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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.

Oortwijn et al continue their guide to good practice in the use of deliberative processes in health technology assessment (HTA) based on a survey of international practice. This is useful, and I applaud their care in maintaining objectivity, especially regarding the treatment of moral and politically controversial issues, in reporting how jurisdictions have handled such matters in designing HTA procedures and in their execution. To their suggestions for future research, I add: the historical development of deliberation in healthcare decision-making and in other fields of public choice, with comparisons of methods, successes and failures; development of guidance on the design and use of deliberative processes that enhance decision-making when there is no consensus amongst the decision-makers; ways of identifying and managing context-free and context-sensitive evidence; and a review of high-level capacity building to raise awareness of HTA and the use of knowledge translation and exchange (KTE) and deliberation amongst policy makers, especially in low and middle-income countries.

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.

Amidst competing priorities for allocating finite health resources, using evidence-informed priority setting is a valuable tool for achieving population-level health goals. The paper by Baltussen et al comprehensively reports on the development of practical guidance for evidence-informed deliberative processes (EDPs) which will help with sustainability of programs aimed at universal health coverage (UHC). The authors’ experience with the Joint Learning Network for UHC’s (JLN) peer-to-peer learning platform on evidence-informed priority setting offers insights on the practical challenges faced by countries in health benefits package (HBP) design, especially to draw in actors to advocate for the priorities and values across the health system. Lessons harvested from JLN countries that have established such advisory committees can provide practical insights for countries in earlier stages of establishing a systematic process for HBP design. Peer-to-peer learning modalities among countries offer viable and effective approaches to institutionalizing EDPs and systematic priority setting.

Abstract Introduction Patient and public involvement (PPI) is an expectation when conducting research, including Health Technology Assessment (HTA), but practical guidance for those wishing to embed PPI into the grant application process is not always easily accessible. We wanted to ensure that PPI was central when preparing a proposal for an investigator‐led evidence synthesis HTA investigating nonsurgical interventions for pelvic organ prolapse (POP) in women. Here, we describe our methods. Methods We recruited two patient co‐applicants separately through an open process to help ensure that patient voice was present within our proposal's management and direction. We invited co‐applicants to attend research team meetings and comment on the full proposal. We designed, recruited to and facilitated a scoping workshop, as well as undertook its subsequent evaluation. The insight shared within the workshop for patients with a lived experience of POP, including our patient co‐applicants, helped us develop the scope and rationale behind our HTA proposal. We particularly considered the interventions to include within the evidence synthesis. We also considered the outcome measures for both the evidence synthesis and economic evaluation. We elicited ideas about where and how results could be disseminated. Feedback suggested the workshop was as valuable for the attendees as it was for the researchers, making them feel valued and listened to. The time spent by researchers working on the activity was substantial and not directly funded but a necessary and valuable activity in developing our potential HTA. Our work was informed using the UK Standards for Public Involvement and the Authors and Consumers Together Impacting on eVidencE (ACTIVE) framework. Conclusions PPI can be enormously valuable in both developing and strengthening research proposals. However, further guidance is needed to help researchers recognise the level and type of involvement to use at this early stage, particularly given the large time investment needed to embed meaningful PPI. Patient and Public Contribution Women with a lived experience of POP were involved at every stage of the grant application process; their involvement is documented in full throughout this work.

Pelabuhan Perikanan Pantai (PPP) Lempasing merupakan pelabuhan perikanan terbesar di Lampung. Salah satu kapal yang paling banyak dioperasikan di Pelabuhan Lempasing yaitu mini purse seine. Terdapat berbagai aktivitas di Pelabuhan Lempasing, yaitu pendaratan (bongkar muat) dan pemasaran ikan. Aktivitas bongkar muat di Pelabuhan Perikanan Lempasing merupakan aktivitas utama setelah kapal berlabuh di dermaga. Kecelakaan yang terjadi pada aktivitas bongkar muat dapat menyebabkan kerugian berupa terhambatnya kegiatan. Tujuan dari penelitian ini adalah mengidentifikasi kegiatan dan potensi bahaya aktivitas bongkar muat kapal mini purse seine, menganalisis tingkat kecelakaan dan peluang risiko yang mungkin dapat terjadi, memberikan rekomendasi/alternatif solusi, serta menentukan tindak pengendalian kecelakaan kerja. Metode survei deskriptif HTA (Hierachy Task Analysis) digunakan dalam penelitian ini. Hasil penelitian menunjukkan terdapat 47 risiko kecelakaan pada aktivitas bongkar muat, kegiatan berisiko ringan 36 (77%), menengah terdapat 5 (11%) kegiatan, 2 (4%) kegiatan berisiko berat, dan 4 (9%) kegiatan berisiko fatal. Risiko kecelakaan kerja terbesar terjadi pada kegiatan bongkar, hal ini disebabkan karena individu yang terlibat cukup banyak (sekitar 20 orang) dan aktivitas yang dilakukan cukup berat.

New therapies in a publicly funded healthcare system are first appraised by health technology assessment agencies that provide funding recommendations to the payers. Treatment with Chimeric Antigen Receptor-T cell (CAR-T) therapy is revolutionizing the management of patients with relapsed/refractory aggressive B-cell lymphoma by providing an effective alternative to the standard of care. Yet, the implementation of CAR-T treatment has a substantial impact on the healthcare system due to its high cost, complex manufacturing process, and requirement for highly specialized services and expertise. CAR-T Cells, as a “living drug”, are fundamentally different from usual medications, and their approvals and funding recommendations pose unique challenges to the health technology agency. In this paper, we explore the specific challenges that face the health technology agencies in reviewing reimbursement recommendations for CAR-T therapy. We take a Canadian perspective and use CAR-T treatment of relapse/refractory aggressive B-cell lymphoma as an example.

Artificial intelligence is a new field that uses computers to act like human intelligence. AI is going to make big changes in healthcare in the next few years and will become much bigger in the next decades. Artificial intelligence is expected to help medical centers work better and efficiently, diagnose diseases accurately, and create treatment plans. Artificial Intelligence has been used in health care fields with some success (1). Even though we have made a lot of progress using artificial intelligence for medical research, there are still differences between what the computers can do and what we need for real-life health care situations (2). The fast growth of AI technology can be used in hospitals to improve how they treat patients. This could make a big difference in how healthcare is delivered. It is important to write down and share information about how AI is used in hospitals, so that healthcare workers have the right tools and know-how to use it properly (3). To make better decisions, we need to evaluate how AI can change our healthcare system. Considering how important AI could be in many areas, we should look at more than just how well it works and how much it costs. We need to think about its overall value in the world and how it can help people in their daily lives (4). Due to the increasing importance of the use and application of artificial intelligence in the field of health technology assessment and evidence-based policymaking, especially after Covid-19 pandemic, “health technology assessment (HTA) in action journal” decided to invite researchers and experts to help to develop this knowledge by publishing specialized papers in this field. It is hoped that the published articles can provide up-to-date results in this field. The editor wants to thank all the authors who submitted their work to the special issue of the "HTA in Action journal" Also, thanks to all the reviewers for working hard to review the articles and help the editors make the final decision.

Introduction. La revue annuelle de la qualité des produits (RAQP), exigence internationale pour les formes finies et les substances actives, est particulièrement scrutée lors d’inspections et d’audits. Elle s'apparente à une validation rétrospective continue permettant de détecter toute dérive et de s’assurer de la fiabilité des procédés et de la qualité des produits. La RAQP du Gardénal 50mg (Phénobarbital) fabrique sur le site de Dakar en boite de 30 comprimes a porté sur cinq (5) lots Matériels et méthodes. L’évaluation des OOS/OOT a suivi la procédure CQ PRO 015. Les fiches de déclaration des résultats hors tendance ou non conformes obtenus lors de l’analyse au laboratoire, la description et la cause d’anomalie, le numéro de la déviation correspondante et de suivi des plans d’actions correctives et préventives (CAPA) ont été renseignées. Résultats. Les rendements, de 82,22-88,05%, étaient inférieurs à 98%. L’évaluation du poids moyen a montré des résultats conformes : 86.695-88.245 mg, pour une valeur cible de 87.500 mg. Les temps de désagrégation étaient conformes (60-637 sec), en dessous de la limite maximale de 900 sec. Il en a été de même pour le titre en Phénobarbital avec des résultats conformes de 47,80-50,80 mg/cp (moyenne 49,21 mg/cp). Deux déviations impactant deux lots ont été notées, respectivement, sur le dosage en principe actif pour le lot 2, le temps de désagrégation in process et le test de dissolution pour le lot 3 occasionnant son rejet après retraitement. Le lot 2 a fait l’objet d’une fiche OOT. Discussion. Quatre lots ont été libérés dans les 19 à 50 jours suivants leur fabrication. Huit actions correctives et préventives ont été clôturées à 100 % dans les délais. Seul le lot 3 a été rejeté après retraitement, suite à une dissolution non conforme 61% (limite 75%). Aucun lot n’a fait l’objet de réclamation, de rappel ou de retour. L’étude permet d’affirmer que le produit détient les qualités attribuées : l’évaluation du dosage en principe actif, des paramètres critiques in process, des paramètres de libération disponibles a donné des résultats conformes. Le process de fabrication a été validé.

Introduction. L’étude entre dans le cadre de valorisation des ressources de la pharmacopée africaine. Elle visait le recensement de plantes utilisées dans de la région de Thiès, centre du Sénégal, pour traiter le diabète et l'hypertension artérielle. Matériel et méthodes. Soixante-quinze (75) tradipraticiens, 78,66% d’hommes et 21,34% de femmes également répartis dans les trois départements de la région ont été interrogés sur un questionnaire et les données analysées quantitativement. Résultats. Sur 49 plantes recensées, 36,73% servaient au traitement du diabète, 26,53% à l’HTA et 36,73% pour les deux pathologies. Les plus citées furent : Sclerocarya birrea (18,05%), Combretum micrantum (16,9%), Rauwolfia vomitoria (9,98%), Catharantus roseus (7,32%), Balanites aegyptiaca (7,14%), Lonchocarpus sepium (7,35%) et Combretum glutinosum (6,62%). Les plus fréquemment prescrites étaient les mêmes : Sclerocarya birrea (15,46%), Combretum micrantum (14,9%), Rauwolfia vomitoria (8,39%), Balanites aegyptiaca (7,14%, Catharantus roseus (6%), Lonchocarpus sepium (5,84%) et Combretum glutinosum (5,84%). L’exploitation des feuilles (48,67%), racines (26,22%), fruits (15,44%), écorces (13,33%), graines (10,88%), fleurs (5,92%), bulbes (5,33%) et plantes entières (4,08%) permettait la préparation de décoctés (58,39%), d’infusés (44,28%), de poudres (18,53%), d’huiles (10,74%) essentiellement. Discussion. La position géographique de la région de Thiès, au centre du Sénégal, a permis d’enrôler des interlocuteurs de diverses ethnies pour une plus grande diversité de remèdes. Bien que nettement minoritaires, les tradipraticiennes avaient un important taux de fréquentation. Une convergence des pratiques est à noter en ce qui concerne les ressources utilisées et les préparations. La standardisation des procédures de prélèvement, de transformations et des doses administrées restent des écueils pour l’exploitation rationnelle de la Pharmacopée traditionnelle.

Introdução: Access to drugs for rare diseases constitutes a challenge to healthcare systems, especially those with public funding. The difficulty of conducting robust clinical trials limits the quality of evidence and elevates the cost of development, later translated into the drug’s prices. Thus, it is necessary for the Health Technology Assessment (HTA) agencies to have differentiated criteria for the evaluation of reimbursement recommendations when dealing with such drugs. Objetivos: The objective of this research is to identify and summarize the specific criteria used when evaluating reimbursement recommendations for orphan drugs that are adopted by HTA agencies in countries with different models of public healthcare systems. Material e Método: A comprehensive literature search was performed on the databases PubMed, LILACS, Scopus and Embase up to March 2022. We included any publication type (opinion articles, commentaries, editorials, original articles and reviews) that addressed the criteria used by HTA agencies in countries with public healthcare systems when evaluating reimbursement recommendations for orphan drugs. Resultados: This scoping review summarizes the identified criteria for 18 countries and ranks them within three models of healthcare systems (NHS, NHI and SHI). We identified that NHS countries, such as the UK, Sweden, and Italy, lean towards innovation, the collection of real-world data, and the impact on organizational aspects of the system. Meanwhile, SHI countries, such as Germany, France and the Netherlands, often employ budget ceilings and expedited evaluation processes. All models shared concern over unmet need and disease nature. The 16 included studies range from 2015 to 2022 and the majority consists of reviews of HTA reports and original articles. Discussão e Conclusões: This review provides a good basis for the understanding of each model’s classification and general tendencies when creating differentiated criteria to accommodate and compensate for the lack of evidence and investment around rare diseases.

Objectives: Assess how relevant precedent within the EMA (a key regulator) and NICE (a key HTA body) can inform how such novel medicines targeting asymptomatic conditions can be brought to market from a regulatory and payor perspective. Methods: All phase 2 or phase 3 clinical trials with "asymptomatic", "presymptomatic", "subclinical", "premanifest", or "preclinical" as a condition key word were downloaded from clinicaltrials.gov. Trials were cleaned to identify those for novel medicines with a primary target to treat asymptomatic conditions. EMA and NICE reports for such drugs were downloaded online in December 2021 and analysed to understand how they assessed the evidence. Results: 278 clinical trials were identified. Of those, only 8 had relevant matching reports from EMA and/or NICE. 7 of these 8 received a positive review from EMA, and 4 of these 8 received a positive recommendation from NICE. Those receiving positive recommendations showed or were assumed to show statistically significant survival benefit given a short life expectancy of untreated patients. Conclusions: There is no precedent within EMA or NICE for approving or funding new medicines for asymptomatic patients where survival benefit cannot be established. Additional research is warranted to understand how regulatory and payor agencies can prepare for future generations of innovative medicines.

BACKGROUND: High-speed health trains are important tools and guarantees in major accidents, epidemic pandemics, disasters, and warfare health care, and the health trains currently developed for common train platforms have more functional defects. OBJECTIVE: The purpose of this study is to analyze the relationship between the medical transfer system and the medical system, and to obtain a better medical transfer train formation through the established model. METHODS: Based on the case study of medical transport tools, this paper analyzes the components and interrelationships of the medical transport system and the medical system, and then analyzes the medical transport task process of the health train by using the hierarchical task analysis (HTA) method. Combined with the Chinese standard EMU, a medical transport task model of the high-speed health train is established. Through this model, the functional compartment unit of the high-speed health train and the marshaling scheme of the high-speed health train are obtained. RESULTS: The expert system is used to evaluate the scheme. The results show that the train formation scheme formulated by the model in this paper is superior to other train formation schemes in three indicators, meeting the requirements of large medical transfer tasks. CONCLUSION: The results of this study can improve the ability of on-site treatment of patients, and can provide a basis for the research and development of a high-speed health train, which has a certain practical application value. [ABSTRACT FROM AUTHOR]

In response to rapidly rising pharmaceutical costs, many countries have introduced health technology assessment (HTA) as a 'fourth hurdle'. We evaluated the causal effect of HTA based regulation on access to pharmaceuticals by using the introduction of Germany's HTA system (AMNOG) in 2011. We obtained launch data on pharmaceuticals for 30 European countries from the IQVIA (formerly IMS) database. Using difference-in-difference models, we estimated the effect of AMNOG on launch delay, the ranking order of launch delays and the availability of pharmaceuticals. We then compared the results for Germany to Austria, Czechia, Italy, Portugal and the UK. Across all six countries, launch delay decreased from the pre-AMNOG period (25.01 months) to the post-AMNOG period (14.34 months). However, the introduction of AMNOG consistently reduced the magnitude of the decrease in launch delay in Germany compared to the comparator countries (staggered DiD: + 4.31 months, p = 0.05). Our logit results indicate that the availability of pharmaceuticals in Germany increased as a result of AMNOG (staggered logit: + 5.78%, p = 0.009). We provide evidence on the trade-off between regulation and access. This can help policymakers make better informed decisions to strike the right balance between cost savings achieved through HTA based regulation and access to pharmaceuticals. [ABSTRACT FROM AUTHOR]

The aim of this study is to explore the current practice in Cyprus regarding the introduction and reimbursement of innovative pharmaceuticals through Managed Entry Agreements (MEA), assess its operational context, and suggest approaches toward spanning the knowledge gap consequential to these efforts, especially the barriers of a small country context. The recent introduction of a National Health System (NHS), brought about fundamental reforms in Cyprus' Healthcare sector. Among such reforms, of particular interest, has been the introduction of a Managed Entry Agreements (MEA) mechanism. The first preliminary results indicate that despite being a small and unattractive market, Cyprus can apply a substantial MEA program. Concomitantly, it annotates the need to design an operational framework which should include, the definition of important technical parameters, clear demarcation of the scope, cooperation principles ensuring the effective operation of scientific committees, and clear delineation of what 'value' is. Moreover, in the context of the unified healthcare market, budget transfers should be considered, which could alleviate the inordinate budget impact of new products, which nevertheless will cut down on hospital expenditures. Narrative synthesis and health policy analysis-related resources were used. The implementation of MEA in Cyprus provides an ideal testing ground for innovative reimbursement approaches. This will streamline the country's efforts toward reimbursement of innovation, while concomitantly add to the collective MEA experience. [ABSTRACT FROM AUTHOR]

Since the groundwork published by Torres-Vega and Frederick, the Quantum Phase Space Representation (QPSR) has been explored as a method for solving a multitude of physical systems and describing phenomena. Most recently, Valentino A. Simpao has developed a method, the Heaviside Operational Ansatz, to solve the Time Dependent Schrodinger Equation (TDSE) in the QPSR, but there are still no general, direct methods to solve the Time Independent Schrodinger Equation in the QPSR. There is also no current formulation of quarkonium in phase space. In this paper, we describe the strong interactions of non-relativistic heavy quarks using the Cornell potential, and present a method, the Half-Transform Ansatz, to cast the Schrodinger Equation into a hyper-geometric form which can be solved for the phase space wave function and its energy eigenvalues using the Nikiforov-Uvarov method. This solution can be generalized for any two particle system with a scleronomic potential made up of polynomial and reciprocal terms. These results are compared to experimental results and other theoretical models. We also analyze the behavior of these wave functions, which suggest a correlation between radial momentum and the upper limit of existence in charm-anticharm mesons. [ABSTRACT FROM AUTHOR]

Objective. This study aims to investigate the risk factors associated with hypertension in pregnant women through a comprehensive literature review. Methodology. A retrospective bibliographic investigation was conducted by searching for relevant information in both Spanish and English languages using databases such as PubMed, Scielo, Medline, NIH, and Elsevier. Results. A total of 33 articles were included in this research, covering various aspects including definitions, etiology, classification, risk factors, and laboratory examinations related to hypertension during pregnancy. Conclusions. Hypertension during pregnancy is a pathological condition that not only affects the mother but also poses risks to the fetus. The mortality rate among pregnant women with hypertension is estimated at 35%. Failure to timely detect and diagnose hypertension can result in complications such as hemorrhages, early placental detachment, spontaneous abortions, or preterm births, which may lead to maternal and fetal mortality. Biochemical markers and regular blood chemistry or urine analysis tests can aid in the diagnosis of this condition. [ABSTRACT FROM AUTHOR]

For many reasons randomized clinical trials today can»t cope with the tasks set by modern health care, which was clearly demonstrated by the COVID-19 pandemic. This gave new impetus to the development of the RWD / RWE. It became obviously that in cases of impossibility, unethical and other reasons, new methods for obtaining high-quality evidence may be effectively used, and later can be used by decision-makers and organizations engaged in the assessment of health technologies.

Abstract Background Few antibiotics have entered the market in recent years despite the need for new treatment options. Some of the challenges of bringing new antibiotics to market are linked to the marketing authorization and health technology assessment (HTA) processes. Research shows great variation in geographic availability of new antibiotics, suggesting that market introduction of new antibiotics is unpredictable. We aimed to investigate regulatory authorities’ and HTA agencies’ role in developing non-financial incentives to stimulate antibiotic research and development (R&D). Methods We conducted individual, semi-structured, stakeholder interviews. Participants were recruited from regulatory authorities (EMA and FDA) and HTA agencies in Europe. Participants had to be experienced with assessment of antibiotics. The data were analyzed using a deductive and inductive approach to develop codes and identify key themes. Data were analyzed using thematic analysis including the constant comparison method to define concepts, and rival thinking to identify alternative explanations. Results We found that (1) interpretation of key concepts guiding the understanding of what type of antibiotics are needed vary (2) lack of a shared approach on how to deal with limited clinical data in the marketing authorization and HTA processes is causing barriers to getting new antibiotics to market (3) necessary adaptations to the marketing authorization process causes uncertainties that transmit to other key stakeholders involved in delivering antibiotics to patients. Conclusions A shared understanding of limited clinical data and how to deal with this issue is needed amongst stakeholders involved in antibiotic R&D, marketing authorization, and market introduction to ensure antibiotics reach the market before resistance levels are out of control. Regulatory authorities and HTA agencies could play an active role in aligning the view of what constitutes an unmet medical need, and direct new economic models towards stimulating greater diversity in the antibiotic armamentarium.

Abstract Background New medicines are increasingly being identified as efficacious across multiple indications. The impact of current pricing and reimbursement policies on launch decisions across these indications remains unclear. Objective This paper, first, maps marketing authorisation and HTA coverage recommendation sequences of multi-indication medicines across Germany, France, England, Scotland, Canada, Australia, and the USA, and, second, evaluates the clinical characteristics, clinical development time and coverage recommendation time of multi-indication medicines, drawing comparisons between the first and subsequent indications of an approved molecule. Methods Medicine approvals by the Food and Drug Administration between 2009–2019 were screened to identify multi-indication products with approved oncology indications. Data on clinical trial characteristics, clinical performance and HTA outcomes were extracted from publicly available regulatory approval and HTA reports. Results Relative to subsequent indications, first indications were more likely to receive conditional marketing authorisation, have an orphan designation, have a single arm phase II pivotal trial and lower MCBS score. Subsequent indications had faster HTA coverage recommendation times in England and Canada. While the majority of first indications received HTA coverage recommendations across all settings, the proportion of subsequent indications with HTA coverage recommendations was lower and uptake varied considerably across settings. Conclusions Discordance in the value of first versus subsequent indications can pose major challenges in systems that define price based on the initial indication. Current pricing and reimbursement systems generate significant fragmentation in the approval and availability of multi-indication products across settings.

Abstract Objectives Dealing with uncertainty is one of the critical topics in health technology assessment. The greater decision uncertainty in appraisals, the less clear the clinical- and cost-effectiveness of the health technology. Although the development of targeted cancer therapies (TCTs) has improved patient health care, additional complexity has been introduced in drug appraisals due to targeting more specific populations. Real-world data (RWD) are expected to provide helpful information to fill the evidence gaps in appraisals. This study compared appraisals of TCTs with those of non-targeted cancer therapies (non-TCTs) regarding sources of uncertainty and reviewed how RWD have been used to supplement the information in these appraisals. Methods This study reviews single technology appraisals (STAs) of oncology medicines performed by the National Institute for Health and Care Excellence (NICE) over 11 years up to December 2021. Three key sources of uncertainty were identified for comparison (generalisability of clinical trials, availability of direct treatment comparison, maturity of survival data in clinical trials). To measure the intensity of use of RWD in appraisals, three components were identified (overall survival, volume of treatment, and choice of comparators). Results TCTs received more recommendations for provision through the Cancer Drugs Fund (27.7, 23.6% for non-TCT), whereas similar proportions were recommended for routine commissioning. With respect to sources of uncertainty, the external validity of clinical trials was greater in TCT appraisals (p = 0.026), whereas mature survival data were available in fewer TCT appraisals (p = 0.027). Both groups showed similar patterns of use of RWD. There was no clear evidence that RWD have been used more intensively in appraisals of TCT. Conclusions Some differences in uncertainty were found between TCT and non-TCT appraisals. The appraisal of TCT is generally challenging, but these challenges are neither new nor distinctive. The same sources of uncertainty were often found in the non-TCT appraisals. The uncertainty when appraising TCT stems from insufficient data rather than the characteristics of the drugs. Although RWD might be expected to play a more active role in appraisals of TCT, the use of RWD has generally been limited.