ICH E11A: Final version published

In August, the final “ICH E11A Guideline on pediatric extrapolation” was published on the ICH website in the “efficacy guidelines” section. As already reported in "Clinical Trials - ICH E11A on Pediatric Extrapolation", this guideline is intended to promote the international harmonization of methods and strategies for the inclusion of pediatric extrapolation in drug development plans and to accelerate access to new medicines for pediatric patients worldwide. It is seen as complementary to the guideline “ADDENDUM TO ICH E11: CLINICAL INVESTIGATION OF MEDICINAL PRODUCTS IN THE PEDIATRIC POPULATION E11 (R1)” and is expected to become effective in January 2025.

The new guideline consists of the following chapters:

1. INTRODUCTION
1.1 Objectives of the Guideline
1.2 Background
1.3 Scope
1.4 General considerations
2. PEDIATRIC EXTRAPOLATION FRAMEWORK
3. PEDIATRIC EXTRAPOLATION CONCEPT
3.1 Disease
3.2 Drug Pharmacology
3.3 Response to Treatment
3.4 Safety Considerations 
3.4.1 Extrapolation of Safety 
3.4.2 Additional Safety Considerations
3.5 Sources and Types of Existing Data
3.6 Integration of Evidence and Development of the Pediatric Extrapolation Concept
3.7 Establishment of the Pediatric Extrapolation Concept
4. PEDIATRIC EXTRAPOLATION PLAN
4.1 General Considerations 
4.1.1 Inclusion of Adolescents in Adult Trials 
4.1.2 Modeling and Simulation Approaches
4.1.3 Dose Selection 
4.1.4 Use of Dose Ranging Data 
4.1.5 Use of Biomarkers 
4.1.6 Establishing relationships to different endpoints between a reference and target population
4.1.7 Safety Extrapolation Plan
4.2 Pediatric Extrapolation Plan Study Design Approaches
4.2.1 Exposure Matching Approach 
4.2.2 PK/PD Approach 
4.2.3 Efficacy Studies 
4.2.3.1 Single-Arm Efficacy Studies 
4.2.3.2 Externally Controlled Studies 
4.2.3.3 Concurrent Controlled Efficacy Studies
4.2.3.4 Incorporation of External Data
4.2.3.5 Quantifying the Impact of Use of Reference Data
4.2.4 Presentation and Justification for the Pediatric Trial
4.2.5 Analysis, Reporting, and Interpretation
4.2.6 Methods of leveraging reference data in the analysis of a pediatric trial

The final version of the “ICH E11A Guideline on pediatric extrapolation” can be viewed on the ICH website.