Critical methodological summary of the SMART trial:
Clesrovimab vs. Palivizumab in high-risk infants

Reference: Zar HJ, Bont LJ, Manzoni P, et al. Clesrovimab in infants and children at increased risk for severe RSV disease. N Engl J Med. 2025;393(13):1343-1345.  This interim analysis from the SMART trial represents a phase 3 randomized controlled study comparing single-dose clesrovimab with monthly palivizumab in infants at increased risk for severe RSV disease. While the study addresses an important clinical question, several methodological limitations compromise the robustness of its conclusions.  Study design strengths The SMART trial employs a randomized, controlled design with appropriate 1:1 allocation across 109 sites in 27 countries, providing broad geographic representation and adequate sample size (901 infants). The stratification by geographic region and medical condition (prematurity ≤35 weeks, chronic lung disease, or congenital heart disease) enhances internal validity by ensuring balanced distribution of key prognostic factors. The choice of palivizumab as an active control rather than placebo is ethically appropriate given the established efficacy of palivizumab in this...