ICH drafts guideline on pediatric extrapolation in drug development

Regulatory NewsRegulatory News | 06 April 2022 |  By 

The International Council for Harmonization (ICH) on Tuesday released a draft ICH E11A guideline that establishes a framework for extrapolating drug development data from adult trials to the pediatric population.
“This new ICH guideline aims to promote international harmonization of methodologies and strategies to incorporate paediatric extrapolation into overall drug development plans and to improve the speed of access to new drugs for paediatric patients, while limiting the number of children required for enrollment in clinical trials,” ICH said in an announcement.
ICH released a concept paper endorsing the need for a guideline in June 2017. The paper was subsequently issued by the European Medicines Agency for consultation. (RELATED: EMA Revises Reflection Paper on Pediatric Extrapolation, Regulatory Focus 13 October 2017)
“Historically, extrapolation of safety generally was considered unacceptable. However, our understanding of similarities and differences between reference and target populations with respect to safety has evolved,” the guideline states. “As described in the ICH E11(R1) guideline, the principle of using data generated in a reference population to define the scope and extent of data that should be collected in a target population can also apply to the generation of safety data.”
The guideline “provides a roadmap to aid drug developers and regulators on the degree to which pediatric extrapolation can be applied, and the information that should be collected to address gaps in knowledge supporting the safe and effective use of medicines in the pediatric population.”
The extrapolation framework consists of a pediatric extrapolation concept, and then the creation and execution of an extrapolation plan. The concept should explore the similarity of the disease and response to treatments between the reference and target pediatric populations, according to a presentation of the guideline.
A key factor in developing the concept is assessing the similarities and differences of the disease between a reference and a target population. The guideline states that “the evaluation of disease similarity is not intended to determine whether the disease in the reference and target populations is ‘exactly the same’ but rather whether the disease is different to a degree that would preclude pediatric extrapolation.”
Once a concept has been developed, the extrapolation plans should address the relevant studies to be performed, such as the dose selection and the dose ranging data to be collected. The plan should also address whether model-informed approaches are appropriate as well as whether biomarkers should be used.
The plan should address potential study designs, such as the use of bridging biomarkers, Bayesian strategies and single arm pharmacokinetic/pharmacodynamic (PK/PD) studies.

ICH anticipates the guidance will be finalized in the second quarter of 2024.
ICH E11A guideline
ICH E11A presentation 


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