Evidence generation throughout paediatric medicines life cycle: findings from collaborative work between European Medicines Agency (EMA) and EUnetHTA on use of extrapolation

Drug development for children presents unique challenges and is highly regulated. Novel approaches, such as the use of extrapolation to address, for example, the need to avoid unethical studies, whilst supporting robust evidence generation have been developed in support of benefit/risk considerations by regulatory authorities. This is only one step in the decision-making process towards access, which in Europe also includes health technology assessment (HTA) bodies. Discussions related to evidentiary requirements in small populations using scientific evidence transfer have been identified as a priority action by European Medicines Agency/European Network for Health Technology Assessment 21 (EMA/EUnetHTA 21). We describe the outcome of this work and reflect on the discussions that had taken place on how to leverage prior knowledge through identifying and addressing uncertainties during life cycle management to support regulatory and HTA decision-making. Using examples, we explore the range of applications for evidence generation and offer regulatory and HTA insights on key design considerations for producing better evidence, reflecting our shared ambition. Early interactions with all respective stakeholders, particularly between regulators and HTA bodies are key to optimise data generation and utility in children. In Europe, the HTA regulation will offer opportunities for collaborations, which are important for all development efforts. We collaboratively explored the unique specific challenges relating to paediatric drug development, ethically and in its ability to leverage prior knowledge, as exemplified using extrapolation. Learnings from these offer opportunities to further develop methodology on how to leverage uncertainties across a product's life cycle for small populations generally.