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Objectives: The aim of the study was to assess the reimbursement policy for orphan drugs (ODs) in selected European countries in relation to the availability and impact of clinical evidence, health technology assessment (HTA) procedures and reimbursement decision-making. Materials and Methods: A list of authorized ODs was extracted from a web-based registry of the European Medicines Agency, including information on active substance, Anatomical Therapeutic Chemical (ATC) classification code, and therapeutic area. A country-based questionnaire survey was conducted between September 2022 and September 2023 among selected experts from 12 European countries. A descriptive and statistical analysis was performed to identify correlations between country characteristic, HTA procedures, drug indication and positive recommendations or reimbursement decisions for ODs. Results: Safety assessment for ODs was mandatory in 10 countries, while it was optional in one country (Italy) and not required in one country (Iceland). Efficacy assessment for ODs was mandatory in 11 countries and not required in one country (Iceland). The impact of safety and efficacy assessment on reimbursement decisions was rated as high in 10 countries and as low in one country (Germany). Dedicated OD legislation and policies were reported in seven countries. In two countries (Belgium, Iceland), the HTA was not mandatory, and in one country (Germany), it only had an informative function. A positive recommendation (from an HTA agency or advisory body) guaranteed reimbursement in four countries, while a negative recommendation excluded reimbursement only in one country (Iceland). The proportion of reimbursed ODs ranged from 23.5% in Iceland to 86% in Germany (p < 0.001). ODs with ATC code L represented the largest group of medicines (n = 49). They were also very frequently reimbursed ODs in the countries studied, with a mean of 61.8% (p < 0.001). Conclusion: European countries differ in terms of the impact of clinical issues and additional clinical aspects on the reimbursement policy for ODs. Reimbursement decisions were affected by OD-specific legislation, policies, and EMA authorization status. HTA dossiers and procedures significantly influenced reimbursement decisions, although some ODs were reimbursed regardless of the positive or negative recommendations. ATC codes were significantly correlated with reimbursement status and positive recommendation. [ABSTRACT FROM AUTHOR]

Purpose: Health technologies are advancing rapidly and becoming more expensive, posing a challenge for financing healthcare systems. Health technology assessment (HTA) improves the efficiency of resource allocation by facilitating evidence-informed decisions on the value of health technologies. Our study aims to create a customized HTA roadmap for Oman based on a gap analysis between the current and future status of HTA implementation. Design/methodology/approach: We surveyed participants of an advanced HTA training program to assess the current state of HTA implementation in Oman and explore long-term goals. A list of draft recommendations was developed in areas with room for improvement. The list was then validated for its feasibility in a round table discussion with senior health policy experts to conclude on specific actions for HTA implementation. Findings: Survey results aligned well with expert discussions. The round table discussion concluded with a phasic action plan for HTA implementation. In the short term (1–2 years), efforts will focus on building capacity through training programs. For medium-term actions (3–5 years), plans include expanding the HTA unit and introducing multiple cost-effectiveness thresholds while from 6–10 years, publishing of HTA recommendations, critical appraisal reports, and timelines is recommended. Originality/value: Although the HTA system in Oman is still in its early stages, strong initiatives are being taken for its advancement. This structured approach ensures a comprehensive integration of HTA into the healthcare system, enhancing decision-making and promoting a sustainable, evidence-based system addressing the population's needs. [ABSTRACT FROM AUTHOR]

Circulating tumor DNA (ctDNA) detection has multiple promising applications in oncology, but the road toward implementation in clinical practice is unclear. We aimed to support the implementation process by exploring potential future pathways of ctDNA testing. To do so, we studied four ctDNA‐testing applications in two cancer types and elicited opinions from 30 ctDNA experts in the Netherlands. Our results showed that the current available evidence differed per application and cancer type. Tumor profiling and monitoring treatment response were found most likely to be implemented in non‐small cell lung cancer (NSCLC) within 5 years. For colorectal cancer, applications of ctDNA testing were found to be at an early stage in the implementation process. Demonstrating clinical utility was found a key aspect for successful implementation, but there was no consensus regarding the evidence requirements. The next step toward implementation is to define how clinical utility of biomarkers should be evaluated. Finally, these data indicate that specific challenges for each clinical application and tumor type should be appropriately addressed in a deliberative process involving all stakeholders to ensure implementation of ctDNA testing and timely access for patients. [ABSTRACT FROM AUTHOR]

Background: According to scientific literature, some 99% of patients affected by Alzheimer's disease (AD) suffer from behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms (NPSs). In particular, agitation is one of the most difficult disorders to treat. States of agitation represent a very serious problem as they make these subjects dangerous for themselves and others and worsen as the disease advances. To date, there are no specific solutions for treating agitation. The only authorized drug is risperidone (as well as brexpiprazole, approved by the FDA on 11 May 2023), which can be used for no longer than 6–12 weeks because it increases the risk of death—owing to cardiocerebrovascular accidents—by 1.6–1.7 times. Methods: In order to address the latter noteworthy unmet medical need, NanoBEO was produced. The aim of the present work is to generate the health technology assessment (HTA) of this nanotechnological device. The latter consists of a controlled release system, based on solid lipid nanoparticles loaded with bergamot essential oil (BEO). Results: The results of the present research assessed the current evidence in the field of non-pharmacological treatments for this condition, including relevant primary preclinical and clinical data studies supporting the use of this device and the production of the operative plan for its launch on the market. The findings offer recommendations for decision-making on its implementation in dementia. Conclusions: NanoBEO represents a public-worth innovation in this neglected area, marking a significant advancement in the history of dementia, moving from academic research to product development. [ABSTRACT FROM AUTHOR]

Background/Objectives. Many vaccines have been developed in recent decades, and many more will be available in the future. When new safe and effective vaccines are available, decision-makers must extensively assess them before including them in the national immunization plan and issuing recommendations. The Health Technology Assessment (HTA) could be an objective, transparent, and comprehensive approach to guiding the decision-making process for the use of vaccines. Objectives and Methods. The aim of this study was to review the indications for HTA use contained in Italian institutional documents on vaccination, namely the National Immunization Plans (NIPs) and available full Italian HTA reports on vaccines, assessing their availability at the time of national recommendations' introductions. Results. HTA has been recognised as an eligible approach to deciding upon the introduction of vaccines through the NIPs of 2012–2014 and 2017–2019, and the last NIP, of 2023–2025, highlights the lack of funding dedicated to the production of independent HTA reports that can be used for issuing recommendations. In 2007–2023, twenty full HTA reports on vaccines were published in Italy: eight reports on influenza vaccines, five on Human Papilloma Virus (HPV), three each on meningococcal and pneumococcal vaccines, and one on rotavirus vaccine. HTA was applied with different purposes, namely the evaluation of new vaccines or their re-assessment, but it was not always timely with respect to both the marketing authorisation and the issuing of national recommendations for use. Conclusions. As HTA can be considered the best tool to disentangle the overall value of vaccines, it would be desirable for it to be used more and more to provide the evidence for efficient resource use. This calls for action to improve the transfer of HTA results to decision-makers, to try to fill the gap between research and decision and foster evidence-based recommendations. [ABSTRACT FROM AUTHOR]

Circulating tumor DNA (ctDNA) detection has multiple promising applications in oncology, but the road toward implementation in clinical practice is unclear. We aimed to support the implementation process by exploring potential future pathways of ctDNA testing. To do so, we studied four ctDNA‐testing applications in two cancer types and elicited opinions from 30 ctDNA experts in the Netherlands. Our results showed that the current available evidence differed per application and cancer type. Tumor profiling and monitoring treatment response were found most likely to be implemented in non‐small cell lung cancer (NSCLC) within 5 years. For colorectal cancer, applications of ctDNA testing were found to be at an early stage in the implementation process. Demonstrating clinical utility was found a key aspect for successful implementation, but there was no consensus regarding the evidence requirements. The next step toward implementation is to define how clinical utility of biomarkers should be evaluated. Finally, these data indicate that specific challenges for each clinical application and tumor type should be appropriately addressed in a deliberative process involving all stakeholders to ensure implementation of ctDNA testing and timely access for patients.

Emanuela Foglia,1 Federica Asperti,1 Grazia Antonacci,2,3 Yogini H Jani,4 Elisabetta Garagiola,1 Daniele Bellavia,1 Lucrezia Ferrario1 1LIUC - University Cattaneo, Healthcare Datascience LAB, Castellanza, Varese, 21053, Italy; 2Department of Primary Care and Public Health, Imperial College London, National Institute of Health Research (NIHR) Applied Research Collaboration (ARC) Northwest London, London, UK; 3Business School, Centre for Health Economics and Policy Innovation (CHEPI), Imperial College London, London, UK; 4Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, UKCorrespondence: Elisabetta Garagiola, Healthcare Datascience Laboratory - HD LAB, LIUC-Università Cattaneo, Corso G. Matteotti, 22, Castellanza, VA, 21053, Italy, Tel +39.0331.572.467, Email egaragiola@liuc.itBackground: Automated Drug Dispensing (ADD) systems are considered to be strategic hospital assets used to reduce errors and enhance economic and organizational sustainability. With regards to efficacy and safety, the literature evidence demonstrates the incremental benefits of centralised or decentralised systems compared to manual dispensing. Analyses about organisational and economic sustainability are still lacking and the present study aims to perform a Health Technology Assessment (HTA), producing multidimensional evidence on the use of ADD systems within hospitals.Methods: In 2023, a comprehensive HTA draws insights from healthcare professionals across six European nations: Italy, France, Germany, the Netherlands, the United Kingdom, and Belgium. This appraisal juxtaposed four drug dispensing scenarios: manual methods, centralized ADD systems, decentralized ADD systems, and integrated solutions employing cutting-edge technologies in both central pharmacies and wards. The study deployed an Activity-Based Costing approach that was combined with a cost-effectiveness and Budget Impact Analysis to evaluate economic impacts. Qualitative questionnaires were implemented to assess ethical, legal, organizational, safety, and efficacy aspects.Results: From a multidimensional perspective, healthcare professionals acknowledged ADD manifold advantages of ADD systems. From an organizational perspective and within a 12-month timeframe, transitioning to automation may face initial challenges that are attributed to potential resistance from professionals and significant investments. However, 36 months past its adoption, automation’s superiority over manual methods was recognized. Economically, savings burgeoned from +17.9% in UK to +26.6% in Belgian hospitals that adopted integrated systems in comparison to traditional manual approaches.Conclusion: Compared to traditional methods, implementing ADD systems could improve the logistic management of drug in the hospital setting, thereby enhancing safety and efficacy, streamlining the healthcare professionals’ workflow, and bolstering financial stability.Keywords: automated drug dispensing systems, HTA, economic impact, drug logistic management, efficiency

Background Moldova strives for universal health coverage (UHC) and considers health technology assessment (HTA) an important policy instrument to inform the choice of services that should be covered to progressively realize UHC. It plays a key role in determining which technologies are coved, considering various dimensions often including cost-effectiveness, budget impact, and feasibility. This paper reports on work undertaken to develop a roadmap for HTA implementation, using evidence-informed deliberative processes (EDPs) as the guiding framework. Methods Between 2020 and 2022, we undertook several activities that informed the roadmap. We conducted a needs assessment and an assessment of European HTA best practices using a combination of desk research, interviews and surveys. We then conducted a document review of six selected HTA systems, complimented by expert interviews from three neighbouring countries. Results The roadmap provided a suggested HTA process, which included instructions on how to execute the different steps of the EDP framework to enhance the legitimacy of HTA-informed decision-making. The roadmap encompasses several aspects such as how to organize stakeholder involvement, how to identify and operationalize decision criteria, and how to make the decision process transparent. Guidance was given to the country on establishing a legal framework for HTA; a communication strategy; strengthening capacity and leveraging HTA expertise. The country was also given tailored advice on the positioning of the HTA-agency, first as an entity within the Ministry of Health or the National Agency of Public Health but with the long-term vision for it to be independent of any state institution. Conclusions Despite several challenges, including a partial disruption because of the Covid-19 pandemic, the development of the roadmap for HTA implementation was completed and agreed upon by the Ministry of Health in Moldova. This work has helped motivate and support the country in HTA institutionalization.

Introduction: Access to medicines is a shared goal across healthcare stakeholders. Since health technology assessment (HTA) informs funding decisions, it shapes access to medicines. Despite its wide implementation, significant access variations due to HTA are observed across Europe. This paper elicited the opinions of European stakeholders on how HTA can be improved to facilitate access. Methods: A scoping review identified HTA features that influence access to medicines within markets and areas for improvement, while three access dimensions were identified (availability, affordability, timeliness). Using the Delphi method, we elicited the opinions of European stakeholders to validate the literature findings. Results: Nineteen participants from 14 countries participated in the Delphi panel. Thirteen HTA features that could be improved to optimise access to medicines in Europe were identified. Of these, 11 recorded a positive impact on at least one of the three access dimensions. HTA features had mostly a positive impact on timeliness and a less clear impact on affordability. 'Early scientific advice' and 'clarity in evidentiary requirements' showed a positive impact on all access dimensions. 'Established ways to deal with uncertainty during HTA' could improve medicines' availability and timeliness, while more 'reliance on real-world evidence' could expedite time to market access. Conclusions: Our results reiterate that increased transparency during HTA and the decision-making processes is essential; the use of and reliance on new evidence generation such as real-world evidence can optimise the availability of medicines; and better collaborations between regulatory institutions within and between countries are paramount for better access to medicines. [ABSTRACT FROM AUTHOR]

A health technology assessment (HTA) does not systematically account for the circumstances and needs of children and youth. To supplement HTA processes, we aimed to develop a child-tailored value assessment framework using a multicriteria decision analysis approach. We constructed a multicriteria-decision-analysis-based model in multiple phases to create the Comprehensive Assessment of Technologies for Child Health (CATCH) framework. Using a modified Delphi process with stakeholders having broad disciplinary and geographic variation (N = 23), we refined previously generated criteria and developed rank-based weights. We established a criterion-pertinent scoring rubric for assessing incremental benefits of new drugs. Three clinicians independently assessed comprehension by pilotscoring 9 drugs. We then validated CATCH for 2 childhood cancer therapies through structured deliberation with an expert panel (N = 10), obtaining individual scores, consensus scores, and verbal feedback. Analyses included descriptive statistics, thematic analysis, exploratory disagreement indices, and sensitivity analysis. The modified Delphi process yielded 10 criteria, based on absolute importance/relevance and agreed importance (median disagreement indices = 0.34): Effectiveness, Child-specific Health-related Quality of Life, Disease Severity, Unmet Need, Therapeutic Safety, Equity, Family Impacts, Life-course Development, Rarity, and Fair Share of Life. Pilot scoring resulted in adjusted criteria definitions and more precise score-scaling guidelines. Validation panelists endorsed the framework's key modifiers of value. Modes of their individual prescores aligned closely with deliberative consensus scores. We iteratively developed a value assessment framework that captures dimensions of child-specific health and nonhealth gains. CATCH could improve the richness and relevance of HTA decision making for children in Canada and comparable health systems. • Health technology assessment (HTA) methods for child health technologies are challenged by evidentiary limitations and incomplete consideration of the unique biological and social circumstances and needs of children and youth. Multicriteria decision analysis has emerged as an HTA tool for explicitly considering nonconventional values. • This article presents novel child-specific value assessment criteria based in societal preferences, which reflect the importance of family impacts and long-term flourishing of children beyond immediate health gains obtained through treatment. • A child-tailored multicriteria decision analysis approach facilitating HTA deliberations may broaden the normative lens through which child health technologies are evaluated, contributing to more comprehensive and relevant decision making. [ABSTRACT FROM AUTHOR]

Abstract Background Moldova strives for universal health coverage (UHC) and considers health technology assessment (HTA) an important policy instrument to inform the choice of services that should be covered to progressively realize UHC. It plays a key role in determining which technologies are coved, considering various dimensions often including cost-effectiveness, budget impact, and feasibility. This paper reports on work undertaken to develop a roadmap for HTA implementation, using evidence-informed deliberative processes (EDPs) as the guiding framework. Methods Between 2020 and 2022, we undertook several activities that informed the roadmap. We conducted a needs assessment and an assessment of European HTA best practices using a combination of desk research, interviews and surveys. We then conducted a document review of six selected HTA systems, complimented by expert interviews from three neighbouring countries. Results The roadmap provided a suggested HTA process, which included instructions on how to execute the different steps of the EDP framework to enhance the legitimacy of HTA-informed decision-making. The roadmap encompasses several aspects such as how to organize stakeholder involvement, how to identify and operationalize decision criteria, and how to make the decision process transparent. Guidance was given to the country on establishing a legal framework for HTA; a communication strategy; strengthening capacity and leveraging HTA expertise. The country was also given tailored advice on the positioning of the HTA-agency, first as an entity within the Ministry of Health or the National Agency of Public Health but with the long-term vision for it to be independent of any state institution. Conclusions Despite several challenges, including a partial disruption because of the Covid-19 pandemic, the development of the roadmap for HTA implementation was completed and agreed upon by the Ministry of Health in Moldova. This work has helped motivate and support the country in HTA institutionalization.

To comprehensively identify and map an exhaustive list of value criteria for the assessment of next-generation sequencing/comprehensive genomic profiling (NGS/CGP), to be used as an aid in decision making. We conducted a systematic review to identify existing value frameworks (VFs) applicable to any type of healthcare technology. VFs and criteria were mapped to a previously published Latin American (LA) VF to harmonize definitions and identify additional criteria and or subcriteria. Based on this analysis, we extracted a comprehensive, evidence-based list of criteria and subcriteria to be considered in the design of a NGS/CGP VF. A total of 42 additional VFs were compared with the LA VF, 88% were developed in high-income countries, 30% targeted genomic testing, and 16% specifically targeted oncology. A total of 242 criteria and subcriteria were extracted; 227 (94%) were fully/partially included in the LA VF; and 15 (6%) were new. Clinical benefit and economic aspects were the most common criteria. VFs oriented to genomic testing showed significant overlap with other VFs. Considering all criteria and subcriteria, a total of 18 criteria and 36 individual subcriteria were identified. Our study provides an evidence-based set of criteria and subcriteria for healthcare decision making useful for NGS/CGP as well as other health technologies. The resulting list can be beneficial to inform decision making and will serve as a foundation to co-create a multistakeholder NGS/CGP VF that is aligned with the needs and values of health systems and could help to improve patient access to high-value technologies. • Value frameworks play a crucial role in enhancing transparency and facilitating informed decision making within the healthcare system. They serve as valuable guides, highlighting key dimensions that need evaluation when assessing various healthcare technologies. • Institute for Clinical Effectiveness and Health Policy recently developed a value framework for diagnostic technologies, based on a targeted systematic review and a participatory process with health technology assessment stakeholders in Latin America. • In this article, we report a systematic review to update the previous framework and develop a comprehensive evidence-based list of criteria and subcriteria that could be considered for creation of a next-generation sequencing/comprehensive genomic profiling-targeted value framework, as well as a starting point for value frameworks targeted to other health technologies. [ABSTRACT FROM AUTHOR]

The new EU Regulation on health technology assessment (HTAR) provides for joint clinical assessments (JCA) of health technologies at EU level. When Member States carry out health technology assessments (HTA) at the national level, they shall give due consideration to the results of a JCA and comply with other obligations of the Regulation. This article aims to clarify what these obligations mean for the Member States and whether JCA results have to be considered outside a national health technology assessment as well. In this context, the question of which processes qualify as 'national HTA' and which requirements need to be fulfilled to trigger the obligations under Article 13 HTAR are discussed in more detail in this paper. [ABSTRACT FROM AUTHOR]

Background: National cancer control plans (NCCPs) are complex public health programs that incorporate evidence‐based cancer control strategies to improve health outcomes for all individuals in a country. Given the scope of NCCPs, small and vulnerable populations, such as patients with childhood cancer, are often missed. To support planning efforts, a rapid, modifiable tool was developed that estimates a context‐specific national budget to fund pediatric cancer programs, provides 5‐year scale‐up scenarios, and calculates annual cost‐effectiveness. Methods: The tool was codeveloped by teams of policymakers, clinicians, and public health advocates in Zimbabwe, Zambia, and Uganda. The 11 costing categories included real‐world data, modeled data, and data from the literature. A base‐case and three 5‐year scale‐up scenarios were created using modifiable inputs. The cost‐effectiveness of the disability‐adjusted life years averted was calculated. Results were compared with each country's projected gross domestic product per capita for 2022 through 2026. Results: The number of patients/total budget for year 1 was 250/$1,109,366 for Zimbabwe, 280/$1,207,555 for Zambia, and 1000/$2,277,397 for Uganda. In year 5, these values were assumed to increase to 398/$5,545,445, 446/$4,926,150, and 1594/$9,059,331, respectively. Base‐case cost per disability‐adjusted life year averted/ratio to gross domestic product per capita for year 1, assuming 20% survival, was: $807/0.5 for Zimbabwe, $785/0.7 for Zambia, and $420/0.5 for Uganda. Conclusions: This costing tool provided a framework to forecast a budget for childhood‐specific cancer services. By leveraging minimal primary data collection with existing secondary data, local teams obtained rapid results, ensuring that childhood cancer budgeting is not neglected once in every 5 to 6 years of planning processes. The Childhood Cancers Budgeting Rapidly to Incorporate Disadvantaged Groups for Equity (CC‐BRIDGE) tool fills a current gap by providing a feasible, simplified toolkit for policymakers and childhood cancer stakeholders to calculate the costs required to develop a multiyear childhood cancer–specific budget, within existing National Cancer Control Plan (NCCP) activities. As governments continue to plan NCCPs, the CC‐BRIDGE tool can ensure that budgeting for vulnerable populations, such as childhood cancer patients, is not neglected once in every 5 to 6 years of planning processes. [ABSTRACT FROM AUTHOR]

Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) represents a condition mainly caused by the type 2 inflammation presence and marked by the existence of polyps within the nasal and paranasal sinuses. The standard of care includes intranasal steroids, additional burst of systemic steroids, if needed, and surgery. However, recurrence is common, especially among patients with comorbid type 2 inflammatory diseases. Recently, biological drugs, addressing the underlying cause of the disease, have been approved in Italy (dupilumab, omalizumab, and mepolizumab). A Health Technology Assessment was conducted to define multidimensional impact, assuming Italian NHS perspective and a 12-month time horizon. The EUnetHTA Core Model was deployed, using the following methods to analyze the domains: (i) literature evidence; (ii) administration of semi-structured questionnaires to 17 healthcare professionals; (iii) health economics tools to define the economic sustainability for the system. Evidence from NMA and ITC showed a more favorable safety profile and better efficacy for dupilumab compared with alternative biologics. All the analyses, synthesizing cost and efficacy measures, showed that dupilumab is the preferable alternative. Specifically, the cost per responder analysis for dupilumab, exhibiting a 67.0% response rate at Week 52, is notably economical at 14,209EUR per responder. This presents a more economical profile compared with the cost per responder for omalizumab (36.2% response rate) at 24,999EUR and mepolizumab (28.5% response rate) at 31,863EUR. These results underscore dupilumab's potential, not merely in terms of clinical outcomes, but also in terms of economic rationality, thereby solidifying its status as a valid and preferrable alternative in the management of CRSwNP, in the context of the Italian NHS. [ABSTRACT FROM AUTHOR]

Aim: Regulatory and health technology assessment (HTA) agencies have increasingly published frameworks, guidelines, and recommendations for the use of real-world evidence (RWE) in healthcare decision-making. Variations in the scope and content of these documents, with updates running in parallel, may create challenges for their implementation especially during the market authorization and reimbursement phases of a medicine’s life cycle. This environmental scan aimed to comprehensively identify and summarize the guidance documents for RWE developed by most well-established regulatory and reimbursement agencies, as well as other organizations focused on healthcare decision-making, and present their similarities and differences. Methods: RWE guidance documents, including white papers from regulatory and HTA agencies, were reviewed in March 2024. Data on scope and recommendations from each body were extracted by two reviewers and similarities and differences were summarized across four topics: study planning, choosing fit-for-purpose data, study conduct, and reporting. Post-authorization or non-pharmacological guidance was excluded. Results: Forty-six documents were identified across multiple agencies; US FDA produced the most RWE-related guidance. All agencies addressed specific and often similar methodological issues related to study design, data fitness-for-purpose, reliability, and reproducibility, although inconsistency in terminologies on these topics was noted. Two HTA bodies (National Institute for Health and Care Excellence [NICE] and Canada’s Drug Agency) each centralized all related RWE guidance under a unified framework. RWE quality tools and checklists were not consistently named and some differences in preferences were noted. European Medicines Agency, NICE, Haute Autorit ´e de Sant´ e, and the Institute for Quality and Efficiency in Health Care included specific recommendations on the use of analytical approaches to address RWE complexities and increase trust in its findings. Conclusion: Similarities in agencies’ expectations on RWE studies design, quality elements, and reporting will facilitate evidence generation strategy and activities for manufacturers facing multiple, including global, regulatory and reimbursement submissions and re-submissions. A strong preference by decision-making bodies for local real-world data generation may hinder opportunities for data sharing and outputs from international federated data networks. Closer collaboration between decision-making agencies towards a harmonized RWE roadmap, which can be centrally preserved in a living mode, will provide manufacturers and researchers clarity on minimum acceptance requirements and expectations, especially as novel methodologies for RWE generation are rapidly emerging.

Abstract Background There is limited evidence-informed guidance on TISP processes for countries where health technology assessment (HTA) is in a nascent phase. We aimed to explore the range of topic identification, selection and prioritization (TISP) processes and practices for HTA in selected countries and identify aspects relevant to emerging HTA systems. Methods This mixed design study included a systematic literature review, an electronic survey, and individual interviews. We conducted a systematic literature review with criteria that were developed a priori to identify countries deemed to have a recently formalized HTA system. Based on the literature review, a twenty-three item online survey was shared with the identified countries, we completed follow-up interviews with ten participants who have experience with HTA. We analyzed documents, survey responses and interview transcripts thematically to identify lessons related to TISP processes and practices. Results The literature review identified 29 nine candidate countries as having a “potential” recently formalized HTA system. Twenty-one survey responses were analyzed and supplemented with ten individual interviews. We found variation in countries’ approaches to TISP — particularly between pharmaceutical and non-pharmaceutical interventions. Results indicate that TISP is heavily driven by policy makers, expert involvement, and to a lesser extent, relevant stakeholders. The use of horizon-scanning and early warning systems is uncommon. Interviewee participants provided further insight to the survey data, reporting that political awareness and an institutional framework were important to support TISP. TISP can be optimized by stronger national regulations and legislative structures, in addition to education and advocacy about HTA among politicians and decision-makers. In some settings regional networks have been useful, particularly in the development of TISP guidelines and methodologies. Additionally, the technical capacity to conduct TISP, and access to relevant local data were factors limiting TISP in national settings. Increased network collaboration and capacity building were reported as future needs. Conclusions This study provides current insights into a topic where there is limited published peer reviewed literature. TISP is an important first step of HTA, and topics should be selected and prioritized based on local need and relevance. The limited capacity for TISP in settings where HTA is emerging may be supported by local and international collaboration to increase capacity and knowledge. To succeed, both TISP and HTA need to be embedded within national health care priority setting and decision-making. More in-depth understanding of where countries are situtated in formalizing the TISP process may help others to overcome factors that facilitate or hinder progress.

* Background Moldova strives for universal health coverage (UHC) and considers health technology assessment (HTA) an important policy instrument to inform the choice of services that should be covered to progressively realize UHC. It plays a key role in determining which technologies are coved, considering various dimensions often including cost-effectiveness, budget impact, and feasibility. This paper reports on work undertaken to develop a roadmap for HTA implementation, using evidence-informed deliberative processes (EDPs) as the guiding framework. Methods Between 2020 and 2022, we undertook several activities that informed the roadmap. We conducted a needs assessment and an assessment of European HTA best practices using a combination of desk research, interviews and surveys. We then conducted a document review of six selected HTA systems, complimented by expert interviews from three neighbouring countries. Results The roadmap provided a suggested HTA process, which included instructions on how to execute the different steps of the EDP framework to enhance the legitimacy of HTA-informed decision-making. The roadmap encompasses several aspects such as how to organize stakeholder involvement, how to identify and operationalize decision criteria, and how to make the decision process transparent. Guidance was given to the country on establishing a legal framework for HTA; a communication strategy; strengthening capacity and leveraging HTA expertise. The country was also given tailored advice on the positioning of the HTA-agency, first as an entity within the Ministry of Health or the National Agency of Public Health but with the long-term vision for it to be independent of any state institution. Conclusions Despite several challenges, including a partial disruption because of the Covid-19 pandemic, the development of the roadmap for HTA implementation was completed and agreed upon by the Ministry of Health in Moldova. This work has helped motivate and support the country in HTA institutionalization.

Objectives: The aim of this study was to characterize the reimbursement policy for orphan drugs (ODs) in Central and Eastern European (CEE) countries in relation to the availability and impact of clinical evidence, health technology assessment (HTA) procedure, selected economic indicators, and the drug type according to indications. Materials and methods: A list of authorized medicines with orphan designation and information about active substance, Anatomical Therapeutic Chemical (ATC) classification, and therapeutic area was extracted from the web-based register of the European Medicines Agency (EMA). A country-based questionnaire survey was performed between September 2021 and January 2022 in a group of selected experts from nine CEE countries (an invitation was sent to 11 countries). A descriptive and statistical analysis was conducted to determine statistical significance, correlations, between the drug or country characteristic and the positive recommendation or reimbursement of ODs. Results: The proportion of reimbursed orphan drugs differed between countries, ranging from 17.7% in Estonia to 49.6% in Hungary (p < 0.001). The odds that ODs were reimbursed were reduced in countries with a "strong" level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), the presence of other additional specific clinical aspects (e.g., genomic data) considered in the reimbursement decision (p < 0.001) and mandatory (without exception) safety assessments (p=0.004). The probability that ODs were reimbursed was increased in countries with a "moderate" level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), when reimbursement decisions are dependent on the EMA registration status and orphan drug designation (p < 0.001), the presence of the "positive HTA recommendation guarantees reimbursement" policy (p < 0.001), higher GDP per inhabitant (p=0.003), and higher healthcare expenditure (p < 0.001). Conclusion: We found that there are differences among CEE countries in the reimbursement of orphan drugs, and we identified aspects that may influence these differences. Safety, efficacy, and specific clinical aspect issues significantly influenced reimbursement decisions. Antineoplastic and immunomodulating agents drugs were the largest group of ODs and increased the chance of getting a positive recommendation. The higher GDP per inhabitant and healthcare expenditures per inhabitant were positively linked to the chance that an OD receives reimbursement. [ABSTRACT FROM AUTHOR]

To ensure that limited domestic resources are invested in the most effective interventions, immunization programs in low- and middle-income countries (LMICs) must prioritize a growing number of new vaccines while considering opportunities to optimize the vaccine portfolio, as well as other components of the health system. There is a strong impetus for immunization decision-making to engage and coordinate various stakeholders across the health system in prioritization. To address this, national immunization program decision-makers in LMICs collaborated with WHO to structure deliberation among stakeholders and document an evidence-based, context-specific, and transparent process for prioritization or selection among multiple vaccination products, services, or strategies. The output of this effort is the Country-led Assessment for Prioritization on Immunization (CAPACITI) decision-support tool, which supports using multiple criteria and stakeholder perspectives to evaluate trade-offs affecting health interventions, taking into account variable data quality. Here, we describe the user feedback from Indonesia and Ethiopia, two initial countries that piloted the CAPACITI decision-support tool, highlighting enabling and constraining factors. Potential immunization program benefits and lessons learned are also summarized for consideration in other settings. [ABSTRACT FROM AUTHOR]

The Half-Transform Ansatz (HTA) is a proposed method to solve hyper-geometric equations in Quantum Phase Space by transforming a differential operator to an algebraic variable and including a specific exponential factor in the wave function, but the mechanism which provides this solution scheme is not known. Analysis of the HTA’s application to the Hydrogen atom suggests an underlying mechanism which the HTA is a part of. Observations of exponential factors that act on the wave function naturally suggest modeling quantum operator definitions as a point on a Riemannian manifold in the 4D Operator Space, a novel idea we call the Operator Space Manifold Theory. On this manifold, we explore the concepts of superposition, regions of unique energy eigenvalues, and translation operators. We also find the theoretical backing to derive the HTA and how Operator Space Manifold Theory can be used to describe and solve quantum systems by manipulating how a quantum state perceives position and momentum. [ABSTRACT FROM AUTHOR]

AlN epilayers were grown on magnetron-sputtered (MS) (11–22) AlN buffers on m-plane sapphire substrates at 1450 °C via hydride vapour phase epitaxy (HVPE). The MS buffers were annealed at high temperatures of 1400–1600 °C. All the samples were characterised using X-ray diffraction, atomic force microscopy, scanning electron microscope and Raman spectrometry. The crystal quality of epilayers regrown by HVPE was improved significantly compared to that of the MS counterpart. With an increasing annealing temperature, the crystal quality of both MS buffers and AlN epilayers measured along [11–23] and [1–100] improved first and then decreased, maybe due to the decomposition of MS buffers, while the corresponding anisotropy along the two directions decreased first and then increased. The optimum quality of the AlN epilayer was obtained at the annealing temperature of around 1500 °C. In addition, it was found that the anisotropy for the epilayers decreased significantly compared to that of annealed MS buffers when the annealing temperature was below 1500 °C. [ABSTRACT FROM AUTHOR]

Objective: To assess the profile of metabolic syndrome (MS) in a hypertensive population in Mali. Patients and methods: Prospective study from June 1, 2022 to June 31, 2022, in the cardiology department of the Mother-Child University Hospital in Bamako, Luxembourg. Our study sample consisted of adult hypertensive patients, aged 18 years and older, received as an outpatient. Patients were included in our study after informed consent. The SM was established based on International Diabetes Federation (IDF) definitions. Results: Out of 520 patients, 238 were included in our study. The prevalence of SM was 30.2% according to IDF criteria. There was a female predominance (66%). The mean age was 57 ± 5 years. Grade II hypertension was in the majority with 39%. Seventy-five percent of patients with metabolic syndrome had 3 risk factors. Ischemic stroke was the most common complication with a rate of 12%. Dual therapy was indicated in 59.23% of patients. Calcium channel blockers were the most prescribed with a rate of 74.5%. SM is a reality in Mali. Adequate preventive measures are necessary to limit its progression. [ABSTRACT FROM AUTHOR]

Since late 2020, the Canadian Agency of Drugs and Technologies in Health (CADTH) has been using a threshold of $50,000 (CAD) per quality-adjusted life-year (QALY) for both oncology and non-oncology drugs. When used for oncology products, this threshold is hypothesized to have a higher impact on the time to access these drugs in Canada. We studied the impact of price reductions on time to engagement and negotiation with the pan-Canadian Pharmaceutical Alliance for oncology drugs reviewed by CADTH between January 2020 and December 2022. Overall, 103 assessments reported data on price reductions recommended by CADTH to meet the cost–effectiveness threshold for reimbursement. Of these assessments, 57% (59/103) recommendations included a price reduction of greater than 70% off the list price. Eight percent (8/103) were not cost-effective even at a 100% price reduction. Of the 47 assessments that had a clear benefit, in 21 (45%) CADTH recommended a price reduction of at least 70%. The median time to price negotiation (not including time to engagement) for assessments that received at least 70% vs >70% price reduction was 2.6 vs 4.8 months. This study showed that there is a divergence between drug sponsor’s incremental cost–effectiveness ratio (ICER) and CADTH revised ICER leading to a price reduction to meet the $50,000/QALY threshold. For the submissions with clear clinical benefit the median length of engagement (2.5 vs 3.3 months) and median length of negotiation (3.1 vs 3.6 months) were slightly shorter compared with the submissions where uncertainties were noted in the clinical benefit according to CADTH. This study shows that using a $50,000 per QALY threshold for oncology products potentially impacts timely access to life saving medications.

Background: According to scientific literature, some 99% of patients affected by Alzheimer’s disease (AD) suffer from behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms (NPSs). In particular, agitation is one of the most difficult disorders to treat. States of agitation represent a very serious problem as they make these subjects dangerous for themselves and others and worsen as the disease advances. To date, there are no specific solutions for treating agitation. The only authorized drug is risperidone (as well as brexpiprazole, approved by the FDA on 11 May 2023), which can be used for no longer than 6–12 weeks because it increases the risk of death—owing to cardiocerebrovascular accidents—by 1.6–1.7 times. Methods: In order to address the latter noteworthy unmet medical need, NanoBEO was produced. The aim of the present work is to generate the health technology assessment (HTA) of this nanotechnological device. The latter consists of a controlled release system, based on solid lipid nanoparticles loaded with bergamot essential oil (BEO). Results: The results of the present research assessed the current evidence in the field of non-pharmacological treatments for this condition, including relevant primary preclinical and clinical data studies supporting the use of this device and the production of the operative plan for its launch on the market. The findings offer recommendations for decision-making on its implementation in dementia. Conclusions: NanoBEO represents a public-worth innovation in this neglected area, marking a significant advancement in the history of dementia, moving from academic research to product development.

Background/Objectives. Many vaccines have been developed in recent decades, and many more will be available in the future. When new safe and effective vaccines are available, decision-makers must extensively assess them before including them in the national immunization plan and issuing recommendations. The Health Technology Assessment (HTA) could be an objective, transparent, and comprehensive approach to guiding the decision-making process for the use of vaccines. Objectives and Methods. The aim of this study was to review the indications for HTA use contained in Italian institutional documents on vaccination, namely the National Immunization Plans (NIPs) and available full Italian HTA reports on vaccines, assessing their availability at the time of national recommendations’ introductions. Results. HTA has been recognised as an eligible approach to deciding upon the introduction of vaccines through the NIPs of 2012–2014 and 2017–2019, and the last NIP, of 2023–2025, highlights the lack of funding dedicated to the production of independent HTA reports that can be used for issuing recommendations. In 2007–2023, twenty full HTA reports on vaccines were published in Italy: eight reports on influenza vaccines, five on Human Papilloma Virus (HPV), three each on meningococcal and pneumococcal vaccines, and one on rotavirus vaccine. HTA was applied with different purposes, namely the evaluation of new vaccines or their re-assessment, but it was not always timely with respect to both the marketing authorisation and the issuing of national recommendations for use. Conclusions. As HTA can be considered the best tool to disentangle the overall value of vaccines, it would be desirable for it to be used more and more to provide the evidence for efficient resource use. This calls for action to improve the transfer of HTA results to decision-makers, to try to fill the gap between research and decision and foster evidence-based recommendations.

Objectives: The aim of this study was to characterize the reimbursement policy for orphan drugs (ODs) in Central and Eastern European (CEE) countries in relation to the availability and impact of clinical evidence, health technology assessment (HTA) procedure, selected economic indicators, and the drug type according to indications.Materials and methods: A list of authorized medicines with orphan designation and information about active substance, Anatomical Therapeutic Chemical (ATC) classification, and therapeutic area was extracted from the web-based register of the European Medicines Agency (EMA). A country-based questionnaire survey was performed between September 2021 and January 2022 in a group of selected experts from nine CEE countries (an invitation was sent to 11 countries). A descriptive and statistical analysis was conducted to determine statistical significance, correlations, between the drug or country characteristic and the positive recommendation or reimbursement of ODs.Results: The proportion of reimbursed orphan drugs differed between countries, ranging from 17.7% in Estonia to 49.6% in Hungary (p < 0.001). The odds that ODs were reimbursed were reduced in countries with a “strong” level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), the presence of other additional specific clinical aspects (e.g., genomic data) considered in the reimbursement decision (p < 0.001) and mandatory (without exception) safety assessments (p=0.004). The probability that ODs were reimbursed was increased in countries with a “moderate” level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), when reimbursement decisions are dependent on the EMA registration status and orphan drug designation (p < 0.001), the presence of the “positive HTA recommendation guarantees reimbursement” policy (p < 0.001), higher GDP per inhabitant (p=0.003), and higher healthcare expenditure (p < 0.001).Conclusion: We found that there are differences among CEE countries in the reimbursement of orphan drugs, and we identified aspects that may influence these differences. Safety, efficacy, and specific clinical aspect issues significantly influenced reimbursement decisions. Antineoplastic and immunomodulating agents drugs were the largest group of ODs and increased the chance of getting a positive recommendation. The higher GDP per inhabitant and healthcare expenditures per inhabitant were positively linked to the chance that an OD receives reimbursement.

To ensure that limited domestic resources are invested in the most effective interventions, immunization programs in low- and middle-income countries (LMICs) must prioritize a growing number of new vaccines while considering opportunities to optimize the vaccine portfolio, as well as other components of the health system. There is a strong impetus for immunization decision-making to engage and coordinate various stakeholders across the health system in prioritization. To address this, national immunization program decision-makers in LMICs collaborated with WHO to structure deliberation among stakeholders and document an evidence-based, context-specific, and transparent process for prioritization or selection among multiple vaccination products, services, or strategies. The output of this effort is the Country-led Assessment for Prioritization on Immunization (CAPACITI) decision-support tool, which supports using multiple criteria and stakeholder perspectives to evaluate trade-offs affecting health interventions, taking into account variable data quality. Here, we describe the user feedback from Indonesia and Ethiopia, two initial countries that piloted the CAPACITI decision-support tool, highlighting enabling and constraining factors. Potential immunization program benefits and lessons learned are also summarized for consideration in other settings.

Introduction: Digital health technologies have been enhancing the capacity of healthcare providers and, thereby, the delivery of targeted health services. The Southeast Asia Region (SEAR) has invested in strengthening digital public health. Many digital health interventions have been implemented in public health settings but are rarely assessed using the holistic health technology assessment (HTA) approach., Methods: A systematic literature review was performed to provide an overview of evaluations of digital public health interventions in the World Health Organization (WHO) SEAR. Searches were conducted on four electronic databases. Screening title abstracts and full texts was independently conducted by two reviewers, followed by data extraction. Dimensions of HTA were analyzed against the EUnetHTA Core Model 3.0. Quality assessment of included articles was conducted using the JBI Checklist for Economic Evaluation and Consolidated Health Economic Evaluation Reporting Standards 2022 checklist to assess the reporting quality. The findings are presented using systematic evidence tables and bar charts., Results: Of the forty-three studies screened at the full-text stage, thirteen studies conducted across six countries were included in the analysis. Telemedicine and m-health interventions were assessed in ten studies. Nine studies conducted cost-effectiveness analysis, and five assessments were conducted from a societal perspective. Four studies utilized more than one perspective for the assessment. Health problem definition and current use of technology, description and technical characteristics of the technology, clinical effectiveness, costs, economic evaluation, and organizational aspects were assessed by all the studies, whereas legal aspects were least assessed., Conclusion: The lack of HTAs on digital public health interventions in the region highlights the need for capacity-building efforts.

Objectives: This study investigates factors associated with use of real-world data (RWD) in economic modelling for single technology appraisals (STAs) of cancer drugs by the National Institute for Health and Care Excellence (NICE) to improve systematic understanding of the use of RWD., Methods: The data were extracted from STAs of cancer drugs, for which NICE issued guidance between January 2011 and December 2022 (n=267). Binary regression was used to test hypotheses concerning the greater or lesser use of RWD. Bonferroni-Holm correction was used to control error rates in multiple hypotheses tests. Several explanatory variables were considered in this analysis, including time (Time), incidence rate of disease (IR), availability of direct treatment comparison (AD), generalisability of trial data (GE), maturity of survival data in trial (MS) and previous technology recommendations by NICE (PR). The primary outcome variable was any use of RWD. Secondary outcome variables were specific uses of RWD in economic models., Results: AD had a statistical negative association with any use of RWD whereas no associations with non-parametric and parametric use of RWD were found. Time had several statistical associations with use of RWD (validating survival distributions for the intervention, estimating progression-free survival for the intervention, estimating overall survival for comparators and transition probabilities)., Conclusions: RWD were more likely to be used in economic modelling of cancer drugs when randomised controlled trials failed to provide relevant clinical information of the drug for appraisals, particularly in the absence of direct treatment comparisons. These results, based on analysis of data systematically collected from previous appraisals, suggest that uses of RWD were associated with data gaps in the economic modelling. While this result may support some of the claimed advantages of using RWD when evidence is absent, the question, the extent to which use of RWD in indirect treatment comparisons reduces uncertainty is still to be determined., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jiyeon Kang is supported by the Centre for Cancer Biomarkers, University of Bergen, funded by the Research Council of Norway grant number (223250). She also holds a ESRC (Economic and Social Research Council) postdoctoral fellowship. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Also, any fellowship or external contribution had no impacts on this paper. John Cairns is a diagnostic advisory committee member of the National Institute for Health and Care Excellence., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The sandbox approach, developed in the financial technologies sector, creates an environment to collaboratively develop and test innovative new products, methods and regulatory approaches, separated from business as usual. It has been used in health care to encourage innovation in response to emerging challenges, but, until recently, has not been used in health technology assessment (HTA). This article summarizes our learnings from using the sandbox approach to address three challenges facing HTA organizations and to identify implications for the use of this approach in HTA., Methods: We identified three challenging contemporary HTA-related topics to explore in a sandbox environment, away from the pressures and interests of "live" assessments. We convened a pool of 120 stakeholders and experts to participate in various sandbox activities and ultimately co-develop solutions to help HTA organizations respond to the identified challenges., Results: Important general learnings about the potential benefits and implementation of a sandbox approach in HTA were identified. Consequently, we developed recommendations to guide its use, including how to implement an HTA sandbox in an effective way and the types of challenges for which it may be best suited., Conclusions: For many HTA organizations, it is difficult to carefully consider emerging challenges and innovate their processes due to risks associated with decision errors and resource limitations. The sandbox approach could reduce these barriers. The potential benefits of addressing HTA challenges in a collaborative "safe space" are considerable.

Objectives: To assess the health technology assessment (HTA) process in Greece from its establishment in 2018 until 2023 in terms of timeliness and productivity., Methods: Data were collected from the HTA Committee's database and other publicly available sources. The overall study timeframe was divided into three periods: (i) July 2018-January 2020, (ii) January 2020-July 2021, and (iii) July 2021-February 2023., Results: During the study period, a total of 1,157 applications for medicinal products (MPs) (including 219 new active substances (NAS) and orphans) were submitted to the HTA Committee. The number of HTA recommendations increased from 60 (first period) to 641 (third period), while the backlog of MPs pending HTA and price negotiations decreased from 89 and 106 (January 2020) to 8 and 44 (February 2023), respectively. The median time intervals for all application types decreased significantly over time. In February 2023, the median time for clinical data assessment of NAS (excluding orphans) almost halved from 207 days in the first period to 114 days; median times for NAS and orphans from regulatory approval to HTA application were 420 and 457 days, and from HTA application to reimbursement 228 and 417 days, respectively., Conclusions: The performance of the HTA process in Greece improved significantly over time, with increased MP appraisals, backlog reduction, and decreased timelines. Delays in reimbursement of NAS were mainly caused by the long gap between regulatory approval and HTA application. Overall, HTA review times in Greece are now on par with that of well-established European HTA systems.

Although collaboration is an intensive way of working together, it is essential for such efforts to achieve shared goals. Health technology assessment (HTA) is transdisciplinary and has an important history of collaboration, with collaboration featuring increasingly in the strategic plans of HTA bodies and stakeholders. Collaboration can be between HTA bodies and between HTA bodies and other stakeholders-most notably regulators but increasingly payers, patient and caregiver organizations, clinicians-clinical societies, and academia. The 2024 HTAi Global Policy Forum (GPF) discussed collaborations involving HTA bodies, reviewing existing and previous collaborations to see what has worked and what can be learned. Core discussion themes included: (i) determining the collaboration purpose is essential but may be dynamic, changing over time; (ii) choosing the collaboration topic takes time, requiring upfront investment and stakeholder mapping; (iii) inviting the right participants and treating them equally is important, including those who can impact HTA, those who will be impacted by HTA and those who bring new information; (iv) collaborations need clear governance, defined roles, responsibilities, metrics, and case study-pilots can be a useful operational model; (v) resourcing collaborations sustainably is a challenge-the time, people, and money required are often under-estimated; (vi) undertaking continual, iterative learning reviews ensures ongoing value and impact of collaborations. Recommendations for future work include the development of a "go/no-go" checklist to determine when collaboration is needed, supplemented with a set of "best practice" principles for establishing and working in collaborations involving HTA bodies.

Ageism in healthcare has received increased attention in recent years, but literature focusing on how it affects individuals living with rare diseases remains scant. The rare disease population already faces obstacles when navigating health systems, and ageism has the potential to exacerbate existing health inequities. We conducted a systematic review of peer-reviewed and gray literature on health inequities in rare disease populations, seeking to identify publications that reported primary or secondary data on the equitable or inequitable treatment of these populations, or that discussed related regulatory, moral, or philosophical issues. Our aims were to understand how health inequities in these populations arise, how they are justified from societal points of view, how they manifest themselves in laws and regulations, and what effects they have on health care access and health outcomes. We retrieved information from 63 publications, which we inductively synthesized into five categories: ethical discussions, societal preferences, regulations, access to care, and health outcomes. Integrating insights from these categories, we developed an Ethical Spectrum and Resource Allocation Framework, which explains the emergence of equity issues and how they are manifested in health systems. By providing a better understanding of the root causes of health inequities, particularly among older adults, the framework can inform health policymaking, improving access to care and health outcomes for rare disease patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Moldova strives for universal health coverage (UHC) and considers health technology assessment (HTA) an important policy instrument to inform the choice of services that should be covered to progressively realize UHC. It plays a key role in determining which technologies are coved, considering various dimensions often including cost-effectiveness, budget impact, and feasibility. This paper reports on work undertaken to develop a roadmap for HTA implementation, using evidence-informed deliberative processes (EDPs) as the guiding framework., Methods: Between 2020 and 2022, we undertook several activities that informed the roadmap. We conducted a needs assessment and an assessment of European HTA best practices using a combination of desk research, interviews and surveys. We then conducted a document review of six selected HTA systems, complimented by expert interviews from three neighbouring countries., Results: The roadmap provided a suggested HTA process, which included instructions on how to execute the different steps of the EDP framework to enhance the legitimacy of HTA-informed decision-making. The roadmap encompasses several aspects such as how to organize stakeholder involvement, how to identify and operationalize decision criteria, and how to make the decision process transparent. Guidance was given to the country on establishing a legal framework for HTA; a communication strategy; strengthening capacity and leveraging HTA expertise. The country was also given tailored advice on the positioning of the HTA-agency, first as an entity within the Ministry of Health or the National Agency of Public Health but with the long-term vision for it to be independent of any state institution., Conclusions: Despite several challenges, including a partial disruption because of the Covid-19 pandemic, the development of the roadmap for HTA implementation was completed and agreed upon by the Ministry of Health in Moldova. This work has helped motivate and support the country in HTA institutionalization., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Surgey G et al.)

Objectives: X-linked retinitis pigmentosa (XLRP) is a rare inherited retinal disease with no available treatment. Gene therapies in clinical trials will pose challenges for health technology assessment (HTA) if found to be safe and effective. We evaluated 2 of these challenges, namely acceptability and difficulties in assessing value beyond short-term patient health and healthcare savings and discounting in economic evaluation., Methods: We conducted a narrative literature review on the socioeconomic burden of XLRP to identify relevant components of value for a hypothetical gene therapy from a societal perspective and to assess their relative importance. We compared the resulting value profile against the value frameworks of three European HTA agencies. We also reviewed their guidelines on discounting and potential discounting issues specific to XLRP., Results: Much of the societal value of an XLRP gene therapy is likely to originate from productivity effects, carer spillovers, and value elements related to patient uncertainty. The evidence on these effects, however, is often limited, making it difficult for HTA agencies to assess them. Cost-effectiveness results are likely to be highly sensitive to the discount rate, and discounting will compound the effects of omitting important sources of value., Conclusions: We have identified and detailed important components of societal value, key evidence gaps, and potential discounting issues for an XLRP gene therapy, which can inform future value assessments. Many of these may apply to gene therapies in other disease areas. Revisiting existing HTA approaches is recommended to ensure these are fit for purpose for such new classes of treatment., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

The focus on health maximisation in a healthcare economic evaluation (HEE) – that is health gains are of equal value regardless of the recipient– has significant implications as health systems attempt to address persistent and growing health inequities. This study aimed to systematically compare and contrast the equity principles of different health technology assessment (HTA) agencies and how equity is addressed in HEE guidelines. HTA agencies were identified through the ISPOR, GEAR, iDSI, HTAi, INAHTA, HTAsiaLink, and RedETSA websites in June 2021 and updated in August 2023. Agencies websites were then searched to retrieve HEE guidelines. The guidelines were grouped into two categories: well-established and newly-developed agency guidelines, based on whether or not they published their first guidelines before 2009. Data extracted summarised the methodological details in the reference cases, including specifics on how equity featured and in what role. In those agencies where equity did not feature explicitly in the HEE guidelines, an additional search of the agency website was undertaken to understand if equity featured in those agencies' decision-making frameworks. The study included 46 guidelines from 51 countries. Only 30% of the guidelines were explicit about the equity assumptions. Health equity (using a broad definition) was mentioned in 29 guidelines and 14 included a specific definition while only seven recommended specific methods to incorporate inequalities. Addressing equity concerns was usually suggested as an additional analyses rather than a key part of the assessment. It was unclear how equity was incorporated into decision-making processes. In addition, equity was mentioned in other guidance – such as decision-making frameworks - provided by five agencies that did not mention it in the HEE guidelines, and 7 of 14 topic selection criteria that were identified. Equity is given less attention than efficiency in HEE guidelines. This indicates that HTA agencies while subscribing to an extra-welfarist approach have a narrow evaluative space – focusing on maximising health and not considering the opportunity cost of the equity constraint. The omission of equity and the lack of systematic approaches in guidelines poses a threat to the international endeavours to reduce inequities. It is timely for HTA agencies to reconsider their positions on equity explicitly. • Equity mentioned in 29 of 46 guidelines of HTA bodies, only 13 give methods to address inequalities. • Equity assumptions underlying economic evaluations is explicit in 14 guidelines. • The guidelines place a greater emphasis on efficiency rather than fairness. • Explicit consideration of equity needed to help deliver equitable health outcomes. [ABSTRACT FROM AUTHOR]

Aim: Regulatory and health technology assessment (HTA) agencies have increasingly published frameworks, guidelines, and recommendations for the use of real-world evidence (RWE) in healthcare decision-making. Variations in the scope and content of these documents, with updates running in parallel, may create challenges for their implementation especially during the market authorization and reimbursement phases of a medicine's life cycle. This environmental scan aimed to comprehensively identify and summarize the guidance documents for RWE developed by most well-established regulatory and reimbursement agencies, as well as other organizations focused on healthcare decision-making, and present their similarities and differences.  Methods: RWE guidance documents, including white papers from regulatory and HTA agencies, were reviewed in March 2024. Data on scope and recommendations from each body were extracted by two reviewers and similarities and differences were summarized across four topics: study planning, choosing fit-for-purpose data, study conduct, and reporting. Post-authorization or non-pharmacological guidance was excluded. Results: Forty-six documents were identified across multiple agencies; US FDA produced the most RWE-related guidance. All agencies addressed specific and often similar methodological issues related to study design, data fitness-for-purpose, reliability, and reproducibility, although inconsistency in terminologies on these topics was noted. Two HTA bodies (National Institute for Health and Care Excellence [NICE] and Canada's Drug Agency) each centralized all related RWE guidance under a unified framework. RWE quality tools and checklists were not consistently named and some differences in preferences were noted. European Medicines Agency, NICE, Haute Autorité de Santé, and the Institute for Quality and Efficiency in Health Care included specific recommendations on the use of analytical approaches to address RWE complexities and increase trust in its findings. Conclusion: Similarities in agencies' expectations on RWE studies design, quality elements, and reporting will facilitate evidence generation strategy and activities for manufacturers facing multiple, including global, regulatory and reimbursement submissions and re-submissions. A strong preference by decision-making bodies for local real-world data generation may hinder opportunities for data sharing and outputs from international federated data networks. Closer collaboration between decision-making agencies towards a harmonized RWE roadmap, which can be centrally preserved in a living mode, will provide manufacturers and researchers clarity on minimum acceptance requirements and expectations, especially as novel methodologies for RWE generation are rapidly emerging.

Background: Whole genome sequencing (WGS) has transformative potential for blood cancer management, but reimbursement is hindered by uncertain benefits relative to added costs. This study employed scenario planning and multi-criteria decision analysis (MCDA) to evaluate stakeholders' preferences for alternative reimbursement pathways, informing future health technology assessment (HTA) submission of WGS in blood cancer., Methods: Key factors influencing WGS reimbursement in blood cancers were identified through a literature search. Hypothetical scenarios describing various evidential characteristics of WGS for HTA were developed using the morphological approach. An online survey, incorporating MCDA weights, was designed to gather stakeholder preferences (consumers/patients, clinicians/health professionals, industry representatives, health economists, and HTA committee members) for these scenarios. The survey assessed participants' approval of WGS reimbursement for each scenario, and scenario preferences were determined using the geometric mean method, applying an algorithm to improve reliability and precision by addressing inconsistent responses., Results: Nineteen participants provided complete survey responses, primarily clinicians or health professionals (n = 6; 32 %), consumers/patients and industry representatives (both at n = 5; 26 %). "Clinical impact of WGS results on patient care" was the most critical criterion (criteria weight of 0.25), followed by "diagnostic accuracy of WGS" (0.21), "cost-effectiveness of WGS" (0.19), "availability of reimbursed treatment after WGS" (0.16), and "eligibility criteria for reimbursed treatment based on actionable WGS results" and "cost comparison of WGS" (both at 0.09). Participants preferred a scenario with substantial clinical evidence, high access to reimbursed targeted treatment, cost-effectiveness below $50,000 per quality-adjusted life year (QALY) gained, and affordability relative to standard molecular tests. Reimbursement was initially opposed until criteria such as equal cost to standard tests and better treatment accessibility were met., Conclusion: Payers commonly emphasize acceptable cost-effectiveness, but strong clinical evidence for many variants and comparable costs to standard tests are likely to drive positive reimbursement decisions for WGS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. M.V. received funding support from Illumina, a supplier of the NovaSeq 6000 that was considered in this study. At the time of publication, K.D. was an employee of Healthcare Consultancy Group, but did not contribute to this research as such and Healthcare Consultancy Group was in no way involved in this research or publication. The other authors declare no competing financial interests, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)