Appropriate selection of participants in pediatric developmental and epileptic encephalopathy trials: Lessons learned...

We evaluate the impact of independent, central review of epilepsy syndromes and seizure classification in randomized controlled treatment trials of Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS). Central review of two recent trials determined that 5.6% of enrolled DS participants and 3.4% of enrolled LGS participants pending randomization did not meet criteria for the epilepsy syndrome under study. Furthermore, 23% of DS participants and 32% of LGS participants had at least one seizure reclassified; 63.8% of DS sites and 78% of LGS sites had at least one participant with a seizure reclassification. Independent, central review of participants in pediatric ASM trials improves consistency across study sites, as well as overall accuracy of syndromic diagnosis and seizure classification, and may reduce placebo response rate.