What is the JCA?

With only a few weeks to go before the implementation of the European Union Health Technology Assessment Regulation (EU HTAR), drug developers and payers are bracing themselves for sweeping changes in their evidence generation and assessment processes. The EU HTAR¹ establishes the framework for joint clinical assessment (JCA) of new medicines, starting with oncology drugs and advanced therapy medicinal products (ATMPs) in January 2025, followed by the remaining orphan drugs in 2028, and all centrally authorised medicines in 2030.

The JCA will run in parallel with the European Medicines Agency (EMA) marketing authorisation process and aims to provide a mandatory centralised scientific analysis of relative safety and effectiveness of new health technologies. It will be managed and assessed by the HTA Coordination Group (HTACG) – a board of representatives from EU member states. EU member states’ regulatory body will be required to give “due consideration” to the JCA report but remain ultimately responsible for determining the added clinical and economic value of health technologies, as well as pricing and reimbursement decisions within their healthcare systems. They can choose to a) agree with the JCA decision and just request economic evidence, b) agree with the JCA decision but ask for further clinical evidence, or c) disagree with the JCA decision with a clear rationale for doing so.

By providing a single standardised HTA process, the JCA aims to gradually replace the currently fragmented national assessments, thus improving efficiency, transparency and access to innovative health technologies for patients across Europe.

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Steps of the JCA process

The JCA process will begin when the health technology developer submits a regulatory dossier to the EMA. The JCA assessors will then receive and consider the (anticipated) product label and characteristics along with clinical guidelines across Europe to define the assessment scope in terms of one or more PICOs - Population, Intervention, Comparator, and Outcomes – as outlined in the EUnetHTA21 scoping guidance.² Each PICO will contain one population or subpopulation and one comparator. These proposed PICOs are to be subsequently shared as a survey with all 27 member states who will have two weeks to respond with any additional PICO requirements not covered by the assessors’ proposal. Member states responses will be reviewed by the assessors and consolidated into the lowest possible number of PICOs that satisfy all national requirements. The consolidated list of PICOs will be validated with patients and clinical experts and then subsequently sent to the health technology developer. Remarkably, health technology developers will be required to address all of the final PICOs in their JCA dossier which will need to be submitted only 90 days after receipt of the final scope. Finally, the assessors will review the dossier to produce the JCA report and overall recommendation on the clinical effectiveness and safety of the health technology developer’s product against comparators specified in the scope.

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Figure 1. Flowchart depicting the JCA process

Challenges: so many PICOs, so little time

Published guidance has left many open questions and associated challenges, particularly with regard to the scoping process and how health technology developers can best prepare. Given disparities in national guidelines, treatment availability and epidemiology across European countries, it is unclear how well the consolidation process will work in practice. Such issues will be especially pronounced for oncology drugs and ATMPs for rare diseases which are often characterised by marked regional variations in standard of care. As there is currently no upper limit to the number of PICOs that could be included in the JCA scope, the industry is justifiably concerned.

An EU consortium consisting of several EU HTA agencies was gathered in 2021 (EUnetHTA21) to support the future HTA system under the new regulation and were tasked with putting together the initial guidance.³ Early EUnetHTA21 exercises using one oncology (Pombliti)and two orphan drugs (Pluvicto, Ebvallo) suggested that the total number of consolidated PICOs might range from five to nine when based on the participation of eight to 10 member states.^4-6 However, it is expected that the number could be significantly higher if all 27 member states were considered. Indeed, an industry-led scoping simulation of 2 hypothetical oncology drugs, utilising EUnetHTA21 guidance and published HTA reports of comparators from six and nine member state, resulted in 10 and 16 PICOs, respectively.⁷ (The count increased to 14 and 18 PICOs, respectively, when England’s NICE was considered as a proxy for remaining member states, which often refer to NICE for reimbursement decisions). Similarly, a simulation on three EMA-approved oncology products, conducted by the European Federation of Pharmaceutical Industries and Associations (EFPIA), resulted in six, seven, and 23 consolidated PICOs, respectively, when considering only 7 countries.⁸

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Table 1. Simulation of PICO scoping exercises: three case studies

Without adequate preparation for the consolidated PICOs, health technology developers could be left ill-equipped to ensure that the JCA submission is completed within the given timeframe as evidence generation will likely require considerably more than the allotted three months. Rather, health technology developers will need to conduct broad systematic literature reviews (and indirect treatment comparisons) based on anticipated PICOs well ahead of regulatory submissions. Ideally, this process will be initiated following phase 2 trials to ensure that pivotal studies are optimally designed in accordance with market access requirements. The initial systematic literature reviews and indirect treatment comparisons can then be adapted and updated 3 months prior to submission based on the actual JCA scope. In this new European HTA environment, accurate prediction of the assessment scope will be critical.

How can Symmetron assist in PICO prediction?

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Figure 2. Steps to assist in PICO prediction

Step 1: Anticipate national PICO requirements                                                                                                                

In preparation for the JCA, the first important step is understanding PICO requirements across member states. To achieve this, health technology developers have four tools at their disposal. Firstly, a comprehensive review of European and national clinical guidelines for the indication of interest can provide an overview of the current standards of care and available treatment options. Secondly, research into past national HTAs, from bodies such as the National Institute for Health and Care Excellence (NICE), Institute for Quality and Efficiency in Health Care (IQWiG) or Haute Autorité de Santé (HAS), or JCAs once available, of similar interventions can yield valuable insights into which populations, comparators and outcomes will likely be expected in a submission. Thirdly, reaching out to representatives of these bodies for insight. Lastly, targeted reviews of the randomised control trials and real-world evidence can help identify future comparators, monitor treatment utilisation patterns and better characterise the target patient population and subgroups in each territory.

Step 2: Simulate JCA scoping

A comprehensive evidence base on national PICO requirements can then be transformed into a final set of anticipated PICOs by simulating the JCA scoping process. A simulation would involve (Symmetron) emulating the JCA scoping process by cross-checking the information collected between member states to consolidate to the fewest PICOs possible. In this regard, the first JCAs conducted in 2025 will be highly informative in illustrating how the scoping process is applied in practice.

Step 3: Validate predicted scope with stakeholders

Once the predicted PICOs have been established, validation with stakeholders should be conducted to affirm their accuracy. Ideally, early engagement with the EU’s upcoming Joint Scientific Consultation (JSC) process would be included in this step.⁹ However, as the available spots will likely be out stripped by the demand for JSCs,¹⁰ national early scientific advice services should also be utilised by health technology developers. Lastly, given the involvement of clinical key opinion leaders and patient organisations in the JCA scoping process, organising advisory boards can provide excellent opportunities to validate the predicted scope, identify requirements and shape JCA strategy early on.

JCA readiness and Symmetron

The JCA represents a significant shift in how clinical evidence for health technologies is evaluated in the EU. By centralising the clinical assessment process, the JCA aims to streamline submissions, reducing redundancy and improving efficiency for health technology developers. However, the introduction of this new regulation presents challenges, particularly around the preparation and response to the consolidated PICO framework within tight timeframes.

Symmetron offers comprehensive support for health technology developers navigating the JCA process. From reviewing clinical guidelines and HTA decisions to simulating scoping exercises and facilitating early advice, Symmetron’s services can equip health technology developers to address PICOs effectively. Scoping, early evidence generation and living (iterative) reviews are at the core of our work and we have extensive experience in producing these deliverables to a high quality. By leveraging Symmetron’s expertise, health technology developers can optimise their evidence generation and submission strategies, ensuring readiness for this new regulatory landscape.

References

1.           European Union. Regulation (EU) 2021/2282 of the European Parliament and of the council of 15 December 2021 on health technology assessment and amending/EU.  2021. http://data.europa.eu/eli/reg/2021/2282/oj

2.           EUnetHTA 21. D4.2 Scoping Process.  2023. https://www.eunethta.eu/wp-content/uploads/2023/10/EUnetHTA-21-D4.2-practical-guideline-on-scoping-process.pdf

3.           EUnetHTA. EUnetHTA 21. 2024. https://www.eunethta.eu/eunethta-21/

4.           EUnetHTA 21. PICO Exercise I - Pluvicto.  2023. https://www.eunethta.eu/wp-content/uploads/2023/09/EUnetHTA-21-PICO-1-Deliverbale-1.pdf

5.           EUnetHTA 21. PICO Exercise II - EBVALLO Tabelecleucel. 2023. https://www.eunethta.eu/wp-content/uploads/2023/09/EUnetHTA-21-PICO-2-Deliverbale.pdf

6.           EUnetHTA 21. PICO Exercise III - Pombilit. 2023. https://www.eunethta.eu/wp-content/uploads/2023/09/EUnetHTA-21-PICO-3-Deliverable.pdf

7.           Anke van Engen, Krüger Robert,Parnaby Adam, et al. The Impact of Additive Population(s), Intervention, Comparator(s), and Outcomes in a European Joint Clinical Health Technology Assessment. Value in Health 2024;27:1722-1731.

9.           European Commission. Health technology assessment – Joint scientific consultations on medicinal products for human use.  2023. https://ec.europa.eu/info/law/better-regulation/have-your-say/initiatives/13759-Health-technology-assessment-Joint-scientific-consultations-on-medicinal-products-for-human-use_en

10.        European Commission. 2025 Annual Work Programme of the Member State Coordination Group on Health Technology Assessment (HTACG).  2024. https://health.ec.europa.eu/document/download/9f1d2ac8-3515-4be1-9a29-db3d9ffb5201_en?filename=hta_hatcg_awp_en.pdf

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