AbstractBackgroundThe Learning Early About Peanut allergy (LEAP) study has shown the effectiveness of early peanut introduction in prevention of peanut allergy (PA). In the Enquiring About Tolerance (EAT) study, a statistically significant reduction in PA was present only in per‐protocol (PP) analyses, which can be subject to bias.ObjectiveThe aim of this study was to combine individual‐level data from the LEAP and EAT trials and provide robust evidence on the bias‐corrected, causal effect of early peanut introduction.MethodAs part of the European Union‐funded iFAAM project, this pooled analysis of individual pediatric patient data combines and compares effectiveness and efficacy estimates of oral tolerance induction among different risk strata and analysis methods.ResultsAn intention‐to‐treat (ITT) analysis of pooled data showed a 75% reduction in PA (p< .0001) among children randomized to consume peanut from early infancy. A protective effect was present across all eczema severity groups, irrespective of enrollment sensitization to peanut, and across different ethnicities. Earlier age of introduction was associated with improved effectiveness of the intervention. In the pooled PP analysis, peanut consumption reduced the risk of PA by 98% (p< .0001). A causal inference analysis confirmed the strong PP effect (89% average treatment effect relative risk reductionp< .0001). A multivariable causal inference analysis approach estimated a large (100%) reduction in PA in children without eczema (p= .004).ConclusionWe demonstrate a significant reduction in PA with early peanut introduction in a large group of pooled, randomized participants. This significant reduction was demonstrated across all risk subgroups, including children with no eczema. Furthermore, our results point to increased efficacy of the intervention with earlier age of introduction.