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.