Why have status epilepticus trials failed: Wrong drugs or wrong trials?

Abstract

Despite burgeoning interest in trials in status epilepticus over the last 20 years, outcomes have yet to improve and a number of high profile studies have failed to deliver for a range of reasons. The range of reasons a trial may fail to meet the intended outcomes are discussed. Recent well designed, adequately powered studies in established status epilepticus failed to meet primary endpoints, but are nonetheless influencing practice, reflecting the importance of interpreting results in the context of broader literature, safety and practical considerations. Studies in refractory and super-refractory status epilepticus have yet to do so, frequently failing to deliver as hoped despite huge financial and human cost. The importance of reviewing regulatory frameworks, and our approach to trial design to address important clinical questions is reviewed, reflecting on lessons from the COVID-19 RECOVERY trials, and other disease areas, together with the potential associated with the use artificial intelligence tools. This paper is based on a presentation made at the 9th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures in April 2024.