From PICO anxiety to PICO strategy: planning for EU HTA success

What is the scoping process in the JCA and why is it important?  

The scoping process in the JCA is crucial as it defines the research questions that manufacturers and HTDs need to address as part of their submission. Starting January 12, 2025, any new oncology or ATMP product application to the European Medicines Agency (EMA) will trigger the JCA process, which follows established health technology assessment (HTA) principles. The scoping process uses the PICO framework—Population, Intervention, Comparator, and Outcome—to formulate these research questions.  

The scoping process attempts to survey the needs of all EU Member States and then consolidating their input into a unified scope for manufacturers. This comprehensive consolidation has spurred industry concerns about accurately predicting PICOs and aligning with the (potentially) diverse Member States' requirements. Manufacturers are particularly apprehensive about how well the consolidation process will work in practice to maintain solidarity across Europe while addressing various national preferences within a compressed process timeframe. 

What challenges does the PICO bring? 

The main challenge with the PICO is the uncertainty in how the consolidation process will unfold in practice. Each Member State may provide different answers, and consolidating these into a manageable number of PICOs is likely to be challenging. Simulations have shown that the number of PICOs can range from 10 to 30, potentially significantly increasing the preparatory workload for manufacturers. They must address each PICO individually, presenting comprehensive evidence, which can be daunting given the tight timelines and unexpected comparisons that may arise. This has led to industry-wide "PICO anxiety," where manufacturers worry about preparing for unexpected research questions and the impact on downstream market access in Europe. 

When should PICO simulations or predictions be done – and why? 

PICO simulations should be done at two key stages: 

End of phase 2 clinical development: When proof of concept is established, companies should start designing their pivotal phase 3 studies. With the new EU HTA processes, there is a heightened emphasis on aligning these pivotal studies with European market access requirements from the beginning. 

18 months before submission: At this stage, companies should refine their PICO predictions based on the current management landscape and comparators. With less uncertainty at this time, a PICO simulation exercise can help in preparing a robust submission with “no surprises”, ensuring all evidence is thoroughly analyzed and aligned with JCA requirements. 

What are the key steps in systematically identifying evidence that addresses the PICO defined during scoping? 

The process can be broken down into five key steps: 

1. Mapping the current and future treatment landscape: Conduct a thorough analysis of the current landscape and predict future scenarios. 
2. Understanding payer decision drivers: Analyze how payers in Europe make decisions for the relevant drug class and indication. 
3. Identifying PICOs: Engage with clinical or market access stakeholders across Europe to predict likely requests. 
4. Feeding insights into payer evidence planning: Integrate findings into the organization's planning processes.
5. Communicating risks and opportunities: Report the implications for JCA strategy, depending on the selected evidence, comparator, outcomes, and costs, ensuring all stakeholders are aligned. 

When doing the PICO simulation 18 months before submission, the process is very similar with the exception that you need take a further simulation step to mimic the consolidation process that will happen as part of JCA. This can be done using techniques such as online Delphi panels. You will then need to validate findings at national levels and report implications for your JCA strategy based on these validated findings.  

We'll learn more about how consolidation happens in practice over time which will help us refine our strategies further. 

How should HTDs address the multiplicity of populations and comparators in their submissions? 

HTDs should prepare their submissions with high transparency and detail, ensuring each PICO is addressed comprehensively. The JCA template requires detailed evidence for each PICO, making it essential to present information clearly and systematically. They will need to make sure they present the right evidence in the right place addressing the right PICO. This will help assessors navigate the dossier efficiently, finding the necessary evidence to address each research question. To do this, HTDs will need to have their evidence reviews conducted early and any statistical analyses of different PICOs ready to go.  

How will the implementation of JCA influence evidence generation planning for Health Technology Developers? 

The JCA has renewed the focus on Europe as a significant regional market, emphasizing the need for early and thorough evidence planning. Companies are now integrating PICO predictions into their phase 3 planning and submission preparations. This process has also influenced global evidence planning, with the PICO framework becoming a common language across the industry. 

How might the implementation of JCA impact the pricing of health technologies across Europe? 

While JCA does not explicitly address pricing, it may empower smaller markets to negotiate from a stronger, evidence-based starting point – especially those that do not have fully developed HTA systems of their own. Over time, this could lead to more equity of access to medical innovations for patients across the region. However, how this develops over time is a notable unknown.  

What best practices can you recommend for HTDs preparing for the new EU HTA requirements? 

• Educate and engage cross-functionally: Ensure all stakeholders involved in evidence development and planning, globally, understand the new requirements and objectives of the EU HTA process. 
• Start early: Integrate PICO predictions into phase 3 planning ( re-do it 12 to 18 months before submission) and prepare thoroughly for submissions well in advance. 
• Keep focus on national procedures: Success still hinges on navigating national procedures effectively post-JCA, as funding decisions remain at the national level. 

This article is intended to communicate Cencora’s capabilities which are backed by the authors’ expertise. However, Cencora strongly encourages readers to review all available information related to the topics discussed in this article and to rely on their own experience and expertise in making decisions related thereto. 

Source: European Union law. Implementing regulation – EU – 2024/1381 - EN - EU-Lex; https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=OJ:L_202401381