European Commission’s New Regulation on Health Technology Assessment Enhances Patient Access to Innovative Medicines

The benefit of public health, facilitating patients’ access to important new medicines, has always been the main objective of the European Commission. To achieve this goal, Regulation (EU) 2021/2282 ⁽¹⁾ on Health Technology Assessment (HTAR) has been drawn up. The HTAR provides a transparent and inclusive framework by establishing a Coordination Group of national or regional Health Technology Assessment (HTA) bodies and laying down rules on the involvement of patients, clinical experts and other relevant experts in Joint Clinical Assessments (JCA) and Joint Scientific Consultations (JCS).

The entry into force of the HTAR is dated January 2022; however, it will be three years before it takes effect (i.e., the JCA and JSC will only be carried out starting from January 2025).

Joint Clinical Assessment (JCA)

Within the context of the HTAR ⁽²⁾, the Joint Clinical Assessments (JCA) aimed to reduce duplication of efforts for both national HTA authorities and medicine developers (avoiding multiple parallel submissions to the different national HTA bodies) and improve the EU HTA cooperation. Health experts, medicine developers and patients will also benefit from implementing these JCAs since this new framework will help address unmet medical needs and facilitate access to innovative medicines and some high-risk medical devices. The possibility to benefit from a unique Union Level Assessment will stop the duplication of submissions across Member States, which represent a significant administrative burden for developers (especially for smaller companies with limited resources) and contribute to impeding market access.

Overall, through the JCA, the different Member States will be supported in the decision-making process. At the same time, the developers will have more clarity and predictability concerning the clinical evidence requirements for HTA. The final goal of implementing this new HTAR is to reduce the time to market across EU member states and to ease the reimbursement process in markets with no (or scarce) pricing and reimbursement infrastructure.

Joint Scientific Consultations (JSC)

To facilitate the process of preparing JCAs, health technology developers will have the opportunity to engage in Joint Scientific Consultations (JSC) with the HTAs Coordination Group to obtain guidance on the information, data, analyses and other evidence that are likely to be required from clinical studies (either clinical trials of medicinal products, clinical investigations for medical devices or performance studies for in vitro diagnostic tests). Given the preliminary nature of the consultation, any guidance offered is not legally binding on the health technology developers or HTA authorities and bodies.

According to the HTAR, a health technology will be eligible for JSC, where the clinical studies and clinical investigations are still in the planning stage. Ideally, consultations should be done during early clinical development, when the clinical programs can still accommodate the recommendations of the HTA bodies. In this regard, the main topics for discussion during the JSC would be those critical to demonstrate clinical effectiveness during the future JCA (e.g. primary efficacy outcomes, comparators, target population, etc.).

JSC on medicinal products may occur in parallel with EMA Scientific Advice (SA). Such parallel consultations will allow information exchange and synchronised timing while preserving the separation of the remits of the HTAs Coordination Group and the EMA. Importantly, these parallel consultations will allow medicine developers to obtain feedback from EU regulators and HTA bodies on their evidence-generation plans to support decision-making on marketing authorisation and reimbursement simultaneously. Similarly, JSC on medical devices may occur in parallel with the consultation of expert panels.

The Coordination Group will publish the dates of the request periods and state the planned number of JSC for each request period. At the end of each request period, where the number of eligible requests exceeds the number of planned JSC, the Coordination Group will select the health technologies that are to be subject to JSC. The selection criteria are those mentioned under Article 17(3) of the HTAR and listed below:

• unmet medical needs;
• first in class;
• potential impact on patients, public health, or healthcare systems;
• significant cross-border dimension;
• major Union-wide added value; or
• Union clinical research priorities.

Within 15 working days after the end of each request period, the Coordination Group will inform the requesting health technology developer whether it will engage in the JSC.

Ongoing Parallel EMA/EUNetHTA Joint Scientific Consultations (JSC)

To be prepared for the implementation of the HTAR, the EMA and the European Network for Health Technology Assessment (EUnetHTA) 21 consortium have already worked closely to set up a Joint Work Plan in the time frame 2021-2023.

EUnetHTA 21 consortium is led by ZIN (The Netherlands). It includes the following HTA agencies: AEMPS (Spain), AIFA (Italy), AIHTA (Austria), GBA (Germany), HAS (France), INFARMED (Portugal), IQWIG (Germany), KCE (Belgium), NCPE (Ireland), NIPN (Hungary), NOMA (Norway) and TLV (Sweden). EUnetHTA 21 was granted a two-year service contract to produce deliverables supporting the HTAR implementation.

The EMA and the EUnetHTA21 set up the so-called Parallel EMA/EUnetHTA21 Joint Scientific Consultation ⁽³⁾. Requests for participation in an EMA/EUnetHTA 21 parallel JSC were allowed during two calls, with up to 8 consultations available. The second open call was last June-August 2022, with the corresponding submission slots and meeting dates in 2023. A prerequisite was that the clinical studies (phase II/ III) were still in the planning stage. The criteria for selecting from eligible requests were the same as listed under Article 17(3) (see above). Oncology products and/or ATMPs and indications for which there is no established clinical guidance (i.e., in the absence of recent HTA evaluation in a similar indication) were also given preferred consideration.

If a product is considered eligible for the JSC, the Applicant is notified by the EUnetHTA 21 after the Open Call and can apply.

The procedure is composed of 2 phases:

• the pre-submission phase, which lasts 30 days;
• the evaluation phase lasts 85 days and includes a face-to-face meeting between all parties.

At the end of the procedure, both the Regulators’ Final Advice Letter adopted by the CHMP and the EUnetHTA 21 Final Written Recommendations are sent to the Applicant.

As for the “traditional” scientific advice, the parallel advice provided by each stakeholder is not legally binding.

The procedure described above follows the main steps and aspects described in Article 18 of the HTAR. The cooperation between the Member States on Union-level health technologies will help make innovative health technologies available to Europe’s patients.

How can Zwiers and PLG help you

Zwiers Regulatory Consulting, a ProductLife Group company, includes a multidisciplinary team of scientists and regulatory experts with deep expertise in the clinical development of new medicinal products and medical devices and decades of experience in interactions with Regulatory Agencies. Importantly, we have expertise with the most innovative therapies, including oncology products and ATMPs, which target reimbursement at (very) high prices. Our team is ready to work in the new scenario set up by the new HTAR; we envisage its challenges and major opportunities. Therefore, we are a great partner for supporting developers or collaborating with market access consultants for Joint Scientific Consultations (JSC). We will leverage our expertise to help you agree with the HTA and EMA on the optimal clinical development plan to succeed in your marketing approval and reimbursement strategy.

Bibliography

1. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32021R2282&qid=1687526521767
2. https://health.ec.europa.eu/health-technology-assessment/regulation-health-technology-assessment_en
3. https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/guidance-parallel-ema/eunethta-21-joint-scientific-consultation_en.pdf