Clinical Trials - ICH E11A on Pediatric Extrapolation

The ICH E11A draft Guideline on Pediatric Extrapolation reached Step 2 of the ICH process in April and is now available for public consultation. For Europe, the deadline for comments is 6 August 2022. According to the ICH, the purpose of this new guideline is to promote international harmonization of methodologies and strategies to incorporate pediatric extrapolation into drug development plans and to improve the speed of access to new drugs for pediatric patients globally, while limiting the number of children required for enrolment in clinical trials. 

Pediatric Extrapolation Framework

The extrapolation framework consists of

• the development of a pediatric extrapolation concept (considering the similarity of disease, the pharmacology of the drug and the response to therapy as well as the safety of use in all the relevant populations),
• the creation and execution of a pediatric extrapolation plan.

All available data should be used to establish the extrapolation concept. Such information may also include data from ongoing adult / pediatric development programs, or relevant data from terminated programs. Examples of data types (e.g. clinical, nonclinical, real-world data) and sources (e.g. regional, national, and international disease registries, electronic health records, health claims databases) that should be evaluated are provided in the draft guideline. The extrapolation concept should include a discussion of the extrapolation of safety and a thorough justification to support any conclusions about the acceptability to extrapolate safety information from the reference to the target population.

Once a pediatric extrapolation concept has been developed, the relevant studies should be detailed in the extrapolation plan. The plan should include the objectives and methodological approaches for the data that need to be generated to support efficacy and safety in the target population. The execution of the plan should also include a review of the data generated to confirm any assumptions made and to address uncertainties identified in the pediatric extrapolation concept. In addition, a review of the results should be used to identify whether a different approach can be considered in pediatric extrapolation plans for subsequent pediatric development programs.

Further information can be found on the ICH E11 webpage.