[Design and implementation of externally controlled trials and their application in field of TCM]

Randomized controlled trial(RCT), recognized as the gold standard for evaluating the efficacy of interventions, is widely applied in various clinical research fields, including pharmaceuticals, medical devices, and TCM therapies. However, RCTs often encounters practical challenges in certain scenarios such as rare diseases, severe diseases without effective therapeutic options, and TCM. These challenges include difficulties in subject recruitment, ethical controversies, and limited external validity in the real world. Consequently, there is a pressing need to explore research designs that integrate clinical practicality with scientific rigor. Externally controlled trial(ECT), a study design that compares patients receiving the experimental treatment with those outside the trials, can efficiently expand the sample size of the control group and enhance the generalizability of research evidence by incorporating external data, thus offering a novel approach to addressing the abovementioned challenges. This paper focused on two design types of ECT: the supplemented single-arm trials and the augmented randomized controlled trials. It elaborated on the design principles and key implementation steps of these approaches, with an emphasis on core methodological aspects, including the Pocock criteria for assessing the exchangeability of external data, propensity score methods(PSMs) and Bayesian methods for external data integration, as well as quantitative bias analysis(QBA). Given that RCT of TCM is characterized by complex interventions, dynamic diagnosis and treatment processes, and challenges in establishing appropriate control groups, the ECT design offers methodological support for integrating real-world data and developing a research paradigm tailored to the unique features of TCM. Furthermore, practical examples were used to highlight the design's utility in TCM. This paper aimed to provide methodological references for relevant research and promote their standardized, high-quality application.