The impact of the COVID-19 pandemic was unequal, leading to losses for specific population groups already exposed to social vulnerabilities in the pre-pandemic period—for example, the inequity in access to health care among people with disabilities. The study aimed to identify strategies for people with disabilities during a public health emergency, in particular the COVID-19 pandemic.

A systematic review was conducted following the PRISMA guidelines. The population was adults with disabilities. There were no restrictions regarding the type of disability, which could include visual, auditory, intellectual, physical, or multiple disabilities. The COVID-19 pandemic was the study exposure and the outcomes were strategies aimed at improving prevention and health care for the target population during the pandemic period. A literature search was conducted in June 2021 and updated in November 2022 in the following databases: PubMed, Web of Science, Scopus, the Virtual Health Library, CINAHL, PDQ-Evidence, Health System Evidence, PEDro, and PsycInfo. The protocol for the systematic review was registered on PROSPERO (CRD42021266341).

The systematic review included 29 studies of 49 non-pharmacological strategies. The evidence was synthesized and structured into categories. The following eight categories were found: habitation and infrastructure; work; occupation and income; planning and management; social assistance; telehealth; communication; comprehensive health care; and education for people with disabilities. The deliberative dialogue allowed stakeholders—represented by people with disabilities, policymakers, decision-makers, health professionals, members of associations, and researchers—to actively engage in constructing the synthesis.

The stakeholder engagement concluded that the project promoted social inclusion and equal, universal, and comprehensive access to social rights by people with disabilities. The experiences of stakeholders in society were incorporated into public policy and guided decision-making in health and social care.

Most HTA processes follow similar institutional mechanisms, starting with topic selection and prioritization, followed by analysis (appraisal, deliberation, and decision-making) and implementation. The process of conducting an HTA is financially and time intensive. Therefore, to sustain HTA decision-makers, especially in countries with limited capacity, selecting topics for HTA that most respond to national needs is crucial.

Information on topic identification, selection, and prioritization (TISP) processes was taken from a recent report published by the Norwegian Institute of Public Health (NIPH) on how to support capacity building for HTA in low- and middle-income countries. An unpublished survey of 29 national HTA organizations around the world was also performed by the NIPH asking about their TISP processes. Issues around the institutional and organizational aspects necessary for explicit and transparent TISP processes were identified and discussed through an iterative process.

The comprehensiveness of TISP processes varied according to each country’s needs and the types of decisions supported by HTA. Accordingly, the resources available for allocation within the health system, the number of dedicated personnel available to complete HTAs, and the number stakeholders and institutions involved in the decision-making process may all be relevant considerations for TISP. In countries where HTA was well-established, the process for TISP was usually institutionalized or at least somewhat formalized. In settings where HTA was emerging or relatively new, or where there may not be the necessary supporting institutional mechanisms, there was limited normative guidance on how to implement TISP.

When institutionalizing HTA, we argue for including formal and explicit processes for the topic selection step that include: (i) a clear link to health system feasibility; (ii) process transparency to ensure legitimacy and impact; and (iii) patient and public engagement. Insights and experiences from countries with more formalized HTA systems can provide valuable lessons.

Incorporating technologies for ultrarare diseases (URD) poses challenges for global health technology assessment (HTA) agencies. Difficulties include defining an analytical framework and establishing differentiated cost-effectiveness thresholds. The rise of technological innovations intensifies demands from healthcare professionals, media, and the general population, placing pressure on healthcare systems in developing countries.

To analyze ultrarare medicine costs in submissions to the Brazilian National Committee for Health Technology Incorporation (CONITEC), data from HTA reports on URD (from 2012 to 2022) were extracted. Diseases were classified as URD based on an epidemiological criterion or Orphanet consultation (prevalence ≤1 per 50,000 inhabitants). Extracted variables included initial and final prices, annual patient cost, incremental cost-effectiveness ratio (ICER), and initial and final CONITEC recommendations. Price differences were calculated by the Brazilian Medicines Market Regulation Chamber.

Among 53 reports, 30 featured economic evaluations, with only 13.3 percent initially receiving positive recommendations. However, eight gained favor, including post-consultation, price-conditioned, and risk sharing-based approvals. Annual medication costs ranged from USD17,439.20 to USD1,108,237.00 per patient, with discounts of between 25 and 64 percent. Despite some technologies having ICERs that were significantly higher than the national threshold, no statistical relationship was found between ICERs and recommendations. Monthly and annual costs varied, with higher costs for heterogeneous diseases and lower costs for metabolic conditions. Sensitivity analyses, using both deterministic and probabilistic analyses, were conducted in 58 percent of the reports.

Incorporation of technologies for URD does not correlate with lower annual costs or increased discounts because costs are not considered in isolation by CONITEC’s decision-making process. Recognizing URD as a subgroup with distinct criteria may enhance the implementation of HTA processes tailored to the unique challenges of these conditions.

Gout is an inflammatory disease that can cause severe pain and permanent joint destruction if it is not treated appropriately. Despite readily available treatments, the management of gout in primary care is suboptimal. Hence, this study aimed to investigate gout knowledge and compliance with evidence-based clinical practice guidelines (CPGs) among private general practitioners (GPs) in Malaysia.

A cross-sectional study using stratified random sampling was conducted among private GPs in Selangor, Putrajaya, and Kuala Lumpur from October to December 2023. The survey consisted of four parts: inclusion and exclusion criteria, sociodemographic data, knowledge, and practice domain. A total of 15 questions were posed in the knowledge domain and nine questions in the practice domain. Statistical analysis was performed using R software (version 4.3.2). Descriptive statistics were used for initial analyses. Proportions were calculated for categorical data, which were tested using a chi-square test. A p-value of less than 0.05 was considered statistically significant.

The preliminary results from 203 private GPs showed that 64 percent had moderate knowledge of the management of gout. About two-thirds of the GPs were aware of local evidence-based CPGs on gout, but only 20 percent had good knowledge of gout. In the practice domain, only 65.5 percent of private GPs were aiming for a serum urate level of less than six milligrams per deciliter when starting urate-lowering therapy for gout.

Although most private GPs had moderate or good knowledge of gout, clinical practice was not fully concordant with the recommendations of local evidence-based CPGs. Our findings provide a foundation for local CPG developers and professional societies to enhance their strategies for implementing evidence-based CPGs and encouraging GPs in Malaysia to incorporate evidence-based practices into their clinical decisions.

In 2017 health technology assessment (HTA) was included in the Ukrainian Health Law fundamentals, and its implementation has accelerated as it became mandatory by 2020. As part of the Safe, Affordable, and Effective Medicines for Ukrainians project, funded by the U.S. Agency for International Development (USAID), to support the Ministry of Health in Ukraine, we developed, conducted, and evaluated a need-based HTA training program for doers, users, and trainers from July 2022 to August 2023.

We developed the training program based on a review of current academic HTA master’s and advanced programs globally, as well as an assessment of the training needs of the intended participants. The program consisted of five modules comprising 30 online sessions of four hours, with a mixture of lectures and work sessions complemented with self-study assignments and a targeted train-the-trainers program. We asked participants to report on their level of confidence in each learning objective at the start and the end of each module. A questionnaire was administered at the end of the program to evaluate participants’ satisfaction with study load, course content, and organization. This research was funded by USAID, reference number RFP-2021-11-18, through a contract with Management Sciences for Health under AID-121-C-17-00004. The contents do not necessarily reflect the views of USAID or the U.S. Government.

The five modules focused on the following: introduction to HTA; comparative effectiveness; health economics; qualitative evidence synthesis; patient and public involvement; and ethical, sociocultural, legal, and other relevant issues. Between 30 and 75 persons attended one or more of the training sessions. For each module, a learning effect was observed among participants. Among the 42 survey respondents, the average grade was excellent (9.5/10). The setup, organization, and content of the program and material provided, as well as the level of expertise provided by the teachers, were rated as very good.

Participants agreed that the program was relevant and contributed to their professional growth. Twelve academics and staff from the HTA body were trained to help sustain the program in Ukraine. The project resulted in HTA training for doers, users, and trainers in Ukraine, and can be an example for other countries wishing to increase sustainable HTA capacity.

Health technology assessment (HTA) became mandatory in Ukraine in 2020 for public coverage of new medicines. This review outlines the steps Ukraine took to introduce HTA at the hospital level through hospital-based HTA (HB-HTA). HB-HTA is a globally recognized, science-based tool that helps hospital stakeholders answer questions on the safety, efficacy, and cost effectiveness of health technologies they are planning to introduce.

The authors examined the steps taken to introduce and implement HB-HTA in Ukraine, the impacts reached thus far, and the implications for further national scale-up. Key steps associated with the intervention included the following: awareness raising activities in HB-HTA; structured stakeholder engagement; review of global HB-HTA tools and their adaptation to the local context; training for key hospital staff; piloting tools in a select hospital; and review of the pilot experience to inform future application.

Starting from 2021, HB-HTA was introduced through awareness raising activities. The regulatory framework for introducing health technologies into hospitals was analyzed, outlining the need for updated regulations. Review of global HB-HTA tools revealed that tools developed by the Adopting Hospital Based Health Technology Assessment in European Union project were the most applicable for Ukraine and were subsequently adapted to the country’s context by an expert panel of 13 hospital stakeholders. Following this, Safe, Affordable, and Effective Medicines for Ukrainians (SAFEMed) organized HB-HTA training for key hospital stakeholders. The Amosov National Institute of Cardiovascular Surgery was chosen for the pilot due to its high level of operational activity. The results of the pilot are expected soon.

Introducing globally recognized HB-HTA tools and piloting them in a real-world setting provides basic concepts to the HTA experts who will be involved in scaling up HB-HTA in Ukraine. Initial recommendations point to the need to scale-up HB-HTA slowly, first working with one hospital to gain HB-HTA experience that will inform further application across the country.

Health technology assessment (HTA) applications in low- and middle-income countries face limited technical capacities. The Institute for Clinical Effectiveness and Health Policy (IECS) is a key player in strengthening HTA expertise in the region and offers a variety of courses. Over 200 students from across Latin America have undertaken our introductory course on HTA and economic evaluation in the last four years.

The IECS provides a nine-week introductory online course focused on the fundamentals of HTA and economic evaluation. The course is designed for healthcare professionals (doctors, administrators, auditors, nurses, pharmacists, lawyers, etc.). The materials are available in Spanish and Portuguese on a virtual campus with asynchronous activities. Students are guided by instructors through an exchange forum. This study aimed to showcase the outcomes of this HTA course. Our analysis encompassed quantitative and qualitative data from a survey administered to nine student cohorts over the last four years. The surveys featured eight question categories covering materials, activities, quizzes, course dynamics, forum usage, tutoring, and satisfaction.

A total of 234 students from Latin America were enrolled in the course. More than half came from Argentina (68%). Of the initial enrollees, 212 (91%) started the course and 192 (91%) of them passed. The satisfaction survey was completed by 168 students. Ninety-six percent of students were satisfied or very satisfied with the course overall, and the same percentage would recommend it to a colleague. Eighty-six percent felt that they could adequately follow the course, and 40 percent of students dedicating an average of two to four hours per week to the course.

Having accessible and feasible training opportunities in the region is important. The IECS HTA and economic course enhances HTA expertise in Latin America, as evidenced by its high rates of enrolment, completion, and satisfaction, with over 90 percent of participants recommending it. This underscores its effectiveness in reinforcing health decision-making knowledge in Latin America and contributing to the advancement of health policy.

The Brazilian Health Technology Assessment (HTA) Network (REBRATS) dates to 2008, when the Ministry of Health (MoH) launched a call to register Brazil’s first HTA groups to promote and disseminate HTA in the country. To understand whether this strategy is succeeding, this paper evaluated the actions of REBRATS and the degree of advancement of the HTA field in Brazil.

The following data on the composition of REBRATS were collected and analyzed: the number of HTA groups and professionals registered in the network, the number of professionals that have benefited from qualifying courses, and the evolution of the Brazilian National Committee for Health Technology Incorporation (CONITEC).

REBRATS expanded from 24 HTA groups to 112 groups in 2023, which includes over 800 professionals. From 2019 to 2023, the MoH financed over 90 courses, which have benefited more than 1,000 professionals. More HTA groups (from five to 23) have been hired to support CONITEC, enabling it to respond to a higher demand and more complex topics. These groups have been contributing to the development of HTA by assisting the MoH in defining a cost-effectiveness threshold; evolving the assessment of medical devices and new technologies (i.e., gene and targeted therapies); and creating methodological guideline–there will be 21 by 2024.

Although the composition and technical capability of its member groups vary greatly, REBRATS has consolidated itself as a key strategy to support decision-making regarding technologies.

Bariatric surgery is a weight loss procedure that supports significant and long-term weight loss for individuals with severe obesity by altering the digestive system. It improves health conditions associated with obesity and can be life changing. The purpose of the study was to examine the reimbursement criteria for bariatric surgery in certain countries.

A detailed review was conducted on bariatric surgery reimbursement criteria across 23 countries, analyzing official policies and guidelines from databases and government websites. The study compared national data to highlight similarities and differences in these criteria, offering insights into the varying reimbursement approaches for bariatric surgery internationally.

The research compared global reimbursement policies for bariatric surgery, revealing that Australia, Belgium, Canada, Denmark, Egypt, France, Germany, Italy, Morocco, Russia, Saudi Arabia, Spain, Sweden, the Netherlands, Türkiye, and the UK support reimbursement for those with a body mass index over 40 kg/m2. However, Hungary, Nigeria, Libya, and Romania do not offer such reimbursements. This discrepancy highlights the diverse healthcare approaches to severe obesity treatment across countries. The absence of financial support in some regions indicates varying health priorities and economic constraints. These findings emphasize the need for harmonized global health policies, especially for obesity, which is a significant public health issue.

The study highlights substantial disparities in bariatric surgery reimbursement criteria across countries. These differences, despite the proven benefits of treating severe obesity and related health issues, suggest a need for more standardized reimbursement approaches. Future research should explore the specific conditions and requirements for reimbursement and how these policies impact access to and outcomes of bariatric surgery.

Economic criteria have become critical for health technology assessment (HTA) due to the rising costs of health technologies. The use of explicit, predefined criteria for economic evaluations enhances the transparency, objectivity, and predictability of the process. We aimed to identify which organizations worldwide integrate explicit and predefined criteria into their health economic analyses during HTA.

We conducted a scoping review to identify organizations responsible for HTA processes at the national level in any country. The identification of eligible organizations was carried out by reviewing members of the EUnetHTA, HTAsiaLink, INAHTA, and RedETSA networks as well as organizations evaluated in reviews with a similar scope. For each eligible organization, information was extracted on the inclusion of economic factors during decision-making and the existence of predefined criteria for judging the results of economic evaluations.

Sixty-nine organizations from 56 countries were identified, of which 66 (96%) considered economic factors for HTA. Fifty-two (79%) organizations conducted cost-effectiveness analyses, 42 (64%) assessed budget impact, and one focused solely on total technology costs. Thirty-four organizations (51%) declare not having criteria for economic evaluation, whereas 14 (21%) from 12 countries had explicit criteria. There were no data found for 18 organizations (27%). Among the organizations with explicit criteria, 11 (17%) applied willingness-to-pay thresholds in cost-effectiveness evaluations and five (8%) applied criteria related to budget impact for decision-making, such as a maximum percentage of budget impact.

Although most organizations consider economic factors for HTA, many do not have explicit, predefined criteria for decision-making. Among those that presented such criteria, willingness-to-pay thresholds for cost-effectiveness analyses were the most common. The findings of this study also help to identify complementary factors that can be considered to promote greater systematization and transparency in the decision-making process.

As health technology assessment (HTA) bodies introduce more rigorous requirements, the submission process is becoming increasingly diverse between countries. This study assessed the HTA submission processes and requirements in Australia, Canada, England, France, and Germany. This helps identify where efficiencies can be made in the global market access strategy, such as when to submit HTA dossiers.

A pragmatic review and desk-based research were conducted in November 2023. Published articles, HTA guidelines, process documents, conference abstracts, and white papers were reviewed to identify country-specific processes with implications for market access strategy. Where available, information was extracted about the general submission process and stakeholders involved (including regulatory, HTA, and pricing authorities), clinical evidence requirements, and pharmacoeconomic evidence requirements for HTA submission. Comparisons of the median time from marketing authorization to HTA decision within each country allowed the identification of efficiencies in individual HTA submission processes. The key findings and between-country differences were summarized narratively.

The review identified several areas with implications for market access strategy. The median HTA review time was shortest in Australia (125 days) and longest in England (266 days). Australia and Canada have both sequential and parallel regulatory and HTA processes. The median time taken from regulatory approval to HTA recommendation was faster with the parallel process than with the sequential process in both countries. All countries required comparative clinical evidence within the indication. The weight placed on pharmacoeconomic evidence varied between countries. In Germany, economic evaluation has yet to play a real role. Requirements for additional information after HTA submission occurred within all HTA bodies.

HTA processes in Australia, Canada, England, France, and Germany differ from one another. This will likely affect the market access strategy for health technology developers. Similar requirements allow efficiencies in the preparation of submission documentation. Future research should investigate the impact of the European Union HTA regulation on market access and how this could affect strategic decision-making.

Hospital-based health technology assessment (HB-HTA) is evolving constantly. In 2023, a survey was conducted by the HB-HTA Interest Group of Health Technology Assessment International with the aim of collecting data on HB-HTA activities, including perceptions of the role of, potential for, and barriers to HB-HTA. Overall, 87 responses were collected: 41 from hospitals performing health technology assessment (HTA), 18 from hospitals not conducting HTA, and 28 from policymakers.

The survey collected data from 28 countries. Italy, Poland, Brazil provided the highest number of responses. We conducted a descriptive comparative analysis focusing on these three countries to investigate whether and how the policies for HB-HTA, the activities of HB-HTA, and the perceptions of HB-HTA differed among policymakers and hospitals not performing HTA.

Overall, 19 responses were collected from Italy and 10 each were collected from Brazil and Poland. While Italy (n=10) and Brazil (n=8) had a high number of responses from hospitals performing HB-HTA, most of the responses from Poland (n=9) were from hospitals not performing HTA. There was a lack of policies for HB-HTA in all three countries. HTA was performed in big hospitals (≥500 beds) in Italy and Brazil. HB-HTA covered all kinds of technologies, including digital health. In Poland, hospitals not conducting HTA recognized the ability of HB-HTA to promote cost containment. Policymakers were open to including HB-HTA in their activities.

Interpreting the diffusion of HB-HTA, its integration with other HTA processes, and the perceptions of its pros and cons should be both country specific and be conducted from an international perspective. The analysis demonstrated the need for specific policies and for better dissemination and promotion of HB-HTA activities and collaborations with HTA agencies.

Quick and equitable market access to vaccines is a global priority. However, market access routes for vaccines are complex and differ from those for pharmaceuticals. Furthermore, there is variation in decision-making between countries due to local requirements. This work aimed to increase awareness of the key elements of these pathways and the stakeholders involved in European Union (EU) and non-EU countries.

Pragmatic desk-based research was undertaken in November 2023 to explore key elements of the market access pathways for vaccines and how these differ between countries. Specifically, the countries of interest were Canada, England, France, Germany, Italy, Spain, and the USA. Where available, information was extracted about the key stages and stakeholders involved in the decision-making pathway as well as details about any post-licensing monitoring, the value assessment framework used, vaccine pricing, and the procurement process. In addition, examples of barriers to vaccine access were extracted. The key findings and between-country differences were summarized narratively.

National Immunization Technical Advisory Groups (NITAGs) were key stakeholders in all countries explored and had varying roles. The evidence requirements differed among countries, such as Germany’s requirement for economic and epidemiological modeling. The Vaccine Monitoring Platform coordinates studies for post-authorization monitoring of vaccines across EU countries. However, England is not part of this network and uses a national agency instead. Vaccine procurement and pricing also differed (e.g., France uses individual reimbursement, England uses national tendering, and Canada uses regional tendering). There was variation in vaccine pricing within the USA, depending on the healthcare provider. Barriers to vaccine access were well reported.

These results can influence the market access strategy of vaccine developers to ensure rapid and equitable vaccine access across countries. Several between-country differences in vaccine market access routes were identified; for example, the role of NITAGs, evidence requirements, and post-licensing monitoring processes. Barriers to vaccine access have been reported in the literature, with some organizations providing recommendations to overcome these.

Last year we developed a survey focused on decision-making in health innovation within the health system of Catalonia. Evaluation of the survey results, coupled with the relationships we established with various members of the Catalan health ecosystem, has highlighted the need for informative activities on health technology assessment (HTA) that aim to bring HTA closer to healthcare professionals.

We designed a two-hour training workshop divided into three thematic blocks and a group dynamic. The first block addressed HTA and the lifecycle of a health technology. The second and third blocks delved into the development of an HTA report, the role of healthcare professionals, and the formulation of a research question. During the workshops, we showcased a video and an infographic and distributed promotional bags to the attendees. A satisfaction survey was distributed at the conclusion of the workshop. We have conducted three editions of the workshop in a face-to-face format and one in a virtual format.

Of the 56 people who participated in the workshops, 48 responded to the satisfaction survey. The most frequent participants were directors, care coordinators, and health managers. The attendees rated the workshops with 4.6 out of five points. About 66.7 percent of attendees indicated that the workshop had met their training needs. Most attendees (79.2%) considered that the workshop had provided knowledge that they could apply to their daily tasks. Finally, when asked about topics of interest for future workshops, the participants voted for advanced HTA methodology, the development of HTA in healthcare centers, and the evaluation of digital health.

The feedback from participants across all the workshops was very positive. The degree of satisfaction among attendees was high, with the main area for improvement being the need to develop new workshops to delve deeper into HTA. In 2024, we aim to design a training program consisting of HTA workshops that fulfil the requests of the attendees.

To enhance the impact of health technology assessment (HTA) on Catalonia’s health system, a summary product called “synthesis” was developed. It presents the key information from HTA reports. After initial development and pilot testing, we developed a final version. Our aim was to evaluate its impact on decision-making at different levels.

We prepared an eight-question survey to assess the impact of the 15 syntheses that were published on the Agency for Health Quality and Assessment of Catalonia (AQuAS) website in 2023. We asked about the role of the healthcare professionals answering the questions, why they used the information of the syntheses, and whether they read the associated HTA report later and recommend it. We invited the professionals of the Catalan health system, providers, and payers to answer the survey by email. The survey also was published on the AQuAS website.

We obtained 31 responses. The roles of the professionals who answered the questions were mainly directors and managers of the institutions of the Catalan health system (45.2%), healthcare professionals (32.3%), and care managers (12.9%). Most of them consulted the synthesis to update their knowledge about a specific topic (71.0%), obtain reliable data (35.5%), or support a strategic or professional decision (29.0%). The HTA report related to each synthesis was only consulted in some cases (38.7%) but was recommended in almost all cases (93.5%).

Summarizing the most important information of an HTA report in a new product can be a useful tool for improving the impact of the HTA on the Catalan health system. Professionals who answered the survey agreed that the syntheses helped them in making decisions related to the health technologies.

If regulation and health technology assessment (HTA) are to be aligned, we must understand regulation and regulatory policy goals. Furthermore, regulatory policy is most likely to achieve its goals if it is informed by theory and underpinned by evidence. However, regulatory theories are rarely explored by HTA bodies. Therefore, this study explored regulatory theories as they relate to medical device regulation.

Literature describing regulatory theories was reviewed and synthesized narratively to explain what is meant by regulation and why governments regulate. Competing theories were discussed, reflecting on their relevance to the regulation of medical devices.

The theory of perfect competition suggests that, when key assumptions hold true, market forces will result in the most efficient allocation of resources. However, when they don’t, market failure results. Governments frequently regulate such markets. Stigler suggests that they do so to serve either public or private interests. Market failure is the norm in health care, so it requires regulation. If medical device regulation is intended to serve the public interest, it should be patient-centered, balance market power amongst many producers, reduce information asymmetry, and ensure that only safe and effective devices enter the market. HTA assumes a public interest perspective.

Regulations that maintain the confidentiality of clinical evidence underpinning medical devices and allow them to enter healthcare markets with insufficient evidence of efficacy do not serve the public interest. This raises the questions of whose interests does medical device regulation serve, and can HTA align with this?

As the newly independent regulator for medicines in the UK post-Brexit, the Medicines and Healthcare products Regulatory Agency (MHRA) has entered international regulatory collaborations, notably Project Orbis (PO) and the Access Consortium (AC), to help expedite marketing authorizations. This research compared regulatory and reimbursement outcomes for medicines approved in Great Britain through PO and the AC with corresponding outcomes from the EU4Health Programme.

Products approved by the MHRA through PO and the AC were identified from the PO and New Active Substance Work Sharing Initiative websites, respectively. Marketing authorization dates and reimbursement outcomes were obtained from the respective regulatory and health technology assessment body websites on 20 November 2023.

A total of 21 products have been authorized by the MHRA through either PO (17/21) or the AC (4/21); 17 of 21 have been authorized in Europe. Approval by the MHRA was 54 days earlier on average than for the European Medicines Agency. The results for various countries were as follows:

• • England: 14 of 21 (67%) products assessed (9/14 [64%] recommended);

• • Scotland: 14 of 21 (67%) products assessed (11/14 [79%] recommended);

• • France: 14 of 21 (67%) products assessed (2/14 [14%] received Amélioration du Service Médical Rendu level I to III);

• • Germany: 14 of 21 (67%) products assessed (5/14 [36%] achieved additional benefit);

• • Italy: 10 of 21 (48%) products assessed (9/10 [90%] reimbursed); and

• • Spain: 10 of 21 (48%) products assessed (7/10 [70%] reimbursed).

Days from regulatory approval to HTA were 306 (Scotland), 308 (France), 310 (UK), 330 (Germany), 398 (Spain), and 404 (Italy).

Compared with the EU4Health Programme, PO and the AC have enabled earlier marketing authorizations for medicines in the UK by an average of seven weeks. However, the proportion of therapies reimbursed and the delay from marketing authorization to reimbursement were comparable or more favorable for UK health technology assessment bodies. Thus, the UK may become a first-to-launch European market for certain therapies through PO and the AC.

The European parliament is working on a proposal for an Artificial Intelligence (AI) Act. The goal is to guarantee that AI systems used in the European Union are “safe, transparent, traceable, non-discriminatory and environmentally friendly.” The Act is not directly linked to health technology assessment (HTA), but implications for HTA are expected.

The final aim of the AI Act is the adoption of harmonized rules for AI foundation models. Foundation models are designed to produce a wide variety of outputs that are being adopted across various sectors. Therefore, their adaptation to specific (clinical) needs plays a key role and has implications on the required training data. The goal of our analysis was to critically investigate the potential implications of the Act’s requirements for HTA. The analysis moves from the technology (foundation models in health care) to the requirements and adopted terminology.

The definition of methods to assess the adaptation of foundation models has become a priority for HTA. The Act focuses on data quality, transparency, human oversight, and accountability. Available frameworks, such as the one developed by the AI MIND project, include them, but experience is required. HTA must define how to adapt its methods and frameworks as well as the risk levels addressed by the Act. In addition, the reference to energy efficiency standards confirms the need for HTA to clarify the role of and methods for environmental impact assessment. Finally, the patient perspective has great relevance in relation to the risk of discrimination.

The AI Act confirms the importance of topics already debated in HTA that still need resolution and testing. Harmonization of rules for AI and approaches for HTA is the main challenge. The AI Act, the HTA regulation, and ongoing European Union projects (i.e., AI-MIND and European Digital Health Technology Assessment) are showing the route to follow in the coming years.

Globally, 7,000 rare diseases affect 300 million people, which poses challenges for developing treatments in these discrete patient populations. Developing medicines for rare diseases requires innovation, but despite regulatory incentives challenges persist for health technology assessment (HTA) and payers. Understanding the current regulatory and HTA decision-making landscape for orphan products is essential for all stakeholders.

Data on new active substances (NAS) approvals (2013 to 2022) by the European Medicines Agency, the United States Food and Drug Administration (FDA), the Pharmaceuticals and Medical Devices Agency (PMDA), Swissmedic, and the Therapeutic Goods Administration were collected to analyze the timing, approval pathways, and global rollout trends for orphan and non-orphan products. Data were collected from HTA agencies in Australia, England, France, Germany, the Netherlands, Poland, Scotland, and Sweden to explore synchronization in decision timing and first HTA decision. Comparative analysis encompassed decision frameworks and funding mechanisms for orphan products among HTA agencies.

Orphan drug approvals increased in the past decade, with the FDA having the highest designation rate (55% for 2018 to 2022). Flexible pathways, mostly used by the FDA (92%) and the PMDA (100%), expedited orphan drug reviews. However, international submissions for orphan drugs experienced longer gaps than non-orphan drugs across the jurisdictions. Divergence in rollout timing to HTA and recommendation resulted from varied submission strategies and review processes. Only the Scottish Medicines Consortium had a dedicated orphan pathway. In England, the National Institute for Health and Care Excellence patient access and managed access agreements (84% of orphan recommendations) and cancer drug fund (45% of orphan recommendations) facilitated patient access.

The study shows a decade long rise in global orphan drug approvals, underpinned by regulatory flexibility, particularly by the FDA and the PMDA. Identified divergences in decision frameworks among regulatory and HTA agencies, as well as HTA agencies themselves, call for increased stakeholder alignment. This necessitates synchronizing evidence generation during development and improving decision frameworks for streamlined review and reimbursement processes.

Randomized controlled trials are ideal for securing marketing authorization (MA) for pharmaceuticals. However, ethical and feasibility constraints have led to the use of noncomparative trials by regulatory bodies to balance evidence uncertainty and patient access, especially for medicines addressing rare diseases or unmet healthcare needs. This research focused on pharmaceuticals approved with noncomparative data and how these translate into reimbursement outcomes.

Indications approved by the European Medicines Agency (EMA) between January 2018 and October 2023 based on noncomparative data were identified. Generics and biosimilars were excluded. Approvals based on non-comparative trial data were identified from European public assessment reports and from “Procedural steps taken and scientific information after authorization” documents. The latter were also used to identify changes in MAs after submission of new data. Missing trial information was extracted from ClinicalTrials.gov. Health technology assessment (HTA) outcomes from the EU4Health programme and the UK were extracted from agency websites.

The EMA approved 46 indications based on noncomparative data: 18 of the 46 (39%) received full MA, 23 (50%) received conditional MA (CMA), and five (11%) had a CMA converted to full MA with additional data. The results for HTAs conducted in various countries were as follows:

• • England: 29 of 46 (63%) indications assessed, (23/29 [79%] recommended);

• • Scotland: 28 of 46 (61%) indications assessed, (20/28 [71%] recommended);

• • France: 33 of 46 (72%) indications assessed, (7/33 [21%] received Amélioration du Service Médical Rendu level I to III);

• • Germany: 37 of 46 (80%) indications assessed, (2/37 [5%] achieved additional benefit);

• • Italy: 37 of 46 (80%) products assessed, (33/37 [89%] reimbursed); and

• • Spain: 34 of 46 (74%) products assessed, (23/34 [68%] reimbursed).

Indications approved by the EMA with noncomparative data achieved mixed HTA outcomes in the EU4Health programme and the UK. More negative outcomes were seen in markets with clinical-benefit payer archetypes (France and Germany). All conversions from CMA to full MA occurred within the last 24 months.