With the implementation of the EU HTA (Regulation (EU) 2025/117) and ongoing adaptation of methods used in national HTAs, manufacturers have uncertainty regarding payer expectations for their asset. HTA early scientific advice (ESA) is a valuable tool to mitigate this uncertainty and align development with payer expectations. However, many companies miss critical opportunities or misinterpret the feedback provided, resulting in costly delays or rejections. This article introduces common pitfalls encountered in ESA and how to avoid them.
What is HTA Scientific Advice?
As full national HTA is resource-intensive, uncertainties in trial design can cause delays for manufacturers. ESA is a formal process for obtaining input from HTA bodies during the development of a new product, providing non-binding feedback on clinical development plans before formal submission. Several HTA bodies offer ESA, including NICE, HAS, and G-BA, with NICE and G-BA also offering joint HTA-regulatory advice alongside the EMA. Additionally, following the implementation of the EU HTA regulations, manufacturers can submit a request for a JSC. JSCs enable health technology developers (HTDs) to obtain scientific consultation during the planning of the clinical studies and clinical investigations of a health technology on the information and evidence needs for a subsequent Joint Clinical Assessment (JCA). JSC access is limited and selective, with regulation stating there will be at least 3 request periods, limiting the access for HTDs to the JSC. Further details on JSCs are available here.
Benefits of Seeking HTA Scientific Advice
The overarching benefit of ESA is the potential to optimise clinical development through recommendations on aspects such as trial populations, comparators, and relevant endpoints, thereby reducing uncertainty during HTA. Moreover, ESA allows for alignment on payer expectations for trial design, enabling anticipation of evidence needs in different markets and strategic adaptation of submissions. ESA can also highlight areas where supplementary evidence may strengthen the evidence package and support payer perception during HTA. As the advice is typically non-binding, manufacturers may choose whether to implement it; however, implementation usually benefits the manufacturer and enhances the likelihood of a positive HTA outcome.
Common Pitfalls in HTA Scientific Advice Interactions
Although ESA provides several benefits, manufacturers should be aware of common pitfalls across different stages of the process. These can hinder progress, lead to suboptimal advice, or ultimately result in an unfavourable HTA outcome.
ESA should be sought at the correct time in the clinical development timeline. HTD’s should have careful consideration of when this period is, avoiding seeking advice too late in the timeline when the design is nearly finished, or too early when the design is still in flux If advice is sought after Phase III trials have begun, there will likely be little room to implement recommendations. Conversely, if sought too early, internal teams may not be aligned, making effective implementation difficult. Manufacturers should include early advice planning as part of the development strategy, and ESA should be sought at a pre-determined point before finalising trial design, allowing adequate time for recommendations to be implemented.
Common pitfalls during briefing book development
Successful ESA requires internal alignment and clear strategic objectives for gaining ESA. When sections of the briefing book are developed by local teams in isolation, without cross-functional collaboration, misalignment may lead to a misrepresentation of the product or neglect of country-specific context, causing uncertainty at the scientific advice meeting and suboptimal advice.
Suggestion for overcoming the pitfall
To avoid this, manufacturers should undertake early cross-functional planning involving medical, regulatory, and market access teams. This includes having relevant internal teams involved in briefing book, question and company positioning development. Manufacturers may also benefit from the inclusion of external expert advisors in the development of the briefing book, as the provision of an outside perspective may allow for more effective cross-functional planning, and refinement of the questions and company positions to be included in the briefing book.
Common pitfalls during engagement and ESA meetings
Additional pitfalls can arise during the engagement and meeting stage, which can hinder manufacturers if not well managed. For example, even with a robust briefing book, team members may falter during the ESA meeting due to inadequate preparation, potentially resulting in unproductive dialogue with limited benefit to the manufacturer. Similarly to inadequate preparation, ineffective management of the discussion during the meeting also risks unproductive dialogue with the HTA bodies. For example, teams may exhibit overly defensive communication or inefficient time management, resulting in an excessive focus on specific issues while neglecting broader discussions. This can prevent all questions being addressed, resulting in incomplete advice being obtained.
Suggestion for overcoming pitfalls
To address these pitfalls, manufacturers should carefully select attendees based on their knowledge of the asset and ensure a balance across functions. In addition to this, manufacturers should conduct rehearsal sessions before the meeting to help team members prepare for and practice responses to possible questions. Manufacturers should also utilise experienced external advisors to guide HTA interactions, as these external advisors can provide support to the manufacturer during discussion of questions or when providing the company positioning. Moreover, rather than focusing primarily on presentation or avoiding difficult conversations, teams should prioritise interactive discussion, ensure comprehensive coverage of the dossier, and request elaboration or suggestions on challenging points. This approach promotes a better understanding of the advisors’ rationale.
Common pitfalls in the post-ESA stage
While the dossier submission and engagement stages require considerable planning, challenges in the post-ESA stage can also negatively impact outcomes if not properly managed. A common mistake that manufacturers make is the misinterpretation or selective use of the HTA feedback received. The misinterpretation of advice as a guaranteed endorsement may lead to complacency and result in the failure to anticipate potential scrutiny or deviation. Even if not misinterpreted, manufacturers may selectively use the HTA feedback achieved, which could result in the failure to adjust clinical development plans in response to critical feedback. For example, manufacturers may continue with their development plan as initially outlined, or implement recommendations only superficially, risking criticism in future HTA submissions.
Suggestion for overcoming the pitfall
Upon receiving the written advice, project teams should critically assess each recommendation, evaluate how they can be implemented in the clinical development plan, and identify those requiring further consideration. Adapting clinical development plans in line with ESA recommendations will likely positively influence HTA outcomes. Moreover, monitoring the evolving landscape, such as emerging comparators or guideline updates—enables timely adjustments and reduces risks at the assessment stage. A rigorous review of the development plan from ESA through to submission is essential for success.
Conclusion
There are several pitfalls that can significantly hinder a manufacturer’s chance of success at assessment. However, with proper consideration and planning, these can be avoided, allowing ESA to provide meaningful insights that support HTA submission. To avoid pitfalls of ESA and ensure success, manufacturers should consider the following:
- Ensure ESA is sought at the correct time in the clinical development timeline, with enough time to allow alteration based on recommendations
- Ensure sufficient cross-functional planning to allow for alignment and input from cross-functional teams.
- Include the correct individuals with knowledge of the asset in the scientific advice meeting, and conduct rehearsal sessions with a focus on effective time management and comprehensive discussion of the questions and company positionings Critically assess the recommendations provided and evaluate how the recommendations can be implemented into the clinical development plan
- Monitor the evolving landscape to enable timely adjustments to the clinical development plan if necessary
Remap Consulting can aid manufacturers as external advisors throughout the duration of ESA, through the development of a briefing book in tandem with manufacturers, support during the ESA, and provision of recommendations for future action following advice is received. This can ensure potential pitfalls are avoided and actionable advice capable of optimising clinical trial design is gained. For further information, please register for our upcoming webinar: Navigating Early Scientific Advice for Pricing and Market Access Success.
References:
- Joint Scientific Consultations – European Commission
- Early Scientific Advice from Regulators and HTA: A NICE Perspective. ISPOR. https://www.ispor.org/docs/default-source/publications/value-outcomes-spotlight/january-february-2015/vos-a-nice-perspective.pdf?sfvrsn=e7fcd97a_2
- NICE advice service. NICE. https://www.nice.org.uk/about/what-we-do/life-sciences/nice-advice-service
- Joint Advice through the BfArM and the Federal Joint Committee (G-BA). BfArM. https://www.bfarm.de/EN/BfArM/Tasks/Advice-procedures/Joint-Advice-BfArM-G-BA/_node.html
- Guidance for national early dialogues on medicinal products. HAS. https://www.has-sante.fr/jcms/c_2623726/en/guidance-for-national-early-dialogues-on-medicinal-products
- Key learnings from one of the first Joint Scientific Consultations. Remap Consulting. https://vimeo.com/1027627358
- Navigating HTA Requirements During Development Through Early HTA Scientific Advice: Insights From Companies’ Strategies, Challenges, And Priorities. CIRS. https://cirsci.org/wp-content/uploads/dlm_uploads/2024/07/Early-advice-Poster-In-person-Final.pdf#:~:text=83,the%20past%20five%20years%2042.
- Early Health Technology Assessment Advice: Opportunities to Achieve Collaborative and Efficient Dialogue. ISPOR. https://www.ispor.org/publications/journals/value-outcomes-spotlight/vos-archives/issue/view/unlocking-the-promise-of-real-world-evidence/early-health-technology-assessment-advice-opportunities-to-achieve-collaborative-and-efficient-dialogue#:~:text=On%20two%20recent%20occasions%2C%20early,requiring%20less%20time%20to%20reach
- Remap Consulting – Navigating Early Scientific Advice for Pricing & Market Access Success. Remap Consulting. Microsoft Virtual Events Powered by Teams