CT or Invasive Coronary Angiography in Stable Chest Pain.

BACKGROUND: In the diagnosis of obstructive coronary artery disease (CAD), computed tomography (CT) is an accurate, noninvasive alternative to invasive coronary angiography (ICA). However, the comparative effectiveness of CT and ICA in the management of CAD to reduce the frequency of major adverse cardiovascular events is uncertain. METHODS: We conducted a pragmatic, randomized trial comparing CT with ICA as initial diagnostic imaging strategies for guiding the treatment of patients with stable chest pain who had an intermediate pretest probability of obstructive CAD and were referred for ICA at one of 26 European centers. The primary outcome was major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) over 3.5 years. Key secondary outcomes were procedure-related complications and angina pectoris. RESULTS: Among 3561 patients (56.2% of whom were women), follow-up was complete for 3523 (98.9%). Major adverse cardiovascular events occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 (3.0%) in the ICA group (hazard ratio, 0.70; 95% confidence interval [CI], 0.46 to 1.07; P = 0.10). Major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13 to 0.55). Angina during the final 4 weeks of follow-up was reported in 8.8% of the patients in the CT group and in 7.5% of those in the ICA group (odds ratio, 1.17; 95% CI, 0.92 to 1.48). CONCLUSIONS: Among patients referred for ICA because of stable chest pain and intermediate pretest probability of CAD, the risk of major adverse cardiovascular events was similar in the CT group and the ICA group. The frequency of major procedure-related complications was lower with an initial CT strategy. (Funded by the European Union Seventh Framework Program and others; DISCHARGE ClinicalTrials.gov number, NCT02400229.).

Uncertainty management in regulatory and health technology assessment decision-making on drugs: guidance of the HTAi-DIA Working Group.

OBJECTIVES: Uncertainty is a fundamental component of decision making regarding access to and pricing and reimbursement of drugs. The context-specific interpretation and mitigation of uncertainty remain major challenges for decision makers. Following the 2021 HTAi Global Policy Forum, a cross-sectoral, interdisciplinary HTAi-DIA Working Group (WG) was initiated to develop guidance to support stakeholder deliberation on the systematic identification and mitigation of uncertainties in the regulatory-HTA interface. METHODS: Six online discussions among WG members (Dec 2021-Sep 2022) who examined the output of a scoping review, two literature-based case studies and a survey; application of the initial guidance to a real-world case study; and two international conference panel discussions. RESULTS: The WG identified key concepts, clustered into twelve building blocks that were collectively perceived to define uncertainty: "unavailable," "inaccurate," "conflicting," "not understandable," "random variation," "information," "prediction," "impact," "risk," "relevance," "context," and "judgment." These were converted into a checklist to explain and define whether any issue constitutes a decision-relevant uncertainty. A taxonomy of domains in which uncertainty may exist within the regulatory-HTA interface was developed to facilitate categorization. The real-world case study was used to demonstrate how the guidance may facilitate deliberation between stakeholders and where additional guidance development may be needed. CONCLUSIONS: The systematic approach taken for the identification of uncertainties in this guidance has the potential to facilitate understanding of uncertainty and its management across different stakeholders involved in drug development and evaluation. This can improve consistency and transparency throughout decision processes. To further support uncertainty management, linkage to suitable mitigation strategies is necessary.

Learning and practicing more value-reflective, problem-setting health technology assessment: experiences and lessons from the VALIDATE project.

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.

Integrating Empirical Analysis and Normative Inquiry in Health Technology Assessment: The Values in Doing Assessments of Health Technologies Approach.

Health technology assessment (HTA) aims, through empirical analysis, to shed light on the value of health technologies (O'Rourke et al. [2020, International Journal of Technology Assessment in Health Care 36, 187-90]). HTA is, then, where facts and values meet. But how, where, and when do facts and values meet in HTA? Currently, HTA is usually portrayed as a sequential process, starting with empirical analysis (assessment), followed by a deliberation on the implications of the findings for a judgment of a health technology's value (appraisal). In this paper, we will argue that in HTA, empirical analysis and normative inquiry are much more closely entwined. In fact, as we hope to show, normative commitments act as an indispensable guide for the collection and interpretation of empirical evidence. Drawing on policy sciences, we will suggest a concrete methodology that can help HTA practitioners to integrate empirical analysis and normative inquiry in a transparent way. The proposed methodology can be conceived as a concrete means for conducting a scoping exercise in HTA. Moreover, it offers a distinct way of giving stakeholders a structural and constructive role in HTA. This paper outlines the approach developed by the values in doing assessments of health technologies project, a project funded by the Erasmus+ program (contract number 2018-1-NL01-KA203-038960), which is the European Union's program to support education, training, youth, and sport in Europe. The project has resulted in an E-learning course, an accompanying handbook, and a consensus statement, all freely available from the project's website www.validatehta.eu.

Postlaunch evidence-generation studies for medical devices in Spain: the RedETS approach to integrate real-world evidence into decision making.

The Monitoring Studies (MS) program, the approach developed by RedETS to generate postlaunch real-world evidence (RWE), is intended to complement and enhance the conventional health technology assessment process to support health policy decision making in Spain, besides informing other interested stakeholders, including clinicians and patients. The MS program is focused on specific uncertainties about the real effect, safety, costs, and routine use of new and insufficiently assessed relevant medical devices carefully selected to ensure the value of the additional research needed, by means of structured, controlled, participative, and transparent procedures. However, despite a clear political commitment and economic support from national and regional health authorities, several difficulties were identified along the development and implementation of the first wave of MS, delaying its execution and final reporting. Resolution of these difficulties at the regional and national levels and a greater collaborative impulse in the European Union, given the availability of an appropriate methodological framework already provided by EUnetHTA, might provide a faster and more efficient comparative RWE of improved quality and reliability at the national and international levels.

Toward a common understanding of competencies for health technology assessment: enhancing educational and training programs around the globe.

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.

An evidence-based framework for identifying technologies of no or low-added value (NLVT).

OBJECTIVE: To synthetize the state of the art of methods for identifying candidate technologies for disinvestment and propose an evidence-based framework for executing this task. METHODS: An interpretative review was conducted. A systematic literature search was performed to identify secondary or tertiary research related to disinvestment initiatives and/or any type of research that specifically described one or more methods for identifying potential candidates technologies, services, or practices for disinvestment. An iterative and critical analysis of the methods described alongside the disinvestment initiatives was performed. RESULTS: Seventeen systematic reviews on disinvestment or related terms (health technology reassessment or medical reversal) were retrieved and methods of 45 disinvestment initiatives were compared. On the basis of this evidence, we proposed a new framework for identifying these technologies based on the wide definition of evidence provided by Lomas et al. The framework comprises seven basic approaches, eleven triggers and thirteen methods for applying these triggers, which were grouped in embedded and ad hoc methods. CONCLUSIONS: Although identification methods have been described in the literature and tested in different contexts, the proliferation of terms and concepts used to describe this process creates considerable confusion. The proposed framework is a rigorous and flexible tool that could guide the implementation of strategies for identifying potential candidates for disinvestment.

Disinvestment Activities and Candidates in the Health Technology Assessment Community: An Online Survey.

OBJECTIVES: As healthcare decision makers continue to face challenges in health services delivery to their patients, disinvestment programs are being established for a sustainable healthcare system. This study aimed to collect data and information by means of a survey of disinvestment candidates and ongoing disinvestment projects in the health technology assessment (HTA) community. METHODS: An online survey was conducted to collect information on disinvestment candidates and activities from members of the Health Technology Assessment International Disinvestment & Early Awareness Interest Group, the EuroScan International Network and International Network of Agencies for Health Technology Assessment. RESULTS: Among the 362 invitees, twenty-four unique responses were received, and almost 70 percent were involved in disinvestment initiatives. The disinvestment candidates identified represented a range of health technologies. Evidence or signaling of clinical ineffectiveness or inappropriate use typically led to the nomination of disinvestment candidates. Health technology assessments and reassessments were usually conducted to evaluate the technology in question, and decisions usually led to the limited use of the technology. Barriers to disinvestment decisions included the strength of interest and advocacy groups, insufficient data for assessments, a systematic decision process and political challenges, while obstacles to their implementation were clinicians' reluctance and insufficient funding and incentives. CONCLUSIONS: The survey results suggested that disinvestment activities are occurring in the HTA community, especially in the public sector. Future research can further investigate the processes and methods used to reach and implement disinvestment decisions from our survey respondents and explore to form closer ties between the HTA and clinical communities.

Factors related to the participation and detection of lesions in colorectal cancer screening programme-based faecal immunochemical test.

Background: The overall aim of this study was to describe trends in participation rates and detection of lesions in a colorectal cancer (CRC) screening programme, during three rounds, using faecal immunochemical test (FIT). Methods: National registers were used to collect data on invitations for CRC screening in the Basque Country (Spain) from 2009 to 2014. Information about participation, age, gender and lesions in each round were collected. Results: A total of 961.533 individuals were included in the analysis; respectively, 584.950, 298.143 and 78.440 in the first, second and third rounds. The average participation rate was 68.4% (66.8, 70.4 and 72.3%, respectively by round; P < 0.001) and the positivity rate was 6.3% (7, 5.5 and 5.4%, respectively by round; P < 0.001). The participation rate increased significantly with age and was found to be higher in women versus men. A total of 15.144 advanced adenomas and 2.131 CRCs were diagnosed, leading to a detection rate of 23.9 and 3.4‰, respectively. Regarding gender, men had the highest rates in all periods and rounds. The detection rate of advanced neoplasia was lower in the regular when compared with irregular paricipants. Conclusions: In a CRC screening, this organization obtained high FIT participation rates. Older participants and women were associated with a higher participation. The detection rate of lesions was higher in men, independent on age and round.

ENVIRONMENTAL IMPACT ASSESSMENT OF A HEALTH TECHNOLOGY: A SCOPING REVIEW.

INTRODUCTION: The Health Technology Expert Review Panel is an advisory body to Canadian Agency for Drugs and Technologies in Health (CADTH) that develops recommendations on health technology assessments (HTAs) for nondrug health technologies using a deliberative framework. The framework spans several domains, including the environmental impact of the health technology(ies). Our research objective was to identify articles on frameworks, methods or case studies on the environmental impact assessment of health technologies. METHODS: A literature search in major databases and a focused gray literature search were conducted. The main search concepts were HTA and environmental impact/sustainability. Eligible articles were those that described a conceptual framework or methods used to conduct an environmental assessment of health technologies, and case studies on the application of an environmental assessment. RESULTS: From the 1,710 citations identified, thirteen publications were included. Two articles presented a framework to incorporate environmental assessment in HTAs. Other approaches described weight of evidence practices and comprehensive and integrated environmental impact assessments. Central themes derived include transparency and repeatability, integration of components in a framework or of evidence into a single outcome, data availability to ensure the accuracy of findings, and familiarity with the approach used. CONCLUSIONS: Each framework and methods presented have different foci related to the ecosystem, health economics, or engineering practices. Their descriptions suggested transparency, repeatability, and the integration of components or of evidence into a single outcome as their main strengths. Our review is an initial step of a larger initiative by CADTH to develop the methods and processes to address the environmental impact question in an HTA.

Population-based colorectal cancer screening programmes using a faecal immunochemical test: should faecal haemoglobin cut-offs differ by age and sex?

BACKGROUND: The Basque Colorectal Cancer Screening Programme has both high participation rate and high compliance rate of colonoscopy after a positive faecal occult blood test (FIT). Although, colorectal cancer (CRC) screening with biannual (FIT) has shown to reduce CRC mortality, the ultimate effectiveness of the screening programmes depends on the accuracy of FIT and post-FIT colonoscopy, and thus, harms related to false results might not be underestimated. Current CRC screening programmes use a single faecal haemoglobin concentration (f-Hb) cut-off for colonoscopy referral for both sexes and all ages. We aimed to determine optimum f-Hb cut-offs by sex and age without compromising neoplasia detection and interval cancer proportion. METHODS: Prospective cohort study using a single-sample faecal immunochemical test (FIT) on 444,582 invited average-risk subjects aged 50-69 years. A result was considered positive at ≥20 µg Hb/g faeces. Outcome measures were analysed by sex and age for a wide range of f-Hb cut-offs. RESULTS: We analysed 17,387 positive participants in the programme who underwent colonoscopy. Participation rate was 66.5%. Men had a positivity rate for f-Hb of 8.3% and women 4.8% (p < 0.0001). The detection rate for advanced neoplasia (cancer plus advanced adenoma) was 44.0‰ for men and 15.9‰ for women (p < 0.0001). The number of colonoscopies required decreased in both sexes and all age groups through increasing the f-Hb cut-off. However, the loss in CRC detection increased by up to 28.1% in men and 22.9% in women. CRC missed were generally at early stages (Stage I-II: from 70.2% in men to 66.3% in women). CONCLUSIONS: This study provides detailed outcomes in men and women of different ages at a range of f-Hb cut-offs. We found differences in positivity rates, neoplasia detection rate, number needed to screen, and interval cancers in men and women and in younger and older groups. However, there are factors other than sex and age to consider when consideration is given to setting the f-Hb cut-off.

STATUS OF DISINVESTMENT INITIATIVES IN LATIN AMERICA: RESULTS FROM A SYSTEMATIC LITERATURE REVIEW AND A QUESTIONNAIRE.

OBJECTIVES: Disinvestment of existing healthcare technologies that deliver low or no health benefit for their cost can be used as a tool to improve access to effective technologies, while ensuring the long-term sustainability of healthcare systems. The objective of this research was to identify disinvestment initiatives in Latin American countries (LAC). METHODS: First, a systematic literature review (SLR) was conducted. In February 2015, MEDLINE, MEDLINE In-Process, EMBASE, The Cochrane Library, and LILACS were searched for relevant journal articles, including terms related to "disinvestment," "reallocation," "obsolete technologies," and "Latin America." Additionally, a manual search of documents from Latin American health technology assessment agencies was performed. Second, an online questionnaire was sent to experts in LAC to assess whether unpublished real-life disinvestment initiatives exist. Questionnaire results were collected in September 2015. RESULTS: From the SLR, 350 records were selected for screening following de-duplication and eleven articles fulfilled inclusion criteria. Only two of these reported information on initiatives potentially identifiable as disinvestment-investment activities in Brazil and Peru. Nine respondents completed the questionnaire, and four reported that disinvestment initiatives had been conducted in their respective organizations in Argentina, Brazil, and Mexico. This lack of agreement between the SLR and the questionnaire responses shows that disinvestment initiatives are ongoing, despite being under reported. CONCLUSIONS: Many challenges need to be overcome for a disinvestment initiative to be successful, and sharing particular experiences with the international community would increase the chances of positive outcomes. The present study highlights the need for publication of such experiences in LAC.

HEALTH TECHNOLOGY PERFORMANCE ASSESSMENT: REAL-WORLD EVIDENCE FOR PUBLIC HEALTHCARE SUSTAINABILITY.

OBJECTIVES: Health technology financing is often based on randomized controlled trials (RCTs), which are often the same ones used for licensing. Because they are designed to show the best possible results, typically Phase III studies are conducted under ideal and highly controlled conditions. Consequently, it is not surprising that technologies do not always perform in real life in the same way as controlled conditions. Because financing (and price paid) decisions can be made with overestimated results, health authorities need to ask whether health systems achieve the results they expect when they choose to pay for a technology. The optimal way to answer this question is to assess the performance of financed technologies in real-world settings. Health technology performance assessment (HTpA) refers to the systematic evaluation of the properties, effects, and/or impact of a health intervention or health technology in the real world to provide information for investment/disinvestment decisions and clinical guideline updates. The objective is to describe the development and principal aspects of the Guideline for HTpA commissioned by the Brazilian Ministry of Health. METHODS: Our methods used include extensive literature review, refinement with experts across countries, and public consultation. RESULTS: A comprehensive guideline was developed, which has been adopted by the Brazilian government. CONCLUSION: We believe the guideline, with its particular focus on disinvestment, along with the creation of a specific program for HTpA, will allow the institutionalization and continuous improvement of the scientific methods to use real-world evidence to optimize available resources not only in Brazil but across countries.

QUALITY ASSESSMENT OF ETHICS ANALYSES FOR HEALTH TECHNOLOGY ASSSESSMENT.

OBJECTIVES: Although consideration of ethical issues is recognized as a crucial part of health technology assessment, ethics analysis for HTA is generally perceived as methodologically underdeveloped in comparison to other HTA domains. The aim of our study is (i) to verify existing tools for quality assessment of ethics analyses for HTA, (ii) to consider some arguments for and against the need for quality assessment tools for ethics analyses for HTA, and (iii) to propose a preliminary set of criteria that could be used for assessing the quality of ethics analyses for HTA. METHODS: We systematically reviewed the literature, reviewed HTA organizations' Web sites, and solicited views from thirty-two experts in the field of ethics for HTA. RESULTS: The database and HTA agency Web site searches yielded 420 references (413 from databases, seven from HTA Web sites). No formal instruments for assessing the quality of ethics analyses for HTA purposes were identified. Thirty-two experts in the field of ethics for HTA from ten countries, who were brought together at two workshops held in Edmonton (Canada) and Cologne (Germany) confirmed the findings from the literature. CONCLUSIONS: Generating a quality assessment tool for ethics analyses in HTA would confer considerable benefits, including methodological alignment with other areas of HTA, increase in transparency and transferability of ethics analyses, and provision of common language between the various participants in the HTA process. We propose key characteristics of quality assessment tools for this purpose, which can be applied to ethics analyses for HTA purposes.

CAPACITY BUILDING IN AGENCIES FOR EFFICIENT AND EFFECTIVE HEALTH TECHNOLOGY ASSESSMENT.

OBJECTIVES: Health technology assessment (HTA) yields information that can be ideally used to address deficiencies in health systems and to create a wider understanding of the impact of different policy considerations around technology reimbursement and use. The structure of HTA programs varies across different jurisdictions according to decision-maker needs. Moreover, conducting HTA requires specialized skills. Effective decision making should include multiple criteria (medical, economic, technical, ethical, social, legal, and cultural) and requires multi-disciplinary teams of experts working together to produce these assessments. A workshop explored the multi-disciplinary skills and competencies required to build an effective and efficient HTA team, with a focus on low- and middle-income settings. METHODS: This proceeding summarizes main points from a workshop on capacity building, drawing on presentations and group discussions among attendees including different points of view. RESULTS AND CONCLUSIONS: The workshop and thus this study would have benefited from a larger variety of stakeholders. Therefore, the conclusions arising from the workshop are not the opinion of a representative sample of HTA professionals. Nonetheless, organizations and speakers were carefully selected to provide a valuable approach to this theme. Thus, these proceedings highlight some of the gaps and needs in the education and training programs offered worldwide and calls for further investigation.

Criteria to define innovation in the field of medical devices: a Delphi approach.

Defining innovation in the field of medical devices can be extremely challenging due to the peculiarity of the products within this class. Short life-cycle, incrementality, learning curve effect, impact of the organizational setting, uncertainty of effect and level of evidence are only some of these aspects. A clear set of criteria to define innovation would be of paramount relevance in this field. Twelve criteria to define innovation were proposed to a multistakeholder panel within a consensus process. A Delphi method on two rounds was used to reach consensus. In total, 53 of the 93 (47%) invited panelists responded to the first round of the survey. Among them, 51 (96%) completed also the second round. At the first round, consensus was reached for four of the 12 proposed criteria. Three of the remaining eight criteria reached consensus at the second round. It was not possible to reach consensus for the remaining five criteria. The criteria that collected the highest scores (close to 100%) were from the clinical impact domain, namely the ability of the technology to offer significant advantages over existing alternatives in terms of improving relevant clinical outcomes, and the ability to address an unmet need defined in terms of unavailability of diagnosis/treatment alternatives. High levels of consensus (about 80%) were registered on criteria belonging to non-clinical domains of analysis and, in particular, the ability of the technology to introduce organizational benefits, and the ability of the technology to bring cost reduction providing the same clinical benefit of current alternatives.

Synthesis of relevant information around non-core domains to support Multi-Criteria Decision Analysis (MCDA) for decision making.

Countries fundamentally base macro and micro decision making in the field of health on economic considerations, the budgetary impact of technologies being a major criterion. Nevertheless, the value of the technology of interest and its dimensions are more complex if we seek to take decisions based on the value itself. The use of structured and explicit approaches that require the assessment of multiple criteria that reflect the dimensions of this value may significantly improve the quality of the decision making. Multi-criteria decision analysis (MCDA) is a complementary decision-making tool that is able to systematically incorporate dimensions or domains such as ethical, organisational, legal, environmental and social considerations, as well as costs and benefits of medical interventions, together with the distinct perspectives of the interested parties. The objective of this article is to propose the implementation of analysis of non-core domains, in reports of Health Technology Assessment (HTA) agencies/units. To assess the scientific evidence on MCDA techniques a systematic review was conducted using structured searches in biomedical databases and websites of various HTA organisations. A consensus group was held using the nominal group technique and involving users of healthcare services, providers, managers and academics. Complementary, a survey was sent to HTA agencies to ascertain the degree of implementation of MCDA in their methods. 42 articles reporting the use of non-core criteria for the assessment of health technologies were included in the analysis. From these articles, a total of 216 non-core criteria were retrieved and categorised into domains by the researchers, and of these, 56 were classified as socioeconomic, 59 as organisational, 10 as legal, 8 as environmental and 47 as ethical, while 36 were considered to relate to other domains. The consensus group, based on the 216 non-core criteria obtained from the systematic review, proposed, and defined 26 criteria that participants considered necessary for decision making in healthcare. The consensus group did not consider that any of the domains should be given more weight than others or that any individual criteria should dominate. These approaches can serve as a framework of reference for a well-structured systematic discussion concerning the basis of individual criteria and the evidence supporting them.

Personalizing health care: feasibility and future implications.

Considerable variety in how patients respond to treatments, driven by differences in their geno- and/ or phenotypes, calls for a more tailored approach. This is already happening, and will accelerate with developments in personalized medicine. However, its promise has not always translated into improvements in patient care due to the complexities involved. There are also concerns that advice for tests has been reversed, current tests can be costly, there is fragmentation of funding of care, and companies may seek high prices for new targeted drugs. There is a need to integrate current knowledge from a payer's perspective to provide future guidance. Multiple findings including general considerations; influence of pharmacogenomics on response and toxicity of drug therapies; value of biomarker tests; limitations and costs of tests; and potentially high acquisition costs of new targeted therapies help to give guidance on potential ways forward for all stakeholder groups. Overall, personalized medicine has the potential to revolutionize care. However, current challenges and concerns need to be addressed to enhance its uptake and funding to benefit patients.

Recommendations for patient involvement in health technology assessment in Central and Eastern European countries.

Introduction: Meaningful patient involvement in health technology assessment (HTA) is essential in ensuring that the interests of the affected patient population, their families, and the general public are accurately reflected in coverage and reimbursement decisions. Central and Eastern European (CEE) countries are generally at less advanced stages of implementing HTA, which is particularly true for patient involvement activities. As part of the Horizon2020 HTx project, this research aimed to form recommendations for critical barriers to patient involvement in HTA in CEE countries. Methods: Built on previous research findings on potential barriers, a prioritisation survey was conducted online with CEE stakeholders. Recommendations for prioritised barriers were formed through a face-to-face workshop by CEE stakeholders and HTx experts. Results: A total of 105 stakeholders from 13 CEE countries completed the prioritisation survey and identified 12 of the 22 potential barriers as highly important. The workshop had 36 participants representing 9 CEE countries, and 5 Western European countries coming together to discuss solutions in order to form recommendations based on best practices, real-life experience, and transferability aspects. Stakeholder groups involved in both phases included HTA organisation representatives, payers, patients, caregivers, patient organisation representatives, patient experts, health care providers, academic and non-academic researchers, health care consultants and health technology manufacturers/providers. As a result, 12 recommendations were formed specified to the CEE region's context, but potentially useful for a broader geographic audience. Conclusion: In this paper, we present 12 recommendations for meaningful, systematic, and sustainable patient involvement in HTA in CEE countries. Our hope is that engaging more than a hundred CEE stakeholders in the study helped to spread awareness of the importance and potential of patient involvement and that the resulting recommendations provide tangible steps for the way forward. Future studies shall focus on country-specific case studies of the implemented recommendations.

Recommendations to overcome barriers to the use of artificial intelligence-driven evidence in health technology assessment.

Background: Artificial intelligence (AI) has attracted much attention because of its enormous potential in healthcare, but uptake has been slow. There are substantial barriers that challenge health technology assessment (HTA) professionals to use AI-generated evidence for decision-making from large real-world databases (e.g., based on claims data). As part of the European Commission-funded HTx H2020 (Next Generation Health Technology Assessment) project, we aimed to put forward recommendations to support healthcare decision-makers in integrating AI into the HTA processes. The barriers, addressed by the paper, are particularly focusing on Central and Eastern European (CEE) countries, where the implementation of HTA and access to health databases lag behind Western European countries. Methods: We constructed a survey to rank the barriers to using AI for HTA purposes, completed by respondents from CEE jurisdictions with expertise in HTA. Using the results, two members of the HTx consortium from CEE developed recommendations on the most critical barriers. Then these recommendations were discussed in a workshop by a wider group of experts, including HTA and reimbursement decision-makers from both CEE countries and Western European countries, and summarized in a consensus report. Results: Recommendations have been developed to address the top 15 barriers in areas of (1) human factor-related barriers, focusing on educating HTA doers and users, establishing collaborations and best practice sharing; (2) regulatory and policy-related barriers, proposing increasing awareness and political commitment and improving the management of sensitive information for AI use; (3) data-related barriers, suggesting enhancing standardization and collaboration with data networks, managing missing and unstructured data, using analytical and statistical approaches to address bias, using quality assessment tools and quality standards, improving reporting, and developing better conditions for the use of data; and (4) technological barriers, suggesting sustainable development of AI infrastructure. Conclusion: In the field of HTA, the great potential of AI to support evidence generation and evaluation has not yet been sufficiently explored and realized. Raising awareness of the intended and unintended consequences of AI-based methods and encouraging political commitment from policymakers is necessary to upgrade the regulatory and infrastructural environment and knowledge base required to integrate AI into HTA-based decision-making processes better.