The first two Joint Clinical Assessments (JCA) for medicines started on 16 April 2025. The first is being conducted by the French National Authority for Health as assessor and the the Polish Agency for HTA and Tariff System as co-assessor and concerns an advanced therapy for the treatment of melanoma. The second procedure will assess tovorafenib, a medicine for the treatment of paediatric low-grade glioma (LLG). This second joint assessment is the responsibility of the Irish National Centre for Pharmacoeconomics (assessor) and the German Institute for Quality and Efficiency in Health Care (co-assessor).
The updated list of ongoing JCAs, published under Regulation (EU) 2021/2282 on Health Technology Assessment (HTA), is available at this link.https://health.ec.europa.eu/document/download/d947533e-7e4e-4e82-a9c6-e06830d708f8_en?filename=hta_ongoing-jca_en.xlsx
The new procedure aims to reduce the time to market for innovative products, as the HTA assessment runs in parallel with the regulatory assessment by the European Medicines Agency (EMA). The resulting draft JCA report and summary report prepared by the designated HTA authorities must be further endorsed by the Member State Coordination Group on HTA (HTACG) within 30 day of the adoption of a Commission decision granting a marketing authorisation (MA) for the medicine. The final JCA report could be used by national competent authorities to speed up their internal assessment and ensure that patients across the EU have access to innovative technologies and medicinal products.
Key features of the JCA procedure
The HTA Regulation (EU) 2021/2282 defines the medicinal products subject to the joint clinical assessment (Art. 7). The new procedures came into force on 12 January 2025; during the first phase of implementation, they will only apply to medicinal products based on new active substances with an oncology indication or advanced therapy medicinal products (ATMPs). From 13 January 2028, JCAs will also cover orphan products, and from January 2030 all other products covered by the HTA Regulation.
JCAs may also be referred to Class IIb and Class III medical devices and Class D in vitro diagnostics for which the relevant expert panels have provided a scientific opinion as part of the clinical evaluation consultation procedure under the MDR and IVDR Regulations.
MA’s applicants and health technologies developers shall submit a pre-submission request to both the EMA and the HTACG secretariat, including a Letter of Intent to declare that the application falls within the scope of the HTA Regulation and will be subject to a joint clinical assessment. Dedicated guidance is provided by both the EMA and the HTACG, including uploading to the HTA IT Platform. The platform is also used to inform the HTACG of any changes to the intended date of submission of the MA application and/or to communicate the intention to discontinue the application.
Joint HTA-regulatory perspectives
Meanwhile, the EMA and the Heads of HTA Agencies Group (HGA) have published a high-level document summarising recent joint HTA-regulatory perspectives on understanding evidence challenges, managing uncertainties and exploring potential solutions (link).
The document is the result of a series of workshops during where several case studies were discussed: on onasemnogene abeparvovec (Zolgensma) indicated for spinal muscular atrophy; on amivantamab (Rybrevant), a monotherapy for locally advanced or metastatic non-small cell lung cancer (NSCLC); and on axicabtagene ciloleucel (Yescarta), for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBCL).
A number of relevant uncertainties still remain at the time of the respective regulatory and HTA decisions, including the lack of (prospective) comparative evidence with relevant comparator(s) and the uncertain relevance of “surrogate” study endpoints. Other outstanding issues include the impact of intercurrent events on the validity and interpretability of estimates of treatment effect, the maturity of data and the length of the follow up in the context of “cure”.
Recruitment could be a challenge, particularly where small patients populations need to be selected (e.g. in paediatric studies or biomarker-guided therapies), as well as the still limited knowledge of the specific characteristics of certain rare diseases (e.g. prognostic factors or treatment pathways). The parallel development of several medicines in a given disease area could also pose some problems, coupled with the often observed limitations in obtaining additional evidence on new treatments that become available.
The suggested solutions
The different objectives of regulatory and HTA decision making should be recognised throughout the entire life cycle of medicines and medical devices subject to joint clinical assessment. Clear research questions of clinical interest should therefore be pre-specified, as they will determine the definition of how adequate evidence will be generated, together with consideration of context-specific feasibility concerns.
This approach implies the need for early collaboration between regulatory authorities and HTA bodies, starting at the design stage and including for example early clinical trials in support of a conditional marketing authorisation, “pivotal” clinical trials, or post-launch studies. Trials should be designed to provide appropriate evidence to answer the different, but often overlapping, questions of regulators and HTA bodies. The parallel EMA-HTA Joint Scientific Consultation should be the reference for improved collaboration, while dialogue on other medicines outside the formal JSC process should be identified on the basis of their scientific importance.
Eight recommendations to address joint evidence
Among the eight key points described in the EMA/HGA document is the strong preference for the use of randomised evidence to assess the benefit/risk and comparative effectiveness of medicines, both from the regulatory and HTA perspective. Randomisation should take place as early as possibile in clinical development, including the use ofnovel randomised designs such as “seamless” phase I-II designs, multi-arm platform studies or other flexible and adaptive designs where appropriate.
Regulatory and HTA decisions could also be informed bycomplementing data from pre-licensing clinical trials with randomised trials in registries and routine care (the so-called “pragmatic RCTs” in real-world conditions). Pragmatic and registry-based studies can be usefully used to generate evidence in the post-marketing phase to address remaining uncertainties.
Where appropriate, the design of the studies should also allow for the parallel estimation of multiple estimands, to balance the different information needs of regulators and HTA bodies. Uncertainties in decision making could also be addressed by improving the collection, analysis and reporting of outcomes other than those from the primary study.
The statistical analysis of data could be improved by the availability of individual participant data (IPD) from clinical trials, so to increase the quality of evidence synthesis and to assess reliable inferences from non-randomised studies. Real-world observational data for effect estimation in indirect comparisons is still an open issue. On the other hand, real-world data may represent an opportunity to complement clinical data for informing decisions. In any case, the joint EMA/HGA document concludes, there is a need for new frameworks to support the identification, assessment, and balancing of remaining uncertainties, particularly in the context of regulatory decisions.
