University of Minnesota and MINCEP Epilepsy Care, Minneapolis, Minnesota, USA, UCB S.A., Brussels, Belgium, Institute of Neurology IRCCS C. Mondino Foundation, Pavia, and Clinical Pharmacology Unit, University of Pavia, Pavia, Italy
Purpose. To assess the advantages and disadvantages of six methodologies used in calculating seizure freedom rates in placebo-controlled, adjunctive therapy trials of new antiepileptic drugs (AEDs) in partial epilepsy, and two methodologies for long-term follow-up studies. Methods. Data from levetiracetam trials were used to illustrate the impact of different methodologies on seizure freedom rates. Seizure-freedom data for several new AEDs were identified from the published medical literature using MEDLINE and from a recent comprehensive textbook. Results. Most randomized, placebo-controlled add-on clinical trials of new AEDs contain little or no information about seizure freedom. Importantly, the methodology used can profoundly affect results when calculating seizure-free rates. Seizure freedom data should be reported as well as the methodology used. The minimum duration for assessing seizure freedom should be the entire stable dose period in short-term trials and at least six months for long-term follow-up studies. It is proposed that the seizure freedom rates be calculated and reported with at least two different methodologies, one that considers patients withdrawing from treatment without having had a seizure as successes, and one that considers the same patients as failures. For an effective and well-tolerated AED, seizure freedom rates will be consistent across the two methodologies. Conclusions. Seizure freedom is the ultimate goal of AED therapy and should be reported for all clinical trials. Methodological differences among the few clinical studies reporting seizure freedom rates make it difficult to compare results across trials. Improved reporting of methodologies and seizure-free rates is warranted.