Navigating the Challenges and Opportunities of the PICO Framework in the New EU HTA Regulation

As the EU prepares to implement new health technology assessment (HTA) regulations in 2025, explore key issues, opportunities and strategies to best navigate the upcoming changes.

The European Union (EU) is on the verge of a significant shift as it prepares to implement new health technology assessment (HTA) regulations in 2025. This change promises a more efficient use of resources, improved patient access to innovative health technologies and strengthened HTAs across the EU. However, it also presents challenges and uncertainties, particularly in relation to the Population, Intervention, Comparator(s) and Outcomes (PICO) framework underpinning the new Joint Clinical Assessments (JCAs). This blog post explores key issues, opportunities and strategies for health technology developers (HTDs) navigating this changing landscape.

Overview of the PICO Framework

The PICO framework underpins the Joint Clinical Assessments (JCAs) and will be the basis for the appraisal of evidence submitted by health technology developers (HTDs). Parameters include:

• Population: Patients/population(s) in which the intervention under assessment should be used
• Intervention: Therapeutic, diagnostic or preventive intervention under assessment
• Comparators: Alternative intervention(s) against which the intervention under assessment should be compared
• Outcomes: Outcomes of interest (including minimum follow-up time, if relevant)

JCAs constitute a scientific analysis of the relative effects of the health technology assessed on the health outcomes against the chosen parameters, based on the assessment scope. The JCA starts with the formulation of a defined research question, based on policy questions from member health care systems. Translation of the policy question into a research question through a PICO provides the ability to specify the data requirements and the framework for the assessment.

Challenges and opportunities of the new EU HTA regulation

The implementation of centralized HTA presents both opportunities and challenges for pharmaceutical companies. Centralized HTA offers the potential for streamlined processes through Joint Scientific Consultations (JSCs), which provide consolidated and non-binding confidential advice, facilitating alignment and ensuring consistent quality of HTA evaluations across the EU. This harmonization aims to enhance the efficient use of resources, reduce duplication in HTA submissions and address inequities in patient access to innovative therapies.

However, challenges persist, including limited early engagement opportunities and the absence of a requirement for consolidated advice engagement. Additionally, there is a lack of consensus on appropriate methodologies, with existing guidelines often deemed insufficiently flexible for novel or pragmatic approaches.

Further, uncertainties arise regarding the applicability of centralized advice at the national level and the potential for longer timeframes to access certain markets. This is due to concurrent processes with the European Medicines Agency (EMA) and national pricing and reimbursement procedures, leading to competition for internal resources within pharmaceutical companies.

PICO challenges and opportunities

One of the main challenges lies in the uncertainties regarding the timelines for PICO scoping. Particularly for small and mid-size pharmaceutical companies, meeting these timelines could be a significant hurdle. Moreover, the impact of the EUnetHTA (a 20-year voluntary network of national authorities) assessment on the expected launch sequence in Europe remains unclear.

Despite these challenges, the new EU HTA regulation presents significant opportunities. By prioritizing PICOs based on their impact rather than developing a lengthy list, HTDs can ensure they meet critical timelines. Early scientific advice, either formal or informal, can shape pivotal study design early in the development process.

Further, the new regulation encourages HTDs to anticipate PICO scoping in their current clinical development strategy, fostering collaboration between internal and external stakeholders at both global and national levels. Other opportunities include the potential to apply for the innovative licensing and access pathway (ILAP) for enhanced regulatory and market access input and encouraging patient engagement to identify appropriate PICOs.

The role of real-world evidence (RWE) in mitigating PICO issues and strengthening the JCA dossier

Another key factor in the new regulation is the role of RWE. A strategically designed RWE plan can mitigate companies’ PICO issues, limit uncertainty and strengthen a JCA dossier. RWE can even serve as an external comparator group for single-arm trials under certain circumstances. By planning for data gaps and supplementing the JCA evidence base with a variety of methodologies, RWE can prove to be a powerful tool for HTDs.

To determine the expected PICO data requirements, review current JCA evidence development plans and plan for filling data gaps with new evidence generation and synthesis, it’s critical that HTDs begin planning.

Conclusion

The implementation of the new EU HTA regulation represents a crucial turning point for health technology in Europe. In this era of change, it is imperative for HTDs to start strategizing now. There are significant opportunities for HTDs to improve patient access, optimize resource use and enhance the quality of HTA across the EU. By understanding and addressing the challenges, leveraging the opportunities and effectively utilizing RWE, HTDs can navigate the complexities of the new regulation and emerge stronger.