Disease Course, Outcome Measures, and Prognostic Predictors in Epilepsy: Opportunities for Improving Outcome of Drug Trials.

BACKGROUND: A major concern over the development of new antiepileptic drugs (AEDs) is that the new AEDs have not added substantial clinical benefit over available antiseizure treatment. Additionally, current AEDs have neither improved the health of epilepsy patients nor been shown to prevent epilepsy or to improve the disease.

SUMMARY: This chapter reviews new data on patterns of epilepsy with remission and relapse, prognostic factors for seizure outcome, and innovative patient-related outcome measures. Applying this knowledge presents opportunities to improve the drug treatment of epilepsy.

KEY MESSAGES: Patient-relevant outcome measures and trial designs may be optimized to provide both evidence for efficacy and safety of AEDs and, in addition, for added clinical benefit over existing treatment. Added benefit of a new AED may be shown by evidence of higher antiseizure efficacy, better health, shorter disease duration, fewer side effects, and improved quality of life compared to available standard treatment. Moving from largely patient-irrelevant outcome measures such as 50% seizure reduction or use of placebo controls to innovative comparison of new AEDs versus standard treatment will revitalize the clinical development of new antiseizure treatments. Hopefully this will usher in a new era of much-needed antiepileptogenic agents that prevent or improve the patterns of epilepsy.