FDA update.

This report addresses: (1) a general update of FDA activity in areas relevant to AED development; (2) an update on issues relevant to the development of AEDs in the pediatric population; and (3) an update on the Agency's approach to the evaluation of AEDs as monotherapy. FDA ACTIONS: Since January 2002, 47 Approval actions for 10 AEDs were issued, but none for a new chemical entity. Nine of the ten Approvable actions taken were relatively minor changes to existing applications. An Approvable letter was issued for Lyrica (pregabalin) for the treatment of post-herpetic neuralgia, painful diabetic neuropathy, and partial seizures in adults. The primary issue to be addressed in the face of post-marketing reports of adverse events is one of causality. The FDA has requested that sponsors search their databases for selected problems under review (e.g., suicidality). PEDIATRICS: The Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA) require studies in pediatric patients for those indications granted for adults that are relevant for the pediatric population. Current FDA policy asks sponsors to undertake a development program in pediatric patients essentially analogous to that for adults. MONOTHERAPY TRIALS: Establishing the effectiveness of AEDs as monotherapy continues to be desirable, but problematic. Problems include the difficulty of performing monotherapy trials, ethical issues, designation of patients as "newly diagnosed," and endpoints. Historical controls may be acceptable if: (a) there is a consensus that it is essentially impossible to conduct controlled trials designed to demonstrate a difference between treatments; (b) there is an adequate historical database against which the seizure rate seen with the new drug can reasonably be compared; and (c) there is evidence from adequate and well-controlled trials that the treatment is effective as adjunctive therapy. FDA is Agency is reviewing analyses describing historical controls.