The EU Joint Clinical Assessment in practice: Early lessons
The EU Health Technology Assessment (HTA) Regulation became applicable on 12th January 2025, marking a fundamental shift in how clinical evidence for new health technologies is assessed across Europe.
At the centre of the Regulation is the Joint Clinical Assessment (JCA), designed to replace multiple, often duplicative national clinical evidence reviews with a single assessment conducted at EU level. While Member States are required to give due consideration to the resulting JCA report, national HTA bodies retain responsibility for drawing conclusions on added clinical value and for decisions relating to cost-effectiveness, pricing, and reimbursement within their respective healthcare systems.
Conducted in parallel with the European Medicines Agency (EMA) regulatory review, the JCA introduces a distinct approach to defining the evidence required for HTA. Central to this is the PICO framework - Population, Intervention, Comparator and Outcomes - through which Member States specify the clinical questions relevant to their national decision-making. These inputs are consolidated into a common JCA assessment scope, creating the evidence framework against which manufacturers must prepare their submissions.
Until recently, however, much of the discussion around the JCA has focused on how the framework is intended to operate, rather than how it works in practice. The publication of the first assessments provides an important opportunity to examine how the Regulation is being implemented and, critically, what its requirements could mean for manufacturers navigating the new EU HTA environment.
In July 2026, JCA reports were published for two treatments in extensive-stage small cell lung cancer (ES-SCLC): Zepzelca (lurbinectedin; chemotherapy) in combination with Tecentriq (atezolizumab; anti-PD-L1) as maintenance treatment following first-line induction, and Imdylltra (tarlatamab; DLL3 T-cell engager) following progression on or after first-line platinum-based chemotherapy.
Together, these early ES-SCLC assessments offer one of the first opportunities to move beyond the mechanics of the Regulation and examine the JCA in practice – from how diverse Member State requirements are translated into a consolidated assessment scope to how evidence gaps and uncertainties are handled within the final assessment.
Four early ‘Learnings’ stand out, with important implications for evidence strategy, JCA preparation, and downstream market access in EU Member States.
Learning 1: Trial design must anticipate European HTA needs
One of the clearest lessons is that a clinical development programme will be assessed not only against the regulatory indication, but against multiple decision problems reflecting treatment pathways across Europe.
The contrast between the two ES-SCLC assessments illustrates this clearly. Zepzelca’s relatively narrow maintenance indication resulted in a single PICO, comparing the combination with Tecentriq monotherapy. The pivotal IMforte trial directly randomised patients between these regimens, enabling the PICO to be addressed with head-to-head evidence.
Imdylltra, by contrast, faced a substantially broader evidence challenge. Member States differed in how they defined platinum sensitivity and the circumstances in which platinum rechallenge following first-line therapy was considered relevant, contributing to four populations and seven PICOs. While the pivotal DeLLphi-304 trial provided direct randomised evidence against topotecan for several populations, other comparisons required indirect approaches, including network meta-analysis, matching-adjusted indirect comparison and other indirect treatment comparisons.
The implications extend beyond ES-SCLC. A broad regulatory indication can translate into multiple HTA decision problems that a single global comparator may not address. Developers may therefore need to anticipate European comparators, eligibility thresholds, and treatment sequences earlier in clinical development. Increasingly, these considerations may need to inform trial design itself, rather than being addressed only once HTA dossier preparation begins.
Learning 2: How a comparison is constructed can matter as much as the method used
The Imdylltra assessment highlights an important methodological lesson: having evidence against a relevant comparator does not necessarily mean that evidence will be suitable for the JCA. How the analysis population is constructed also matters.
In DeLLphi-304, investigators selected each patient’s intended control treatment (topotecan, lurbinectedin, or amrubicin) before randomisation. For the topotecan comparison, an analysis including all Imdylltra patients, but only topotecan patients from the control arm, was not accepted, as this disrupted the original randomised comparison. Instead, the JCA focused on patients in both arms for whom topotecan had been selected before randomisation. This preserved randomisation, but reduced the sample size available for the relevant PICO comparisons.
The broader lesson is that meeting JCA evidence needs is not simply about including the right comparators in a trial; the trial must also support valid comparisons within the populations defined by each PICO. Developers should therefore anticipate how PICO-specific analyses may be constructed – and whether they preserve the integrity of the original trial design.
Learning 3: JCA methodological critiques may carry forwards into national HTA
The JCA creates a common clinical evidence critique that national HTA bodies can draw on in their own assessments. While the JCA does not determine reimbursement, cost-effectiveness, or price, methodological limitations identified at EU level are now documented and available to national agencies. This could change the starting point for national HTA: rather than each agency independently identifying evidence gaps, national assessments can begin with a shared European assessment of the evidence and its uncertainties.
The SCLC assessments illustrate the types of issues that may carry forward. For Imdylltra, evidence beyond the direct topotecan comparisons was substantially more uncertain. The JCA highlighted limitations, including differences in patient characteristics and treatment pathways across studies, concerns around similarity assumptions within the evidence networks, and residual confounding of the statistical test used. For Zepzelca, the JCA similarly documented limitations in the evidence base, including differences between the trial and licensed population, and methodological issues affecting the interpretation of patient-reported and safety outcomes.
These findings do not predetermine national reimbursement decisions, as individual countries will continue to apply their own HTA frameworks and may assign different weight to each limitation. It is also too early to determine how national HTA bodies will interpret or use the first JCA findings in practice. However, their reusability is important: once an evidence limitation has been formally documented through the JCA, manufacturers may enter subsequent national appraisals with key uncertainties already established and available for national HTA bodies to scrutinise.
Learning 4: The JCA brings greater visibility to evidence expectations
The JCA provides substantial transparency on clinical evidence requirements and the resulting assessment, while the published reports offer a more high-level view of how individual elements of the assessment scope were developed. Reports set out the final PICO scope, evidence submitted, and methodological limitations in considerable detail, giving manufacturers and national HTA bodies a common public record of what was assessed and where uncertainties were identified.
The Imdylltra assessment illustrates this distinction. The report identifies four populations and seven PICOs and documents the evidence submitted against each, providing a clear view of the final assessment requirements. It also records the involvement of two carers and clinical experts and confirms that their input was considered during development of the assessment scope and review of the draft reports. Understandably, the published report provides less detail on how individual stakeholder and Member State inputs shaped specific elements of the consolidated scope, such as the inclusion of particular populations or comparators.
For manufacturers, this highlights the distinction between visibility of the final assessment requirements and insight into how the scope was developed. Published JCAs can nevertheless provide useful precedent on the types of PICO requirements, evidence limitations, and methodological considerations that may arise in future joint assessments, even where the considerations informing individual scoping choices are not described in detail. As experience with JCA accumulates, these reports should therefore become an increasingly valuable resource for informing evidence planning and preparing for potential JCA requirements. However, this greater EU-level transparency does not remove the need to anticipate country-specific evidence requirements and decision criteria, which may continue to differ across Member States.
The impact on national access is only beginning to emerge
The first SCLC JCAs provide an early indication of how the EU framework may reshape evidence assessment, but their impact on reimbursement and patient access is not yet established.
Importantly, national processes do not necessarily wait for the JCA to conclude. Germany opened its national benefit assessments for Imdylltra and Zepzelca on 1st July 2026, before publication of the final JCA reports. France had already granted Imdylltra early access for a narrower patient population before the final JCA was available. Other Member States may make greater use of the finalised JCA as the clinical foundation for their subsequent national processes.
Early experience with Ojemda (tovorafenib, selective type II RAF kinase inhibitor), approved relapsed or refractory paediatric low-grade glioma (pLGG), may provide an important test case with it becoming the first product to complete a JCA. Germany’s Federal Joint Committee (G-BA) initiated its national benefit assessment before the final JCA report was available, and the initial German assessment took a more critical view of parts of the evidence package than the JCA, including rejection of Ipsen's matching-adjusted indirect comparison (MAIC) from the JCA dossier and instead based its assessment primarily on the single-arm FIREFLY-1 study, using a newer three-year data cut. With the final G-BA decision expected in November 2026, the outcome should provide an early indication of how JCA findings interact with country-specific methodological requirements and ultimately feed into national market access and reimbursement decision-making.
These facts reinforce what the JCA is, and what it is not. It does not harmonise national reimbursement decisions or eliminate country-specific HTA requirements. Instead, it establishes a shared clinical evidence assessment that Member States can incorporate into their own decision-making.
What remains to be seen is whether this common clinical foundation ultimately accelerates real-world reimbursement and patient access. The SCLC assessments provide some of the first evidence of how the JCA operates; the next learning will come from observing how quickly Member States translate those assessments into national access decisions.
About the authors
Furkan Guvenc, PhD, is a senior business analyst at Lifescience Dynamics with robust consulting experience in the life sciences sector. He holds a PhD in Molecular Genetics and has supported clients across a wide range of therapeutic areas, including oncology, immunology, haematology, infectious diseases, and neuroscience. Guvenc specialises in competitive intelligence, market research, and market forecasting to support clients with evidence-based insights to drive informed decision making.
Jaehyuk Lee, MSc, is a senior business analyst at Lifescience Dynamics, specialising in oncology. He has supported clients across GYN and breast cancers, pan-tumour indications, GI and GU cancers, and B-cell malignancies. His expertise in competitive intelligence, market research, and market access helps clients evaluate portfolio opportunities and guide corporate strategy.
Pooja Goyal is an engagement manager based out of Lifescience Dynamics’ Toronto office. She has over nine years of experience in the pharmaceutical consulting industry. Goyal brings expertise in competitive intelligence, opportunity assessment, market access and pricing, and disease area strategy projects in immunology and other therapy areas. During the early part of her career, she also worked in the analytical R&D of a leading ophthalmic manufacturing firm. Goyal holds an MS(Pharm) in Medicinal Chemistry from the National Institute of Pharmaceutical Education and Research (NIPER), Mohali, India, and a Bachelor in Pharmaceutical Science from Panjab University, Chandigarh, India.
