Introduction
In public policy, harmonization refers to aligning governmental policies and regulations across jurisdictions to create consistency and advance cross-border efficiency and cooperation (Reference Majone1). In Europe, policy harmonization was advanced by the 1957 Treaty of Rome, which established the European Economic Community (EEC), and the 1993 Treaty of Maastricht, which formally established the European Union (EU) (2;3). Together, these treaties laid the foundation for European economic and political integration.
In the domain of public health, Member States remain primarily responsible for organizing and delivering healthcare. Nevertheless, the EU plays an important supporting role by helping governments achieve shared goals, pool resources, and address common challenges. A prime example is the EU system for regulating medicines, organized through the European medicines regulatory network. This network brings together national competent authorities, the European Medicines Agency (EMA), and the European Commission (EC) (4;5). The EMA, established in 1995, operates at the heart of the network. By working closely together, this network ensures that medicines authorized in the EU are safe, effective, and of high quality.
Despite this long-standing cooperation in medicines regulation, health technology assessment (HTA) remained largely a national responsibility. This changed with the adoption of Regulation (EU) 2021/2282 on HTA (EU HTAR) in December 2021, a pivotal step in the EU’s approach to HTA (6). The Regulation builds on decades of voluntary cooperation and EU-funded projects that laid the groundwork for the current framework. It introduces joint work and common methodologies to reduce duplication and strengthen cooperation in HTA (6–Reference Brinkhuis, Julian and van den Ham8). Under the Regulation, Member States collaborate on the clinical domains of HTA through Joint Clinical Assessments (JCAs). Value judgments, pricing, and reimbursement remain national responsibilities (6).
Medicines regulation and HTA in the EU have distinct remits and purposes. Regulatory assessments determine whether medicines have a positive benefit–risk balance for EU-wide marketing authorization. JCAs, by contrast, assess their effectiveness relative to relevant comparators to inform national HTA processes. Despite these differences, both assess clinical evidence and play a key role in the pathway to patient access in the EU. Both evolved from national arrangements toward more formal EU-level structures, although this process began much earlier in medicines regulation than in HTA. The longer experience of EU-level harmonization in medicines regulation may therefore offer lessons for the implementation and further development of the EU HTAR.
This study compares the harmonization trajectories of EU medicines regulation and EU HTA, which culminated in the establishment of the EMA and the adoption of the EU HTAR, respectively. We analyze their historical and policy development and examine common dynamics related to harmonization, collaboration, and stakeholder engagement. Our aim is to identify lessons that can support the effective implementation and ongoing development of the EU HTAR.
Methods
We used a multi-method qualitative approach combining a narrative literature review and online focus groups. The review explored the historical development of harmonization in EU medicines regulation and EU HTA. The focus groups captured reflections on the evolution of both policy areas and on broader mechanisms of policy harmonization. The literature and focus-group data were analyzed separately and subsequently integrated during interpretation. This study focused on pharmaceuticals; other health technologies (e.g., medical devices) were outside its scope. To ensure consistent interpretation of the terminology used throughout this study, Box 1 provides working definitions of the key terms used to describe different forms of interaction and alignment. The definitions were informed by frameworks on interorganizational collaboration and related literature and tailored to the context of EU-level governance (Reference Himmelman9;Reference Mashek and Nanfito10).
Definitions of key terms used throughout this study
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• Coordination: Aligning activities, responsibilities, and interactions between actors.
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• Cooperation: Working toward shared or compatible objectives while retaining separate responsibilities and decision making.
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• Collaboration: Working jointly toward a shared objective by sharing tasks, resources, and responsibilities.
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• Harmonization: Aligning rules, standards, methods, or procedures across jurisdictions.
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• Integration: Structurally linking or consolidating systems, functions, or institutions.
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• Centralization: Concentrating authority and decision-making in a single body or at a higher level of governance.
Narrative review
Data collection and analysis
We conducted a narrative review (June–November 2024; updated during manuscript preparation) across PubMed, Google Scholar, and Overton to identify literature on harmonization in EU/European medicines regulation and HTA. Separate searches addressed the two policy areas, focusing on historical background, institutional development, and collaboration, with the EMA and the EU HTAR as key milestones. Search terms included “EMA,” “medicines regulation,” “health technology assessment,” “EU HTAR,” combined with terms such as “collaboration” and “harmonization”; further details are provided in Appendix A of the Supplementary Material. Additional sources were identified through (reverse) snowballing, gray literature searches, and relevant organizational websites. Peer-reviewed and gray-literature sources were selected when they described the historical or institutional development of harmonization in either policy area. Source identification continued until the main developments could be adequately described. No publication date restrictions were applied, but only English-language sources were included.
Online focus groups
Study design
The present study reports a secondary analysis of data collected from a broader qualitative study on harmonization in medicines regulation and health policy in Europe and Africa Narsai et al. (Reference Narsai, Leufkens, Brinkhuis, Mantel-Teeuwisse and van den Ham11). The original study was not designed specifically to investigate EU HTA. However, before data collection, the researchers recognized that European medicines regulation and EU HTA involve related processes of cross-country harmonization. The study design and discussion guide were therefore also relevant to comparing their development and implementation.
To inform the original study design, two researchers (KN and HGML) conducted a preliminary literature review and developed a semi-structured discussion guide. The guide covered five predefined domains relevant to regulatory harmonization: (i) power dynamics between stakeholders, (ii) regulatory philosophy, (iii) funding, (iv) product scope, and (v) health-systems integration. The latter concerned the relationship between medicines regulation and wider health-system functions, including HTA and reimbursement, although EU HTA was not a separate focus of the original study. Prompting questions explored, for example, facilitators and barriers to harmonization, stakeholder interests and influence, trust, regional differences, sustainable funding, and evolving regulatory responsibilities. The domains were used to structure the focus-group discussions and provided an initial deductive framework for the analysis, but were not intended to define the final thematic structure. The guide and additional methodological details have been published previously (Reference Narsai, Leufkens, Brinkhuis, Mantel-Teeuwisse and van den Ham11).
EU HTA-related issues were further explored through follow-up prompts when they arose during discussions of European harmonization processes and comparisons with medicines regulation. The present analysis focused on these discussions and on broader harmonization themes relevant to the comparison.
Participants
Participants were purposively sampled for the original study based on senior-level experience in medicines regulation, health policy, or cross-country harmonization. Potential participants were identified through professional networks of the authors and were invited via email. The sample included senior regulatory and policy experts in public and private sectors, including academia, regulators, industry, international organizations, nongovernmental organizations, and consultancy. As the original study examined harmonization in Europe and Africa, experts from both regions were included. The regional composition of the sample therefore reflects the scope of the original study and was not intended to represent the EU HTA stakeholder community.
Invitees were offered five scheduling options for the online focus groups, which were held in November 2023. Participants were allocated to sessions primarily according to availability, while seeking professional and geographic diversity where possible. Each focus group included three to five participants.
A moderator (HGML) facilitated the sessions, supported by two to three observers (FB, KN, and HAvdH). Sessions were conducted in English, lasted approximately 90 minutes, and followed a semi-structured format based on the discussion guide. Participants did not receive financial compensation.
Data collection and analysis
Observers took detailed notes during each session. The moderator used the discussion guide flexibly and formulated follow-up questions as needed. Session notes were imported into NVivo and analyzed iteratively. Initial deductive coding was based on the predefined domains of the discussion guide, while inductive coding captured emergent insights. Codes were subsequently organized in themes and subthemes. FB conducted the coding and discussed interpretations and emerging themes with HAvdH. Observer notes were compared to assess whether themes were consistently supported across session records.
For the present secondary analysis, coding focused on discussion segments concerning EU medicines regulation, EU HTA, or broader harmonization dynamics relevant to the comparison. Africa-specific content and segments unrelated to policy harmonization were reviewed but not coded. We compared both policy areas within each theme, summarized key similarities and differences, and triangulated the focus-group findings with the narrative review.
Ethical considerations
Participants were informed that the Chatham House Rule applied, protecting the identity and affiliation of individual speakers (12). Participants were also informed that no recordings were made, and all provided verbal consent. In compliance with Dutch law, ethical approval was not required because no interventions were applied to participants (13).
Results
Narrative review
To contextualize the comparison of harmonization in EU medicines regulation and EU HTA, we briefly describe the main historical and policy developments shaping both trajectories. Table 1 summarizes their key characteristics, while the full narrative review is provided in the Appendix B of the Supplementary Material.
Historical development of harmonization and key characteristics of EU medicines regulation and EU HTA
Table 1. Long description
The table presents EU medicines regulation and EU HTA across the same characteristics. Medicines regulation began with Directive 65/65/EEC in 1965 and the EMA was established in 1995; EU HTA cooperation began with EUR-ASSESS in 1994 and the EU HTA Regulation was adopted in 2021. Medicines regulation aims to protect public health and assesses quality, safety, efficacy and benefit–risk through activities including marketing authorization, scientific advice and safety monitoring. EU HTA aims to strengthen cooperation and reduce duplication through Joint Clinical Assessments and Joint Scientific Consultations focused on comparative clinical effectiveness and safety. EMA opinions can lead to binding EU authorizations, while EU HTA reports are non-binding and Member States retain pricing and reimbursement authority. Medicines regulation is mainly industry-funded; EU HTA combines EU and national resources. National authorities and external stakeholders contribute to both frameworks.
Note: The comparison is limited to pharmaceuticals.
Abbreviations: ATMP, advanced therapy medicinal product; EMA, European Medicines Agency; EU, European Union; HTA, health technology assessment; JCA, Joint Clinical Assessment; JSC, Joint Scientific Consultation.
Harmonization in EU medicines regulation began in the 1960s, when the thalidomide tragedy exposed major weaknesses in medicines safety regulation across Europe (Reference Fornasier, Francescon, Leone and Baldo21;Reference Krapohl22). This contributed to the adoption of Directive 65/65/EEC in 1965, which introduced mandatory marketing authorization requirements and common standards for the authorization of medicines across Member States (14). However, authorization remained largely national, and differences in regulatory standards and limited mutual trust hindered effective cooperation (Reference Kidd23;Reference Orzack, Kaitin and Lasagna24). The establishment of the EMA in 1995 marked a shift toward a more institutionalized system of EU-level scientific assessment (Reference Gardner25;Reference Cuvillier, Goldberg and Lonbay26). Within this system, assessments are coordinated at EU level and conducted through the European medicines regulatory network, drawing on expertise from national competent authorities. Based on EMA’s scientific opinion, the EC grants a legally binding marketing authorization valid throughout the EU (4).
European cooperation on HTA began considerably later, in the mid-1990s, through EU-funded initiatives such as EUR-ASSESS (Reference Banta, Kristensen and Jonsson15;Reference Ruether, Imaz-Iglesia and Bélorgey27). Subsequent projects and networks, particularly EUnetHTA, promoted information exchange, common methodologies, and joint assessments, but remained voluntary and project-based (Reference Ruether, Imaz-Iglesia and Bélorgey27–Reference Lampe, Mäkelä and Garrido29). The adoption of the EU HTA Regulation in 2021 established a permanent framework for cooperation. This was followed by a three-year implementation period, during which the HTA Coordination Group and its subgroups developed the methodological, procedural, and operational framework for joint work, supported by the EUnetHTA 21 consortium (30). Since January 2025, JCAs have become mandatory for oncology medicines and advanced therapy medicinal products, with the scope gradually expanding through 2030 (6). Unlike EU marketing authorizations, JCA reports are not legally binding. Member States must give them due consideration but retain responsibility for value judgments, pricing, and reimbursement decisions.
Focus-group findings
The final sample included eighteen participants (n = 6 from Europe, n = 8 from Africa, and n = 4 with mixed/global backgrounds). Further participant details are provided in the Appendix C of the Supplementary Material. Table 2 presents the focus-group themes and subthemes and integrates the comparison between harmonization in EU medicines regulation and EU HTA with contextual evidence from the narrative review. Similarities were most pronounced in the theme “collaboration and pathways to harmonization,” whereas differences related mostly to “scope and standardization of assessment processes” and “regulatory and health-systems integration.”
Focus-group themes and integrated comparison of harmonization in EU medicines regulation and EU HTA
Table 2. Long description
The table integrates focus-group and narrative-review findings to compare EU medicines regulation and EU HTA across four themes: Governance and power dynamics, Collaboration and pathways to harmonization, Regulatory and health-systems integration, and Scope and standardization of assessment processes. The first shows similarity in EU coordination and partial similarity in sovereignty, industry engagement, and financing. The second shows similarity in willingness to collaborate and work sharing, but partial similarity in capacity and trust. The third shows partial similarity in legal development and readiness, but national uptake differs: regulatory assessments support EU-wide authorization, while JCA reports enter national HTA processes with national value judgments, causing variation in use and impact. The fourth shows partial similarity in product scope and procedures, but evidence requirements differ: EMA uses one dossier; EU HTA uses consolidated PICOs and national interpretation.
Note: The integrated comparison combines focus-group findings with relevant evidence from the narrative review. Symbols indicate substantial similarity (=), partial similarity (~), or substantial difference (≠) between the two policy areas.
Abbreviations: EMA, European Medicines Agency; EU, European Union; EU HTAR, EU Health Technology Assessment Regulation; HTA, health technology assessment; JCA, Joint Clinical Assessment; JSC, Joint Scientific Consultation; PICO, population, intervention, comparator, and outcome.
Governance and power dynamics
Participants described the EU’s wider political and economic framework as an important foundation for collaboration. The EMA was described as facilitating Member State-led assessment work through scientific, organizational, and secretarial support. More generally, delegating national responsibilities to supranational structures was described as a recurring source of resistance. Within this broader dynamic, participants highlighted the division of responsibilities between EU and national levels as a key governance difference between medicines regulation and EU HTA. Medicines regulation was described as involving greater delegation to the EU level, whereas EU HTA retains more responsibilities at the national level.
Industry engagement was discussed mainly in relation to medicines regulation and European scientific advice. Participants considered early dialogue between manufacturers and assessors useful and highlighted industry’s preference for a single dossier, fewer divergent requirements, and less duplication. Current European advice processes within medicines regulation were described as fragmented and lacking continuity.
Financing was discussed mainly in relation to medicines regulation and broader harmonization initiatives. Participants emphasized sustainable funding, transparency, and safeguards for institutional independence. User fees were described as a potential funding source, whereas reliance on donor funding was considered less sustainable.
Collaboration and pathways to harmonization
In discussions of both medicines regulation and EU HTA, participants linked willingness to collaborate to differences in the institutional maturity and capacity of national systems. In this context, maturity refers to the extent of institutional experience and formalization of procedures. Systems with more limited capacity or shorter experience were described as more receptive to collaboration and harmonization, whereas long-established systems could be more reluctant to change existing procedures or transfer responsibilities. In medicines regulation, authorities with greater capacity were also described as taking on more work and supporting those with fewer resources. Participants described voluntary cooperation among coalitions of willing countries as an important starting point for harmonization in medicines regulation. The HTA Joint Actions similarly provided a voluntary basis for developing collaboration.
As a broader dynamic in harmonization processes, trust was described as developing gradually through repeated interaction, communication, training, and shared platforms. Participants emphasized the importance of understanding differences in national decision-making frameworks, while differences in legal structures, institutional maturity, and sociocultural contexts were described as barriers to trust. Most concrete examples concerned medicines regulation, including EMA working parties. In relation to EU HTA, participants noted that mutual trust would similarly require time and continued collaboration.
Work and knowledge sharing were discussed mainly in relation to medicines regulation. Participants described joint assessments, assessor networks, and rapporteur/co-rapporteur arrangements as mechanisms for sharing expertise and reducing duplication. Work sharing was also viewed as a means of advancing harmonization by creating structured collaboration and repeated interaction between authorities, thereby supporting trust-building. For HTA, the Joint Actions were described as enabling Member States to develop shared methods and working practices.
Regulatory and health-systems integration
More broadly, participants highlighted the importance of a common legal foundation for cross-border policy harmonization and the challenges posed by national legal and procedural differences. They described regulatory collaboration as developing within an earlier common EU legal framework and culminating in centralized assessment and a single EU-wide marketing authorization, whereas EU HTA practices were first aligned through voluntary Joint Actions before being formalized under the EU HTAR.
Participants also contrasted the authority and scope of joint outputs. Regulatory assessments were described as supporting binding EU-wide authorization decisions, whereas EU HTA joint work covers the scientific assessment of relative effects, with national bodies retaining responsibility for value judgments, pricing, and reimbursement. Participants therefore expected the uptake and impact of EU HTA joint work to vary according to Member States’ readiness and willingness to adapt their HTA structures and procedures. Indeed, some Member States already had well-established HTA systems, whereas others were developing new structures in response to the Regulation.
Scope and standardization of assessment processes
Participants described a limited initial product scope followed by gradual expansion as a pragmatic approach to harmonization in medicines regulation. They referred to an initial focus on biotechnology-derived products, followed over time by other priority areas, including HIV and oncology.
In medicines regulation, participants identified common procedures, quality assurance, and transparency as important for consistency. They nevertheless noted continuing differences between national authorities in technical, data, and dossier requirements, particularly for generic medicines. Greater alignment of these national requirements was considered important for reducing duplication and improving efficiency.
Discussion
Summary of findings
The evolution of EU-level HTA can be understood in light of the EU’s earlier trajectory toward harmonized medicines regulation. Both policy areas moved from voluntary cooperation and work sharing toward more formal arrangements. Across both trajectories, trust, national capacity, and willingness to delegate responsibilities shaped harmonization. However, the degree and form of harmonization differed. Medicines regulation ultimately resulted in more centralized procedures and binding EU-wide authorization decisions. EU HTA remains more closely embedded in national health systems, with greater responsibilities retained at the national level. It therefore faces familiar challenges, but in a different institutional context and at an earlier stage of implementation. The experience of medicines regulation suggests that trust and effective joint work develop gradually through dialogue, transparency, shared platforms, and repeated collaboration.
Historical context and evolution
In Europe, harmonization has followed different trajectories in medicines regulation and HTA. Marketing authorization is closely linked to the EU internal market, rooted in the Treaty of Rome and reinforced through subsequent EU legislation (2;36). HTA, by contrast, has traditionally remained a national responsibility, linked to national healthcare priorities and budgetary constraints (Reference Vreman, Mantel-Teeuwisse, Hövels, Leufkens and Goettsch37–Reference Allen, Liberti, Walker and Salek40). EU medicines regulation therefore developed around common scientific standards and EU-wide procedures, whereas HTA remained more strongly shaped by national contexts.
These trajectories partly reflect different initial drivers. Harmonization in EU medicines regulation was driven by both public-health protection and the free movement of medicines within the internal market (Reference Narsai, Leufkens, Brinkhuis, Mantel-Teeuwisse and van den Ham11;Reference Krapohl22;Reference Gardner25). HTA cooperation emerged later, primarily to optimize resource use, reduce duplication, and support timely and equitable access to new technologies (Reference Boers39;Reference Allen, Liberti, Walker and Salek40). Today, their objectives partly overlap, particularly in supporting access to innovation and making efficient use of shared expertise and capacity. However, HTA remains more directly linked to national resource allocation. Although JCAs exclude economic evaluation and reimbursement decisions, their findings inform national decision-making. Differences in national interests and capacities may therefore create tensions that affect collaboration. While similar tensions arose in EU medicines regulation, they may be more pronounced in HTA (Reference Gardner25).
Another key difference lies in the timing and political context in which harmonization took place. The EMA was established in 1995 during a period of strong European integration, marked by milestones such as the Maastricht Treaty and the Schengen Agreement (3;41). In contrast, EU HTA evolved later in a more complex political environment. Longstanding national responsibilities and diverse HTA systems resulted in slower, incremental collaboration through voluntary initiatives and pilot projects. Progress required careful navigation of concerns about subsidiarity and, therefore, relied more on consensus-building and flexible structures than on centralized authority (6;Reference Löblová31). A key challenge remains to demonstrate that JCAs add value while respecting national processes and securing lasting commitment.
These concerns also help explain why EU HTA developed institutionally separate from the EMA’s regulatory activities. Although the EC explored assigning JCAs to the EMA (42), Member State resistance and the distinction between regulatory assessment and HTA’s broader responsibilities led to the establishment of a separate EU HTA framework (Reference Löblová31). Nonetheless, the EMA was explicitly cited as an illustrative example in the EC’s impact assessment (42). Medicines regulation and HTA also remain closely linked in practice, requiring mutual understanding between regulators and HTA assessors. The two communities have therefore increasingly collaborated, particularly through scientific consultations (Reference Wang, McAuslane, Liberti, Leufkens and Hövels43;Reference Wang, McAuslane, Goettsch, Leufkens and De Bruin44).
Regulatory objectives and scope
Unlike EMA assessments, which produce a single EU-level conclusion on the benefit–risk balance, JCAs exclude value judgments and are interpreted within national HTA processes. While this preserves national autonomy, it may create uncertainty about JCA uptake and practical relevance. Consistent with this, focus-group participants expected implementation and impact to vary across Member States. Member States are legally required to give due consideration to JCA reports and explain how they were considered in national HTA processes (6). However, the Regulation does not specify how extensively JCA findings should shape national assessments. This leaves uncertainty about what constitutes meaningful uptake. Transparent monitoring could help assess how JCA reports are used in practice.
Timing poses another challenge. JCAs run in parallel with EMA procedures, but delays could reduce their relevance, particularly for Member States accustomed to rapid reimbursement decisions. The Regulation states that the absence of a JCA report should not delay national processes (6). If reports are not available in time, countries may therefore proceed independently, reducing incentives to engage actively in the joint work.
In terms of assessment scope, EMA’s evaluations follow more standardized frameworks for product quality, safety, and efficacy. In contrast, JCAs may include multiple PICOs to reflect diverse national healthcare needs and priorities. The first three published JCAs included one, seven, and eight PICOs, respectively (45–47). This variation is consistent with preparatory PICO exercises conducted in 2024, which produced 7–13 consolidated PICOs across 21–23 Member States (35). While multiple PICOs increase the relevance of JCAs across Member States, they also add methodological and analytical complexity. Moreover, national appraisal requirements may still necessitate additional assessment work at Member State level, thereby limiting the intended reduction in duplication. Monitoring the extent of this additional work could guide further refinement of JCA scoping and implementation procedures.
Cross-border collaboration in pharmaceutical policy: a broader reflection
Our findings are consistent with a recent perspective by Broich and Löbker, which explicitly connects EU HTA implementation to earlier experience with European medicines regulatory harmonization (Reference Broich and Löbker48). In particular, they highlight trust-building through sustained collaboration and a stepwise approach with iterative optimization, both closely aligned with our findings. They also emphasize centralized coordination alongside decentralized implementation, standardized procedures, capacity-building, knowledge-sharing, transparency, and reduced duplication. These points align with several themes identified in our analysis.
While our study focused on the harmonization trajectories of EU medicines regulation and EU HTA, with the EMA and EU HTAR as key milestones, other cross-country collaborations in European pharmaceutical policy also offer valuable insights. The 2020 WHO report on Cross-Country Collaborations examined five voluntary, government-led initiatives to improve access to essential medicines (49). It found that differences in national processes complicate initial collaboration and that tangible benefits may take years to appear. Success depended on political support, adequate resources, leadership, system organization, and stakeholder engagement. This aligns with our findings that cross-country harmonization is gradual and depends on EU-level support, sustainable financing, and accommodating differences between healthcare systems. Unlike the voluntary collaborations in the WHO report, EU medicines regulation and EU HTA operate within formal legislative frameworks, in which political commitment and governance are more firmly embedded. This may support their long-term sustainability.
Trust-building emerged as a critical success factor for harmonization in our study. The WHO report similarly identified trust as key to successful collaboration and emphasized the need for sufficient time, mutual understanding, and shared values and goals (49). Studies by Boers et al., Kleijnen et al., and Lipska et al. likewise emphasized the importance of trust in EU HTA collaboration (Reference Lipska, Meyer, Canonico, Altman and Solà-Morales18;Reference Boers39;Reference Kleijnen, Toenders and de Groot50). Related research also shows that effective communication helps foster collaboration, secure commitment, and establish shared goals (Reference Brinkhuis, Julian and van den Ham8;Reference Hogervorst, Møllebaek and Vreman51). Together, these findings support our emphasis on transparency and stakeholder communication as enabling factors.
Our study further showed that differences in the institutional maturity and capacity of national HTA systems shape harmonization efforts. More mature systems may perceive fewer immediate gains and be more reluctant to adapt established procedures, although harmonization still requires them to allocate resources. This pattern was also observed by Löblová et al. (Reference Löblová31) and Kleijnen et al. (Reference Kleijnen, Toenders and de Groot50), who found fewer incentives for harmonization among more established systems. Systems with less experience or capacity may benefit more from the resulting efficiency and quality gains of harmonization. Beyond these direct gains, harmonization may create broader benefits across systems by catalyzing complementary research and collaboration initiatives. Notable examples include SUSTAIN-HTA (52), which supports capacity building and the implementation of innovative HTA methods, and IMPACT-HTA (53), which develops improved methods for economic evaluations. By bringing together HTA organizations and academia, these initiatives illustrate that harmonization is not merely a compromise but can also drive collective learning and improvement across systems with different levels of maturity.
Future directions of pharmaceutical innovation in Europe
Beyond developments in EU HTA, broader concerns about Europe’s position in pharmaceutical innovation have drawn political attention. In September 2024, Mario Draghi published a report outlining urgent challenges to EU competitiveness (Reference Draghi54). The report linked Europe’s widening pharmaceutical competitiveness gap to slow and complex regulatory processes, longer approval times than in other regions, and fragmented national pricing and reimbursement systems. Draghi proposed measures to attract R&D investment, accelerate market access, and enhance innovation funding. One recommendation was to “rapidly and fully implement the HTA Regulation” with the longer-term goal of creating a dedicated EU agency. The report also raised concerns about the sustainability of EU-level HTA and suggested cost recovery through industry fees. This aligns with our focus-group findings on the importance of stable and transparent financing.
Draghi’s recommendations coincide with the broader reform of EU Pharmaceutical Legislation, on which the European Parliament and the Council of the EU reached political agreement in December 2025 (55). Both the EU HTAR and Pharmaceutical Legislation aim to improve timely and equitable access while strengthening Europe’s position in pharmaceutical innovation. Their success depends on coordinated implementation. Additional complexity or delays could otherwise weaken Europe’s position relative to regions with faster and more predictable pathways.
Strengths and limitations
By combining a narrative review with focus groups, we examined policy evolution alongside stakeholder perspectives and interpreted the findings within a broader historical and policy context. Given its narrative design, the review may have missed relevant sources, although we aimed to enhance completeness through multiple databases, snowballing, and targeted hand searches.
The focus groups were originally designed to examine harmonization in medicines regulation and health policy across Europe and Africa, rather than EU HTA specifically. The sample therefore included European and African regulatory and policy experts. The relatively high proportion of participants from Africa reflected the cross-regional scope of the original study. Although EU HTA was not the primary focus, it arose explicitly in discussions of European harmonization processes and comparisons with medicines regulation. The present findings therefore derive from a secondary analysis of these discussions and broader harmonization themes relevant to the comparison. Africa-specific discussions without such relevance were excluded.
Participants were not selected specifically for HTA expertise or direct involvement in EU HTA. The findings should therefore be interpreted with caution and may not capture the full range of EU HTA stakeholder perspectives. Nonetheless, the sample included senior experts with experience in cross-country harmonization and policy processes relevant to HTA. Future research could build on these findings by engaging EU HTA-specific stakeholder panels as implementation progresses.
Conclusions
By comparing the harmonization trajectories of EU medicines regulation and EU HTA, this study identifies lessons for EU HTAR implementation. First, trust must be built through transparency, sustained dialogue, shared platforms, and practical work sharing. Second, differences in national system maturity and priorities are not just challenges but also opportunities for mutual learning and complementary collaboration when recognized and addressed. Third, even within a formal legal framework, effective harmonization will develop gradually through ongoing learning and refinement across diverse national legal and procedural contexts. Monitoring meaningful JCA uptake, remaining duplication, and variation in implementation could guide further refinement of EU HTAR implementation.
Despite these challenges, the EU’s move toward more coordinated HTA is a meaningful step toward greater efficiency, transparency, and equity. Although focused on the EU HTAR, these lessons may also inform wider cross-country alignment in health policy and regulation.
Supplementary material
The supplementary material for this article can be found at http://doi.org/10.1017/S0266462326104267.
Acknowledgments
The authors would like to gratefully acknowledge the regulatory and policy experts for their input during the online focus groups.
Funding statement
This research received no specific grant from any funding agency, commercial, or not-for-profit sectors.
Competing interest
The authors declare none.
Declaration of the use of AI tools
During the preparation of this work, the authors used ChatGPT (OpenAI) for language editing support (e.g., grammar, spelling, and phrasing). After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.
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