Meet DLRC’s Expert: EU HTA and Market Access

In our Meet the Expert series, we sit down with the specialists behind DLRC’s regulatory and advisory services to share practical insight for the sponsors we support. In this edition, we talk to Carolin Knorr, Market Access/HTA Principal Consultant, about navigating Europe’s fast-evolving HTA landscape.

The introduction of the EU HTA Regulation and Joint Clinical Assessments has fundamentally changed what drug developers need to plan for, and how early they need to start. For sponsors in oncology, orphan drugs and beyond, the pressure to align regulatory and market access strategies has never been greater – and the cost of getting it wrong has never been higher.

Carolin brings deep expertise in EU HTA strategy, JCA and JSC preparation, PICO-based evidence planning, national HTA submissions and the integration of regulatory and market access thinking from early development onwards. Read on to meet Carolin and take away practical guidance you can apply to your own EU market access journey.

 

Meet Carolin, our EU HTA and Market Access Expert

Tell us a bit about yourself – what is your role at DLRC and what does your position typically involve?

“Thanks for having me! I work as a Market Access and HTA Principal Consultant at DLRC. In short, I help companies connect regulatory development with future HTA, reimbursement and access requirements. That means looking beyond the approval question and asking early: How will this product be assessed? What evidence will HTA bodies expect? What will national payers ask? And which development decisions need to be made to support future access?

Much of my work sits between strategic advice and hands-on project support. I look closely at clinical development programmes and ask what evidence will be needed to support them from an HTA perspective. I discuss PICO strategy and help prepare HTA advice, so overall, I help clients understand what future JCA could mean for their launch sequence in Europe.

Alongside client work, I am also developing DLRC’s HTA and Market Access business, for example, by translating new EU HTA requirements into practical services, tools and guidance that help sponsors prepare earlier and more effectively.

For me, a lot of work is about making complex HTA requirements practical: turning them into clear development decisions and priorities.”

 

How did you come to specialise in HTA and market access, and what drew you to this area?

“I have always been interested in the point where science, policy, healthcare decision-making and business strategy meet. Regulatory approval is, of course, essential, but it is only one part of the access journey. A medicine can be approved and still face major barriers before patients can actually access it.

That is what brought me into HTA and market access. It is a very fascinating and also a practical field, because the questions are directly relevant to a product’s success. They directly affect launch timing, reimbursement, price potential and the overall commercial viability of a product in Europe.

For me, the interesting question is: What will it take for this product to achieve appropriate reimbursement and pricing in the patient population for which it is developed?”

 

HTA is a rapidly changing field right now. What excites you most about working in it at the moment?

“HTA is moving much earlier into clinical development. In the past, companies often thought about market access close to launch. That is no longer sufficient. With EU HTA and especially Joint Clinical Assessment, access-relevant questions are moving closer to development and regulatory strategy.

That creates pressure, but it also creates opportunity. If you think early about comparators, endpoints, and subgroups relevant to HTA bodies, you can make better choices. You can avoid building a beautiful regulatory package that is difficult to use in HTA. For me, that is the exciting part: helping developers design evidence that is not only approval-ready, but also access-ready.”

 

What is the most rewarding part of helping a sponsor prepare for HTA?

“When a team starts to realise that an early trial design choice can later influence HTA and market access, that is usually the moment when the discussion becomes really valuable.

For example, a client may initially focus on whether the trial can support approval. That is completely understandable. But then we look at the same trial design through an HTA lens and ask: Is the comparator relevant for national HTA bodies? Are the endpoints accepted? Will subpopulation data be available, and will it be included in the assessment? Can the study answer the questions that will come up in Germany, France, or other European countries?

When clients see that these are not abstract “market access” questions, but very concrete evidence questions, the discussion changes. That is when HTA becomes useful.”

 

Understanding EU HTA: the questions sponsors ask most

The EU HTA Regulation is generating a lot of conversation. In plain terms, what has actually changed for drug developers, and why does it matter?

“The biggest change is that clinical evidence for certain medicines is now assessed jointly at the EU level through the Joint Clinical Assessment, or JCA. That EU-wide assessment does not replace national pricing and reimbursement decisions, but it creates a shared clinical assessment that national HTA bodies will use for their subsequent decisions.

For developers, this is important because the JCA runs close to the regulatory process. The HTA timelines are tight, and the assessment focuses on the product’s relative clinical value. That means that companies need to be ready for HTA at the same time as for their approval process. They need to understand likely PICO questions, HTA comparator expectations, endpoint relevance and evidence gaps. A data package that supports approval may still leave important HTA questions unanswered. For example, if the evidence is based on a single-arm trial, if overall survival data are immature, or if the main benefit is shown in progression-free-survival, while the comparative patient-relevant benefit remains uncertain.”

 

What exactly is a Joint Clinical Assessment (JCA), and, equally important, what is it not?

“A JCA is the new EU-level clinical assessment of a health technology under the HTA Regulation. It provides a joint scientific analysis of the clinical evidence for a medicine, in particular its relative clinical effectiveness and relative safety compared with relevant alternatives, the so-called standard of care.

What is important to understand is that the JCA does not make the final decision on added value, nor does it decide how a product will be priced or funded in the European Union.

Instead, the JCA creates a common clinical evidence base. Member States will still interpret that evidence in their own national context. So, the JCA is highly relevant, but it is not the end of the access journey. It is the central clinical evidence assessment that sits before, and then feeds into national HTA, pricing and reimbursement processes.”

 

Which programmes are in scope for JCAs right now, and how will that expand over the next few years?

“The EU-wide assessment is being introduced in stages. Since 2025, the JCA applies to new active substances in oncology and to ATMPs. From 2028, orphan drugs will be added. From 2030, all centrally authorised medicinal products that fall within the EU HTA Regulation will be in scope.

That stage rollout is important. Some companies may think, “our product is not in scope yet, so we can wait”. But that can be risky. If a product is expected to submit for marketing authorisation in 2028 or 2030, decisions being made today may already shape the future JCA evidence package.”

 

JCAs run in parallel with EMA procedures, and the dossier preparation window can be as short as 100 days. How should sponsors be thinking about timelines?

“We generally work backwards from the regulatory timeline and advise starting JCA preparation months before the EMA submission.

The 100-day window starts when the European Commission sends the initial request for the JCA dossier to the company, together with the final assessment scope, meaning the final PICO questions that the dossier needs to address. From that point, in standard processes, the company has 100 days to submit the dossier; in accelerated procedures or variations, the time window is even shorter.

That means the 100-day window is much too late to start preparing the JCA strategy. It is time to execute the dossier submission. By then, the company should have already completed the key strategic and technical preparations: evidence gap analysis, PICO and comparator thinking, strategic positioning, review of key JCA issues, and planning or procuring additional statistical analyses where needed.

Ideally, we would plan at least 12 months for meaningful JCA preparation before that window opens. We would usually start with a strategic advisory phase across all relevant parts of the future JCA dossier. Only after that does the actual dossier-writing phase begin, using the EU HTA template and translating the available evidence, analyses and argumentation into the required structure.

After submission, the process moves into the interaction and review phase. The assessors may request additional information, the draft report will be prepared, and the company will then have the opportunity to check the draft report for technical or tactual amendments. So, the dossier submission is the point at which the company needs to have its core evidence story, analyses, and positioning already in place.”

 

What is a Joint Scientific Consultation (JSC), and when should a sponsor consider requesting one?

“Under the HTA Regulation, developers have access to a dedicated advice procedure: the Joint Scientific Consultation. The JSC is a way to discuss the planned pivotal trial programme with HTA bodies. The value is that companies can test whether their planned study design is likely to answer future JCA questions.

Therefore, a sponsor should consider a JSC when there is still time to act on the advice. That is the key point. For example, HTA bodies may later split the target population into different subpopulations, each with its own relevant comparator. In that situation, the JSC can help the sponsor critically test the planned study design against the likely PICOs and the PICOs it wants and can realistically address. This is also a pricing and reimbursement question: if different subpopulations have different comparators, the level of added value may differ substantially between them, and that can later have a major impact on pricing potential and reimbursement conditions.”

 

PICO scoping is at the heart of the JCA process. Can you explain what it involves and why getting it right early matters so much?

“PICO stands for Population, Intervention, Comparator and Outcomes. It sounds technical, but the basic idea is simple: Which patients are we talking about? What is the new treatment? What should it be compared with? And which outcomes matter?

The challenge is that different Member States may have different views on relevant comparators or subpopulations. For example, in oncology, one country may consider a specific targeted therapy the relevant comparator for a biomarker-defined subgroup, while another may still focus on a broader approach.

In practice, a pivotal trial will rarely be able to cover all potential PICOs equally well. The key strategic decision is therefore which PICOs the sponsor should prioritise: where the product can realistically demonstrate added value, with subpopulations that are most relevant for an access perspective, and where evidence gaps may need to be explained or managed later in the JCA and national HTA processes.”

 

Where do you most often find evidence gaps when you carry out an HTA evidence gap analysis on an incoming programme?

“Developers usually design their pivotal clinical programme based on earlier clinical data and in anticipation of regulatory requirements. The issue is that the study design and the resulting evidence may then not be fully usable for the specific PICO question that the JCA or a national HTA body wants to answer.

We can see this in the first JCA reports. In one case, the tovorafenib JCA, single-arm data were submitted for several PICOs but not discussed in the JCA report because there was no comparator evidence. In another case, the tarlatamab JCA, some subgroup analyses were challenged because the submitted results were not considered reliable for specific patients.

This is exactly where our evidence gap analyses come in. We ask: Will the study evidence actually be usable for the assumed assessment questions? That means looking very closely at whether the trial population maps to the likely PICOs, whether the comparator reflects European or national standard of care, whether the endpoints are aligned, whether and which subgroups could be defined and whether indirect comparisons can be supported by sufficiently comparable external data.

We also look at the more technical gaps: potentially missing patient-level data, immature overall survival, weak quality-of-life data, inconsistent outcome definitions, limited follow-up or subgroup analyses that were not planned.

So for us, an evidence gap analysis is really a stress test of the future JCA and national HTA package. It helps identify which gaps can still be addressed by additional data or analyses or better subgroup planning, and which gaps will need to be managed strategically because they may affect the perceived added value, pricing potential and reimbursement conditions later on.”

 

National HTA processes still exist alongside the JCA. How do sponsors manage both, and does the JCA simplify things or add complexity?

“This is a great question. The idea behind EU HTA is understandable: before the Regulation, companies had to submit clinical evidence multiple times across different national HTA processes. So, one aim of the JCA is to reduce duplication and create a common EU-level clinical assessment that national bodies can use.

At the same time, the JCA itself requires comprehensive upfront preparation. One EU-level dossier may need to address several PICOs at once. This significantly increases the analytical workload, and, even more importantly, it has direct strategic relevance: companies need to decide early which PICOs they can realistically support, where added value is most likely to be demonstrated, where the evidence may be weaker, and what this could mean for national HTA, pricing and reimbursement.

If these questions have been properly addressed upfront and the JCA has been completed, national HTA processes may become somewhat less burdensome than before. National bodies draw on the JCA report, so the remaining work should increasingly focus on the national translation: the specific national PICOs, additional statistical work and added-benefit interpretation.”

 

Integrating regulatory and market access strategy

How early in development should a sponsor be thinking about HTA, and why?

“The timing is almost built into the EU HTA framework itself. A Joint Clinical Consultation is designed to take place while the pivotal evidence-generation strategy can still be influenced. In other words, before the pivotal clinical programme is fully started or locked.

That tells us something important about the intention of the HTA Regulation, too. The aim is not only to assess evidence once it is available, but to encourage evidence generation that is more relevant for future HTA. So, the practical answer is: If sponsors want to design studies that support approval and provide a stronger basis for JCA and national HTA, they need to consider HTA before pivotal trial planning is finalised.”

 

What does it mean in practise to align a regulatory strategy with HTA expectations – and what happens when the two are not aligned?

“Regulatory authorities, HTA bodies and national payers all look at the same clinical evidence, but they use it for different decisions.

For regulatory purposes, the key question is whether a medicine has demonstrated efficacy, safety and quality. HTA bodies assess the evidence from a comparative perspective: Is the product better than the most relevant standard of care for the defined patient population?

Regulatory and market access alignment means bringing these different perspectives into the development strategy early. For example, when a pivotal trial is being planned, we consider the regulatory comparator and endpoint package, as well as the likely HTA comparators, patient-relevant outcomes, and subpopulation and subgroup requirements.

If this is not done or done too late, when the clinical trial programme can no longer be changed, sponsors can end up with evidence that supports approval but may not be sufficient for HTA. The comparator may not match national expectations, the endpoints may not be accepted, or the trial may not provide the subgroup evidence needed for a favourable assessment.

That is why regulatory and market access alignment is so important. It helps sponsors make smarter evidence-generation choices. The aim is to understand which PICOs and subpopulations the development programme can most support, where added value is most likely to be demonstrated, and how these choices may later influence national HTA conclusions, pricing potential, and reimbursement conditions.”

 

You work at the intersection of regulatory affairs and market access. How does DLRC’s integrated approach change what a sponsor can achieve?

“In many development programmes, sponsors receive regulatory and HTA advice from different providers. They discuss the same study programme several times, with different teams, different assumptions and likely without a fully coordinated view across approval, JCA and national access.

At DLRC, regulatory, HTA and market access teams are ultimately working with the same development programme at the same time. That means the sponsor does not need to translate regulatory advice into HTA implications on their own, or manage separate workstreams that may point in different directions. We can look at the same development programme and jointly assess what it means for regulatory approval, JCA readiness, national HTA expectations, payer relevance and future pricing and reimbursement.

The sponsor receives a more efficient and more coherent advisory process. The value is that the advice is connected across the full path from approval to market access.”

 

Can you share an example of a programme where an early HTA strategy changed the evidence plan or the outcome?

“One good example is a global biotech developing an innovative genetic medicine for a rare neurological disorder. The initial focus of the company was mainly on the regulatory route and on whether the planned pivotal study could support approval. That was an important starting point, but several future HTA questions were still unsolved.

When we reviewed the planned Phase III programme from an HTA perspective, the discussion became more specific, and the subsequent JSC process helped bring out several important HTA considerations.

For example, the JSC discussion showed that the intended indication had to be critically assessed against the planned trial population and the evidence that could realistically be generated. This included considering whether the indication should be narrowed or the trial population broadened, and where additional evidence would be needed for patient groups or genotype-defined subpopulations expected to remain within the future claim.

For me, this shows the practical value of early HTA input: It allowed the company to draw clear conclusions on how the protocol and evidence-generation strategy should be adapted to better meet both EMA and HTA expectations.”

 

For sponsors with strong regulatory expertise but limited experience with HTA, what are the most common blind spots?

“I have already mentioned some of the technical blind spots: comparators, endpoints, subpopulations and timing. What I would add is that in practice, the challenge is often not a lack of awareness, but prioritisation.

We may identify HTA risks early and propose ways to mitigate them, for example, through subpopulation planning, considerations to narrow the study population, additional analyses or a more targeted comparator strategy. But if HTA is still seen mainly as a launch-related topic, these activities can easily be deprioritised while regulatory milestones take precedence.

That is understandable, because regulatory approval is the core regulatory activity. At the same time, we hope to see companies adapt their internal planning more strongly to the new EU HTA reality. JCA should be seen as an opportunity to improve the future HTA outcome, strengthen the value story and ultimately support better market access for the product.”

 

Looking ahead

How do you see the EU HTA landscape evolving between now and 2030 as JCA rolls out to all centrally authorised medicines?

“This is indeed a complex question because the answer depends on several levels: the expansion of the JCA’s scope, the adaptations of national HTA systems, and the future development of the EU HTA framework itself.

By 2030, EU HTA will become relevant for a much broader set of companies and products. Today, the focus remains on new active substances in oncology and ATMPs, with orphan drugs following soon. But the 2030 expansion will bring in large, non-orphan indications into scope, where HTA can be very demanding. That matters commercially as well as procedurally. Areas such as immunology, diabetes and non-new active substances in oncology account for a very large share of global pharmaceutical value and growth. IQVIA reported that oncology, immunology and diabetes accounted for more than 40% of global pharmaceutical value in 2025. Furthermore, non-rare neurological diseases may also become highly relevant from an HTA perspective because endpoints, long-term outcomes, disease progression and patient-relevant benefit can be difficult to capture convincingly.

I also expect national HTA procedures to evolve. The JCA does not currently replace national HTA or national added-benefit discussions. This creates an important question for national systems: which parts of the assessment will remain national in future, and how far should national procedures be adapted to make use of the JCA? Germany illustrates the broader issue quite well. The current AMNOG system is mainly built around new active substances and certain protected new authorisations. The JCA scope from 2030 is broader. This may create EU-level clinical assessments for products or indications that do not fit neatly into today’s national HTA triggers. So important will be how national systems make use of this evidence, and whether national procedures will gradually be adapted to the broader EU HTA framework.

The third, most far-reaching question is whether EU HTA could one day move beyond clinical assessment and start making conclusions on added benefit. Personally, I think a full replacement of national HTA is unlikely in the foreseeable future, because pricing, reimbursement and value conclusions are still deeply linked to national healthcare systems. But I believe the JCA will become increasingly influential. Even without formally replacing national HTA, it may shape the evidence basis on which national added-benefit, reimbursement and pricing discussion are built.”

 

What is one piece of advice you would give a sponsor preparing for their first JCA submission?

“I would encourage companies to engage with EU HTA early and to view it as a strategic opportunity rather than a procedural requirement. A JCA is demanding, but it also creates a structured moment to think very clearly about the future value story of a product: which patients matter most, where added value can realistically be shown, and which evidence gaps may affect later national HTA, pricing and reimbursement.

But the starting point will be different for different companies. Larger pharmaceutical companies often have experienced HTA and market access teams. For them, the key is usually stronger internal alignment: regulatory, clinical, medical, HTA and market access teams need to work together earlier, before pivotal design choices, analysis plans and evidence-generation strategies are fixed.

For smaller biotech companies, the situation can be different. They may be highly experienced in science and development but may not yet have dedicated HTA or market access functions, especially if the business model is focused on bringing products to a partnering or licensing stage. For these companies, my advice would be: do not underestimate HTA. Ultimately, HTA will strongly influence the commercial value of the product, because it shapes how the evidence is assessed, how added value is perceived and how future access and reimbursement can be achieved.

So the practical advice is to start the JCA thinking early, at a level that fits the company. For some, that means tighter internal cross-functional alignment. For others, it means bringing in HTA and market access expertise from the outside very early. In both cases, the aim is the same: to use the JCA preparation to strengthen the evidence strategy and improve the product’s chances of successful assessment and market access.”

 

What is a common misconception about EU HTA that you would love to clear up?

“I would frame this question less as a misconception and more as a lack of prior HTA exposure. In our work, we often support small and mid-sized biotech and pharmaceutical companies. Many of them have very strong scientific and regulatory teams, but less direct experience with European HTA and reimbursement decision-making.

What we often see is surprise at how differently HTA bodies may look at the same development programme. A study design that is acceptable for EMA may still be challenged in HTA, for example, because the comparator is not considered relevant, because the patient population is split into different subpopulations, or because the endpoint package does not sufficiently demonstrate patient-relevant benefit. The latter is particularly relevant in oncology, where surrogate endpoints like PFS may support the regulatory pathway, but may not be enough to demonstrate added value from certain Member States’ HTA perspective.

The second issue is the strong focus on the fastest possible route to marketing authorisation. That is understandable, especially for innovative products. However, earlier approval, for example by pursuing a conditional marketing authorisation, can come with a less mature evidence package, and that can create real challenges for JCA, national HTA and market access.

So, my message would be: Sponsors should actively assess the trade-off between earlier market entry and the potential loss of economic value later on. If the evidence package introduces high uncertainty in HTA, it may affect the assessed added value, pricing potential, and reimbursement conditions. EU HTA should therefore be considered as an integral part of the overall development and value strategy.”

 

And finally… For a sponsor just starting to consider EU market access, what is the best first step to take?

“In our experience, the first step is simply to engage with EU market access proactively. Once sponsors start working through the key HTA questions in a structured way, confidence often increases quickly because the process becomes more tangible and manageable.

The chances of a successful outcome are highest when there is still time and willingness to adapt the clinical development plan to future HTA requirements. That is where sponsors can still influence the evidence base, strengthen the value story and improve the basis for later reimbursement and pricing discussions.

In Darwinian terms, it is about being fit for the environment in which the product will be assessed. For EU market access, that means preparing early, adapting intelligently and making evidence-based decisions that are robust enough for approval, JCA and national HTA.”

 

Conclusion

The EU HTA Regulation is not a procedural update – it is a fundamental shift in how clinical evidence is evaluated for market access across Europe. As Carolin’s insights make clear, the sponsors who succeed are those who start planning for HTA long before the EMA submission, who align regulatory and access strategies from early development, and who understand that PICO-driven scoping and the 100-day JCA dossier window leave very little room for reactive preparation.

From evidence gap analysis and PICO strategy through to JSC preparation, JCA dossier authoring, national HTA submissions and integrated regulatory and access planning, DLRC’s HTA and Market Access advisory service is designed to support sponsors at every stage.

If you are preparing for your first JCA or want expert guidance on aligning your EU regulatory and market access strategy, DLRC’s team is ready to help. Get in touch to start the conversation by emailing us at hello@dlrcgroup.com.