title: New anti-epileptic drugs: overcoming the limits of randomised controlled trials.
abstract: This commentary focuses on the designs of randomised controlled trials of new anti-epileptic drugs as treatment for focal epilepsy. Limits of these trials, with particular focus on placebo-controlled designs, are discussed and strategies to overcoming them proposed. To date there are only few head-to-head comparison trials between new anti-epileptic drugs. Ideally, direct head-to-head comparisons of new anti-epileptic drugs should be available in order to get the whole picture of each treatment, but usually randomised controlled trials have not such a direct-comparison design. Multiple-treatment meta-analysis may represent a promising way of overcoming this limit, providing information on ranking efficacy of new anti-epileptic drugs, thus allowing to answer several relevant questions regarding daily practice and decision-making. Although not free from concerns, also historical design trials might have several advantages in that all patients receive a promising anti-epileptic drug at dose(s) that are expected to be fully effective and eliminate the need for a parallel group on suboptimal treatment or placebo. All these strategies aimed to overcome the lack of head-to-head comparisons can't anyway be considered as a substitute for properly conducted direct-comparison randomised trials, which remain the most relevant source of data to inform clinical decisions.
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Movement Sciences, Section of Clinical Neurology, University of Verona, Italy. dr.francescobrigo@gmail.com
authors.forename: Francesco
authors.initials: F
authors.lastname: Brigo
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D004828:Epilepsies, Partial / Q000188:drug therapy*; D019317:Evidence-Based Medicine; D006801:Humans; D010919:Placebos; D016032:Randomized Controlled Trials as Topic / Q000639:trends*; D012107:Research Design
chemical_list: D000927:Anticonvulsants; D010919:Placebos