Implications of PICO Scoping in the European JCA for Health Technology Developers

The implementation of the Joint Clinical Assessment (JCA) under Regulation (EU) 2021/2282 marks a significant shift in the European health technology assessment (HTA) landscape. As of January 12, 2025, new oncology products and advanced therapy medicinal products (ATMPs) submitted to the European Medicines Agency (EMA) will automatically undergo a JCA process.

A critical component of this process is the scoping phase, which defines the research questions health technology developers must address in their submissions based on the PICO framework (Population, Intervention, Comparator, Outcome). In a recent post, we highlighted the importance of proactively navigating PICO scoping. It emphasized that early planning and anticipating multiple PICO scenarios are key for health technology developers to align with the diverse requirements of EU member states.

How PICO Scoping Shapes JCA Submissions

The JCA scoping process aims to integrate the assessment needs of all EU member states into a harmonized evaluation framework. However, this comes with significant implications for health technology developers:

• Diverse national HTA requirements: Each member state may have different preferences regarding patient populations, comparators, and outcomes. Consolidating these variations into a single assessment framework often results in multiple PICO scenarios, increasing complexity.

• Unexpected comparators: The scoping process may introduce unexpected comparators that were not included in clinical trials. This can require additional analyses or real-world evidence (RWE) to ensure comparability.

• Tight timelines: The JCA process operates on a strict timeline, requiring manufacturers to quickly align their submissions with the defined PICO criteria and provide relevant data.

Strategic Approaches to Address PICO-Driven JCA Requirements

To navigate these implications effectively, health technology developers should adopt a structured and proactive approach:

• Early PICO Simulations: Health technology developers should simulate possible PICO scenarios as early as late Phase 2 of clinical development. Anticipating regional differences in comparators, endpoints, and population criteria allows for early adjustments to clinical trial designs.

• Stakeholder Engagement: A proactive dialogue with clinical experts, patient representatives, and HTA bodies in key EU countries can provide insights into the JCA requirements. This helps prioritize the most relevant PICO frameworks and ensure alignment with payer expectations.

• Consolidating PICO Requirements with EVIGATOR: Given the complexity of aligning PICO requirements across multiple countries, health technology developers must ensure efficient management of PICO-driven evidence. EVIGATOR provides an effective solution to aggregate, align, and prioritize PICO criteria across EU markets, ensuring that developers:

1. Identify overlapping PICO requirements

2. Streamline data preparation and submission

3. Reduce the risk of unexpected HTA demands

4. Improve efficiency in responding to JCA (re-)assessments

• Building a Live Evidence Library: To effectively address the evolving comparative effectiveness landscape, developers should establish a live evidence library that continuously monitors available data for each PICO scenario. This library helps to:

1. Track available evidence supporting comparative effectiveness for each PICO

2. Prioritize specific PICO questions based on emerging data trends

3. Identify data gaps that may need to be addressed through additional RWE studies

EVIGATOR can support the maintenance of this evidence library by providing a shared collaboration space where teams can continuously update information, track changes in available data, and streamline preparation for the final JCA dossier. By ensuring all relevant stakeholders have access to the latest evidence, developers can be better prepared for the rigorous demands of JCA submission

• Bridging Evidence Gaps to Strengthen JCA Submissions: When gaps in comparative effectiveness data are identified, developers must explore options to fill these gaps effectively. This may include:

1. Using AI-supported literature searches, such as ANCHOR, to update systematic literature reviews (SLRs) with the latest available data

2. Developing synthetic control arms using RWD to provide indirect comparisons where randomized controlled trials are not feasible and no suitable literature data is available

3. Assessing the feasibility of using real-world data (RWD) to supplement missing evidence, which may include:

• Evaluating existing databases (e.g. insurance claims) to determine the availability and quality of data related to the targeted patient population, treatment pathways, and Real-world outcomes,

• Evaluating the feasibility of medical chart reviews by identifying healthcare institutions with relevant patient records and ensuring access to clinical parameters measured in routine practice.

By simulating PICO scenarios early, engaging with stakeholders, consolidating PICO requirements with EVIGATOR, building a live evidence library, and addressing evidence gaps proactively, developers can align their evidence generation strategies with JCA requirements and strengthen their position in the European market.