Writing in the July 2024 edition of DIA’s Global Forum magazine Mingcan DU and Fengyun (Vicky) HAN of Johnson & Johnson Global Regulatory Policy and Intelligence look back at the evolution of the use of real-world evidence (RWE) in regulatory decision-making in China, including key use cases and future prospects.
In recent years, real-world evidence (RWE) developed from real-world data (RWD) has become one of the hottest topics worldwide in the practice of drug and medical device registration and supervision. China’s regulatory authorities have also shown positive attitudes toward the role of RWE in drug R&D and registration review.
To facilitate the generation of better and high-quality evidence to underpin healthcare decision-making, several initiatives have advanced in the development of RWD/RWE standards and frameworks.
RWE Policy Development in China
In 2015 and 2016, the State Council of China issued the Action Plan for Promoting the Development of Big Data, which requires promoting the development and sharing of public resource data, including big data for medical and health services, and promoting the development and application of big data through top-level design. In 2016, the introduction of Guiding Opinions of the General Office of the State Council on Promoting and Regulating the Application and Development of Big Data in Health Care put forward a series of guiding principles to promote and standardize the development of health and medical big data applications, providing the basis for carrying out real-world studies (RWS) in terms of data resources and technical support establishment.
In 2018, the Wu Jieping Medical Foundation and China Chest Cancer Research Cooperation Group released the China Real-World Research Guide, which is the first RWS-related guide in China. In July 2019, the China REal world-data and studies ALliance (ChinaREAL) published a series of articles in the Chinese Journal of Evidence-Based Medicine explaining the application of RWD regarding technical specifications, research design, data management, and statistical analysis. In October 2019, the real-world research professional committee of China’s traditional Chinese Medicine Association released the draft of the technical guidelines for real-world research of Chinese patent medicine at the first academic seminar on real-world research of traditional Chinese medicine.
In this same timeframe, the National Medical Products Administration (NMPA) also issued corresponding guiding principles. From May 2019 to December 2023, NMPA and its Center for Drug Evaluation (CDE) successively issued the below and officially initiated construction of the RWE framework system by China’s regulators.
May 2019: The Basic Considerations of Real-World Evidence Supporting Drug Research and Development: This guideline aims to provide clarity on the definition of real-world research, outline the use and scope of real-world evidence in drug R&D, explore the basic principles for the evaluation of RWE, and consequently provide scientific and practical guidance for industry to consider when utilizing RWE to support drug development.
January 2020: Guiding Principles of Real-World Evidence Supporting Drug R&D and Evaluation (Trial Implementation): This guideline aims to provide clarity on the definition of RWE; guide the collection and suitability assessment of RWD; specify the status and applicable scope of RWE in drug regulatory decision-making; explore principles for the evaluation of RWE; and consequently provide reference for industry and regulatory agencies in utilizing RWE to support drug regulatory decision-making. This Guideline represents current thinking and knowledge and will be constantly revised and improved by deepening of research and knowledge.
August 2020: CDE released Technical Guiding Principles of Real World Evidence Supporting Drug R&D and Evaluation for Children (Trial Implementation): This guideline is formulated to address the actual research and development and registration needs for pediatric drugs, and to communicate considerations for drug regulatory agencies in response to new research methods, in China. It is designed to echo implementation of the ICH E11 (R1) Guideline in China, and to help drug developers and clinical researchers better understand the application of Guiding Principles of Real World Evidence Supporting Drug R&D and Evaluation (Trial Implementation) in research and development of pediatric drugs.
April 2021: CDE released The Guiding Principles for Real-World Data Used to Generate Real World Evidence (Trial Implementation): As a supplement to the above Guidelines for Real-World Evidence to Support Drug Development and Evaluation (Trial implementation), this guideline provides specific requirements and guiding suggestions for the definition, source, evaluation, curation, standards, safety compliance, quality assurance, applicability, and other aspects of RWD, to help sponsors evaluate the applicability of RWD, better curate RWD, and adequately prepare to generate reliable RWE.
February 2023: CDE released Guidelines for Design and Protocol Framework of the Real-World Studies of Drugs (Trial implementation): To guide sponsors in scientifically and rationally designing real-world studies and specify technical requirements for writing real-world study protocols, these guidelines illustrate the basic considerations of real-world study design and establishing the study protocol in drug research and development and evaluation, and provides other guidance on conducting real-world studies in drug research and development.
February 2023: Guidelines for the Communication of Real-World Evidence Supporting Drug Registration Applications (Trial implementation): Based on the Drug Registration Regulation released by the State Administration for Market Regulation (SAMR) and Measures for Administration of Communication for Drug R&D Activities and Technical Review released by CDE, this CDE guideline identifies core issues to discuss in communication, requirements of data to be used in meetings, and other aspects of using RWE to support registration applications, and provides recommendations for applicant communication at critical junctures to improve the efficiency of clinical drug research and development.
Draft released in November 2023: Guidelines for Application of Real-World Data Based on Disease Registry (Draft for Comment): The CDE issued this as a draft to guide sponsors in how to establish a disease registry and how to assess and utilize existing disease registry data to generate RWE sufficient to support administration of regulatory decision-making.
The definition of real-world research in NMPA’s Guiding Principles of Real-World Evidence to Support Drug R&D and Evaluation (Trial Implementation) refers to the research process of collecting data related to the health of the research object or summary data derived from these data in the real-world environment to address predefined clinical problems and obtain clinical evidence of drug use and potential benefit-risk through analysis. Real-world data (RWD) is data related to patients’ health status and medical behavior obtained through various channels. Real-world evidence (RWE) is clinical evidence about the use and potential benefits or risks of medical products obtained through the analysis of real-world data. These definitions are aligned with US FDA’s.
