基于真实世界数据的观察性因果推断研究新框架(目标试验模拟)及其在中医药领域中的应用展望

Novel Framework(Target Trial Emulation)in Observational Causal Inference Research Based on Real⁃world Data and Its Application Prospects in Traditional Chinese Medicine

“目标试验模拟”(target trial emulation)作为一种新的真实世界研究框架在近年来被正式确立,其可用于指导基于真实世界数据开展观察性因果推断研究,继而进行医疗干预有效性和安全性评价。该框架的核心思想是参照随机对照试验的原则,利用真实世界数据模拟相应的随机对照试验,进而得出干预措施与临床结局间因果关联的结论。其主要实施要点可总结为“3⁃7⁃2”,即声明因果问题、制订模拟方案和模拟目标研究3个实施步骤,纳排标准、治疗策略、干预分配、随访期、结局指标、因果比较和分析计划7个设计要素,对永恒时间偏倚和现用药者偏倚2个关键偏倚的控制。本文通过对该框架的历史与现状、实施要点、经典案例、优势与局限性及其在中医药领域中的应用前景进行概述,以期帮助中医药学者开展中医药真实世界研究,并为构建具有中医药特色的临床评价体系提供新思路。

“Target trial emulation”(TTE),as a new framework in real⁃world research,has been for⁃mally established in recent years.It can be used to guide the evaluation of the effectiveness and safety of medi⁃cal interventions based on real⁃world data for observational causal inference.The core idea of this framework is to follow the principles of randomized controlled trial(RCT),emulate a corresponding RCT using real⁃world data,and then draw conclusions about the causal relationship between interventions and outcomes.The main implementation tips of TTE can be summarized as“3⁃7⁃2”:3 implementation steps including formulating the causal question,designing the emulation plan,and emulating the target study;7 design elements including eligibility criteria,treatment strategies,intervention allocation,follow⁃up period,outcome,causal contrast of interest,and analysis plan;and control of 2 critical biases including immortal time bias and prevalent user bias.In this article,we present an overview of the development,current status,implementation steps,classic exam⁃ples,advantages and limitations of TTE,and its application prospects in traditional Chinese medicine(TCM).It is hoped that this article can assist researchers in TCM to utilize this method for real⁃world research and con⁃tribute to the construction of a clinical evaluation system with distinctive features of TCM.