Extrapolating evidence of antiepileptic drug efficacy in adults to children ≥2 years of age with focal seizures: The case for disease similarity

the Pediatric Epilepsy Academic Consortium for Extrapolation

Research output: Contribution to journalReview articlepeer-review

38 Scopus citations


Expediting pediatric access to new antiseizure drugs is particularly compelling, because epileptic seizures are the most common serious neurological symptom in children. Analysis of antiepileptic drug (AED) efficacy outcomes of randomized controlled trials, conducted during the past 20 years in different populations and a broad range of study sites and countries, has shown considerable consistency for each drug between adult and pediatric populations. Historically, the majority of regulatory approvals for AEDs have been for seizure types and not for specific epilepsy syndromes. Available data, both anatomical and neurophysiological, support a similar pathophysiology of focal seizures in adults and young children, and suggest that by age 2 years the structural and physiological milieu upon which seizures develop is similar. Although the distribution of specific etiologies and epilepsy syndromes is different in children from in adults, this should not impact approvals of efficacy based on seizure type, because the pathophysiology of focal seizures and the drug responsiveness of these seizure types are quite similar. Safety and pharmacokinetics cannot be extrapolated from adults to children. The scientific rationale, clinical consensus, and published data support a future approach accepting efficacy data from adult trials and focusing exclusively on prospective pharmacokinetic, tolerability, and safety studies and long-term follow-up in children. Whereas tolerability studies can be compared easily in children and adults, safety studies require large numbers of patients followed for many years.

Original languageEnglish (US)
Pages (from-to)1686-1696
Number of pages11
Issue number10
StatePublished - Oct 2017


  • AMPA
  • GABA
  • NMDA
  • Pharmacokinetics
  • Potassium channels
  • Sodium channels

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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