Target trial emulation in paediatric research: how can causal effects be estimated from observational data?

Abstract

Conducting randomised controlled trials (RCTs) in rare paediatric diseases is often impractical or prohibitively expensive. Observational data from longitudinal cohort studies, disease registries, and population-based databases exist for children and adolescents, but standard observational analyses are typically limited by bias. Target trial emulation methods can improve the quality of observational analysis, address common sources of bias, and help fill evidence gaps in paediatric clinical practice. Applying target trial emulation methods in paediatric research creates unique opportunities, but also poses specific challenges. Tailored approaches are needed to address issues with small sample size, treatment-effect heterogeneity, longitudinal follow-up, and missing data. This Review aims to outline key concepts, such as what causal inference and target trial emulation are, justify the use of target trial emulation methods in paediatric observational research, discuss approaches to emulating key elements of an RCT protocol, and highlight unique paediatric applications of target trial emulation.