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After much anticipation, the EU Health Technology Assessment Regulation  2021/2282 (HTAR) has officially arrived. On the 11^th January 2025, the long-awaited new HTAR entered into force (1), marking a significant milestone towards harmonising HTA across the EU-27.  Since the launch of the EUnetHTA project in 2006 (Figure 1), a primary objective has been to reduce duplication in HTA processes by standardising evidence submissions, ensuring greater consistency and efficiency across EU member states (2). Starting with oncology drugs, advanced therapy medicinal products (ATMPs) in 2025, and high-risk medical devices in 2026 (Figure 2), the HTAR will expand to orphan medicinal products in 2028, before ultimately incorporating all medicinal products by 2030 (1).

Figure 1. Timeline of the establishment of a health technology assessment network in Europe

 Source: Ruther et al. (2022) (3)

Figure 2. Phases of the HTAR Implementation

  Source: Adapted from published report: Regulation (EU) 2021/2282 on health technology assessment.

What does the HTA Regulation Entail?

The HTAR introduces three interconnected mechanisms designed to transform how the EU evaluates health technologies. Joint Clinical Assessments (JCA) have been introduced, which are mandatory, unifed clinical evaluations that assess the relative clinical effectiveness of new technologies across all Member States, replacing duplicative national assessments with a single evidence base. Importantly, economic evaluations and final decision-making remain within national remit, with Member States only required to take JCA reports under “due consideration” and retain the right to request additional data from manufacturers if needed. Supporting this process is Joint Scientific Consultation (JSC), a voluntary service that provides early guidance to manufacturers on clinical trial design and evidence generation, at times coordinated with the EMA. The third component, horizon scanning, proactively identifies and monitors emerging health technologies to forecast and identify future innovations and their potential implications.

What does the new HTAR mean for national HTA bodies, industry and patients?

Crucially, the first phase of the HTAR aims to address inefficiencies in current HTA processes and promote fair and timely access to oncology treatments across the EU (4). Given the significant variations in oncology standards of care throughout Europe, pragmatism, policy adaptation, and coordinated efforts among diverse stakeholders will be essential to ensure a smooth progression through this initial phase and to enable its success (4).

Previously, manufacturers submitted the same evidence to different national HTA bodies, often in varying formats and with differing requirements. This duplication is both time-consuming and resource-intensive. The JCA is harmonising the clinical assessment part of the HTA process, and aims to establish a more unified system that enables Member State collaboration by drawing on a wide range of expertise through the joint clinical assessment (JCA) reports (5). After a medicine receives regulatory approval from the EMA, manufacturers will be required to submit specific clinical sections of the EMA report to the JCA committee.

Based on the clinical data submitted, experts from participating countries will define the information required for the JCA process in a scoping report, using the PICO framework (Population, Intervention, Comparator, and Outcome). The resulting PICO framework will outline the essential evidence manufacturers must provide. This standardised approach will ensure that all participating countries assess the same core data, aiming to reduce redundancy while leaving room for national HTA bodies to address country-specific needs required for their own decision-making at the national level (1,5). Following the JCA submission, manufacturers will continue discussions with national HTA bodies to fulfil additional requirements, such as cost-effectiveness and budget impact. While this system aims to improve efficiency, it also introduces new complexities such as readiness of national HTA bodies, multiplicity in PICO outcomes, tight timelines, and patient involvement that need to be addressed.

What are the ongoing concerns surrounding HTAR implementation?

Concerns about HTAR implementation can be summed up in four main points:

• Are HTA bodies ready? It is not immediately compelling that the HTAR will reduce duplication. HTA bodies across the EU still need to adjust their national processes, and there is uncertainty about whether these processes will be streamlined or whether they will introduce additional complexity. To support these transitions, EU Member States can access technical assistance through the Technical Support Instrument (TSI), an EU program providing tailored expertise to help design and implement reforms, including those related to the HTAR (6). As part of the HTAR framework, the Coordination Group on Health Technology Assessment (HTACG) was also established, to oversee the adoption of the joint HTA work carried out by its sub-groups, ensure alignment with the regulation, and foster collaboration with relevant EU bodies such as the European Medicines Agency (EMA) (7). While these structures have been put in place to address readiness issues, the real impact on reducing duplication and streamlining HTA processes remains to be seen.
• Is industry ready? Manufacturers are concerned that they will need significantly more preparation before engaging in randomised controlled trials (RCTs) and may find it difficult to generate the necessary PICOs evidence for current and future RCTs. The EU has committed to conducting Joint Scientific Consultations (JSC) with manufacturers and the EMA as early as the RCT design stage, to help them align with HTAR requirements and proactively identify the evidence needed for future assessments (8). However, JSC slots need to be increased to meet industry demand, and additional support and guidance are required for smaller companies.
• PICO framework challenges and varying standards of care: A major challenge of the new system is the variation in standards of care across the EU. Each Member State might request a different comparators and populations, which makes generating relevant data difficult. Indirect treatment comparisons (ITCs) are often necessary when direct evidence is not available, however, they are not always reliable or accepted by HTA agencies as reliable forms of evidence. For example, GBA in Germany rejected the majority of indirect comparisons (71.5 %) on methodological grounds, demonstrating just how high the risk is for manufacturers (9). Another analysis examining the acceptance rates of ITC methods in Oncology across England, France, Germany, Italy, and Spain found an overall acceptance rate of 30%, with France demonstrating the lowest acceptance rate (0%) within this sample (10). Consequently, developing PICO parameters and real-world evidence (RWE) will be crucial for the success of the HTAR.
• Tight Timelines: The EU-27 HTA timelines are strict, starting from the day of marketing authorisation (1). Manufacturers are concerned about whether they will be able to keep up, especially given all the evidence requirements as well as the need to wait for expert consensus regarding JCA reports. Any delays in meeting these timelines could mean delays in reimbursement decisions—and ultimately, slower patient access to new treatments. Ultimately, the success of the EU HTA will be measured by its impact on patient access to innovative treatments. However, delays in finalising JCAs and additional evidence burdens on manufacturers could undermine these benefits.

What can patients expect from HTAR?

The HTAR promises that patients will be at the center of the process, ultimately improving their access to innovative treatments. However, while it has the potential to reduce disparities in medicines’ availability, the extent to which it is patient-centered remains uncertain. Currently, there are significant disparities in patient access to medicinal products across the EU. According to the 2022 W.A.I.T. indicator, significant differences in patient access to innovative therapies remain, ranging from as little as four months in Germany and Denmark to over 28 months (~2.5 years) in Poland and Romania (11).

A core principle of patient-centered healthcare is meaningful patient involvement in decision-making. While the HTAR framework has made efforts to encourage patient involvement in the JCA process through training opportunities (12), the specifics of when and how patients will be engaged remain unclear. Despite these efforts, concerns persist regarding the practical implementation of patient involvement; for example, individual patients may not have the ability to understand the topics and effectively contribute to JCAs. It will also be challenging to verify individual conflicts of interest compared to those of patient organisations. Although the HTAR acknowledges the value of patient input, there is no clear guidance yet on how “patient-preferred trials”, “patient organisation surveys on preferred patient-reported outcomes (PROMs)”, and “real-world evidence (RWE) studies” will be systematically incorporated into JCAs.

What do we still not know?

Several critical questions remain unanswered: 

• First, knowing that national HTA agencies will need to improve their capacity to align their processes with HTAR, the question remains: how fast will they be able to adapt to the new system?
  
• Second, it remains to be seen to what extent JCAs will incorporate relevant data that national HTA bodies can adapt to their healthcare contexts, particularly given the significant variations in the standard of care across member states. As a result, the extent to which additional data will be requested by national HTA bodies and the actual reduction in duplication of efforts remain uncertain.
  
• Third, international reference pricing practices across Europe create a complex web of price interdependencies that drive strategic launch pricing by manufacturers, focusing on countries with a higher willingness-to-pay first. If JCAs can expedite reimbursement processes, will this affect the sequencing of drug launches across Europe?
• Ultimately, will the HTAR truly improve access to novel drugs in smaller countries with limited markets (improving equitable access to patients) as it promises, especially as no newly developed medicine have successfully launched in all 27 MS?
  

Since the implementation of the HTAR in January 2025, six medicines have entered the system, although no JCA reports have been published yet, according to a panel of experts at the Galien Forum in London on 5 June 2025. On 2^nd  July 2025, the European Commission hosted its International Conference on Health Technology Assessment (14). The published minutes of the meeting confirm progress on the first and second JSC medicinal products, but provide no details on the specifics of the evaluation process. Further developments are therefore expected in the near future (14).  

Moving forward, as these reports begin to emerge, each will offer valuable insights into how the process functions in practice, which will inform future assessments, improve predictability for manufacturers, and enable refining of procedures for greater efficiency and consistency.

As the initiative unfolds, its implications for stakeholders—from industry to patients—will become clearer, shaping how HTA processes evolve across the EU. For now, the HTAR offers a promising framework for addressing long-standing bottlenecks in HTA processes, paving the way for a more coordinated and patient-centred approach to assessing novel health technologies. While only time will provide definitive answers to these questions, one thing is certain: the HTAR is set to significantly reshape the landscape for industry and HTA bodies in the EU and, possibly, beyond.

If you are interested in reading more about the EU HTAR and its potential impact on oncology medicines, please read our recent paper:

References

1. European Union. (2024.). Health technology assessment (HTA) – EU-wide assessment of health technologies. EUR-Lex. Retrieved February 11, 2025, from
2. European Network for Health Technology Assessment. (2021). Joint Action 3 (2016-2021) [Conference presentation]. Retrieved February 13, 2025, from
3. Ruether A, Imaz-Iglesia I, Bélorgey C, Lo Scalzo A, Garrett Z, Guardian M. European collaboration on health technology assessment: looking backward and forward. International Journal of Technology Assessment in Health Care. 2022;38(1):e34. doi:10.1017/S026646232200006X
4. Main, C., Schäfer, C. & Kanavos, P. From Vision to Reality: The EU’s Pharmaceutical Reforms and the Path to Improved Access. PharmacoEconomics Open (2025).
5. Urbina I, Adams R, Fernandez J, Willemsen A, Hedberg N, Rüther A. Advancing cooperation in Health Technology Assessment in Europe: insights from the EUnetHTA 21 project amidst the evolving legal landscape of European HTA. Int J Technol Assess Health Care. 2024 Dec 12;40(1):e75. doi: 10.1017/S0266462324004689. PMID: 39663913; PMCID: PMC11703613.
6. European Commission. Technical Support Instrument (TSI). Retrieved February 14, 2025, from
7. European Commission. Member State Coordination Group on Health Technology Assessment (HTACG). Retrieved February 14, 2025, from https://health.ec.europa.eu/health-technology-assessment/implementation-regulation-health-technology-assessment/member-state-coordination-group-hta-htacg_en
8. European Commission. Joint scientific consultations. Health Technology Assessment. Retrieved February 11, 2025, from
9. Ecker & Ecker. (2023, April 20). Implications of EU HTA on Acceptance of Indirect Treatment Comparisons in National Assessments. Presentation at ISPOR ITC 2023 [PowerPoint slides]. February 14, 2025, from
10. Macabeo B, Rotrou T, Millier A, François C, Laramée P. The Acceptance of Indirect Treatment Comparison Methods in Oncology by Health Technology Assessment Agencies in England, France, Germany, Italy, and Spain. Pharmacoecon Open. 2024 Jan;8(1):5-18. doi: 10.1007/s41669-023-00455-6. Epub 2023 Dec 14. PMID: 38097828; PMCID: PMC10781913.
11. Newton M, Stoddart K, Travaglio M, Troein P. EFPIA Patients W.A.I.T. Indicator 2022 Survey. IQVIA, Apr. 2023. February 14, 2025, from
12. European Commission. HTA4Patients. Health Technology Assessment. Retrieved February 11, 2025, from
13. Galien Forum UK 2025. Advances in International HTA collaboration: How will joint clinical assessments impact patient access to medicines in Europe? Retrieved July 8 2025, from :
14.  European Commission. Joint scientific consultations. Health Technology Assessment. 19th Meeting of the Subgroup on Joint Scientific Consultations (JSCs) of the Member State Coordination Group on HTA.Retrieved August 10, 2025, from: https://health.ec.europa.eu/document/download/939f2e10-a136-486d-9cdf-faae6aff5ed6_en?filename=hta_20250611_min_en.pdf