Q&A – Preparing for the EU Joint Clinical Assessment (JCA) process

During a recent panel discussion on the European Joint Clinical Assessment (JCA) process, led by Tommy Bramley, Senior Vice President, Global Consulting and Market Access, Cencora, market access and healthcare system experts offered their perspectives on the challenges and opportunities pharmaceutical and biotechnology companies are likely to encounter. In this article, panelists Herbert Altmann, Head Commercialization and Access Solutions Europe at PharmaLex, Jurgen Huismans, Global Director Access & HTA Strategy at MSD, Casper Paardekooper, Partner at Vintura, and Mihai Rotaru, Senior Manager Market Access at EFPIA, delve into the questions received from the audience.

Q1: How early will pharmaceutical companies need to start their preparation? And what will be the knock-on consequence of that?

In general, it is recommended that pharmaceutical companies initiate their internal market access planning already during the strategic planning phase to identify and agree on the most promising evidence package. Best practice examples show that internal processes should get aligned after phase II clinical data read out, before phase III clinical trial design is finished. This could mean four years before potential EMA approval. This point in time is critical because it aligns with the joint scientific consultation (JSC), which could be most insightful before finalizing the phase III clinical trial design. Taking appropriate action within this timeframe allows companies to adequately prepare for the cross-functional process and avoid potential delays or setbacks in the JCA process.

Q2: Is there any information on the timing and plans for the Joint Scientific Consultations (JSCs)?

In the EUnetHTA 21 service contract, six to eight European JSCs were foreseen to be conducted during EUnetHTA 21, which will end in September 2023¹. The JSC is a very good opportunity for manufacturers, to have an early exchange with the European Medicines Agency (EMA) and HTA bodies in Europe at the same time. 

Between September 2023 and the end of 2024, health technology developers will be able to seek advice from both national HTA bodies and the EMA through a parallel procedure termed "Parallel EMA/HTA body (HTAb) Scientific Advice." This advice-seeking process is aimed at planning pivotal studies in preparation for the application of the EU HTA Regulation. The Federal Joint Committee (G-BA: Gemeinsamer Bundesausschuss), the highest decision-making authority for self-regulatory bodies within the German health system, announced in a press release earlier in July, that they will serve as the central HTA coordination contact, overseeing all incoming requests for parallel scientific advice and streamlining the procedure with the involvement of national HTA bodies².

For more details regarding the timing and plans, we advise reviewing the draft proposal outlined by EUNetHTA 21³. It is crucial to initiate strategic planning for JSCs at the earliest opportunity, as the available slots might be limited and in high demand. Taking prompt action ensures better chances of securing a consultation slot when needed and facilitating the process effectively.

Q3: Would manufacturers have any impact on the PICO (Population, Intervention, Comparison, Outcome) scope on the JCA level, and on the final assessment? Would they be able to comment on the final outcomes of assessment?

“In EUnetHTA 21, the scoping process starts with submission of a request for assessment by the health technology developer (HTD) and ends when the consolidated final PICO is communicated to the HTD”⁴. During this scoping process, manufacturers do not have any influence on the PICO (Population, Intervention, Comparison, Outcome) scope. The JCA secretariat will ask all member states to fill in a PICO survey. This survey will be summarized by the assessors/co-assessors and PICOs are planned to be presented to the Committee for Scientific Consistency and Quality (CSCQ) as well as patients and clinical experts, which are invited to comment on the consolidated PICOs. Validated and final PICOs will be shared with the manufacturer. Manufacturers are not involved in this scoping phase, and the selected PICOs are communicated to them without any opportunity for discussion. In terms of the final assessment outcome, manufacturers are given the opportunity to review the JCA report in its draft form. However, this review is solely for the purpose of ensuring technical correctness and accuracy, and not for engaging in “negotiations” about the assessment's results. It is important to note that the process and guidelines are not finalized and are subject to change or further updates in the future.

Q4: Will companies have the opportunity to discuss the PICO with national HTA bodies for the JCA, before the coordination group?

It is advisable for companies to maintain a continuous dialogue with local HTA bodies. However, once the EU Joint Clinical Assessment (JCA) procedure has commenced, manufacturers will no longer have the opportunity to interact with the HTA bodies. This measure is taken to ensure the independence of the HTA bodies, and any direct interaction with the manufacturers during this process is not anticipated.

After the JCA report is published, it becomes crucial for manufacturers to establish and maintain good communication with the local HTA bodies. This is necessary to facilitate the use of the JCA report findings into the specific requirements and context of the local healthcare environment.

Q5: For advanced therapy medicinal products (ATMPs), should the filing to the European Medicines Agency (EMA) be submitted in 2024 to go through the JCA process (e.g. if the filing has been done in December 2023, then the product is not eligible for the JCA in 2024)?

The EU HTA Regulation specifies that it will apply for those oncology medicines and ATMPs for which an EMA dossier will have been introduced after 12 January 2025 (Art 7.1.a and Art 7.2.a). This means that any products for which an EMA application has been submitted before that date is not eligible for EU JCA. What still needs to be clarified from a legal perspective is if the Regulation refers to the date of submission by manufacturer or the date when EMA has formally accepted the regulatory dossier (we suspect the later).

Q6: The JCA is, as all HTA bodies, looking at evidence at population level for inclusion in the insured package. However, for certain orphan drugs and ATMPs, this will never be feasible. So, in case of accelerated assessment at EMA, for PRIME product, how will this constrain the JCA? What can we do to ensure that individual efficacy is seen as an important outcome for which tailormade reimbursement can be achieved? 

The JCA solely focuses on the clinical assessment aspect, while the final decision regarding inclusion in the insured package considers both clinical and local economic assessments. In the case of certain orphan drugs and ATMPs, where evidence at the population level might not be feasible, it becomes essential to address how individual efficacy can be recognized as a significant outcome. It might be worth looking into tailormade reimbursement strategies to possibly accommodate these unique situations. 

PRIME is a scheme run by the EMA to enhance support for the development of medicines that target an unmet medical need⁵. Accelerated EMA approval, particularly for PRIME products, can pose challenges for the JCA process, as it reduces the available time for assessment. The commissioning group responsible for JCA might want to consider a suitable solution and seek clarification to manage this impact effectively. As of now, the implications of the accelerated process on JCA timelines are not entirely clear, making it crucial to address this issue and develop strategies for seamless coordination. Notably, organizations like the European Confederation of Pharmaceutical Entrepreneurs (EUCOPE) and Alliance for Regenerative Medicine (ARM) advocate for specific and purposeful methodologies in assessing ATMPs and orphan drugs, which can further contribute to the overall process.

Q7: Can companies withdraw from the JCA process? And if so, what is the consequence? Could they then proceed directly with local HTA? 

The JCA process does not allow companies to voluntarily withdraw once initiated. According to the legislation, the JCA is a mandatory procedure and can only be halted if the labeling process is discontinued. For example, if the EMA determines that the data provided is unsafe or inaccurate and decides not to grant a label, the JCA process would also come to a stop.

Companies must complete the JCA process before proceeding to the local pricing and reimbursement stage. The JCA is anticipated to serve as a prerequisite before engaging with local HTA bodies for pricing and reimbursement considerations.

Q8: Is there any information about patient involvement (patient organizations) in JCA?

It is foreseen that patient organizations are incorporated in JCA. Member States are free to engage national patient organizations when responding to the intended PICO survey. Furthermore, a specific pathway for engaging patient organizations directly at EU level in the scoping process is foreseen however the concrete mechanics for how this will be done are still being discussed/negotiated in the Member States Coordination Group. There is clear appetite and demand from patient organizations at EU level to be meaningfully involved in the JCA process.

Q9: Will it be mandatory for national HTA bodies to respect the JCA report and included recommendations?

As per the formal HTA Regulation text, member states are required to give the JCA report "due consideration", but it will not be obligatory.

While national HTA bodies will have the option to complement the joint report, they should not duplicate the assessment that has already been collectively evaluated. This approach aims to ensure efficiency and prevent unnecessary redundancy in the assessment process across different HTA bodies.

Q10: How is the PICO consolidation step foreseen to happen in practice? How will complex comparator situations be handled (e.g. combination regimen)?

We envision the PICO consolidation step being carried out through a highly coordinated scoping phase and a well-structured process. During this phase, the designated assessors/co-assessors will diligently collect the PICO requirements from all Member States, streamline and condense them as much as possible, and subsequently communicate the consolidated information to the manufacturer after sign off from the CSCQ. This approach is anticipated to ensure a systematic and organized handling of complex comparator situations, such as combination regimens. 

Q11: Will the JCA strengthen the relationship between EMA rapporteurs with HTA rapporteurs? Is any impact anticipated?

A rapporteur is a designated expert or representative responsible for leading and coordinating the evaluation process of a specific medicinal product or health technology within regulatory or HTA agencies. They play a crucial role in assessing the data, compiling reports, and providing recommendations to support the decision-making process.

The Joint Clinical Assessment (JCA) is expected to enhance the collaboration between EMA rapporteurs and HTA rapporteurs, fostering a stronger relationship between them. This closer working relationship is likely to result in a deeper understanding of each other's processes, preventing delays in bringing innovative treatments to the market and reducing unnecessary bureaucracy between the regulatory and HTA processes. By aligning their efforts, both EMA and HTA rapporteurs can facilitate a more streamlined and efficient evaluation of new therapies, ultimately benefiting patients and healthcare systems.

It is anticipated that EMA rapporteurs and HTA rapporteurs will work more closely with each other and will generate a better understanding of the two processes.

With the same goal, not to delay any innovation coming to the market and further reduce bureaucracy between the two processes.

Q12: Can the JCA challenge the Committee for Medicinal Products for Human Use (CHMP)’s conclusions?

The primary aim of the JCA is not to challenge the conclusions made by the Committee for Medicinal Products for Human Use (CHMP). Instead, the final label recommended by the CHMP will have an impact on the JCA process, influencing the validation of the evidence provided by the manufacturer. The JCA process is designed to consider and align with the CHMP's opinion and label rather than challenge them.

Q13: Is it anticipated that companies with oncology products or advanced therapy medicinal products (ATMPs) will delay submissions due to the current lack of clarity, with less than 18 months until policy comes into effect?

As of now, there are no indications that companies developing oncology products or advanced therapy medicinal products (ATMPs) are delaying their submissions because of the current lack of clarity. The pharmaceutical industry is keen on expediting the introduction of innovative medicines to reach a broader patient population as swiftly as possible. Thus, despite the less than 18 months until the policy comes into effect, there seems to be a commitment to pushing forward with submissions and not allowing uncertainties to hinder progress.

Q14: What is the benefit of Joint Clinical Assessments if Member States can carry out their own assessments?

The Joint Clinical Assessment (JCA) offers several benefits despite Member States having the option to conduct their own assessments. Firstly, the JCA is a mandatory process, ensuring a standardized approach across all Member States. By streamlining the assessment process, it is expected to reduce redundancies and achieve the intended goals more efficiently. The involvement of local HTA bodies can be optimized by leveraging the state JCA report and the Health Technology Assessment Scientific Support (HSS) conducted in this process, as they won't need to repeat these assessments.

It is important to note that there is no single European HTA body conducting the assessment. Instead, local HTA bodies collaborate in the European JCA process, with one or two taking on the main coordinating responsibility. Subsequently, each country's local HTA body takes over the assessment within their own environment. This collaborative approach allows for greater harmonization and cooperation while respecting the specific requirements and context of each Member State.

Q15: Is a common definition for added therapeutic benefit across EU expected or we will still have ASMR/SMR (France), and different levels seen in Germany? 

Currently, we do not anticipate a common definition for added therapeutic benefit across the EU, as these definitions align closely with the local healthcare environments and facilitate the compound journey from the clinical HTA assessment of the data to the pricing and reimbursement process. The varying level of clinical benefit and added therapeutic value assessed locally and compared to the available therapeutic alternatives in a country (e.g. in France SMR - Service Médical Rendu, and ASMR - Amélioration du Service Médical Rendu), will contribute to different local pricing and reimbursement rules. As a result, harmonization of these definitions is not currently expected.

Q16: What is the anticipated impact on companies working in ultra rare diseases with regards to evidentiary needs for JCA?

No distinction is expected for companies working in ultra rare diseases concerning the evidentiary needs for JCA. Clinical trial evidence will continue to be crucial in demonstrating the efficacy and safety of the product, particularly when compared to the standard of care and unmet medical needs. Ultra rare disease products will undergo an assessment similar to other products, with the same level of scrutiny and requirements for evidence to support their efficacy and safety claims resulting in a JCA report.

Q17: How will the unique characteristics of ATMPs be addressed by the EU JCA to ensure none is rejected because long-term durability can’t be proved, and they are not studied in randomized trials?

The unique characteristics of ATMPs will be given special consideration by the EU JCA to prevent their rejection solely based on challenges related to long-term durability or the absence of randomized trials. A multitude of healthcare system stakeholders, including prominent organizations like EUCOPE and ARM, are keen to facilitate the speedy market entry of ATMPs. 

A recent article from ARM delves into the methodology adopted by the Joint Clinical Assessment process and offers insights into how ATMPs are being handled to ensure their timely and efficient evaluation and market accessibility⁶.

Q18: What are the learnings from the Joint Action 3 pilot?

Insights derived from the Joint Action 3 pilot can be found in EFPIA's report⁷.

The key learnings encompass several aspects, including the complexity of the process, a very limited level of interaction between manufacturers and JCA bodies, and challenges related to capacity shortage. These learnings provide valuable feedback for refining and improving the joint clinical assessment process, aiming for more efficient and effective collaboration between all involved parties.

Q19: Is JCA a step towards Joint Reimbursement Assessment?

The JCA is not envisioned as a step towards Joint Reimbursement Assessment, as long as healthcare budgets remain the responsibility of individual member states. The reimbursement decisions will continue to be made at the local level, and the JCA process is focused on clinical assessment and cooperation, rather than harmonizing reimbursement decisions across all member states.

Q20: Is JCA a steppingstone to joint procurement? 

As of now, the JCA is not considered a steppingstone to joint procurement. The procurement, pricing, and reimbursement processes are distinct and separate from the JCA. While the JCA focuses on clinical assessments and cooperation, joint procurement involves collaborative efforts in purchasing medical products and services. These two processes serve different purposes and are not currently interconnected.

Q21: Will this regulation achieve its intention of reducing duplication/streamlining the HTA process? 

We foresee that the regulation will indeed accomplish its intention of reducing duplication and streamlining the HTA process. However, its success will depend on effective collaboration among all stakeholders in the ecosystem. It's important to acknowledge that a transition and learning period will be necessary to fully implement and optimize the regulation's impact. By working together and adapting as needed, we can maximize the potential benefits of this regulatory initiative.

Q22: Will the Joint HTA process introduce efficiencies in the HTA process?  What metrics will the JCA institute to ensure there is an improvement in the process from the current status quo such that small and mid-size companies will benefit from it?

The Joint HTA process is expected to bring about efficiencies and work toward achieving that objective. To ensure a continuous improvement in the process, it will be iterative in nature. To benefit small and mid-size biotech companies, it is crucial to leverage additional platforms for knowledge transfer. By doing so, these companies will not be at a disadvantage compared to larger pharmaceutical companies when navigating through the Joint HTA process. The aim is to create an inclusive and equitable environment that allows all stakeholders to benefit from the potential improvements introduced by the Joint HTA process.

Q23: Who is measuring each of the objectives: speed to market, reduction of redundancies, equality?

Various stakeholders within healthcare systems, as well as the commissioning group, will be responsible for measuring each of the objectives: speed to market, reduction of redundancies, and reduction of inequalities. These Key Performance Indicators (KPIs) should be monitored to ensure continuous improvement, streamline processes, accelerate the speed to market, and promote equitable access to innovative medicines for all patients throughout Europe. Regular assessment of these metrics will enable the identification of areas for improvement and help drive advancements in the joint clinical assessment process.

The contents of this communication contain opinions of the participants of the disclosed panel which may not represent the opinions of AmerisourceBergen. AmerisourceBergen strongly encourages readers to review all available information about the particular issues discussed and to rely on their experience and expertise in making decisions around bringing products or services to market.

1. EUnetHTA. Joint Scientific Consultations (JCS) – EUnetHTA. Accessed on July 18. Available at: https://www.eunethta.eu/jsc/ 
2. G-BA. EU-HTA: G-BA coordinates parallel scientific advice for manufacturers from September onwards. Accessed on July 13, 2023. Available at: https://www.g-ba.de/presse/pressemitteilungen-meldungen/1118/
 3. EUnetHTA-21. D7.1.2 Procedure and Framework for the Factual Accuracy Check. Accessed on July 14, 2023. Available at: https://www.eunethta.eu/wp-content/uploads/2023/02/EUnetHTA-21-D7.1.2-Procedure-and-Framework-for-the-Factual-Accuracy-Check-v1.0.pdf
 4. EUnetHTA. EUnetHTA D4.2 practical guidelines on scoping process. Accessed on July 18. Available at: https://www.eunethta.eu/wp-content/uploads/2022/09/EUnetHTA-21-D4.2-practical-guideline-on-scoping-process-v1.0.pdf
  5. European Medicines Agency. PRIME: priority medicines. Accessed on July 17, 2023. Available at: https://www.ema.europa.eu/en/human-regulatory/research-development/prime-priority-medicines
 6. Alliance for Regenerative Medicine. Proposed joint clinical assessment methodology would have rejected nearly 90% of the ATMPS currently authorized in the EU. Accessed on July 14, 2023. Available at: https://alliancerm.org/press-release/joint-clinical-assessment-methodology/
7. EFPIA. EU REA – Learnings from the first three EUnetHTA Joint Action 3 assessments. Final Report. Accessed on July 14, 2023. Available at: https://www.efpia.eu/media/361736/cra-efpia-learnings-from-the-first-three-eunethta-joint-action-3-assessments-final-report.pdf