Recent Use of Pediatric Extrapolation in Pediatric Drug Development in US

Area of Science:

• Pharmacology and Regulatory Science
• Pediatric Drug Development
• Drug Efficacy and Safety

Background:

• United States Food and Drug Administration (FDA) requires robust evidence for pediatric drug approval, allowing extrapolation when justified.
• Historical FDA guidance on extrapolation (full, partial, none) differed from the European Medicines Agency (EMA).
• A transition period (2015-2021) aimed to harmonize FDA's extrapolation approach with EMA's, influencing pediatric drug development.

Approach:

• Reviewed FDA pediatric labeling changes from January 1, 2015, to July 31, 2021.
• Analyzed 265 pediatric labeling updates to identify the use and extent of extrapolation.
• Categorized extrapolation into full, partial, and none based on FDA's framework.

Key Points:

• Extrapolation was used in 169 (63.8%) of 265 pediatric labeling changes during the study period.
• Full extrapolation accounted for 64 (24.2%) and partial extrapolation for 105 (39.6%) of these changes.
• Neuroscience and infectious diseases were major areas utilizing extrapolation (75.5% and 71.4% respectively).

Conclusions:

• Extrapolation significantly increased new and expanded pediatric indications.
• The findings offer a contemporary view of pediatric labeling changes driven by extrapolation.
• Insights are provided for future pediatric drug development, considering recent International Council for Harmonization (ICH) E11A guidance.