New anti-epileptic drugs: overcoming the limits of randomised controlled trials

Authors

  • Francesco Brigo MD

    Corresponding author
    1. Department of Neurological, Neuropsychological, Morphological and Movement Sciences, Section of Clinical Neurology, University of Verona, Verona, Italy
    Search for more papers by this author

Dr Francesco Brigo, Department of Neurological, Neuropsychological, Morphological and Movement Sciences, Section of Clinical Neurology, University of Verona, P.le L.A. Scuro, Verona 37134, Italy. Email: dr.francescobrigo@gmail.com

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.

Ancillary