Robinson Cal H, Fan Eddy, Grandi Sonia M, Urner Martin, Parekh Rulan S
Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada; Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; SickKids Research Institute, Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada.
Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Interdepartmental Division of Critical Care Medicine, University of Toronto, ON, Canada.
Lancet Child Adolesc Health. 2025 Sep;9(9):663-672. doi: 10.1016/S2352-4642(25)00131-2. Epub 2025 Jul 11.
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.
在罕见儿科疾病中开展随机对照试验（RCT）往往不切实际或成本过高。儿童和青少年有来自纵向队列研究、疾病登记处及基于人群的数据库的观察性数据，但标准的观察性分析通常受偏差限制。目标试验模拟方法可提高观察性分析的质量，解决常见的偏差来源，并有助于填补儿科临床实践中的证据空白。在儿科研究中应用目标试验模拟方法创造了独特机遇，但也带来了特定挑战。需要采用量身定制的方法来解决样本量小、治疗效果异质性、纵向随访和数据缺失等问题。本综述旨在概述关键概念，如因果推断和目标试验模拟是什么，论证在儿科观察性研究中使用目标试验模拟方法的合理性，讨论模拟RCT方案关键要素的方法，并强调目标试验模拟在儿科中的独特应用。
