Changes in Market Access in Europe and Implications for Clinical Development Planning: Joint Clinical Assessments
This article focuses on areas that drug developers should be considering as they pursue their clinical and regulatory development plans and finishes with some questions to pressure check readiness.
What is new about the JCA process?
JCAs are part of a broader initiative to harmonise the assessment of new health technologies across Europe, aiming to reduce duplication of work and speed up access. Traditionally, drug developers would need to submit clinical evidence to multiple HTA bodies across Europe for individual assessments, each with their own requirements. With the introduction of JCAs, clinical assessments will be performed once and then made available to national HTA bodies across the EU.
Key characteristics of JCAs include:
Simultaneous Clinical Review: JCAs will be conducted in parallel with the European Medicines Agency review process for marketing authorisation. This means that as the EMA evaluates the drug for safety, efficacy and quality, the JCA will assess the same clinical evidence with a focus on its effectiveness. As such, drug developers must ensure regulatory and market access alignment throughout the filing and assessment period. Uncertainty remains over the methdologies that will be used in the assessment, meaning sponsors may need to adapt their development plans if significant changes are introduced.
Non-Binding Nature: JCAs provide a common clinical assessment for all EU member states, however the outcomes are non-binding for national HTA bodies. This means that while JCAs will influence national decision-making, individual countries will still make independent decisions about pricing, reimbursement and the overall value of the new drug. It follows that there is a risk that individual countries use the JCAs in different ways, resulting in varied access decisions across the EU. Therefore, companies seeking market access should be taking actions to mitigate this risk.
Focus on Clinical Evidence: JCAs will concentrate on the clinical aspects of health technology assessments. National bodies will be responsible for other elements of the HTA process, such as economic assessments and budget impact analyses.
Applicability to multiple countries: The JCA will be an assessment representative of all member states and therefore applicable across the EU region. This raises the critical issue of defining and agreeing the right scope for the assessment and in particular the PICOs (Patients/Population, Intervention, Comparator, Outcomes) all of which can impact the final price and reimbursement significantly. (1, 2)
Key Considerations for Drug Developers
The introduction of JCAs means that drug developers will need to rethink how they approach both clinical trial designs and their regulatory strategy. Planning for these changes early in the development process is critical to ensuring that their products meet the requirements of both regulators and HTA bodies across Europe. Below are some core considerations for drug developers as they prepare for the JCA framework:
Align Clinical Trial Design with Both Regulatory and HTA Expectations: Under the JCA framework, clinical trials must meet the requirements of both the EMA and the HTA bodies. This means developers need to think beyond just demonstrating safety and efficacy to the EMA; they must also consider how HTA bodies will assess the drug's value in their respective health systems. The selection of end points in the clinical trials is particularly critical. While regulatory agencies focus on traditional end points such as overall survival, progression free survival in oncology for example, HTA bodies are likely to require additional patient-centered outcomes like quality of measures and real world effectiveness data.
Choose the Right Comparator: One of the key elements of JCA evaluations will be the choice of comparator used in clinical trials. HTA bodies typically expect new drugs to be compared to the current standard of care, rather than a placebo, to assess the drug's added value. Drug developers need to ensure that the comparator used in clinical trials reflects the most relevant and up-to-date standard of care in European healthcare systems. If the wrong comparator is used, HTA bodies may reject the clinical evidence, leading to delays in market access.
Plan for Representative Patient Populations: Given the harmonised approach across member states, it follows that clinical trials should include representative patient populations. Trials that focus too narrowly on specific patient groups may not provide the necessary evidence for widespread adoption across Europe. Additionally, developers should anticipate the need for subgroup analyses, which help HTA bodies understand the drug's efficacy and safety in different demographics or patient subpopulations.
Engage Early with Regulators and HTA Bodies: Early engagement with both the EMA and HTA bodies through Joint Scientific Consultations is crucial for ensuring that clinical trial designs meet the requirements of both regulatory and HTA assessments. This helps reduce the risk of misalignment and delays during the approval and reimbursement processes. These are excellent opportunities to find ways to optimise the critical path to approval and reimbursement by checking on the appropriateness of end points, types of health economic data, real world evidence, novel trial designs etc., all of which could contribute to earlier approval and or better pricing and reimbursement outcomes.
Five Key Questions to Assess Your Readiness for JCAs
To help prepare for the introduction of Joint Clinical Assessments, here some questions to sense check your readiness:
- Have you organised your internal teams including regulatory affairs, clinical, HEOR and market access teams to adapt to the new procedures? Have you defined responsibilities between global, regional and national level teams?
- Have you planned appropriate touch points with the EMA and HTA bodies to discuss your development plans?
- Are the endpoints of your clinical trials aligned with both regulatory (EMA) and HTA body expectations/guidelines, including patient-centered and real-world outcomes? Have you selected the most appropriate comparator that reflects the current standard of care across different countries in Europe?
- Have you considered how to collect real world and health economic data alongside clinical evidence to support future cost-effectiveness assessments by HTA bodies?
- Have you undertaken a risk analysis of the proposed policy changes to your asset development program? What steps have you taken to mitigate these risks?
The introduction of JCAs represents a major shift in how new drugs are assessed in Europe. By proactively addressing these questions and incorporating these considerations into their clinical and regulatory plans, drug developers can better navigate the new system and improve their chances of successful market access across Europe.
Contact
If you are interested in discussing any of the issues above for your company/drug development program, please contact me through my email address dniven@nivenbiopharma.com . Feel free to also visit my website at www.nivenbiopharma.com for more information.
Sources
1. Health technology assessment - joint clinical assessments of medicinal products, EU Commission Web Page
2. EU HTA Regulation and Joint Clinical Assessment—Threat or Opportunity?, Schuster et al, J Mark Access Health Policy, May 24
