Extrapolation is changing how paediatric trials are designed
Regulators increasingly accept that adult efficacy data can carry over to children when the disease and the drug’s effect are similar enough. The argument is about how much.
In brief
How paediatric extrapolation and the ICH E11A guideline let adult data support children’s trials, shrinking efficacy studies to dosing and safety work.
- Extrapolation uses existing adult or older-child data to reduce what must be proven again in children.
- The ICH E11A guideline, finalised in 2024, sets out a common international framework.
- Modelling and simulation often replace large efficacy trials with targeted dosing and safety studies.
Running a full efficacy trial in every paediatric age group is often impractical. Many conditions are rare in children, recruitment is slow, and exposing more children than necessary to experimental treatment is an ethical problem in its own right.
The logic of extrapolation
If a disease progresses in a similar way in adults and children, and a drug is expected to work in a similar way, regulators can accept that efficacy shown in adults will largely hold in children. The paediatric programme can then focus on what genuinely differs, usually dose and safety.
The ICH E11A guideline on paediatric extrapolation, finalised in 2024, gives regulators and sponsors a shared vocabulary for this. It treats extrapolation as a spectrum rather than a yes-or-no decision. The more confidence there is in the similarity of disease and drug response, the less new efficacy evidence is needed.
Building the case
A credible extrapolation plan sets out:
- the evidence that the disease is similar across age groups, from pathophysiology to clinical course;
- the evidence that the drug’s effect is similar, ideally through a shared biomarker or exposure-response relationship;
- the gaps, and what paediatric data will fill them.
Models in place of trials
Pharmacokinetic studies, population modelling and exposure matching do much of the work. The aim is to find the paediatric dose that produces drug exposure comparable to the effective adult dose, then confirm safety and, where needed, efficacy in a smaller cohort.
Where extrapolation does not fit
Some conditions are fundamentally different in children, and some drug effects depend on development, such as those acting on growth, puberty or the developing brain. In those cases, full paediatric efficacy trials remain necessary. The skill lies in being honest about which situation a programme is in.
