Curr Opin Immunol. 2026 Aug 3;102:102832. doi: 10.1016/j.coi.2026.102832. Online ahead of print.
ABSTRACT
Real-world data (RWD) from nonrandomized clinical settings, such as registries and observational cohorts, can be used to address research questions for which randomized controlled trials (RCTs) are not feasible or appropriate. However, these data are susceptible to important sources of bias, including confounding by indication and immortal time bias. Target trial emulation (TTE) has emerged as a framework to improve the quality, credibility, and reproducibility of observational causal inference by aligning the design and analysis of observational studies with the structure of a hypothetical RCT. Appropriate application of the TTE framework requires careful specification of key design elements. Recent methodological guidance documents and reporting guidelines now provide practical support for researchers seeking to specify, conduct, and report TTE studies. Although TTE is increasingly used in rheumatology, its application in pediatric rheumatology remains limited despite the expanding availability of RWD. This review details the most recent methodological developments and guidelines, outlining the core concepts needed to apply the framework appropriately. The aim of this review is also to summarize recent applications in adult and pediatric immune-mediated diseases, and to explore the opportunities and limitations of this approach with a specific focus on pediatric rheumatology.
PMID:42546592 | DOI:10.1016/j.coi.2026.102832