Time to Change the Drug Trial Paradigm for Dravet Syndrome: Designing Trials for the Disease Rather than Squeezing the Disease into the Trial.

Abstract

Drug trial design is at an inflection point in epilepsy and neurological disorders. We are moving from conventional parallel-group randomized controlled trials (RCTs) to other designs, such as n-of-1 trials. Historically, inclusion criteria for antiseizure medicine (ASM) RCTs have stipulated a minimum number of seizures in the baseline period to judge ASM efficacy. For Dravet syndrome, RCTs have demanded 4 or more seizures/month in the baseline period. However, only 25% of children have sufficiently frequent seizures to qualify for RCTs. Trial outcomes should be tailored to the disease and long-term issues for patients, a much broader remit than seizure frequency alone. ANN NEUROL 2026;99:792-795.