The European Parliament, in its resolution of March 2nd, 2017, on European Union (EU) options for improving access to medicines, called on the Commission to propose legislation on a European system for health technology assessment (HTA) to harmonize transparent HTA criteria to assess the added therapeutic value and relative effectiveness of health technologies compared with the best available alternative (1). In December 2021, the EU-HTA R, formally known as ‘Regulation (EU) 2021/2282 of the European Parliament and of the Council of December 15th, 2021’ (2), on HTA and amending Directive 2011/24/EU (3) was adopted. It entered into force with implementation starting in January 2022 for oncology products and advanced therapeutic medicinal products (ATMP) in January 2028 for orphan designated products and in January 2030 for all products.

The practice of Health Technology Assessment (HTA) inherently involves moral, epistemological, and ontological commitments, which shape how assessments are conducted, interpreted, and used for decision-making

Health Technology Assessment (HTA) is shaped by moral (what makes a health technology desirable or acceptable, e.g., beneficence, justice), epistemological (how reliable knowledge is obtained and validated, e.g., evidence standards, uncertainty handling), and ontological (what effects and outcomes are considered real and relevant for assessment) commitments. The EU Joint Clinical Assessment (JCA), intended to harmonize relative effectiveness evaluation, embeds these commitments implicitly rather than explicitly, creating transparency and consistency issues. Critical concerns include: rigid reliance on the PICO framework privileging RCTs and quantifiable outcomes, proliferation of PICOs leading to infeasible evidence requirements, inadequate handling of multiplicity and post-hoc analyses, conflation of certainty and uncertainty, and exclusion of qualitative evidence and stakeholder input. Guidance documents, criticized for methodological weaknesses (e.g., outdated tools, poor external validity assessment, nominal p-values acceptance), further undermine epistemic robustness. These structural flaws risk producing assessments that are non-inclusive, reductionist, and epistemologically inconsistent. Future EU HTA frameworks should explicitly align on foundational commitments and integrate stakeholder perspectives to ensure transparency, scientific credibility, and ethical legitimacy.

Background: The EU Health Technology Assessment Regulation (EU-HTA R), effective January 2025, mandates Joint Clinical Assessments (JCAs) to harmonize HTA across Member States. However, its implementation raises fundamental questions about methodological coherence, institutional capacity, and epistemological alignment. Objectives: This manuscript (1) systematically assesses whether the stated strategic and operational objectives of the EU-HTA R are achievable under current implementation conditions; (2) examines the implications for EU institutional legitimacy if these objectives are not met; and (3) proposes an epistemological framework as a prerequisite for developing a coherent joint HTA methodology. Methods: We conducted a critical policy analysis of the EU-HTA R, its implementing guidance documents, and published templates, supplemented by a comparative review of Member State HTA methodologies and their underlying philosophical foundations. Results: The analysis reveals that the EU-HTA R is unlikely to achieve its strategic goals under current conditions. Key findings include: guidance documents of substandard methodological quality; a restricted assessment scope that excludes scientific judgement and contextualization; insufficient resources and additional workload for national HTA bodies without reducing existing obligations; unresolved epistemological divergences among Member States spanning Bayesian vs. frequentist approaches, Fisher vs. Neyman–Pearson frameworks, and utilitarian vs. deontological ethical foundations; and procedural shortcomings in stakeholder consultation and expert involvement. These shortcomings risk undermining the epistemic authority and legitimacy of EU institutions. Conclusions: Prior epistemological and normative alignment across Member States is a prerequisite for any robust shared HTA methodology. Revisions to the EU-HTA R and comprehensive updates of guidance documents are necessary, with concrete safeguards—including independent peer review, identified authorship, and adequate resourcing—to ensure substantive rather than merely nominal implementation. A phased roadmap is proposed: establishing clear objectives, aligning epistemological foundations, developing institutional structures, and creating operationally consistent guidance.