In the current pharmaceutical environment, obtaining regulatory approval is no longer enough to ensure patient access. Across markets, payers require robust, relevant evidence that not only demonstrates clinical efficacy but also justifies real-world value and cost-effectiveness. As a result, market access can be a significant hurdle, especially if payer expectations are not incorporated early into development planning.
These requirements are driving a growing recognition of the importance of obtaining early scientific advice from health technology assessment (HTA) bodies. Far from being a box-ticking exercise, early HTA engagement is a strategic opportunity to allow manufacturers to align development plans with the realities of reimbursement, reducing market access risks and building a stronger, more credible value proposition.
What is Early HTA Scientific Advice?
Early HTA scientific advice is a formal process through which pharmaceutical manufacturers can consult HTA agencies, often during Phase II or early Phase III of development, to seek feedback on planned evidence generation strategies. The focus is typically on:
- Clinical trial design: Are the chosen comparators, endpoints, and patient populations appropriate from a reimbursement perspective?
- Economic models: Do the proposed structures and data inputs align with how value is assessed in a given country?
- Real-world evidence plans: Are there opportunities to strengthen the submission with observational or registry data?
There are multiple formats for engaging with HTA bodies:
- National HTA scientific advice (e.g., National Institute for Health and Care Excellence (NICE) in the UK, The Federal Joint Committee (G-BA) in Germany, French National Authority for Health (HAS) in France)
- Parallel consultations with regulators and HTAs, such as European Medicines Agency’s (EMA)–HTA advice
- The new EU HTA regulation – which became effective on the 12th January 2025, creating an EU framework to allow member states to jointly assess pharmaceutical products 1
What are the key Benefits of Early HTA Scientific advice?
Reduces Evidence Uncertainty
Negative HTA outcomes often hinge on misaligned clinical development programmes, such as inappropriate comparators, surrogate endpoints that lack payer acceptance, or limited subgroup analyses. Early HTA scientific advice gives manufacturers the opportunity to pre-empt these pitfalls, enabling them to refine study designs while there is still time. This helps reduce the risk of a negative or delayed reimbursement decision.
Improves Clinical and Economic Study Design
Early HTA scientific advice can be invaluable in ensuring that payer-relevant endpoints are captured in pivotal trials, not just those needed for regulatory approval. It also highlights the need for data on quality of life, resource use, and subgroups that may drive value differentiation. In parallel, advice can shape economic model assumptions, helping companies align with national preferences for utility measures, time horizons, and extrapolation methods.
Strengthens the Value Proposition
A value story developed in isolation from HTA feedback risks falling flat. By engaging early, manufacturers can tailor their evidence plans to resonate with the specific value frameworks used by different HTA bodies. For example, in Germany, patient-relevant outcomes, such as improvements in quality of life, symptom relief, or how well patients manage daily life, are central to how added benefit is assessed. If these endpoints are missing or poorly defined, it can seriously impact the chances of receiving a positive HTA outcome, even if the treatment is clinically effective. By engaging early, manufacturers can make sure that messaging and data generation are fully synchronised.
Optimizes Resource Allocation
Early HTA scientific advice highlights what is essential versus optional from a payer perspective, helping manufacturers invest wisely. For instance, advice might reveal that a planned real-world evidence study is unlikely to influence a reimbursement decision, while underscoring the need for additional endpoints. This targeted insight prevents wasted efforts and focuses manufacturers on high-impact activities.
Builds Payer Trust
Early HTA scientific advice sends a clear message that manufacturers are listening. By involving HTA bodies in the development journey, manufacturers demonstrate transparency, responsiveness, and commitment to delivering value, qualities that are increasingly valued by payers. This can set a more collaborative tone for post-launch discussions, including managed entry agreements or price negotiations.
Best Practices for Seeking Early HTA Scientific Advice
While the “when” of early HTA scientific advice matters (typically before pivotal trial initiation), it is equally important to focus on how to make early engagement count:
- Choose the right HTA agencies: Prioritise markets that are commercially significant or have high HTA uncertainty.
- Be prepared: Define clear questions, share draft protocols or models, and ensure cross-functional alignment between clinical, health economics and outcomes research (HEOR), and access teams.
- Integrate the feedback: Early HTA scientific advice should feed directly into trial amendments, evidence generation plans, and overall access strategy, not just sit in a drawer.
- Choose a mix of HTA types: If you are seeking advice from more than one HTA body, avoid selecting countries that evaluate products in the same way (e.g., two that both focus mainly on budget impact). Instead, choose a mix of HTA “archetypes”. For instance, choose one HTA body that focuses heavily on clinical benefit (like Germany) and another that puts more weight on cost-effectiveness (like the UK). This gives you broader, more useful insights and helps future-proof your strategy for different markets.
Looking Ahead: HTA Advice in a Changing Regulatory Landscape
The HTA environment in Europe is evolving. With the introduction of the Regulation (EU) 2021/2282 on 12th January 2025 2, Joint Clinical Assessment (JCA) has become mandatory for new cancer medicine or an advanced therapy medicinal product (ATMP). The rules will be extended to orphan medicines in January 2028 and will as of 2030 cover all new medicinal products 1. These changes aim to foster greater harmonization across Europe, but also increase the stakes for aligning development across countries.
In this context, early HTA scientific advice will become even more critical, not only to navigate differences in evidence expectations, but also to future-proof submissions against a more centralised, and possibly more rigid, evaluation process. The JCA introduces a centralised clinical evaluation process for certain products across EU member states, starting with oncology and ATMPs. While this aims to streamline assessments, it also means the evidence requirements will be more standardised—and potentially more rigid. Engaging early with HTA bodies can help companies anticipate these expectations, design clinical trials that meet JCA standards, and avoid having to rework submissions post-assessment. Early advice is therefore key to building a JCA-ready evidence package that supports faster, smoother access across the EU.
Conclusion
In an era of growing scrutiny and rising evidence standards, early HTA scientific advice is becoming a competitive necessity. By engaging early, developers can mitigate risk, build stronger value narratives, and ultimately improve the chances of successful reimbursement.
At Remap Consulting, we have supported clients with obtaining early scientific advice for various rare diseases, such as cystic fibrosis, maple syrup urine disease (MSUD), and Rett syndrome. For manufacturers seeking to unlock payer confidence, early HTA scientific advice is crucial for transforming good science into accessible innovation. The key takeaway is simple: incorporate early payer engagement into your development strategy, do it early, strategically, and frequently.
To understand more about how to approach early scientific advice, register to attend Remap’s upcoming webinar “Navigating Early Scientific Advice for Pricing & Market Access Success”.
References
- New EU rules on Health Technology Assessment open up a new era for patient access to innovation https://ec.europa.eu/commission/presscorner/detail/en/ip_25_226
- Regulation (EU) 2021/2282 of the European Parliament and of the Council of 15 December 2021 https://eur-lex.europa.eu/eli/reg/2021/2282/oj/eng