process may be pragmatic at the beginning, as suggested by the International Decision Support Initiative, but it should be transparent and explicit. When adopting or adapting approaches and topics from other countries, it is important to take account of experiences from third countries. ii) Our research identified a gradient of TISP options from simpler to more complex processes. In a formalized HTA system, TISP includes a mix of reactive and proactive Topic Identification methods, whereas the more complex approaches (i.e., horizon scanning systems, and disinvestment strategies) are only used in a few HTA systems. Typically, HTA process stakeholders, including policy makers, clinical experts, health care workers, industry, donors and patient/users, are involved in the identification step to propose or nominate topics. Different TISP approaches may be used for different technologies. While experienced European HTA systems rely exclusively on industry submissions or industry solicitations to identify topics, countries new to HTA often rely on commissions from the Ministry of Health, and proposals or nominations made by stakeholders. For LMICs, it has been proposed that it would be beneficial to start with relatively simple, proactive approaches such as stakeholder involvement, adoption of topics from other HTA systems and identifying topics from essential technology lists, before moving to more complex approaches. Selection (also called filtration) is not clearly distinguished from prioritisation. During selection, details regarding the topic may need to be collected, and in some cases explicit yes/no selection criteria can be established. Selection is commonly informed by stakeholders, including clinical experts, industry, and the public or patients/users. Outputs of identification and selection such as lists of topics, short written vignettes or briefs, or even pragmatic assessments, are commonly used to inform HTA Prioritisation. The depth of information will depend on who is involved in prioritisation and how transparent the process is. Information included in the output can be categorised as: technology related; patient and setting related; policy related; evidence related; impact predictions; information on knowledge gaps. If all eligible topics are identified and all selected topics can be assessed (e.g., all new childhood vaccines, or all new medicines to be reimbursed), prioritisation at the level of the HTA process is not needed. In such cases, outputs of identification and selection can directly inform initiation of HTA. However, in most cases, prioritisation is needed, at least to ensure timeliness of the most important topics. Explicit criteria for prioritisation typically reflect: (unmet) needs, potential impact (on patient health, public health, costs, health service, and/or society), and alignment with national priorities. Scoring or ranking to prioritise identified topics is most commonly done by clinical experts, but may also involve other stakeholders, including policy makers, end users of the HTA and patient/user representatives. Ranking may be implicit or explicit. Tools to assist in prioritisation include the use of a Delphi panel, multi criteria decision analysis (MCDA), and on-line ranking tools. Involvement of industry stakeholders and donors in prioritisation is often avoided. Final decisions on prioritisation are commonly performed at governmental level or by a relevant government authority. iii) Our research identified three other aspects related to the TISP process: 1) governance and coordination, 2) evaluation and development, and 3) initiatives and networks for TISP. What is commonly understood as governance for TISP are the aims of the HTA process and funds for its conduct. Governance and coordination of TISP are typically defined politically by the HTA system owner (e.g. regional health authorities) or government-appointed institutions. Recommended evaluation methods include external and internal audits, surveys, interviews and focus groups. Survey respondents reported steps taken to improve the TISP process including: revising criteria and/or weighting, publication of tasks assigned by government authorities on websites, meetings with stakeholders and international partners, and support from external partners through training and capacity building. Collaboration and participation in scientific networks and bilateral capacity-building projects are good for the development of practices in HTA and TISP. We identified one scientific network (International Health TechScan (IHTS)) and one global initiative (The International Horizon Scanning Initiative (IHSI)) that engage specifically in TISP. Influential factors for the choice of TISP approach are contextual and similar to factors influencing other aspects of HTA. These include political support, the aims of the HTA process, experiences with TISP and HTA, national priorities, legislation, human resources and economic resource availability and values. Partnerships for capacity building and scientific networks are valuable, and also influential in choosing TISP approaches. As with the HTA process, the TISP approach can be evaluated and systematically improved to become more efficient and transparent. However, we found no evidence of comparative TISP evaluations. Discussion: This report is based on a systematic scoping review of TISP approaches, a country survey on TISP used in selected African, Asian, Latin America and Eastern European countries with a formalised HTA system, and feedback gathered during a webinar. This report aims to point to the range of TISP options, present examples and look critically at evidence, but makes no claims to be exhaustive. Rather, the results represent our understanding of how different approaches towards prioritising topics for HTA can be categorised by applying TISP. The results are intended to provide additional facts about TISP to supplement existing guidance on HTA implementation. Further work may include more detailed analysis of context-specific needs, comparisons of different approaches and structural limitations. Conclusions: Our findings suggest that: • As with the HTA process, it is important to ensure that TISP is transparent with regard to criteria, procedures and involvement of stakeholders. • The TISP approach should be carefully selected to acknowledge the relationship with the health system context (i.e. politics, needs, resources and values) to which it is applied. • For resourced limited settings, a simple TISP approach may be a starting point, but partnerships with more experienced countries, scientific networks and initiatives should be explored for solidification and comprehensiveness.

ObjectivesThere is no consensus on who might be qualified to conduct ethical analysis in the field of health technology assessment (HTA). Is there a specific expertise or skill set for doing this work? The aim of this article is to (i) clarify the concept of ethics expertise and, based on this, (ii) describe and specify the characteristics of ethics expertise in HTA.MethodsBased on the current literature and experiences in conducting ethical analysis in HTA, a group of members of the Health Technology Assessment International (HTAi) Interest Group on Ethical Issues in HTA critically analyzed the collected information during two face-to-face workshops. On the basis of the analysis, working definitions of “ethics expertise” and “core competencies” of ethics experts in HTA were developed. This paper reports the output of the workshop and subsequent revisions and discussions online among the authors.ResultsExpertise in a domain consists of both explicit and tacit knowledge and is acquired by formal training and social learning. There is a ubiquitous ethical expertise shared by most people in society; nevertheless, some people acquire specialist ethical expertise. To become an ethics expert in the field of HTA, one needs to acquire general knowledge about ethical issues as well as specific knowledge of the ethical domain in HTA. The core competencies of ethics experts in HTA consist of three fundamental elements: knowledge, skills, and attitudes.ConclusionsThe competencies described here can be used by HTA agencies and others involved in HTA to call attention to and strengthen ethical analysis in HTA.

IntroductionIn healthcare policy and economic literature, research on the health technology assessment (HTA) of complex interventions (CIs) is becoming increasingly important. In many developed countries, HTA guides decision-making to help achieve greater value for money when funding health care. However, research has yet to identify the forms of evidence and evaluation criteria that should be used in the HTA of CIs. Previous research has established that the HTA of CIs requires multiple factors to be evaluated but there is no agreement on which factors ought always to be considered. There is equally little agreement on which forms of evidence ought to be collected or synthesised and how. We plan to perform a systematic scoping review in order to identify the range of evaluation criteria and types of evidence currently used in the HTA of CIs.Method and analysisThis protocol was developed to guide the methodological framework for the conduct of a scoping review on health technology assessment (HTA) of complex interventions (CIs), using the Joanna Briggs Institute guidelines and the six-stage framework proposed by Arksey and O’Malley, in addition to more recent innovations in scoping review methodology. A grey literature search will supplement the primary searches of seven electronic databases for studies available in English between January 2000 and August 2020. Two reviewers will independently screen all search results for inclusion and data will be extracted using a customised data extraction or charting form. Any dispute will be resolved by consensus or through arbitration by a third author. The mnemonic Population, Concept and Context will be adopted to establish criteria for selecting relevant literature, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: Extension for Scoping Review will be used for reporting the results. Several explanatory-descriptive methods will be used for analysing the extracted data including frequency and trend analyses as well as reflexive thematic coding and analysis.Mapping evidence on the HTA of CIs will allow us to gain a better understanding of both established and emerging practices, including the information types, requirements, values and parameters that are incorporated in the HTA of CIs. We also expect the findings of the scoping review to help identify research gaps that will guide future studies. As healthcare becomes more complex in its delivery, it is timely to determine how these complex interventions should be assessed so that policy decisions can be made about whether implementation and public funding is warranted.Ethics and DisseminationThis scoping review will involve secondary analysis of already collected data, and thus, does not require ethics approval. The research findings will be submitted to peer-reviewed journals for publication and will also be disseminated at conferences and seminars.

Background Advanced therapy medicinal products (ATMPs) represent an important cornerstone for innovation in healthcare. However, uncertainty on the value, the high average cost per patient and their one-shot nature has raised a debate on their assessment and appraisal process for pricing and reimbursement (P&R) purposes. This debate led experts providing for recommendations on this topic. Our primary objective is to investigate the ATMPs P&R process in the main five European countries and to understand if this process is consistent with published P&R expert recommendations. We also investigated the current ATMP pipelines to understand if future ATMPs will create challenges for their P&R process. Methods P&R framework for ATMPs in the European Major five (EU5) countries was investigated through a literature search on PubMed, institutional websites of National Health Authorities and grey literature. The ATMPs pipeline database was populated from a clinical trial database (clinicaltrials.gov), relying on inclusion and exclusion criteria retrieved from the literature. Results Reimbursement status of ATMPs is different across the EU5 countries, with the exception of CAR-Ts which are reimbursed in all countries. Standard P&R process in place for other medicinal products is extended to ATMPs, with the exception of some cases in Germany. List prices, where available, are high and, tend to be aligned across countries. Outcome-based Managed Entry Agreements (MEAs) have been extensively used for ATMPs. Extra-funds for hospitals managing ATMPs were provided only in Germany and, as additional fund per episode, in France. The accreditation process of hospitals for ATMPs management was in most countries managed by the national authorities. As far as ATMPs pipeline is concerned, ATMPs in development are mostly targeting non-rare diseases. Conclusions Expert recommendations for ATMPs P&R were partially applied: the role of outcome-based MEAs has increased and the selection process of the centres authorized to use these treatments has been enhanced; additional funding for ATMPs management to accredited centres has not been completely considered and annuity payment and broader perspective in cost considerations are far from being put in place. These recommendations should be considered for future P&R negotiations to pursue rational resource allocation and deal with budget constraints.

There has been continuous development in the field of health technology assessment (HTA) owing to the added value of HTA in supporting healthcare reimbursement decisions. Collaboration and engagement among countries in Asia has been carried out to share experiences and learning on the barriers and factors facilitating the implementation and use of HTA in policy making. A symposium on the topic of Health Technology Assessment (HTA): Selecting the Highest Value Care was held on January 10, 2019 at the National University of Singapore, during which 3 major challenges confronting HTA development in Asia were identified. The symposium also offered possible ways to overcome the challenges., Highlights • Countries in Asia increasingly recognize and adopt health technology assessment (HTA) in setting priorities for healthcare. Nevertheless, 2 common challenges can be identified, namely, lack of infrastructure and technical capacity to cope with the increasing demand for HTA, and the inadequate involvement of stakeholders in the HTA process. • Solutions identified at the HTA symposium in Singapore to overcome these challenges were that countries should implement a tailored and transparent mechanism for using HTA, promote existing HTA capacity, and strengthen the understanding of HTA among the stakeholders. • Health technology assessment symposia such as the one organized in Singapore provide a platform for countries to share knowledge and challenges, and bring different views to build into something greater and overcome the challenges. Such symposia should be organized regularly.

All health economics reviews on chronic and episodic migraine published to date underline the heterogeneity of results. Currently, the need for the generalizability of economic evaluations across different jurisdictions is considered a key issue to avoid unnecessary overlaps and to minimize the time to reimbursement decisions. The aim of this study was to review the economic evaluations on the prophylaxis and treatments for migraine published in the previous 10 years (since 2009) and to perform a critical assessment of their generalizability. We searched PubMed, EMBASE, and EconLit databases. Articles underwent a three-stage selection process. To assess the level of generalizability, we used the checklist implemented by Augustovski et al. Studies were classified as: (1) generalizable; (2) transferable; and (3) context specific. In total, 227 articles were identified after running the search string and 11 studies were included in our review. Overall, none of the studies was judged as generalizable and three were judged transferable according to the established criteria. Our review suggests that no evidence on the economic value of either acute or prophylactic treatments against migraine is generalizable to different jurisdictions. However, the majority of studies reporting results about prophylactic treatments were found to be transferable.

Background Depending on the health system context and the demands of relevant stakeholders in countries, the need, organizational structure, and prerequisites for enabling capacity building and development in health technology assessment (HTA) will vary. Core competencies are instrumental in this and include essential knowledge, skills, and attitudes (KSAs). They provide building blocks for delivering high-quality and effective practices of HTA. We aimed to systematically explore and develop an overview of the core competencies necessary for HTA. Methods This study was conducted during 2016–19 using different methods in a structured manner. We drew concepts of KSAs from various literature sources, surveyed universities and HTA professionals, and conducted expert workshops to arrive at a common understanding of the required competencies. Results The terminology for KSAs defining competencies in HTA programs has been clarified. In addition, a list of competencies offered through different educational and training programs has been created. The surveys provided clarity on a common understanding of KSAs among HTA stakeholders. Thereafter, a set of competencies was described and classified according to the HTA domains. Conclusions Our study shows that there is diversity in HTA programs offered by educational institutions. The content of the programs varies due to differences between countries regarding the level of HTA development and the need for HTA, including the understanding of what HTA is. The preparation of a competency checklist or a “menu” of options mirroring the diversity of HTA will ensure that the specific needs of the HTA community will be covered.

Objectives: Coverage with evidence development (CED) schemes are particularly relevant for medical devices (MDs), since clinical evidence is often limited at the time of launch and their long-term (cost- ) effectiveness heavily depends on how they are adopted into routine clinical practice. The objective of this study was to identify and describe the challenges that payers and manufacturers might face when assessing the desirability of, choosing the research design for, implementing, and evaluating CED schemes for MDs. Methods: A systematic literature review was performed on six databases following PRISMA guidelines. Two independent reviewers assessed the eligibility of studies based on predefined criteria and extracted data from the included articles by using a pre-defined extraction template. The data were synthesised in a narrative review. Results: The systematic search yielded 4293 articles of which 27 were eligible for inclusion. We identified 20 challenges that are associated with CED schemes for MDs. Five of these challenges relate directly to the characteristics of MDs, and hence are specific to MDs. These challenges concern deciding on whether a CED scheme is required, understanding the relevant uncertainties and risks, identifying meaningful out- comes, defining an adequate duration for a scheme, and market entry of new technologies. Conclusions: Payers and manufacturers of MDs have to address the identified challenges to improve a CED scheme’s chance of success. This can be further improved by public sharing of information about the outcome of applied schemes and way in which stakeholders have addressed the challenges they faced when applying a CED scheme.

In the article, we analyze the current version of Government Regulation No. 871 where the principles of health technologies assessment (HTA) and the reimbursement strategies in Russia have been put forward. We conclude that the HTA methodology in Russia is consistent with the multi-criteria decision analysis. Recommendations on the improvement of the assessment methodology in Regulation No. 871 are provided.

Objectives:The emergence of new medical technologies and budget restrictions has led to a substantial increase in the use of hospital-based health technology assessment (HB-HTA). This qualitative study explores whether there is a possibility and interest to realize the collection and dissemination of HB-HTA reports on an international scale by exploring the opinions from HB-HTA experts.Methods:A survey was designed and sent to an international group of experts knowledgeable in HB-HTA from eighteen different countries. The survey contained questions about their opinions on the collection and distribution of HB-HTA information, and about the meaningful dimensions, barriers and values about a database. The data obtained were analyzed through the method of content analysis.Results:A total of thirty-six experts (response rate of 18.3 percent) responded to the survey. The obtained data shows that all respondents agree that the collection of HB-HTA reports is useful. Moreover, 41.7 percent of respondents that are in the position of sharing HB-HTA reports (n = 24) mentioned that full HB-HTA reports can be shared. Many other respondents reported that confidentiality (45.7 percent) and investment into a database (40.0 percent) are important barriers for the dissemination of HB-HTA reports.Conclusions:There seem to be enough demand and willingness to share all or most reports by a large community of HB-HTA producers. Therefore, there is a need for a well-designed database with regular maintenance and complete, comparable, and qualitative HB-HTA reports. The database of the AdHopHTA project could potentially facilitate this process.

Objectives Universal healthcare coverage in low- and middle-income countries requires challenging resource allocation decisions. Health technology assessment is one important tool to support such decision making. The International Decision Support Initiative worked with the Ghanaian Ministry of Health to strengthen health technology assessment capacity building, identifying hypertension as a priority topic area for a relevant case study. Methods Based on guidance from a national technical working group of researchers and policy makers, an economic evaluation and budget impact analysis were undertaken for the main antihypertensive medicines used for uncomplicated, essential hypertension. The analysis aimed to address specific policy questions relevant to the National Health Insurance Scheme. Results The evaluation found that first-line management of essential hypertension with diuretics has an incremental cost per disability-adjusted life-year avoided of GH¢ 276 ($179 in 2017, 4% of gross national income per capita) compared with no treatment. Calcium channel blockers were more effective than diuretics but at a higher incremental cost: GH¢ 11 061 per disability-adjusted life-year avoided ($7189 in 2017; 160% of gross national income per capita). Diuretics provide better health outcomes at a lower cost than angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta-blockers. Budget impact analysis highlighted the potential for cost saving through enhanced price negotiation and increased use of better-value drugs. We also illustrate how savings could be reinvested to improve population health. Conclusions Economic evaluation enabled decision makers to assess hypertension medicines in a Ghanaian context and estimate the impact of using such evidence to change policy. This study contributes to addressing challenges associated with the drive for universal healthcare coverage in the context of constrained budgets., Highlights • This article provides details of a technical modeling work collaboratively built in Ghana with a high-level policy orientation. • Recent developments in Ghana further highlight the constraints imposed on current resources available for health. • This is the first national health technology assessment study to be commissioned and conducted under Ghanaian government supervision. There are no other studies that offer the same level of contextualized information to support the National Health Insurance Authority and the Ghanaian Ministry of Health in their policy-making efforts toward improving value for money in hypertension management. • A range of cost-saving and health-improving policy scenarios were identified that could have a major impact on reducing the burden of hypertension and contribute to the financial sustainability of the National Health Insurance Scheme.

Economic models are used in health technology assessments (HTAs) to evaluate the cost-effectiveness of competing medical technologies and inform the efficient use of healthcare resources. Historically, these models have been developed with specialized commercial software (such as TreeAge) or more commonly with spreadsheet software (almost always Microsoft Excel). Although these tools may be sufficient for relatively simple analyses, they put unnecessary constraints on the analysis that may ultimately limit its credibility and relevance. In contrast, modern programming languages such as R, Python, Matlab, and Julia facilitate the development of models that are (i) clinically realistic, (ii) capable of quantifying decision uncertainty, (iii) transparent and reproducible, and (iv) reusable and adaptable. An HTA environment that encourages use of modern software can therefore help ensure that coverage and pricing decisions confer greatest possible benefit and capture all scientific uncertainty, thus enabling correct prioritization of future research.

This article provides a practical overview of cost-effectiveness analyses and their application in respiratory medicine. It serves as a guide to explain non-health economists the key concepts and methods of cost-effectiveness analyses. The case for health economics is made, some key methodological issues are explained, using non-expert terminology and easy to understand examples from the fields of asthma, COPD, tuberculosis, lung cancer and other respiratory diseases. The current state-of-the-art as well as a future perspective is provided.

Objectives The aim of this study was to review legislative provisions for the reimbursement of biosimilars, assess the impact of the implemented regulations on access to biosimilars, and to calculate the lost opportunity for savings due to the limited availability of biosimilars in Slovakia. Methods The Slovak legislation concerning the reimbursement of biosimilars was reviewed. The reimbursement dossiers of medicines, health technology assessments and appraisals, justification of the reimbursement decisions, final reimbursement decisions and all aspects of the appeal mechanisms are transparently published on the website of the Slovak Ministry of Health ( http://kategorizacia.mzsr.sk/Lieky ), and these were used for this analysis. Results Only 14 reimbursement dossiers were submitted for biosimilars between 2006 and September 2018 in Slovakia. In 2016 and 2017, no reimbursement dossiers were submitted. The results, based on data provided by wholesalers who are legally obliged to deliver information to the State Institute for Drug Control, showed that the Slovak health budget could save €28.26-€39.56 million per year if biosimilars with marketing authorisations were available in the Slovak market, and a 25–35% decrease in price compared with that of biological medicinal products. Conclusions Our findings show that proactive strategies and policies should be implemented to increase availability and penetration of biosimilars on the Slovak pharmaceutical market to reduce societal losses that are caused by the lack of biosimilar medicines availability.

Background The relevance of studies focusing on patient satisfaction becomes imperative for patients with cancer, who often face major changes in their lifestyles. Their perceived uncertainty in illness and their personal experiences with the services received are crucial factors for a qualitatively adequate assistance. Objectives To assess the determinants of patient satisfaction, using a sample of 306 Bulgarian oncology outpatients. Methods The hypotheses tested concern the extent to which patient satisfaction depends on the uncertainty in illness; the patients' assessment of technical and interpersonal skills of nurses and medical staff; the information provision; and some organizational aspects. Patients were asked to answer a questionnaire composed of internationally validated scales assessing the determinants of patient satisfaction (measured through the European Organization for Research and Treatment of Cancer), uncertainty in illness (assessed through the Mishel Uncertainty in Illness Scale), and patients' health status (assessed through the EuroQol 5-dimensional questionnaire and the visual analogue scale). An ordered logit model was run, using the level of overall patient satisfaction as a dependent variable. Results This is one of the first studies carried out in Bulgaria for oncology patient satisfaction of subjective factors related to the frailty of the oncology patient status such as age, self-assessed health-related quality of life, and uncertainty in illness. Nevertheless, other determinants, reflecting the quality of the care provided, also have an impact on patient satisfaction, namely, the assessment of the nonmedical personnel, the perception of medical technical skills, and the access to a medical center. Conclusions Results stress the relevance of reducing uncertainty in illness in patients with cancer by implementing a satisfactory patient-physician relationship in the management of the disease.

Background Previous evaluations of oncological medicines in the German early benefit assessment (EBA) procedure have demonstrated inconsistent acceptance of endpoints by regulatory authorities and the Federal Joint Committee (G-BA). Accepted standard endpoints for regulatory purposes are frequently not considered as patient-relevant in the German EBA system. In this study the acceptance of clinically acknowledged primary endpoints (PEPs) from regulatory trials in EBAs conducted by the G-BA was evaluated across three therapeutic areas. Methods Medicines for oncological, metabolic and infectious diseases with EBAs finalised before 25 January 2016 were evaluated. Respective manufacturer’s dossiers, regulatory assessments, G-BA appraisals and oral hearing minutes were reviewed, and PEPs were examined to determine whether they were considered relevant to patients by the G-BA. Furthermore, the acceptance of symptomatic vs asymptomatic PEPs was also analysed. Results A total of 65 EBAs were evaluated. Mortality PEPs were widely accepted as patient-relevant but were only used in a minority of EBAs and exclusively in oncological diseases. Morbidity PEPs constituted around 72 % of assessed PEPs, but were excluded from the EBA in over half of the corresponding assessments as they were not considered patient-relevant. Symptomatic endpoints were largely deemed patient-relevant, whereas acceptance of asymptomatic endpoints varied between therapeutic areas. Conclusions This evaluation identified inconsistencies in patient relevance of morbidity-related PEPs as well as in acceptance of asymptomatic endpoints by the G-BA in all three disease areas examined. Better harmonisation between the regulatory authorities and the G-BA is still required after 5 years of AMNOG health technology assessment in Germany. Electronic supplementary material The online version of this article (doi:10.1186/s12913-016-1902-8) contains supplementary material, which is available to authorized users.

Regulatory decisions are often based on multiple clinical end points, but the perspectives used to judge the relative importance of those end points are predominantly those of expert decision makers rather than of the patient. However, there is a growing awareness that active patient and public participation can improve decision making, increase acceptance of decisions, and improve adherence to treatments. The assessment of risk versus benefit requires not only information on clinical outcomes but also value judgments about which outcomes are important and whether the potential benefits outweigh the harms. There are a number of mechanisms for capturing the input of patients, and regulatory bodies within the European Union are participating in several initiatives. These can include patients directly participating in the regulatory decision-making process or using information derived from patients in empirical studies as part of the evidence considered. One promising method that is being explored is the elicitation of "patient preferences." Preferences, in this context, refer to the individual's evaluation of health outcomes and can be understood as statements regarding the relative desirability of a range of treatment options, treatment characteristics, and health states. Several methods for preference measurement have been proposed, and pilot studies have been undertaken to use patient preference information in regulatory decision making. This article describes how preferences are currently being considered in the benefit-risk assessment context, and shows how different methods of preference elicitation are used to support decision making within the European context.

La stenosi aortica degenerativa calcifica e la valvulopatia piu frequente nella popolazione occidentale, con circa 5 milioni di pazienti nei soli paesi europei. Per un terzo circa di questi, giudicati inoperabili, e disponibile dal 2007 una nuova tecnica di trattamento, l’impianto di valvola aortica transcatetere (TAVI). L’obiettivo del presente lavoro e stato di realizzare una mappatura delle politiche e degli strumenti di governo regionali che hanno guidato l’introduzione della TAVI in Italia, finalizzata a fornire raccomandazioni ai decisori pubblici. I dati sono stati acquisiti attraverso la revisione della letteratura internazionale e delle delibere regionali ed il confronto con attori istituzionali. L’analisi ha messo in luce la crescente diffusione della TAVI nelle regioni italiane e al tempo stesso la grande eterogeneita interregionale dei percorsi intrapresi per il governo della sua introduzione, diffusione e rimborsabilita in Italia.

Background Health technology assessment (HTA) is currently one of the major challenges in assessing medical innovations and healthcare systems. In Europe, the European Network for Health Technology Assessment (EUnetHTA) has been aspiring to develop and implement standards for international sharing of HTA results and studies. Slovakia and many other EU countries do not have an established HTA system yet. This paper is focused on an exact description of the EUnetHTA Core Model individual domains applied to the process of selecting patients in the terminal stage of prostate cancer for Radium-223 treatment under particular conditions of the Institute of Nuclear and Molecular Medicine (INMM) in Košice, Slovakia. Results We produced the first pilot HTA report using the HTA Core Model in Slovakia. The main objective was to collect all relevant information on the particular technology, and provide its summary to the interested stakeholders on one spot. Rather than applying detailed individual items, i.e. assessment elements and assessment element cards, we concentrated on the content of individual domains and tried to fill them with the best country, facility and intervention related data. The dataset consisted of 52 patients that finished the treatment in the period 2015–2017. The patients were carefully selected according to the Radium-223 producer’s criteria. Only 33 patients received the full therapy consisting of six applications; their average survival was 10.5 months from the application of the last dose. Conclusions Based on the results of our analyzes, we recommended several changes to the INMM processes and patient follow-up checks during the treatment process in order to make the therapy more effective. The greatest benefit is expected after the implementation of a 68Ge/68Ga generator in 2018, as the selection of patients suitable for the Radium-223 treatment will improve. We showed that the HTA Core Model can be implemented in Slovakia, even under conditions of no formal HTA support or institutionalization.