he implementation of the EU Health Technology Assessment Regulation (HTAR) in January of 2025 marks a new era of joint scientific consultations (JSC) and joint clinical assessments (JCA) for products seeking market access in Europe. Six months in, the transition remains challenging. The broader implications across the healthcare ecosystem are still unclear regarding the impact of the HTAR on time to patient access, innovation, and the adoption of findings or related assessment mechanisms in other jurisdictions and regions.

The initial implementation of the regulation focuses on oncology and advanced medicinal therapies, such as cell and gene therapy and medical devices, with rare diseases to be added in 2028; the regulation will be expanded to include all therapies in 2030. The HTAR aims to harmonize clinical comparative assessments across EU Member States, seeking to reduce duplication of effort for both HTA bodies and manufacturers, improve efficiency in the process and, ultimately, accelerate access and improve equity to innovative therapies for citizens in the EU. How has our knowledge of this new era of JCA evolved as we entered the first year of real-life implementation?

Six Months In: What’s Happening on the Ground?

Three products—all in oncology indications—are officially moving through the JCA process (Table 1), although the EU stated that up to 25 JCAs may be initiated in the first year; official communication remains fragmented and, in some instances, an enigma. Operationally, the European Commission is intensively preparing to support EU Member States to adapt to this new regulation, not only in their responsibility to support bodies acting as assessors and co-assessors, but also to integrate the findings of JCAs into national healthcare decision-making.

Manufacturers and other stakeholders have been eagerly anticipating further announcements relating to JCA and local HTA alignment challenges and local methodological innovations to integrate the requirements; however, the recent EU HTAR workshop in July fell short of addressing these issues. The communication at the workshop was restricted to the ongoing operational and financial challenges of individual Member States to acclimatize to the new regulation, particularly for smaller countries with less-established HTA frameworks, as well as a description of the preparatory activities in terms of staff training and pilot assessments.

Abbreviations: EMA, European Medicines Agency; MAA, Marketing Authorization Application

Abbreviations: EMA, European Medicines Agency; MAA, Marketing Authorization Application

Real-World Readiness: Challenges and Learnings

Unquestionably, the new EU HTAR represents a transformative step in EU market access for new health technologies. As the new regulation begins to take shape in the first real-life JCA product submissions, it is becoming increasingly evident that all stakeholders need to stay vigilant on the live updates. While navigating the first year of HTAR implementation and facing delays in much-anticipated public communication of Member State local adaptations, manufacturers have realized that JCA is not just a procedural shift. Rather, JCA is a strategic turning point with far-reaching implications for evidence generation and market access of new products, not only for regulatory alignment within the EU but also for transporting the impact of JCA findings for market access engagements around the world.

With key milestones for the expansion of JCA implementation on the horizon, identifying current challenges and learnings from early assessments can create future opportunities.

Anticipating the Methodological and Operational EU JCA Challenges

The EU HTAR guidance documents on evidentiary requirements to support JCAs for new products are both detailed and, at times, ambiguous. At the heart of JCA preparation lies the population, intervention, comparator, and outcome (PICO) framework, with most of the challenges being identified around the population characteristics (including numerous potential subgroups) and the list of comparators. The disconnect between the potential PICO requests, particularly the possibility of a request for a blended comparator, otherwise called “individualized treatment” (comprising different treatments under one comparator umbrella), and the recommended evidence synthesis options to cover such analytical scenarios remains a significant concern for manufacturers.

Preparing evidence strategies for the JCA based on prediction of the JCA scope assessment remains a worrisome reality. Through our growing experience in conducting PICO simulation exercises at different phases of product development to support future JCAs, it has become apparent that the potential impact of unforeseen PICO requests in evidence generation and synthesis activities may be resource-intensive to cover multiple uncertainties, especially if performed closer to the JCA submission deadline than earlier in the process. PICO uncertainties can arise from variations in treatment recommendations and off-label drug use across Member States as well as from quickly evolving treatment landscapes. These complex preparatory activities may be considered high risk for the return on investment in terms of final product market access success. Early evidence generation planning, preferably at the stage of clinical trial development, to align regulatory and EU HTA requirements and the early assessment of the potential effect of clinical evidence gaps to support JCAs will significantly mitigate last-minute blows to resource and schedule planning.

However, early evidence planning can only prove successful if manufacturers fully consider strategic opportunities for internal early engagement and alignment between different stakeholders (clinical trial developers, regulatory, market access, and medical affairs teams), considering the impact of methodological developments and JCA procedural learnings. Pilot testing risks and mitigation strategies for evidence generation and comparative analysis in the context of JCA remains critical.

Timely Positioning for EU JCA Success

For medicinal products early in the lifecycle, before confirmatory trials are developed, early assessment of JCA requirements along with other regulatory and local market expectations provides a unique opportunity to build a cohesive target product profile that maximizes the development of timely integrated evidence generation plans and product value story alignment (Figure 1). Given the EU’s clear legal mandate to involve patients in the new EU HTA process, patient input in informing early product development is considered of paramount importance. For products already in phase 2 or 3 development, and around two years before the JCA submission milestone, creating living evidence libraries (treatment guidelines, landscape analyses, systematic literature reviews, additional reviews to support evidence synthesis assumptions) and thorough assessments of comparative analysis plans for each anticipated PICO are the cornerstones of a robust JCA preparatory strategy. As the JCA preparatory activities for new products reach the final year before submission, evidence strategy is re-aligned as new data become available from both the product’s clinical trial program and from competitors, and all activities (reviews, evidence synthesis analyses, dossier preparation) will intensify, especially with the requirement for literature searches to be updated at least three months prior to submission. Clarity of medical writing and robust justification of any clinical and methodological decisions supporting the JCA submissions are considered a key successful factor for health technologies to allow not only transparency in data and analyses but also to create a trusted setting for EU and national HTA bodies’ assessments. Remaining vigilant and staying current on local EU HTA methods changes and the evolving EU healthcare data ecosystem will provide manufacturers with strategic clarity on potential data opportunities and create synergies between JCA and local market access strategies.

Source: Heads of HTA Agencies Group, European Medicines Agency. “Joint HTAb-regulatory perspectives on understanding evidence challenges, managing uncertainties and exploring potential solutions.”

National Realities: Germany and France in Focus

Once the first JCAs are completed, the focus will shift to integration with the national HTA submission process, where the efficiency is expected to be realized. In Germany, for example, the JCA dossier does not replace the need for a national AMNOG (Arzneimittelmarktneuordnungsgesetz) benefit assessment, which remains evaluative in nature rather than purely descriptive in terms of its conclusions. Still, the contents of the JCA can be integrated into the AMNOG dossier, but several practical aspects have to be considered to meet the AMNOG guidelines, for example, very specific referencing by corresponding subsection between the dossier templates.

Although the methodological alignment between the EU HTAR guidance and the local German HTA practices is closer than that of any other EU Member State, there is a noticeable difference in the choice of comparator(s) for the clinical comparative assessment. Although both JCA and AMNOG allow multiple treatment options to be covered under one umbrella comparator, in Germany, sponsors need to justify the selection of one treatment comparator only, following the results of a systematic literature review. In addition, since randomized controlled trials (RCT) reign supreme in the German AMNOG assessment, a comparison only needs to be demonstrated in an RCT, and if this direct comparison is not available, indirect comparisons are not required.

In France, the Haute Autorité de Santé (HAS) is actively engaged in adapting their methods and processes to accommodate the JCA outputs and avoid duplication of efforts already undertaken at the EU level. Although an update of HAS documentation is expected soon, no law adaptation is planned; changes are also not expected to the SMR (clinical benefit) and ASMR (clinical added value) appraisal criteria, which continue to set a high acceptance bar for clinical evidence. To create efficiencies, companies may submit their local French dossiers as soon as Committee for Medicinal Products for Human Use opinion is positive (before JCA output becomes publicly available), therefore requiring close alignment of EU JCA and the preparation of local dossiers.

Navigating the Transition

The EU HTAR is a bold step toward harmonized clinical assessments, but the road ahead is foreseen as complex for all stakeholders involved. As the first year unfolds, stakeholders must balance early evidence planning, methodological rigor, and local adaptability while accounting for the real learnings in the first year’s implementation of JCA cases. In addition to the EU HTAR guidance, insights from this first wave of JCAs will provide an invaluable source of real-world guidance for the growing number of manufacturers embarking on this new and potentially turbulent journey. Some key learnings are outlined in Figure 2.

The JCA is not just a regulatory requirement; it is a strategic opportunity to shape the future of market access for new technologies entering the EU and beyond.