Towards a coordinated approach for managing accelerated patient access to potentially beneficial medicines: reporting the perspectives of a multi-stakeholder, international workshop.

Accelerated and conditional regulatory pathways for drug approvals are intended to enable earlier patient access to potentially life-saving treatments, or treatments that provide benefits in addressing a significant unmet need. However, there are questions about how well such pathways work, how appropriately they are applied, and how the work of regulators can be better coordinated with that of health technology assessment (HTA) and payer bodies, providers and health systems, and other stakeholders. In June 2023, a multi-stakeholder, international workshop was convened in Adelaide, Australia, to deliberate the challenges, goals, and opportunities to improve accelerated access pathways. Workshop attendees included representatives from patient organizations, regulators, HTA/payer bodies, universities (ethicists, health economists), and companies developing and marketing new medicines from Australia, Asia, Europe, and North America. We reviewed the contents of this workshop to identify areas of agreement and disagreement, report the key themes of the discussion, and delineate next steps for improving accelerated access pathways. We found that there was general agreement among workshop attendees that accelerated access could be improved significantly by strengthening processes for stakeholder coordination, and that coordinated efforts will be required to implement meaningful change moving forward.

Patient-Informed Value Elements in Cost-Effectiveness Analyses of Major Depressive Disorder Treatment: A Literature Review and Synthesis.

OBJECTIVES: Prior work identified six key value elements (attributes of treatment and desired outcomes) for individuals living with major depressive disorder (MDD) in managing their condition: Mode of Treatment, Time to Treatment Helpfulness, MDD Relief, Quality of Work, Interaction with Others, and Affordability. The objective of our study was to identify whether previous cost-effectiveness analyses (CEAs) for MDD treatment addressed any of these value elements. A secondary objective was to identify whether any study engaged patients, family members, and caregivers in the model development process. METHODS: We conducted a systematic literature review to identify published model-based CEAs. We compared the elements of the published studies to the MDD patient value elements elicited in prior work to identify gaps and areas for future research. RESULTS: Of 86 published CEAs, we found that seven included patient out-of-pocket costs, and 32 included measures of productivity, which were both priorities for individuals with MDD. We found that only two studies elicited measures from patients for their model and two studies engaged patients in the modeling process. CONCLUSIONS: Published CEA models for MDD treatment do not regularly include value elements that are a priority for this patient population, nor do they include patients in their modeling process. Flexible models that can accommodate elements consistent with patient experience are needed and a multi-stakeholder engagement approach would help accomplish this.

Health technology assessment in musculoskeletal radiology: the case study of EOSedge™.

OBJECTIVES: Health technology assessment (HTA) is a systematic process used to evaluate the properties and effects of healthcare technologies within their intended use context. This paper describes the adoption of HTA process to assess the adoption of the EOSedge™ system in clinical practice. METHODS: The EOSedge™ system is a digital radiography system that delivers whole-body, high-quality 2D/3D biplanar images covering the complete set of musculoskeletal and orthopedic exams. Full HTA model was chosen using the EUnetHTA Core Model® version 3.0. The HTA Core Model organizes the information into nine domains. Information was researched and obtained by consulting the manufacturers' user manuals, scientific literature, and institutional sites for regulatory aspects. RESULTS: All nine domains of the EUnetHTA Core Model® helped conduct the HTA of the EOSedge, including (1) description and technical characteristics of the technology; (2) health problem and current clinical practice; (3) safety; (4) clinical effectiveness; (5) organizational aspects; (6) economic evaluation; (7) impact on the patient; (8) ethical aspects; and (9) legal aspects. CONCLUSIONS: EOS technologies may be a viable alternative to conventional radiographs. EOSedge has the same intended use and similar indications for use, technological characteristics, and operation principles as the EOS System and provides significant dose reduction factors for whole spine imaging compared to the EOS System without compromising image quality. Regarding the impact of EOS imaging on patient outcomes, most studies aim to establish technical ability without evaluating their ability to improve patient outcomes; thus, more studies on this aspect are warranted.

[Challenges of Delivering Healthcare from an Economic and Public Finance Perspective].

As populations grow older, the sustainability of current healthcare systems is being questioned. This paper considers what is necessary to ensure the sustainability of the healthcare system in Japan from the perspective of economics and public finance. In particular, it addresses the cost-effective use of limited medical resources. It also considers the problems of current regulations and regulatory regimes, which tend to protect vested interests. It may be necessary to carry out fundamental reforms of the regulatory system to deliver a sustainable healthcare system.

Assessing Real-World Data From Electronic Health Records for Health Technology Assessment: The SUITABILITY Checklist: A Good Practices Report of an ISPOR Task Force.

This ISPOR Good Practices report provides a framework for assessing the suitability of electronic health records data for use in health technology assessments (HTAs). Although electronic health record (EHR) data can fill evidence gaps and improve decisions, several important limitations can affect its validity and relevance. The ISPOR framework includes 2 components: data delineation and data fitness for purpose. Data delineation provides a complete understanding of the data and an assessment of its trustworthiness by describing (1) data characteristics; (2) data provenance; and (3) data governance. Fitness for purpose comprises (1) data reliability items, ie, how accurate and complete the estimates are for answering the question at hand and (2) data relevance items, which assess how well the data are suited to answer the particular question from a decision-making perspective. The report includes a checklist specific to EHR data reporting: the ISPOR SUITABILITY Checklist. It also provides recommendations for HTA agencies and policy makers to improve the use of EHR-derived data over time. The report concludes with a discussion of limitations and future directions in the field, including the potential impact from the substantial and rapid advances in the diffusion and capabilities of large language models and generative artificial intelligence. The report's immediate audiences are HTA evidence developers and users. We anticipate that it will also be useful to other stakeholders, particularly regulators and manufacturers, in the future.

Pharmaceutical innovativeness index: methodological approach for assessing the value of medicines - a case study of oncology drugs.

BACKGROUND: We propose a framework to assess the value of pharmaceutical innovations, with explicit clinical and methodological parameters, based on the therapeutic value and health needs. RESEARCH DESIGN AND METHODS: The study was based on the adaptation of health technology assessment methods documented in the literature, which was applied to a sample of oncological drugs. Difficulties and issues during the application of those tools were identified and addressed to develop a new framework with new and revised domains and clear classification criterion for each domain. Scores were assigned to each level and domain according to their relevance to generate the final score of innovativeness. RESULTS: The Pharmaceutical Innovation Index (PII) includes four domains, two related to clinical and social dimensions - Therapeutic Need and Added Therapeutic Value - and other two about methodological features - Study Design and Quality (risk of bias). The scores combined after assigned to each domain results Index of the Innovativeness of the medicines represents the degree of pharmaceutical innovation. CONCLUSION: This work proposes a transparent methodology with well-defined criteria and script; the algorithm developed with authors' weightings and criteria may be switched to best adjust to other applications, perspective or clinical indications, while keeping the transparency and objectiveness.

A targeted review of worldwide indirect treatment comparison (ITC) guidelines and best practices.

OBJECTIVES: Controls and governance over the methodology and reporting of indirect treatment comparisons (ITCs) have been introduced to minimize bias and ensure scientific credibility and transparency in healthcare decision-making. The objective of this study was to highlight ITC techniques that are key to conducting objective and analytically-sound analyses, and to ascertain circumstantial suitability of ITCs as a source of comparative evidence for healthcare interventions. METHODS: Ovid MEDLINE® was searched from January 2010 through August 2023 to identify publicly available ITC-related documents (i.e., guidelines and best practices) in the English language. This was supplemented with hand-searches of websites of various international organizations, regulatory agencies, and reimbursement agencies of Europe, North America, and Asia-Pacific. The jurisdiction-specific ITC methodology and reporting recommendations were reviewed. RESULTS: Sixty-eight guidelines from 10 authorities worldwide were included for synthesis. Many of the included guidelines were updated within the last five years and commonly cited the absence of direct comparative studies as primary justification for employing ITCs. Most jurisdictions favored population-adjusted or anchored ITC techniques opposed to naïve comparisons. Recommendations on the reporting and presentation of these ITCs varied across authorities; however, there was some overlap among the key elements. CONCLUSIONS: Given the challenges of conducting head-to-head randomized controlled trials, comparative data from ITCs offer valuable insights into clinical effectiveness. As such, multiple ITC guidelines have emerged worldwide. According to the most recent versions of the guidelines, the suitability and subsequent acceptability of the ITC technique employed depends on the data sources, available evidence, and magnitude of benefit/uncertainty.

Consensus-Based Recommendations for the Implementation of Health Technology Assessment in the United Arab Emirates.

OBJECTIVES: Healthcare research and development have accelerated at an unprecedented rate creating a challenge even for high-income countries to finance all new technologies. Health technology assessment (HTA) aims to maximize health gains out of available resources. Our study aimed to provide tailor-made recommendations for HTA implementation in the United Arab Emirates (UAE). METHODS: We conducted a policy survey to explore the gap between the current and preferred future environment of HTA implementation in the UAE. The survey was distributed in 2 workshops discussing the importance of HTA implementation, and results were further aggregated to yield a list of draft recommendations. Recommendations were then assessed for their feasibility in a round table discussion with experts in the field to generate actions for HTA implementation. RESULTS: Survey results and round table discussion indicated the need to leverage HTA for value-based decision making. Experts confirmed the unmet need for broader coverage of graduate and postgraduate HTA training with the aim of specific PhD programs in the UAE. Public funding for HTA appraisals and expanding the scope of HTA to nonpharmaceuticals was recommended. Furthermore, experts recommended that several HTA bodies should be coordinated centrally and highlighted the importance of having an explicit soft cost-effectiveness threshold for common technologies and a higher threshold for orphan drugs. CONCLUSIONS: Although HTA in the UAE is still in its early stages, strong initiatives are being taken for its implementation. Our survey results served as a step in developing a detailed action plan for HTA implementation that will enhance the sustainability of the healthcare system.

Understanding the Normativity of Health Technology Assessment: Ontological, Moral, and Epistemological Commitments.

The inherent normativity of HTA can be conceptualized as a result of normative commitments, a concept that we further specify to encompass moral, epistemological and ontological commitments at play in the practice of HTA. Based on examples from literature, and an analysis of the example of assessing Non-Invasive Prenatal Testing (NIPT), we will show that inevitable normative decisions in conducting an assessment commits the HTA practitioner to moral (regarding what makes a health technology desirable), ontological (regarding which effects of health technology are conceivable), and epistemological (regarding how to obtain reliable information about health technology) norms. This highlights and supports the need for integrating normative analysis and stakeholder participation, providing guidance to HTA practitioners when making normative choices. This will foster a shared understanding between those who conduct, use, or are impacted by assessments regarding what are conceivable and desirable outcomes of using health technology, and how to collect reliable information to assess whether these outcomes are (going to be) realized. It also provides more insight into the implications of different normative choices.

Project SATURN- a real-world evidence data collaboration with existing European datasets in Osteogenesis Imperfecta to support future therapies.

Regulatory marketing authorisation is not enough to ensure patient access to new medicinal products. Health Technology Assessment bodies may require data on effectiveness, relative effectiveness, and cost-effectiveness. Healthcare systems may require data on clinical utility, savings, and budget impact. Furthermore, the exact requirements of these bodies vary country by country and sometimes even region to region, resulting in a patchwork of different data requirements to achieve effective, reimbursed patient access to new therapies. In addition, clinicians require data to make informed clinical management decisions. This requirement is of key importance in rare diseases where there is often limited data and clinical experience at the time of regulatory approval.This paper describes an innovative initiative that is called Project SATURN: Systematic Accumulation of Treatment practices and Utilization, Real world evidence, and Natural history data for the rare disease Osteogenesis Imperfecta. The objective of this project is to generate a common core dataset by utilising existing data sources to meet the needs of the various stakeholders and avoiding fragmentation through multiple approaches (e.g., a series of individual national requests/approaches, and unconnected with the regulators' potential requirements). It is expected that such an approach will reduce the time for patient access to life-changing medications. Whilst Project SATURN applies to Osteogenesis Imperfecta, it is anticipated that the principles could also be applied to other rare diseases and reduce the time for patient access to new medications.

Evaluation of sustainable hydrogen production technologies on an industrial scale using comparative analysis of decision-making methods.

Due to its various advantages in different industrial fields, hydrogen can provide energy based on sustainability goals and recreates a critical function in the economy of countries. In this regard, evaluating hydrogen production technologies on an industrial scale is necessary for industrial development and economic growth. Therefore, this study proposes a comprehensive, integrated framework of hybrid fuzzy decision-making for assessing hydrogen production technologies in Iran. In addition to considering sustainability factors, political, technical, and reliability indicators are also assessed in this research to make a comprehensive assessment. The Fuzzy Step-wise Weight Assessment Ratio Analysis (F-SWARA) technique determines the importance of indicators, and the Fuzzy Weighted Aggregates Sum-Product Assessment (F-WASPAS) approach ranks technologies. The weighing findings indicated that the sub-indices of investment cost, technical infrastructure development, and implementation costs were introduced as the most significant sub-indices with weights of 0.226, 0.151, and 0.126, respectively. The evaluation findings with the F-WASPAS method and comparative analysis with various decision-making methods revealed that electrolysis based on solar energy and electrolysis based on wind energy technologies had the highest preference. In this regard, the infrastructure and costs of hydrogen production can be improved by presenting various incentives, such as improving financial conditions while attracting investment and increasing cooperation with top companies. So, sustainable development, economic growth, and industrial development are provided.

Mapping Health Technology Assessment Agency Approaches for Biosimilar Value Assessment: An ISPOR Special Interest Group Report.

OBJECTIVES: A systematic literature review undertaken by the ISPOR Biosimilar Special Interest Group highlighted that limited guidance exists on how to assess biosimilars value and on appropriate economic evaluation techniques. This study described current health technology assessment (HTA) agency approaches for biosimilar value assessment. METHODS: Semi-structured interviews (n = 16) were carried out with HTA experts in Africa, America, Asia, Australia, and Europe to investigate current HTA practices for biosimilars. Data categorization was based on a thematic analysis approach. Findings from the qualitative data analysis were interpreted in view of relevant published literature. RESULTS: Our research suggests that in systems in which frameworks for biosimilar regulatory approval are well established, HTA agencies can accept the regulators' comparability exercise, and reimbursement decisions can generally be based on price comparisons. This approach is accepted in practice and allows streamlining of biosimilars value assessment. Nevertheless, conducting HTAs for biosimilars can be relevant when (1) the originator is not reimbursed, (2) the biosimilar marketing authorization holder seeks reimbursement for indications/populations, pharmaceutical forms, methods and routes of administration that differ with respect to the originator, and (3) a price premium is sought for a biosimilar based on an added-value claim. Further, HTA agencies' role conducting class-review updates following biosimilar availability can support greater patients' access to biologics. CONCLUSIONS: Internationally, there are differences in how national competent authorities on pricing and reimbursement of pharmaceuticals perceive HTA's role for biosimilars. Therefore, HTA agencies are encouraged to issue clear guidance on when and how to conduct HTAs for biosimilars, and on which economic techniques to apply.

Estimating Taiwan's QALY league table for catastrophic illnesses: Providing real-world evidence to integrate prevention with treatment for resources allocation.

BACKGROUND/PURPOSE: Curative technologies improve patient's survival and/or quality of life but increase financial burdens. Effective prevention benefits all three. We summarize estimation methods and provide examples of how much money is spent per quality-adjusted life year (QALY) or life year (LY) on treating a catastrophic illness under a lifetime horizon and how many QALYs/LYs and lifetime medical costs (LMC) could be potentially saved by prevention. METHODS: We established cohorts by interlinkages of Taiwan's nation-wide databases including National Health Insurance. We developed methods to estimate lifetime survival functions, which were multiplied with the medical costs and/or quality of life and summed up to estimate LMC, quality-adjusted life expectancy (QALE) and lifetime average cost per QALY/LY for catastrophic illnesses. By comparing with the age-, sex-, and calendar year-matched referents simulated from vital statistics, we obtained the loss-of-QALE and loss-of-life expectancy (LE). RESULTS: The lifetime cost-effectiveness ratios of ventilator-dependent comatose patients, dialysis, spinal cord injury, major trauma, and cancers were US$ 96,800, 16,200-20,000, 5500-5,900, 3400-3,600, and 2900-11,900 per QALY or LY, respectively. The successful prevention of lung, liver, oral, esophagus, stomach, nasopharynx, or ovary cancer would potentially save US$ 28,000-97,000 and > 10 QALYs; whereas those for end-stage kidney disease, stroke, spinal injury, or major trauma would be US$ 55,000-300,000 and 10-14 QALYs. Loss-of-QALE and loss-of-LE were less confounded indicators for comparing the lifetime health benefits of different technologies estimated from real-world data. CONCLUSIONS: Integration of prevention with treatment for resources allocation seems feasible and would improve equity and efficiency.

Health technology assessment and healthcare environmental sustainability: Prioritizing effort and maximizing impact.

The growing global focus on and sense of urgency toward improving healthcare environmental sustainability and moving to low-carbon and resilient healthcare systems is increasingly mirrored in discussions of the role of health technology assessment (HTA). This Perspective considers how HTA can most effectively contribute to these goals and where other policy tools may be more effective in driving sustainability, especially given the highly limited pool of resources available to conduct environmental assessments within HTA. It suggests that HTA might most productively focus on assessing those technologies that have intrinsic characteristics which may cause specific environmental harms or vulnerabilities, while the generic environmental impacts of most other products may be better addressed through other policy and regulatory mechanisms.

Stakeholders' Involvement in Health Technology Assessment in Kazakhstan, Poland and Bulgaria.

Background: In recent years, involvement of healthcare stakeholders in health technology assessment (HTA) has been discussed as helping the inclusion of social values in the decision-making process. The aim of our research was to identify and compare details from Kazakhstan, Poland and Bulgaria on their stakeholders' involvement in the HTA process. Information was sought on their identification, responsibilities, and regulation. Methods: We conducted a survey of seven types of stakeholders in the healthcare systems of Kazakhstan, Poland, and Bulgaria. They included patients and the public, providers, purchasers, payers, policy makers, product makers, and principal investigators. They were questioned on their involvement in the HTA process, and on the objectives of their participation. Results: Levels of involvement of different kinds of stakeholder varied between countries, reflecting political and administrative developments. There was full or partial agreement on the objectives of stakeholder participation. All respondents agreed that representatives of the ministry of health should be involved in selection of stakeholders for HTA. Conclusion: Progress has been made in the involvement of stakeholders, with interest in further development in all three countries.

EU HTA Regulation and Joint Clinical Assessment-Threat or Opportunity?

The vision of a unified European HTA is by no means a new endeavor. At its core are the publicly declared ambitions to harmonize assessments of clinical data within the EU and avoid the duplication of efforts. Not surprisingly, these ambitions are publicly announced to be motivating the new 2022 EU HTA regulation. However, industry experts typically see more of a risk for additional bureaucracy resulting in delays, further scrutiny, and one additional EU (clinical) dossier to submit on top of all national HTA dossiers, which could be considered a duplication of effort and therefore counterproductive. Regardless of how the details of the process will be defined and how the entire process will work in practice, we can be sure that EU officials will refer to the EU HTA and Joint Clinical Assessment (JCA) in particular as a learning system. The purpose of this article is to take a closer look at the new EU HTA regulation and analyze threats and opportunities for manufacturers and what the resulting opportunities and threats will be at the affiliate level throughout the EU.

Real-World Evidence to Reinforce Clinical Trial Evidence in Health Technology Assessment: A Critical Review of Real-World Evidence Requirements from Seven Countries and Recommendations to Improve Acceptance.

BACKGROUND: Real-world evidence (RWE) can reinforce clinical trial evidence in health technology assessment (HTA). OBJECTIVES: Review HTA bodies' (HTAbs) requirements for RWE, real uses, and acceptance across seven countries (Brazil, Canada, France, Germany, Italy, Spain, and the United Kingdom) and outline recommendations that may improve acceptance of RWE in efficacy/effectiveness assessments and appraisals processes. METHODS: RWE requirements were summarized based on HTAbs' guidelines. Acceptance by HTAbs was evaluated based on industry experience and case studies. RESULTS: As of June 2022, RWE methodological guidelines were in place in three of the seven countries. HTAbs typically requested analyses based on local data sources, but the preferred study design and data sources differed. HTAbs had individual submission, assessment, and appraisal processes; some allowed early meetings for the protocol and/or results validation, though few involved external experts or medical societies to provide input to assessment and appraisal. The extent of submission, assessment, and appraisal requirements did not necessarily reflect the degree of acceptance. CONCLUSION: All the countries reviewed face common challenges regarding the use of RWE. Our proposals address the need to facilitate collaboration and communication with industry and regulatory agencies and the need for specific guidelines describing RWE design and criteria of acceptance throughout the assessment and appraisal processes.

Suitability of the Current Health Technology Assessment of Innovative Artificial Intelligence-Based Medical Devices: Scoping Literature Review.

BACKGROUND: Artificial intelligence (AI)-based medical devices have garnered attention due to their ability to revolutionize medicine. Their health technology assessment framework is lacking. OBJECTIVE: This study aims to analyze the suitability of each health technology assessment (HTA) domain for the assessment of AI-based medical devices. METHODS: We conducted a scoping literature review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. We searched databases (PubMed, Embase, and Cochrane Library), gray literature, and HTA agency websites. RESULTS: A total of 10.1% (78/775) of the references were included. Data quality and integration are vital aspects to consider when describing and assessing the technical characteristics of AI-based medical devices during an HTA process. When it comes to implementing specialized HTA for AI-based medical devices, several practical challenges and potential barriers could be highlighted and should be taken into account (AI technological evolution timeline, data requirements, complexity and transparency, clinical validation and safety requirements, regulatory and ethical considerations, and economic evaluation). CONCLUSIONS: The adaptation of the HTA process through a methodological framework for AI-based medical devices enhances the comparability of results across different evaluations and jurisdictions. By defining the necessary expertise, the framework supports the development of a skilled workforce capable of conducting robust and reliable HTAs of AI-based medical devices. A comprehensive adapted HTA framework for AI-based medical devices can provide valuable insights into the effectiveness, cost-effectiveness, and societal impact of AI-based medical devices, guiding their responsible implementation and maximizing their benefits for patients and health care systems.