Special CommunicationPrevention of epilepsy: Should we be avoiding clinical trials?

•Epilepsy prevention is high priority, yet no new phase 3 and only 2 phase 2 preventive studies have been funded since 2000.•PTE preventive studies are feasible.•There are approved drugs with demonstrated antiepileptogenic potential that could be tested in preventive trials.•A new approach to PTE prevention development is needed and should include•close collaboration between basic scientists and clinicians to ensure clinical relevance of preclinical therapeutic testing•evaluation of combination prevention therapy as well as single agents•Development of PTE biomarkers and PTE prevention use the same platform, and can be done simultaneously rather than sequentially

Epilepsy prevention is one of the great unmet needs in epilepsy. Approximately 15% of all epilepsy is caused by an acute acquired CNS insult such as traumatic brain injury (TBI), stroke or encephalitis. There is a latent period between the insult and epilepsy onset that presents an opportunity to intervene with preventive treatment that is unique in neurology. Yet no phase 3 epilepsy prevention studies, and only 2 phase 2 studies have been initiated in the last 16 years. Current prevailing opinion is that the research community is not ready for clinical preventive epilepsy studies, and that animal models should first be refined and biomarkers of epileptogenesis and of epilepsy discovered before clinical studies are embarked upon. We review data to suggest that there is basis to do epilepsy prevention studies now with the current knowledge and available drugs, and that those studies are feasible with currently available tools. We suggest that a different approach is needed from the past in order to maximize chances of success, minimize the cost, and set up platform for future preventive treatment development. That approach should include close coordination of preclinical and clinical development programs in a combined PTE prevention strategy, consideration of polytherapy, and simultaneous, combined clinical development of preventive treatment and of biomarker discovery. We argue that the currently favored approach of eschewing clinical studies until biomarkers are available will delay the discovery of epilepsy prevention treatment by at least 10 years and significantly increase the cost of such discovery.