Features at a glance

In the 11th issue of 2021, the magazine "China Food and Drug Administration" and the Hainan Real World Data Research Institute jointly set up a special issue on "Real World Data Research and Drug and Device Regulatory Innovation", with special issues, clinical research methodology, registration and listing. post-clinical. Research, real-world evidence and regulatory science, etc., introduce the research progress of real-world data research design, data governance technology and statistical analysis methods, summarize the current status of real-world evidence supporting global medical device regulatory decision-making, and demonstrate Hainan Boao Lecheng International Medical Tourism Real data research results and case introductions in pilot areas, with high-quality academic construction

PART 01

Featured in this issue

In 2018, the State Council entrusted the Hainan Provincial Government with a unique policy for the licensed use of imported medical devices and drugs that are urgently needed for clinical use in Lecheng, making Lecheng the only area in my country that can use licensed medical devices that have been approved for marketing abroad and unregistered in China. At present, Lecheng has carried out real-world data research on two batches of medical device products, which has received extensive attention from medical enterprises and society. The demand for using Lecheng's real-world data to support medical device approval and listing is increasing. How to carry out scientific and reasonable research design and adopt corresponding rigorous statistical analysis according to the characteristics of Lecheng has become an urgent problem to be solved in the real world data research of Lecheng. A key link in the transformation of evidence.

The "Special Issue" column publishes data from Peking University First Hospital Cao Han, Shang Meixia, Peking University Clinical Research Institute Yan Xiaoyan, Yu Yongpei, Peking University First Hospital, Peking University Clinical Research Institute, and Hainan Real World Data Research Institute Yao Chen Co-authored "Exploration of Design Types and Statistical Analysis Methods for Clinical Research on Licensed Medical Devices Based on Boao Lecheng Real-World Data" , through analyzing the key characteristics of Lecheng's real-world data research, and exploring suitable methods for Lecheng based on these characteristics. Types of study designs and methods of statistical analysis.

2021

Issue 11

About the first author

Cao Han, postdoctoral fellow, Department of Medical Statistics, Peking University First Hospital. Specialties: Statistical Design and Analysis of Clinical Research

About the corresponding author

Yao Chen, Master of Health Statistics, Professor, Doctoral Supervisor of Clinical Research Methodology, Director of Medical Statistics Office of Peking University First Hospital, Deputy Director of Peking University Clinical Research Institute and Deputy Director of Hainan Real World Data Research Institute. Specialties: Statistical Design and Analysis of Clinical Research

 

 

Based on the policy support of licensed medicinal devices, the real-world data research of licensed medicinal devices in the Hainan Boao Lecheng International Medical Tourism Pilot Zone has carried out two batches of real-world clinical data research pilots. During the period, the licensed innovative medical device "Glaucoma Drainage Tube" based on real-world data from Boao Lecheng was approved by the State Food and Drug Administration, indicating that real-world data can be used as an effective scientific basis for drug approval, and is considered to be of great significance for reform and innovation.

The "Special Issue" is published by Yao Minghong, Ren Yan, Jia Yulong, Wang Yuning from the China Center for Evidence-Based Medicine, West China Hospital of Sichuan University, Hainan Key Laboratory of Real World Data Research and Evaluation of the State Food and Drug Administration, and Sichuan Real World Data Technology Innovation Center. , Tan Jing, Wang Wen, Li Ling, Xu Jiayue, Xiong Yiquan, Sun Xin, as well as the State Food and Drug Administration Hainan Key Laboratory of Real World Data Research and Evaluation, Hainan Provincial Drug Administration, Hainan Province Boao Pilot Area Adverse Drug Reaction Monitoring Center Lin Kai, Li Yaohua, Wei Chunmin, and Zhu Ning of the Hainan Provincial Drug Administration co-authored "Constructing a Real-World Data Research Model Based on Licensed Drug Device Policy" , based on the previous methodological theoretical research and the practice of licensed drug device real-world clinical evaluation , combined with the latest technical guiding principles and technical specifications of real-world data research at home and abroad, to discuss the model, design and database construction of real-world data research on Boao Lecheng licensed pharmaceutical equipment, with a view to conducting research in Boao Lecheng for regulatory authorities, sponsors and related scholars Provide reference for the real-world data research of licensed pharmaceutical equipment.

2021

Issue 11

Biography of the first author

Yao Minghong, China Evidence-Based Medicine Center, West China Hospital, Sichuan University, Hainan Key Laboratory of Real World Data Research and Evaluation, State Food and Drug Administration. Specialties: Clinical evaluation of medical devices based on real-world data

Biography of the first author

Ren Yan, China Evidence-Based Medicine Center, West China Hospital, Sichuan University, Hainan Key Laboratory of Real World Data Research and Evaluation, State Food and Drug Administration. Specialties: Clinical evaluation of medical devices based on real-world data

About the corresponding author

Sun Xin, Professor, Director of the Hainan Key Laboratory of Real-World Data Research and Evaluation of the State Food and Drug Administration, Director of the China Evidence-Based Medicine Center, West China Hospital, Sichuan University. Specialties: Clinical Epidemiology and Evidence-Based Medicine, Real World Data Research, Clinical R&D Evaluation and Regulatory Scientific Research of Pharmaceutical Devices and Traditional Chinese Medicine, Digital Medical Product R&D and Evaluation

Zhu Ning, Secretary of the Party Leadership Group and Director of the Hainan Provincial Drug Administration. Specialties: Medical Device Regulation

 

 

CATALYS ophthalmic femtosecond laser therapy machine has been approved for marketing in many countries or regions around the world, and the safety and effectiveness of CATALYS have been proven. Consistency of clinical benefits achieved in national and other femtosecond laser cataract surgery systems remains to be demonstrated.

"Special Issue" is published by Qu Jia, Chen Wei, Liu Mimi, International Center for Optometry, Boao Super Hospital, and Johnson & Johnson Surgical Vision, Inc. Ying Wang, Luis Atiles, Peking University First Hospital, Peking University Clinic The Institute and Hainan Real World Data Research Institute Yao Chen co-authored "The Application of 3D Optical Coherence Tomography Femtosecond Laser-Assisted Cataract Surgery in Real-World Evidence Research", which aims to evaluate the acceptance of femtosecond laser-assisted cataract surgery in a real-world evidence study Visual outcomes of patients treated with cataract surgery in order to provide reference for the RWE study of CATALYS.

2021

Issue 11

About the first author

Qu Jia, Ph.D., Chief Physician, International Optometry and Ophthalmology Center of Boao Super Hospital. Specialties: Ophthalmology

About the corresponding author

Luis Atiles, Ph.D., Chief Clinical Research Scientist, Johnson & Johnson Surgical Vision, Inc. Specialties: Ophthalmology

 

 

Through the use of imported medical devices urgently needed for clinical use in the Boao Lecheng International Medical Tourism Pilot Zone, under the premise of following the principles of science, law and ethics, it will provide new ways and methods for the reform of the national medical device review and approval system, promote the scientific development of medical device supervision, and update Good service to public health needs. With the promulgation and implementation of the "Data Security Law" and "Personal Information Protection Law", my country's data security legal system has been basically completed. The data involved in real-world research must meet the requirements of the entire national data security system, not only the protection of personal privacy And data security requirements, but also to ensure the legitimacy of real-world research results themselves. When the regulatory authorities are exploring the use of clinical real-world data for drug product registration and regulatory decision-making practices, they will judge the authenticity, completeness and accessibility of the data, and also need to judge the compliance of the data involved in real-world research. .

The "Special Issue" column publishes "Analysis of Data Compliance Issues in the Process of Real World Data Research in the Lecheng Pioneer Area," co-authored by Beijing Haotianxinhe Law Firm and Boao Lecheng Pioneer Area Development Research Institute Li Yanlong, Yan Lin, and Bai Yujing ", from the "collection" and "use" in the process of real-world research data flow, the key compliance contents that need to be paid attention to, prevent data violation risks through data compliance management, protect personal information, and promote the safe and orderly flow of real-world data .

2021

Issue 11

About the first author

Li Yanlong is a partner lawyer of Beijing Haotianxinhe Law Firm, and an expert member of the Law and Policy Research Center of the Boao Lecheng Development Research Institute. Specialties: Corporate Compliance, Healthcare, Data Compliance Legal Services

 

 

02 PART

clinical research methodology

For electronic case report form (eCRF) data collection in clinical research, clinical research coordinators (CRCs) traditionally read electronic medical record (EMR) data and manually enter relevant content into electronic data capture (EDC) systems. In order to reduce the burden of CRC, existing researches are exploring the method of converting EMR source data directly into research data sets through data standardization transformation. The large amount of unstructured text data in EMR makes data extraction difficult and cannot be used directly for clinical research.

"Clinical Research Methodology" column published by Peking University First Hospital, Peking University Clinical Research Institute Lai Junkai, Wang Bin, Yao Chen, Wang Kai and Hangzhou Laimai Medical Information Technology Co., Ltd. Ren Yuankai, Peking University People's Hospital, National Trauma Medicine Center Jin Feifei co-authored "Standard Translational Research from Real World Data to Clinical Research Data", introducing the development of a data standardization method, based on EMR source data, automatically populates the Clinical Data Interchange Standards Consortium (CDISC) standard eCRF through data standardization , and meet the data submission requirements of the regulatory authorities.

2021

Issue 11

About the first author

Lai Junkai, PhD candidate, Department of Medical Statistics, Peking University First Hospital, Peking University Clinical Research Institute. Specialties: Statistical Design and Analysis of Clinical Research

About the corresponding author

Yao Chen, Master of Health Statistics, Professor, Doctoral Supervisor of Clinical Research Methodology, Director of Medical Statistics Office of Peking University First Hospital, Deputy Director of Peking University Clinical Research Institute and Deputy Director of Hainan Real World Data Research Institute. Specialties: Statistical Design and Analysis of Clinical Research

 

 

In recent years, real-world studies comparing efficacy and safety using routinely collected health data, such as administrative and clinical care databases, have increasingly influenced drug regulation, reimbursement, and other health care decisions. Electronic health records (Electronic Health Records, EHR), especially the unstructured data in electronic medical record data, contain a large amount of symptoms, signs, and diagnosis-related data, and combine them with efficient and feasible clinical real-world data collection modes to organize them for analysis. structured data, which can be better used for research. However, existing reporting specifications do not distinguish between structured and unstructured information contained in electronic medical records, enrollment data, or other healthcare data sources. How to report in a more transparent and standardized manner, that is, extracting unstructured texts and organizing them into structured fields that can be used for comparative effect research and safety research analysis, is of great significance for such causal inference research and result interpretation.

The "Clinical Research Methodology" column was published by National Children's Medical Center / Center for Clinical Epidemiology and Evidence-Based Medicine of Beijing Children's Hospital Affiliated to Capital Medical University, Nie Xiaolu, Yu Yuncui, Sun Zimo, Department of Epidemiology and Health Statistics, School of Public Health, Peking University , Peng Xiaoxia, and Lei Yi and Wang Qing of the Digital Medical Health Engineering Research Center of the Department of Automation, Tsinghua University, "Interpretation and Reflections on the Key Points of "Reporting Specifications for Using Unstructured Electronic Health Data to Conduct Real-World Comparative Effects and Security Research". A brief summary of the terminology and related techniques involved in conducting real-world comparative effectiveness and safety research based on unstructured EHRs, focusing on unstructured text processing in published reporting specifications, such as the use of natural language processing or machine tools When learning the method, focus on the core points of the report, in order to provide a reference for researchers to better conduct and report such research in the future.

2021

Issue 11

About the first author

Nie Xiaolu, Master, National Children's Medical Center / Center for Clinical Epidemiology and Evidence-Based Medicine, Beijing Children's Hospital Affiliated to Capital Medical University. Specialties: Pharmacoepidemiology and Evidence-Based Medicine

About the corresponding author

Peng Xiaoxia, Ph.D., Research Fellow, National Children's Medical Center / Center for Clinical Epidemiology and Evidence-Based Medicine, Beijing Children's Hospital Affiliated to Capital Medical University. Specialties: Clinical Epidemiology and Evidence-Based Medicine

 

 

In the evaluation of drugs and medical devices, the use of real-world data to conduct research has attracted the attention of regulatory decision-making bodies of various governments, and countries have successively issued policies and regulations to support the use of such research evidence to evaluate the safety and efficacy of products. Real-world data is multi-source and heterogeneous, and conducting high-quality real-world data research requires the participation of multiple disciplines. The "Clinical Research Methodology" column was published by Li Ge, School of Health Science and Engineering, Tianjin University of Traditional Chinese Medicine; School of Computer Science and Control Engineering, Shenzhen University of Technology, Chinese Academy of Sciences; Zhao Houyu, Sun Feng, and Zhan Siyan of the Department of Disease and Health Statistics co-authored "Current Situation and Case Interpretation of External Controls in Research Based on Real World Data" . , setting a suitable external control is helpful for the reasonable interpretation of the results and promotes the transformation of evidence.

2021

Issue 11

About the first author

Li Ge, Ph.D., associate professor, School of Health Science and Engineering, Tianjin University of Traditional Chinese Medicine. Specialties: Medical Statistics, Evidence-Based Medicine

About the corresponding author

Zhan Siyan, professor, doctoral supervisor, School of Public Health, Peking University. Specialties: Evidence-Based Medicine and Pharmacoepidemiology

Sun Feng, Ph.D., associate professor, doctoral supervisor, School of Public Health, Peking University. Specialties: Evidence-Based Medicine and Pharmacoepidemiology

 

 

With the improvement of network information technology, the electronicization of medical and health-related data has reached a high level. In traditional research methods, it usually takes a lot of labor and time to sort out and extract relevant information. The application of natural language processing technology to automatically extract data from medical texts can significantly improve research efficiency and reduce research costs.

"Clinical Research Methodology" column published by Peking University First Hospital, Peking University Clinical Research Institute, Hainan Real World Data Research Institute Yao Chen, Wang Bin, Lai Junkai and the Second Affiliated Hospital of Hainan Medical College Plastic Surgery, Boao Yiling Life Care Xie Hongju of the Center, Department of Hematology, The First Affiliated Hospital of Hainan Medical College, Hao Xinbao of Boao Lecheng Tiger Clinical Research Center, Tan Yun of Hangzhou Laimai Medical Information Technology Co., Ltd., Li Wei of Boao Yiling Life Care Center, Peking University People's Hospital, National Trauma Jin Feifei of the Medical Center co-authored "Research on Integrated Solution Tools for Real-World Data Collection, Governance and Management" . Based on the generation and application scenarios of real-world data, and meeting the regulatory requirements of regulatory authorities, a system for real-world data was constructed. The integrated solution tool for collection, governance and management, namely the electronic source data record (eSource record, ESR) tool, the functional design mainly includes three parts: source data collection, data extraction and management, and electronic data collection system docking.

2021

Issue 11

About the Author

Yao Chen, Master of Health Statistics, Professor, Doctoral Supervisor of Clinical Research Methodology, Director of Medical Statistics Office of Peking University First Hospital, Deputy Director of Peking University Clinical Research Institute and Deputy Director of Hainan Real World Data Research Institute. Specialties: Statistical Design and Analysis of Clinical Research

Xie Hongju, Professor, Master of Medicine, Chief Physician, Master Supervisor, Director of Plastic Surgery of the Second Affiliated Hospital of Hainan Medical College. Specialties: Cosmetic Surgery, Microplastic Surgery, Anti-aging Facial Rejuvenation

 

 

PART 03

Registration and post-marketing clinical studies

Adverse drug reactions, especially life-threatening adverse drug reactions, are an important concern for patients, clinicians and regulatory agencies. The discovery of serious adverse drug reactions is often accompanied by mandatory Phase IV clinical trials, boxed warnings in the package insert, or eventually forced withdrawal from the market. Regulators, payers and suppliers have been committed to using real-world data to provide high-quality and efficient decision-making support for drug life-cycle management, including post-market drug safety monitoring.

"Registration and Post-Marketing Clinical Research" column published "Post- marketing Drugs Using Real-World Data" co-authored by BeiGene (Shanghai) Biotechnology Co., Ltd. Xu Sheng, Liao Shanmei, Peking University First Hospital and Peking University Clinical Research Institute Wang Kai Review of Statistical Methods for Safety Monitoring, which reviews and outlines statistical methods related to post-marketing drug safety monitoring, based on different types of real-world data, including methods based on spontaneous reporting systems, electronic health records, insurance claims data, and mixed data sources .

2021

Issue 11

About the first author

Xu Sheng, Ph.D., BeiGene (Shanghai) Biotechnology Co., Ltd., senior statistician of post-listing statistics. Specialties: Real-World Data Analysis, Statistical Methods

About the corresponding author

Liao Shanmei, PhD, BeiGene (Shanghai) Biotechnology Co., Ltd., Head of Post-Listing Statistics/Executive Director. Specialties: Real World Data Analysis, Biostatistics

 

 

Drug-induced kidney injury (DIKI) is a common adverse drug reaction that can lead to clinical symptoms such as acute renal failure, oliguria, and anuria. Children are more prone to DIKI than adults due to incomplete development of liver and kidney functions, and have a greater risk of prognosis. The rapid development of real-world research has brought more opportunities and challenges to the monitoring and evaluation of children's DIKI.

"Registration and post-marketing clinical research" column published by the National Children's Medical Center / Beijing Children's Hospital Affiliated to Capital Medical University Clinical Research Center, National Children's Medical Center / Beijing Children's Hospital Affiliated to Capital Medical University Department of Pharmacy Yu Yuncui, Peng Xiaoxia, Nie Xiaolu, Jia Lulu , Cao Wang, Wang Xiaoling, and Zhao Yiming from the National Children's Medical Center/Beijing Children's Hospital affiliated to Capital Medical University, co-authored "Progress and Strategies in the Application of Real-World Data in the Monitoring of Drug-induced Kidney Injury in Children" , aiming at the problem of DIKI in children, from the real world. From the perspective of data, sort out and analyze the progress and strategies of real-world data in the monitoring and evaluation of children's DIKI, in order to provide more reference for the decision-making of clinical rational drug use in children in China.

2021

Issue 11

About the first author

Yu Yuncui, Master, National Children's Medical Center/Beijing Children's Hospital Affiliated to Capital Medical University. Specialties: Pharmacoepidemiology

About the corresponding author

Wang Xiaoling, Master, National Children's Medical Center/Beijing Children's Hospital Affiliated to Capital Medical University, Chief Pharmacist. Specialties: Pediatric Pharmacy

 

 

Real-world evidence is one of the hot spots in the practice of medical device and drug registration supervision in recent years. At present, there are not many actual cases of real-world evidence to support product registration supervision in my country, and most of them are concentrated in Boao Lecheng, mainly for products that have been listed abroad.

"Registration and Post-marketing Clinical Research" column published "Real-World Evidence for Registration Supervision Case Analysis" co-authored by Poco International Medical Trading (Shanghai) Co., Ltd. Zeng Zhiyu, Peng Lin, Zhang Fang, Zhang Xiaoxing, Zeng Li, and Han Lei. Five typical cases of domestic and foreign real-world evidence supporting product registration supervision are selected for analysis and evaluation, in order to bring reference and inspiration for the application of real-world evidence in the future.

2021

Issue 11

About the first author

Zeng Zhiyu, Ph.D., Senior Director of Medical Affairs at Poco International Medical Trading (Shanghai) Co., Ltd. Specialties: Clinical Trials of Medical Devices

 

 

CHAPTER 04

Real World Evidence and Regulatory Science

Regulatory approval of medical devices has traditionally relied primarily on randomized controlled trials (RCTs) known as the gold standard for clinical research. The rapidly evolving real-world data (RWD) and real-world evidence (RWE) fields hold great promise for regulators and the healthcare industry in terms of data-driven innovation. Under the right conditions, leveraging high-quality RWD as a complement to RCT data can lead to more efficient medical device development and optimized regulatory decision-making throughout the product life cycle. However, there are still differences in the acceptability and applicability of RWD/RWE by regulatory authorities around the world.

"Real World Evidence and Regulatory Science" column published by Peking University First Hospital, Peking University Clinical Research Institute Liao Qianwen, Peking University People's Hospital, National Trauma Medicine Center Jin Feifei and Peking University First Hospital, Peking University Clinical Research Institute, Hainan Yao Chen from the Provincial Real-World Data Research Institute co-authored "Current Situation of Using Real-World Evidence to Support Global Medical Device Regulatory Decision-Making", reviewed the existing global guidelines for RWD and RWE, and summarized the macroscopic picture of the systematic use of RWE in the United States to support medical device regulatory decision-making Policy elements and related considerations.

2021

Issue 11

About the first author

Liao Qianwen, PhD candidate, Department of Medical Statistics, Peking University First Hospital, Peking University Clinical Research Institute. Specialties: Statistical Design and Analysis of Clinical Research

About the corresponding author

Yao Chen, Master of Health Statistics, Professor, Doctoral Supervisor of Clinical Research Methodology, Director of Medical Statistics Office of Peking University First Hospital, Deputy Director of Peking University Clinical Research Institute and Deputy Director of Hainan Real World Data Research Institute. Specialties: Statistical Design and Analysis of Clinical Research

 

 

In order to promote drug research and development and accelerate the launch of new drugs, the National Medical Products Administration issued the "Guiding Principles for Real-World Evidence Supporting Drug Development and Review (Trial)" in January 2020, which is of great significance to the research and development of new Chinese medicines.

The "Real World Evidence and Regulatory Science" column published "Thinking about Chinese Pharmacological Evidence in Real World Research on New Chinese Medicines" co-authored by Li Can, Wu Chenyue and Han Wei from the Center for Drug Evaluation of the State Drug Administration. Learning and understanding, combined with the technical requirements of new traditional Chinese medicine pharmaceutical research, preliminarily analyze the method of applying real-world research concepts to new traditional Chinese medicine pharmaceutical research, and provide reference for new traditional Chinese medicine research.

2021

Issue 11

About the first author

Li Can, Master, Center for Drug Evaluation, State Drug Administration, Senior Engineer. Specialties: Pharmacy research and evaluation of new traditional Chinese medicines

About the corresponding author

Han Wei, Ph.D., Chief Pharmacist, Center for Drug Evaluation, State Drug Administration. Specialties: Pharmacy research and evaluation of new traditional Chinese medicines

 

 

Primary liver cancer is one of the most common digestive system malignancies worldwide. Hepatocellular carcinoma (HCC) is the most common pathological type of liver cancer, accounting for 85% to 90% of liver cancer patients in my country. Currently, liver cancer is the fifth most common malignant tumor and the second leading cause of death in my country. , a serious threat to the lives and health of the Chinese people, and brought a heavy economic burden to the patient's family and society. At present, only a few literatures have reported the per-time hospitalization cost or per capita cost of HCC patients in mainland my country, and no research has paid attention to the long-term medical costs of HCC patients in mainland China.

The "Real World Evidence and Regulatory Science" column published "Real-World-Based Study on Survival Time and Medical Expenses of Hepatocellular Carcinoma Patients" co-authored by Wu Jing, Liu Chengyu and He Xiaoning from the School of Pharmaceutical Science and Technology of Tianjin University and the Social Science Survey and Data Center of Tianjin University , based on real-world data, to explore the survival time and medical expenses of HCC patients, in order to provide evidence support for understanding the disease burden of HCC patients in China, in order to provide a reference for the formulation of relevant policies to reduce the disease burden of patients.

2021

Issue 11

About the Author

吴静，博士，天津大学药学院教授。专业：卫生经济学和卫生政策评估