Randomized controlled trials are considered as the gold standard for determining the causality, and are usually used to evaluate the efficacy and safety of medical interventions. However, in some cases it is not feasible to conduct a randomized controlled trial. In recent years, a framework called “target trial emulation study” has been formally established to guide the design and analysis of observational studies based on real-world data. This framework provides an effective method for causal inference based on observational studies. In order to facilitate domestic scholars to understand and apply the framework to solve related clinical problems, this article introduces it from the basic concept, framework structure and implementation steps, development status, and prospects.
The rapid advancement of causal inference is driving a paradigm shift across various disciplines. "Target trial emulation" has emerged as an exceptionally promising framework for observational real-world studies, attracting substantial attention from medical scholars and regulatory agencies worldwide. This article aims to provide an introduction to CERBOT, an online tool that assists in implementing target trial emulation studies, while highlighting the advancements in this domain. Additionally, the article provides an illustrative example to elucidate the operational process of CERBOT. The objectives are to support domestic researchers in conducting target trial emulation studies and enhance the quality of real-world studies in the domestic medical field, as well as improve the medical service level in clinical practice.
Randomized controlled trials (RCTs) are considered the “gold standard” for evaluating the causal effects of interventions on outcome measures. However, due to high research costs and ethical constraints, conducting RCTs in clinical practice, especially in the surgical field, faces numerous challenges such as difficulties in subject recruitment, implementation of blinding, and standardization of interventions. In such cases, using real-world data to perform causal inference under the framework of target trial emulation (TTE), based on the principles of RCT design, helps to identify and reduce biases arising from design flaws in traditional observational studies, such as immortal time bias, confounding, selection bias, or collider bias. This approach can produce high-quality evidence comparable to that of RCTs, thereby enhancing the clinical guidance value of real-world data studies. However, TTE has limitations, such as the inability to completely eliminate confounding, high quality requirements for source data, and the current lack of reporting standards. Therefore, researchers should be fully aware of these limitations to avoid making incorrect causal inferences. This article intends to provide an overview of the TTE framework, implementation points, application scope, application cases, and advantages and disadvantages of the framework.