Critically appraising noninferiority randomized controlled trials: a primer for emergency physicians

Abstract

Noninferiority (NI) trials aim to show that a new treatment or drug is not inferior to a standard, accepted treatment. The rapid proliferation of NI trials within the literature makes it imperative for emergency physicians to be able to read, interpret, and appraise critically this type of research study. Using several emergency medicine examples from the recent literature, this article outlines the key differences between traditional, superiority randomized controlled trials and NI trials. We summarize four important points that an emergency physician should consider when critically appraising an NI trial: 1) Does the new treatment have tangible benefits over the standard treatment? 2) Was the choice of the NI margin appropriate? 3) Was the effect of the standard treatment preserved? Does the trial have assay sensitivity? and 4) What type of analysis strategy was employed: intention-to-treat (ITT) or per protocol (PP)? RÉ SUMÉLes essais de non-infé riorité (ENI) visent à dé montrer qu'un nouveau traitement ou un nouveau mé dicament n'est pas infé rieur au traitement de ré fé rence, reconnu. La prolifé ration des ENI dans la documentation rend impé rative la capacité des urgentologues à comprendre, à interpré ter et à é valuer d'un oeil critique ce type de recherche. Ainsi, l'article fera ressortir, à l'aide de plusieurs exemples tiré s de la documentation ré cente en mé decine d'urgence, les principales diffé rences qui existent entre le modè le classique d'essai comparatif, hasardisé , de supé riorité , et le modè le d'ENI. Seront ré sumé s quatre points importants qu'un urgentologue devrait envisager lorsqu'il é value de faç on critique un ENI: 1) Le nouveau traitement offre-t-il des avantages tangibles comparativement au traitement habituel? 2) Le choix de l'intervalle de non-infé riorité est-il pertinent? 3) L'effet du traitement de ré fé rence est-il conservé ? L'essai est-il sensible? 4) Quel type de straté gie d'analyse a é té employé : selon l'intention de traiter ou selon le protocole?

Re: A Note on Non-Inferiority Margins

“…Our paper was intended to provide a logical framework on how to critically appraise existing NI trials and NI trials to come. 3 We perceived a possible misconception in the way that NI margins were addressed in the letter by Berger and would like to address that. Ideally, an NI margin should represent the most allowable inferiority that has no clinical significance even though it might have a statistically significant inferiority.…”