“…In addition, the efficacy of a drug may change depending on when it is administered (prior to a seizure, immediately after a brief seizure, or after established status epilepticus),34, 35, 36 and can be altered by multiple factors including vehicle, species, age and sex factors, brain permeability, and pharmacokinetics. Drug effects in disease‐naive conditions may be very different from those during an established disease process, due to changes in the expression or function of key drug targets during the course of a disease 37, 38, 39, 40, 41, 42, 43. Testing a drug with clinically relevant vehicles, testing for target relevance of engagement, using more than one model of seizures including a relevant model of epilepsy or targeted disease or models with different induction methods, and testing across species, ages, and in both sexes may abrogate some of these issues.…”