Selection of Appropriate Endpoints for the EU JCA and National Assessments in Select Member States and England for ATMPs

OBJECTIVES: Surrogates are widely used for Advanced Therapy Medicinal Products (ATMPs) trials to assess their safety and efficacy. However, the use of surrogates is associated with limitations in the context of assessing added benefit for health technologies, as they do not measure long-term/final clinical endpoints. With the first wave of Joint Clinical Assessments (JCA) approaching, our research aimed to explore differences between JCA and local EU methods for the appraisal of endpoints.

METHODS: We conducted a review of Health Technology Assessment (HTA) methodological guidelines from EUnetHTA21, EU HTA bodies and NICE, to identify areas of harmonization and difference for endpoint assessment.

RESULTS: All guidelines state final endpoints are the most relevant. NICE highlights relevant outcomes measure health benefits and adverse effects that are important to patients and caregivers.

All guidelines accept use of surrogates in specific cases. French methods state surrogates are acceptable if the link with a final endpoint has been established within the disease. German methods specify this link should also be established for the appropriate patient population and interventions.

EUnetHTA21 methods state the strength of the association between the surrogate and the final outcome should be established ideally at individual and trial level. EUnetHTA21 methods also include specific guidance related to oncology outcomes.

NICE methods state there must be good evidence that the surrogate is predictive of the final outcome. Ideally, this evidence should come from a meta-analysis from randomized controlled trials and the validation should be specific to the population and technology type.

CONCLUSIONS: Our review identified mostly areas of similarity between guidelines, but differences in definitions of relevant endpoints and the requirements to demonstrate the relevance of surrogates. Further research is required to understand how EUnetHTA21 guidelines will be interpreted by different assessors, especially in circumstances where surrogates are appropriate, and how JCA outcomes will impact US access.