The U.S. Food and Drug Administration (FDA) has issued guidance titled “Drugs for the Treatment of Partial Onset Seizures: Extrapolation of Efficacy from Adults to Pediatric Patients 1 Month of Age and Older.” This document provides recommendations for sponsors on the clinical development of drugs aimed at treating partial onset seizures (POS) in pediatric patients, specifically addressing the extrapolation of efficacy data from adults to children aged one month and older. U.S. Food and Drug Administration
Background
Traditionally, establishing the efficacy of POS treatments in pediatric patients required conducting well-controlled clinical studies within this population. Dosing in these studies was typically based on body weight and age to achieve blood concentrations similar to those effective in adults, supplemented by safety and tolerability data from open-label pediatric studies. However, the FDA now recognizes that if the disease progression, treatment response, and exposure-response relationships are sufficiently similar between adults and pediatric patients, efficacy data can be extrapolated from adult studies to the pediatric population. U.S. Food and Drug Administration
Key Considerations for Extrapolation
- Formulation Development: Pediatric patients may have different administration requirements and taste preferences compared to adults. Sponsors are encouraged to develop formulations that are appropriate for a child’s age, size, and physiological condition, exploring innovative approaches to pediatric formulation development and testing. U.S. Food and Drug Administration
- Efficacy Considerations: The FDA has concluded that the efficacy of drugs approved for treating POS in adults can be extrapolated to pediatric patients aged one month and older. This conclusion is based on analyses indicating that POS are phenomenologically and pathophysiologically similar across these age groups, and that treatment responses are comparable. This extrapolation does not apply to other types of seizures. U.S. Food and Drug Administration
- Clinical Pharmacology and Dosing: While efficacy can be extrapolated, appropriate dosing for pediatric patients must be determined to achieve drug exposures similar to those in adults. This involves conducting pharmacokinetic studies in pediatric patients to inform dosing strategies that ensure safety and effectiveness. U.S. Food and Drug Administration
- Safety Considerations: Although efficacy data can be extrapolated, safety data cannot. Sponsors should collect sufficient safety data in pediatric patients to identify any age-specific adverse reactions and to characterize the overall safety profile of the drug in this population. U.S. Food and Drug Administration
By adhering to these guidelines, sponsors can streamline the development process for pediatric POS treatments, potentially reducing the need for extensive pediatric efficacy trials while ensuring that dosing and safety evaluations are appropriately addressed.U.S. Food and Drug Administration
