Xia Mingge, Xue Yan, Zhu Luwei, Chen Xianwen, Ung Carolina Oi Lam, Han Sheng, Lai Yunfeng, Hu Hao
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao.
Department of Medical Insurance, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
BMC Complement Med Ther. 2025 May 14;25(1):174. doi: 10.1186/s12906-025-04906-x.
The registration application of traditional Chinese medicine (TCM) products as new drugs often meets the challenges of lacking clinical evidence from randomized controlled trials (RCT). In recent years, China has introduced a new evidence system for the review and approval of TCM products, which proposed using human-use experience (HUE) for real-world evidence (RWE) to support the safety and effectiveness of TCM.
This study aimed to comprehensively analyse the regulatory concerns, policy guidances, and approved cases of using HUE to register TCM products.
Literature search and thematic analysis were conducted to identify and synthesize the regulatory concerns. A documentary analysis of policy guidances was employed to present the evolving regulatory framework for incorporating HUE into TCM registration in China. Case studies of approved TCM products using HUE to support registration were conducted, and the study design, study population, and postmarked requirements of these cases were analyzed.
Four main themes and 12 sub-themes regarding regulatory concerns of applying HUE in the registration of TCM products were identified. The 4 main themes are HUE quality, HUE applicability, HUE governance, and HUE regulation. Six policy documents and seven technical guidances were released to facilitate the application of HUE in TCM registration, founding a practical regulatory framework for TCM product registration. In China, six cases that employed HUE to support registration were approved. Of these, five cases utilized HUE to support direct registration, while one utilized HUE to lay the foundation for subsequent phase III clinical trial. Regarding study design and data types, retrospective observational studies were the predominant approach and electronic health records from the hospital information systems were the most commonly used data source. Among the five cases of direct registration, three relied solely on retrospective observational studies, while two conducted small-sample prospective studies in conjunction with retrospective observational studies.
HUE can be advanced to generate RWE for the safety and effectiveness of TCM products, which provides potential support for registering new TCM products. Leveraging HUE for registration can shorten research and development period, reduce development costs, and promote innovation, ultimately driving the growth of the TCM industry. However, several challenges remain in using HUE to support the registration of TCM products in China, including difficulties in data accessibility, lack of standardized protocols for HUE collection and reporting, and obstacles in transforming TCM preparations from hospitals into new TCM products using HUE. Furthermore, ensuring high-quality HUE requires future attention to data applicability, data infrastructure, and research design.
中药产品作为新药的注册申请常常面临缺乏随机对照试验（RCT）临床证据的挑战。近年来，中国引入了一套新的中药产品审评审批证据体系，提出利用人用经验（HUE）获取真实世界证据（RWE），以支持中药的安全性和有效性。
本研究旨在全面分析利用人用经验进行中药产品注册的监管关注点、政策指导及获批案例。
通过文献检索和主题分析来识别并综合监管关注点。采用政策指导文件的文献分析，呈现中国将人用经验纳入中药注册的不断演变的监管框架。对获批的利用人用经验支持注册的中药产品进行案例研究，并分析这些案例的研究设计、研究人群及邮戳要求。
确定了关于在中药产品注册中应用人用经验的监管关注点的四个主要主题和十二个子主题。四个主要主题为人用经验质量、人用经验适用性、人用经验治理和人用经验监管。发布了六项政策文件和七项技术指导，以促进人用经验在中药注册中的应用，建立了中药产品注册的实用监管框架。在中国，六项利用人用经验支持注册的案例获批。其中，五项案例利用人用经验支持直接注册，一项利用人用经验为后续的III期临床试验奠定基础。关于研究设计和数据类型，回顾性观察研究是主要方法，医院信息系统中的电子健康记录是最常用的数据来源。在五项直接注册案例中，三项仅依赖回顾性观察研究，两项结合回顾性观察研究进行了小样本前瞻性研究。
人用经验可用于生成中药产品安全性和有效性的真实世界证据，为新中药产品注册提供潜在支持。利用人用经验进行注册可缩短研发周期、降低研发成本并促进创新，最终推动中药产业发展。然而，在中国利用人用经验支持中药产品注册仍存在若干挑战，包括数据获取困难、缺乏人用经验收集和报告的标准化方案，以及将医院中药制剂利用人用经验转化为新中药产品的障碍。此外，确保高质量的人用经验未来需要关注数据适用性、数据基础设施和研究设计。
