Reappraisal of the Efficacy of a Simplified Artesunate Regimen in Falciparum Malaria

TO THE EDITOR—Kremsner and colleagues report a pharmacodynamic comparison of standard 5-dose intravenous artesunate with a simplified 3-dose regimen (same total dose) in hospitalized African children with malaria [1]. Graphical display of the primary outcome data (Figure 1) shows that the 3-dose regimen is probably worse than the 5-dose standard regimen, yet the article states that the 5-dose regimen does not confer any pharmacodynamic advantage over the 3-dose regimen. This apparent contradiction led us to examine key elements of the trial methodology in the context of established guidelines on the conduct and reporting of randomized controlled trials [2–4]. This was a noninferiority trial, a design that aims to show whether a new treatment is worse than an established treatment. The key decision is “how much worse can the new treatment be