Managed Entry Agreements for High-Cost, One-Off Potentially Curative Therapies: A Framework and Calculation Tool to Determine Their Suitability.

Objective: To construct a framework and calculation tool to compare the consequences of implementing different payment models for high-cost, one-off potentially curative therapies and enable decision making to ultimately enhance timely patient access to innovative health interventions.

Methods: A framework outlining steps to determine potentially suitable payment models was developed. Based on the framework, a supporting calculation tool operationalised as an Excel-based model was constructed to quantify the associated costs for an average patient during the timeframe of the intended payment agreement, the total budget impact and associated benefits expressed in quality-adjusted life-years for the total expected lifetime of the patient population.

Analytical Methods for Comparing Uncontrolled Trials With External Controls From Real-World Data: A Systematic Literature Review and Comparison With European Regulatory and Health Technology Assessment Practice.

Objectives: This study aimed to provide an overview of analytical methods in scientific literature for comparing uncontrolled medicine trials with external controls from individual patient data real-world data (IPD-RWD) and to compare these methods with recommendations made in guidelines from European regulatory and health technology assessment (HTA) organizations and with their evaluations described in assessment reports.

Methods: A systematic literature review (until March 1, 2023) in PubMed and Connected Papers was performed to identify analytical methods for comparing uncontrolled trials with external controls from IPD-RWD. These methods were compared descriptively with methods recommended in method guidelines and encountered in assessment reports of the European Medicines Agency (2015-2020) and 4 European HTA organizations (2015-2023).

The Role of Medical Societies and the Relevance of Clinical Perspective in the Evolving EU HTA Process: Insights Generated at the 2023 Fall Convention and Survey of the European Access Academy.

Background: This work aimed to determine the role and action points for the involvement of medical societies in the European Health Technology Assessment (EU HTA) Methods: An online pre-convention survey was developed addressing four areas related to the EU HTA: (i) medical societies' role; (ii) role of clinical guidelines; (iii) interface with the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS); and (iv) approaching 'best-available evidence' (BAE). A descriptive analysis of questionnaire outcomes was conducted to inform the European Access Academy (EAA) Fall Convention 2023. Within the working groups (WGs), action points were identified and prioritised.

Uncertainty in Long-Term Relative Effectiveness of Medicines in Health Technology Assessment.

Objectives: Uncertainty regarding the long-term relative effectiveness is an important factor in health technology assessment (HTA) of medicines. This study investigated how different HTA bodies address this uncertainty in their assessments.

Methods: A total of 49 HTA reports from 6 national HTA bodies, assessing 9 medicines for spinal muscular atrophy, cystic fibrosis, and hypercholesterolemia, were included.

Navigating the path towards successful implementation of the EU HTA Regulation: key takeaways from the 2023 Spring Convention of the European Access Academy.

Background: The European Regulation on Health Technology Assessment (EU HTA R), effective since January 2022, aims to harmonize and improve the efficiency of common HTA across Member States (MS), with a phased implementation from January 2025. At "midterms" of the preparation phase for the implementation of the Regulation our aim was to identify and prioritize tangible action points to move forward.

Methods: During the 2023 Spring Convention of the European Access Academy (EAA), participants from different nationalities and stakeholder backgrounds discussed readiness and remaining challenges for the Regulation's implementation and identified and prioritized action points.

Creating win-win-win situations with managed entry agreements? Prioritizing gene and cell therapies within the window of opportunity.

Outcome-based reimbursement models are gaining attention for managing the clinical uncertainties and financial impact of gene and cell therapies. Little guidance exists on how such models can create win-win-win situations, benefiting health-care payers, health-technology developers and patients. Our innovative approach prospectively prioritizes therapies for which a 'window of opportunity' might occur through the analysis of health-technology assessments and product characteristics.

Healthcare decision-making for tumour-agnostic therapies in Europe: lessons learned.

The tumour-agnostic authorisations of larotrectinib and entrectinib shifted the paradigm for indication setting. European healthcare decision-makers agreed on their therapeutic potential but diverged primarily in identified uncertainties concerning basket trial designs and endpoints, prognostic value of neurotrophic tropomyosin receptor kinase (NTRK) gene fusions, and resistance mechanisms. In addition, assessments of relevant comparators, unmet medical needs (UMNs), and implementation of NTRK-testing strategies diverged.

An operationalization framework for lifecycle health technology assessment: a Health Technology Assessment International Global Policy Forum Task Force report.

Operationalization guidance is needed to support health technology assessment (HTA) bodies considering implementing lifecycle HTA (LC-HTA) approaches. The 2022 Health Technology Assessment International (HTAi) Global Policy Forum (GPF) established a Task Force to develop a position paper on LC-HTA. In its first paper, the Task Force established a definition and framework for LC-HTA in order to tailor it to specific decision problems.

Lifecycle HTA: promising applications and a framework for implementation. An HTAi Global Policy Forum Task Force report.

The 2022 Health Technology Assessment International (HTAi) Global Policy Forum (GPF) established the goal of developing a position statement and framework for lifecycle HTA (LC-HTA), through a Task Force leveraging multi-stakeholder monthly discussions and GPF member input. The Task Force developed a working definition: LC-HTA is a systematic process utilizing sequential HTA activities to inform decision making where the evidence base, the health technology itself, or the context in which it is applied, has a potential to meaningfully change at different points in its LC. Four key scenarios were identified where it was considered that an LC-HTA approach would add sufficient value to HTA bodies and their key stakeholders to justify the additional resource burden.

An Inclusive Civil Society Dialogue for Successful Implementation of the EU HTA Regulation: Call to Action to Ensure Appropriate Involvement of Stakeholders and Collaborators.

Objectives: Stakeholder involvement has long been considered a success factor for a joint European health technology assessment (HTA) process, and its relevance is now anchored in the EU HTA Regulation's (EU HTAR) legislative wording. Therefore, we aimed to explore the roles, challenges, and most important activities to increase the level of involvement per stakeholder group.

Methods: At the 2022 Fall Convention of the European Access Academy (EAA), working groups addressed the involvement of patients, clinicians, regulators, health technology developers (HTD), and national HTA bodies and payers within the EU HTA process.

A blueprint for health technology assessment capacity building: lessons learned from Malta.

Objectives: The development and strengthening of health technology assessment (HTA) capacity on the individual and organizational level and the wider environment is relevant for cooperation on HTAs. Based on the Maltese case, we provide a blueprint for building HTA capacity.

Methods: A set of activities were developed based on Pichler et al.

Added benefit and revenues of oncology drugs approved by the European Medicines Agency between 1995 and 2020: retrospective cohort study.

Objectives: To evaluate the added benefit and revenues of oncology drugs, explore their association, and investigate potential discrepancies between added benefit and revenues across different approval pathways of the European Medicines Agency (EMA).

Design: Retrospective cohort study.

Setting: Oncology drugs and their indications approved by the EMA between 1995 and 2020.

Tools for assessing quality of studies investigating health interventions using real-world data: a literature review and content analysis.

Objectives: We aimed to identify existing appraisal tools for non-randomised studies of interventions (NRSIs) and to compare the criteria that the tools provide at the quality-item level.

Design: Literature review through three approaches: systematic search of journal articles, snowballing search of reviews on appraisal tools and grey literature search on websites of health technology assessment (HTA) agencies.

Data Sources: Systematic search: Medline; Snowballing: starting from three articles (D'Andrea , Quigley and Faria ); Grey literature: websites of European HTA agencies listed by the International Network of Agencies for Health Technology Assessment.

A literature review of quality assessment and applicability to HTA of risk prediction models of coronary heart disease in patients with diabetes.

This literature review had two objectives: to identify models for predicting the risk of coronary heart diseases in patients with diabetes (DM); and to assess model quality in terms of risk of bias (RoB) and applicability for the purpose of health technology assessment (HTA). We undertook a targeted review of journal articles published in English, Dutch, Chinese, or Spanish in 5 databases from 1st January 2016 to 18th December 2022, and searched three systematic reviews for the models published after 2012. We used PROBAST (Prediction model Risk Of Bias Assessment Tool) to assess RoB, and used findings from Betts et al.

Disease severity-based subgrouping of type 2 diabetes does not parallel differences in quality of life: the Maastricht Study.

Aims/hypothesis: Type 2 diabetes is a highly heterogeneous disease for which new subgroups ('clusters') have been proposed based on disease severity: moderate age-related diabetes (MARD), moderate obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD) and severe insulin-resistant diabetes (SIRD). It is unknown how disease severity is reflected in terms of quality of life in these clusters. Therefore, we aimed to investigate the cluster characteristics and cluster-wise evolution of quality of life in the previously defined clusters of type 2 diabetes.

Opportunities and Challenges for Decentralized Clinical Trial Approaches: European Health Technology Assessment Perspective.

Objectives: Decentralized clinical trial (DCT) approaches are clinical trials in which some or all trial activities take place closer to participants' proximities instead of a traditional investigative site. Data from DCTs may be used for clinical and economic evaluations by health technology assessment (HTA) bodies to support reimbursement decision making. This study aimed to explore the opportunities and challenges for DCT approaches from an HTA perspective by interviewing representatives from European HTA bodies.

Importance of aligning the implementation of new payment models for innovative pharmaceuticals in European countries.

Introduction: The uptake of complex technologies and platforms has resulted in several challenges in the pricing and reimbursement of innovative pharmaceuticals. To address these challenges, plenty of concepts have already been described in the scientific literature about innovative value judgment or payment models, which are either (1) remaining theoretical; or (2) applied only in pilots with limited impact on patient access; or (3) applied so heterogeneously in many different countries that it prevents the health care industry from meeting expectations of HTA bodies and health care payers in the evidence requirements or offerings in different jurisdictions.

Areas Covered: This paper provides perspectives on how to reduce the heterogeneity of pharmaceutical payment models across European countries in five areas, including 1) extended evaluation frameworks, 2) performance-based risk-sharing agreements, 3) pooled procurement for low volume or urgent technologies, 4) alternative access schemes, and 5) delayed payment models for technologies with high upfront costs.

Perspectives on how to build bridges between regulation, health technology assessment and clinical guideline development: a qualitative focus group study with European experts.

Objective: Improving synergy among regulation, health technology assessment (HTA) and clinical guideline development is relevant as these independent processes are building on shared evidence-based grounds. The two objectives were first to assess how convergence of evidentiary needs among stakeholders may be achieved, and second, to determine to what extent convergence can be achieved.

Design: Qualitative study using eight online dual-moderator focus groups.

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

Introduction: Meaningful patient involvement in health technology assessment (HTA) is essential in ensuring that the interests of the affected patient population, their families, and the general public are accurately reflected in coverage and reimbursement decisions. Central and Eastern European (CEE) countries are generally at less advanced stages of implementing HTA, which is particularly true for patient involvement activities. As part of the Horizon2020 HTx project, this research aimed to form recommendations for critical barriers to patient involvement in HTA in CEE countries.

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

Objectives: Uncertainty is a fundamental component of decision making regarding access to and pricing and reimbursement of drugs. The context-specific interpretation and mitigation of uncertainty remain major challenges for decision makers. Following the 2021 HTAi Global Policy Forum, a cross-sectoral, interdisciplinary HTAi-DIA Working Group (WG) was initiated to develop guidance to support stakeholder deliberation on the systematic identification and mitigation of uncertainties in the regulatory-HTA interface.