Welfare release! Issuance of guidelines for real world evidence supporting drug development and review

In order to further guide and standardize the use of real world evidence in supporting drug R & D and review, and to ensure the quality and efficiency of drug R & D, the State Drug Administration has organized and formulated the guiding principles of real world evidence in supporting drug R & D and review (for Trial Implementation), which are now published Notice is hereby given Annex: 1 Guiding principles of real world evidence supporting drug R & D and review (Trial) Doc 2 Drafting notes of guiding principles of real world evidence supporting drug R & D and review (Trial) Drafting notes of guiding principles of real world evidence supporting drug R & D and review (Trial) issued by State Food and Drug Administration on January 3, 2020 1 Background The State Council's opinions on the reform of the review and approval system for pharmaceutical and medical devices (GF [2015] No 44) and the general office of the CPC Central Committee and the general office of the State Council's opinions on deepening the reform of the review and approval system to encourage the innovation of pharmaceutical and medical devices all proposed to encourage the research and development of new drugs With the implementation of a series of reform measures, the rapid development of drug research and development, and the acceleration of the new drug market, the quality and efficiency of drug research and development work put forward higher requirements Randomized controlled clinical trials (RCTs) are generally regarded as the gold standard to evaluate the safety and effectiveness of drugs, but their research conclusions may face challenges when extrapolated to clinical application, or there may be problems such as difficult to implement traditional clinical trials or high time cost In recent years, how to use real world evidence to evaluate the effectiveness and safety of drugs has become a hot issue in drug development and regulatory decision-making at home and abroad Some foreign drug regulatory agencies have carried out more discussions on how to use real world evidence to support regulatory decision-making, which are reflected in relevant guiding principles or framework documents There is no guidance document on how to use real world evidence to support drug development and evaluation in China In order to further standardize the relevant work and promote the improvement of the quality and efficiency of drug research and development, the relevant departments of the State Food and Drug Administration organized a research group composed of representatives from academia, pharmaceutical industry and relevant institutions, and launched the drafting of the guiding principles in November 2018 Based on the work framework and technical requirements of foreign drug regulatory agencies, combined with the domestic R & D practice, the research team combed, researched and refined the general principles and basic technical requirements of using real world evidence to support drug R & D and evaluation, and formed the first draft of guiding principles After several discussions, the basic consideration of real world evidence supporting drug research and development (Draft for comments) was formed, and opinions were widely solicited from May to August 2019, and more than 1000 feedback opinions were received The drug audit center of the State Administration organized the summary and analysis of relevant opinions, further listened to the opinions of the industry, clinical experts and other interested parties, and organized the expert finalization meeting and internal discussion again, finally forming the guiding principles of real world evidence supporting drug research and development and evaluation (Trial) 2、 The main content of "guiding principles of real world evidence supporting drug research and development and review (Trial)" mainly includes six parts, with relevant glossary, examples, commonly used statistical analysis methods and four annexes of Chinese and English vocabulary comparison The main contents are as follows: (1) the definition of real world research real world evidence is used to support drug research and evaluation First of all, we should clarify the related concepts of real world research to avoid falling into some common misunderstandings Relevant definitions include real world research, real world data, real world evidence, etc It is necessary to avoid misunderstanding that observational research is equivalent to real world research, real world data analysis results that are real world evidence, real world evidence and traditional RCT test are opposite （2） The source and applicability guidelines of real world data sort out the potential sources of domestic real world data, including but not limited to health information system, medical insurance system, disease registration system, data actively collected in prospective research and design to reflect the health status of patients, so as to open up ideas for selecting applicable real world data in drug research and development The applicability of real world data is mainly evaluated by data relevance and reliability The sponsor shall analyze the applicable real world data to form effective real world evidence to answer specific clinical questions （3） Real world evidence supports drug regulatory decision-making Real world evidence is used to support drug regulatory decision-making, including providing evidence of effectiveness and safety for the registration and listing of new drugs, providing evidence for the change of instructions of listed drugs, providing evidence for post market requirements or re evaluation of drugs, etc According to the experience summary and clinical research and development of famous traditional Chinese medicine prescriptions and preparations of traditional Chinese medicine medical institutions in China, the guide puts forward the research and development strategy of combining real world research and randomized clinical trials, which provides a reference for the evaluation of such traditional Chinese medicine In addition, real-world evidence can also be used to guide clinical research design and accurately locate the target population （4） The basic design of real world research the basic design of real world research includes practical clinical trials, single arm trials using real world data as control and observational studies It should be clear that real world research design does not mean that it is mutually exclusive with random quality control measures, and which research design should be selected should be considered in combination with specific research and development purposes Compared with RCT research, causal inference in real world research needs to pay special attention to the adjustment of hybrid effect, and some relatively complex statistical models and analysis methods are needed Annex 3 provides statistical analysis methods commonly used in real world research （5） The evaluation of real world evidence should follow two main principles: first, whether the real world evidence can support the clinical questions to be answered; second, whether the existing real world data can be obtained by scientific research and design, rigorous organization and implementation and reasonable statistical analysis （6） Communication and exchange with the review agency any use of real world evidence for the purpose of drug registration requires full communication and exchange with the review agency, so as to ensure that both parties can reach common understanding on the strategy of using real world evidence and real world research and design scheme The guide defines the time point, communication channel and content of communication 37