ICH Harmonised guideline paediatric extrapolation E11A

This guideline provides an internationally harmonised framework for applying paediatric extrapolation to support the development and regulatory authorisation of medicines for children. It describes a structured, iterative approach for determining when and how existing evidence from adults or other paediatric populations can be used to inform clinical development, while identifying the additional data needed to address remaining uncertainties. The guidance complements ICH E11(R1) and supports researchers in integrating extrapolation strategies into protocol development from the earliest stages.

For protocol development, the guideline assists researchers in defining an appropriate evidence-generation strategy based on the similarity of disease progression, drug pharmacology and treatment response between the reference and target paediatric populations. It provides recommendations on the use of pharmacokinetic and pharmacodynamic data, modelling and simulation, biomarkers, statistical methods, and targeted clinical studies to reduce uncertainty and optimise study design. These approaches can inform decisions on sample size, endpoint selection, dose justification, and the scope of clinical data collection, while reducing unnecessary participation of children in clinical trials where existing evidence can be appropriately leveraged.

The guidance is particularly relevant for rare diseases, where paediatric populations are small and recruitment is challenging. By promoting the systematic use of existing evidence, quantitative methods, and scientifically justified extrapolation, it supports the development of feasible, efficient and ethically sound clinical trial protocols. Researchers developing paediatric rare disease studies can use this guideline to strengthen the scientific rationale for their protocol, optimise evidence generation, and align their development strategy with international regulatory expectations.