European evidence requirements are fundamentally changing. Regulatory approval and market access can no longer be addressed sequentially.
Mandated under EU HTA Regulation (EU 2021/2282), the EU Joint Clinical Assessment (JCA) is intended to streamline evidence assessments while leaving national pricing and reimbursement decisions to individual member states. In January 2025, new oncology medicinal products and advanced therapy medicinal products (ATMPs) became the first to fall under the JCA in a staggered, multi-year approach that will include all new medicinal products by 2030.
The first six publicly reported JCA cases provide early insights into what may differentiate successful submissions from unsuccessful ones. As of July 2026, three JCAs have been completed, and three have been discontinued. Early evidence planning, robust comparative effectiveness evidence, and proactive management of PICO (Population, Intervention, Comparator, Outcomes) complexity have emerged as key success factors. Ultimately, these cases demonstrate that Europe is moving toward a model where approval and access are increasingly inseparable.
Completed and Discontinued JCAs
Based on JCA reports, European Commission communications, and other publicly available sources, it is apparent that JCA success is dependent on synchronization of regulatory and HTA pathways.
Tovorafenib (Ojemda®, Day One Biopharmaceuticals) was the first completed JCA and demonstrated feasibility of the JCA process. Completed JCAs also include tarlatamab (Imdelltra®, Amgen Inc.) and lurbinectedin (Zepzelca®, PharmaMar, S.A.). These three products successfully advanced through EMA review, achieved marketing authorization, and reached JCA endorsement.
Overall, the three completed JCAs demonstrate the sponsors’ ability to navigate complex timelines, multi-country evidence requirements, and stakeholder needs, demonstrating that operational execution may be just as important as clinical evidence.
Discontinued JCAs include sasanlimab (Pfizer, Inc.), catequentinib (Advenchen Laboratories), and tacquell (Netherlands Cancer Institute). The sasanlimab JCA was terminated when Pfizer Europe MA EEIG withdrew its application for marketing authorization. The European Commission discontinued the JCA for catequentinib after the manufacturer failed to provide requested missing information, including PICO mismatches and missing data. And the tacquell JCA was terminated after the manufacturer failed to address information requests, including for deficiencies across PICOs; dossier gaps included incomplete relative effectiveness data, missing comparative safety results, and poor methodological reporting.
Discontinuation illustrates how vulnerable the process can be when development, regulatory, and HTA strategies are not appropriately aligned. Compressed timelines, early dossier requirements and evolving regulatory status introduce risk, resulting in potential discontinuation.
The Traditional Disconnect
Historically, pharma companies have conducted regulatory evidence generation (e.g., safety, efficacy, risk-benefit) through separate teams than those responsible for HTA evidence generation (e.g., budget impact, cost-effectiveness, value demonstration, comparative effectiveness). Given that the JCA runs in parallel with EMA review, evidence planning is no longer just an approval exercise, but an approval and access exercise. This means that a product with evidence to secure regulatory approval, but without evidence designed to meet HTA requirements, will likely face significant access challenges.
Expectations Versus Reality
The original expectations of the JCA included reduced duplication (one clinical assessment replacing multiple country-specific reviews), harmonized evidence requirements (resulting in more predictable evidence planning), faster patient access (across EU member states), and improved alignment between regulators and HTA agencies.
| Expectations |
| One clinical assessment for all EU member states |
| Reduced duplication of national clinical assessments |
| Greater methodological consistency |
| Earlier and more predictable HTA planning |
| Faster, more equitable patient access |
| Better alignment between EMA and HTA requirements |
A frequent misconception is that one JCA means one European reimbursement decision. It does not. Although the JCA provides a common clinical assessment, Member States may still reach different conclusions regarding magnitude of benefit and reimbursement value during national appraisal processes. Member states continue to determine added value, cost effectiveness, budget impact, pricing, and reimbursement. Consequently, national HTA submissions remain necessary. This challenges the anticipated efficiency that the JCA was intended to bring.
Notably, the most commonly cited challenge in the JCA process is the need to accommodate multiple country-specific PICOs. Even though the JCA produces a single assessment, individual member states have their own preferred PICOs, which can result in multiple comparators, different lines of therapy, different treatment pathways, and different outcomes expectations. PICO management is emerging as a central operating challenge under the JCA framework. Sponsors may need network meta-analyses, indirect treatment comparisons, subgroup analyses, and supplemental real-world evidence (RWE) to satisfy the breadth of PICOs required.
| Challenges |
| Multiple and potentially conflicting PICOs |
| Compressed evidence-generation timelines |
| Limited flexibility when evidence is immature |
| Resource constraints among HTA agencies |
| National HTAs still retain decision-making authority |
| Uncertainty regarding adoption and interpretation by member states |
In addition to increased PICO complexity, compressed timelines (often with unresolved regulatory questions), persisting national HTA requirements, and increased evidence requirements (e.g. more comparative evidence) are increasing burden on sponsors.
The Solution: The “One Evidence Package” Mindset
The need has surfaced to simultaneously optimize evidence for EMA review, JCA requirements, and national HTA decision-making, rather than addressing these sequentially, transforming evidence generation from a regulatory exercise into an approval-and-access strategy. To be successful, sponsors should adopt a “One Evidence Package” approach in which evidence generation is planned simultaneously for EMA regulatory approval, JCA, and National HTA and reimbursement decisions. Given timelines and emerging complexities, this should start no later than Phase II development.
Joint Scientific Consultations (JSCs) are the only formal opportunity for sponsors to obtain EU HTA feedback on their evidence strategy prior to submission. JSCs are performed by the EU HTA Coordination Group through JCA subgroups, allowing health technology developers to obtain scientific consultation while planning clinical studies and evidence generation in preparation for subsequent JCAs. For sponsors, the greatest value of a JSC is reducing the risk of evidence misalignment before pivotal studies are completed. Considering the challenges that emerge with multiple country-specific PICOs across Member states, the JSC provides an opportunity to ask if proposed comparators are relevant, if endpoints are likely to satisfy HTA expectations, if indirect treatment comparisons will be acceptable, and what subgroup analyses may be required.
If selected by the JCA subgroup, sponsors must prepare and submit a detailed briefing document that describes the product, the development program, proposed clinical studies, the evidence generation strategy, and specific questions for HTA bodies regarding PICOs, comparators, endpoints, statistical analyses, etc. Strategically, the optimal time to request a JSC is before pivotal trial design is finalized, while there is still an opportunity to modify comparator selection, endpoint strategy, subgroup analyses, RWE approaches, and other evidence generations plans.
Traditionally, integrated evidence generation planning (IEGP) has served as an established framework that aligns clinical, medical, regulatory, and commercial teams, eliminating silos, identifying data gaps, and planning evidence generation across the product lifecycle. IEGP that also includes considerations specifically for JCAs and national HTAs, will become one of the most strategic enablers of JCA success, and serve as the operational bridge between development, JSC, JCA, and reimbursement. Without it, sponsors risk generating evidence that achieves approval but fails to optimize HTA and market access outcomes.
As a core principle, this “One Evidence Package” Mindset should include one integrated target product profile (TPP), one cross-functional IEGP, and a unified launch objective. The TPP should integrate regulatory value, clinical value, patient value, and economic value. The IEGP should span Clinical Development, Regulatory Affairs, HEOR, Market Access, Medical Affairs, Biostatistics, and RWE Teams. The ultimate launch objective is to achieve approval, reimbursement, and patient access simultaneously.
This “One-Evidence Package” Strategy should be established as follows:
- Start the IEGP process early, establishing your strategy in phase I/II. Treat your IEGP as an evolving, living document. Activities should include competitive landscaping, treatment pathway mapping, patient-relevant outcomes (e.g., function, symptoms, QoL, caregiver burden, treatment burden), evidence gap assessments, and HTA risk assessments.
- Start planning for JCA requirements in phase II.
- Proactively manage PICOs. Develop a prospective, EU-wide PICO map that includes major market PICO and evidence gap matrices.
- Plan on generating comparative evidence, e.g., using head-to-head trials (preferable), network meta-analyses, indirect treatment comparisons, and RWE.
Many therapies reach submission with immature overall survival data, single-arm studies, small populations, and limited long-term safety evidence. This is particularly problematic for precision oncology, ATMPs, and rare diseases. The combination of short timelines and incomplete evidence packages have resulted in RWE becoming a necessary evidence source, especially to strengthen comparative effectiveness evidence and to address heterogeneous PICO requirements. While RWE is becoming more important in establishing the totality of evidence, it is important to note that the value of RWE depends on fitness-for-purpose, methodological rigor, transparency, and acceptability to HTA assessors.
Moreover, it is important to include RWE in evidence planning from the start, and not as a secondary consideration to fill an evidence gap that arises late in the development process. Pre-submission, RWE supports disease burden, epidemiology, and standard-of-care characterization. For submission, RWE can support external control arms, and comparator analyses. Post-launch, RWE supports durability, long-term effectiveness, and safety monitoring.
Conclusion
The promise of JCA is one European clinical assessment, reduced duplication, and more consistent evidence expectations across the EU. What we have learned from the first implementation experience is that heterogeneous PICOs, immature evidence, compressed timelines, and ongoing national HTA requirements are likely to remain major challenges. The organizations expected to be most successful are those that build JCA requirements into evidence planning early and leverage RWE, indirect comparisons, and proactive PICO mapping rather than treating HTA as a post-approval activity.
The question is no longer whether a product can achieve regulatory approval. The question is whether the development program was designed to generate the evidence needed for approval, reimbursement, and patient access simultaneously. The most successful organizations will:
- Establish an integrated evidence generation plan (IEGP) earlier
- Align regulatory and HTA requirements
- Build evidence around anticipated/future PICOs
- Integrate RWE strategically
- Operate from a single evidence-generation framework.
Future success will depend not only on evidence quality, but also organizational integration across Clinical Development, Regulatory Affairs, HEOR, Market Access, Medical Affairs, Biostatistics, and RWE Teams.
About UBC
United BioSource LLC (UBC) is the leading provider of evidence development solutions with expertise in uniting evidence and access. UBC helps biopharma mitigate risk, address product hurdles, and demonstrate safety, efficacy, and value under real-world conditions. UBC leads the market in providing integrated, comprehensive clinical, safety, and commercialization services and is uniquely positioned to seamlessly integrate best-in-class services throughout the lifecycle of a product.
References
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About the Author
Judy Lytle, Executive Director of Evidence Development Study Solutions
Judy Lytle serves as the Executive Director of Evidence Development Study Solutions for UBC. Dr. Lytle joined UBC in 2023, bringing more than 15 years of experience in life science and healthcare strategy development, implementation, and execution. With a background in medical affairs and real-world evidence, she brings together differentiated study design and evidence generation solutions for value demonstration. She also has oversight of epidemiology, patient and physician services, scientific/clinical strategy, and medical writing teams.
Dr. Lytle holds a PhD in Neuroscience from Georgetown University as well as a Master of Biotechnology Enterprise & Entrepreneurship (MBEE) from Johns Hopkins University. A fellow of the American Association for the Advancement of Science (AAAS), and certified Project Management Professional (PMP), her approach is systematic and grounded in science.
