1. The scope of overseas clinical trial data acceptance
The research data generated in the process of confirming the safety and effectiveness of medical devices to be registered in China under normal use conditions in clinical trial institutions with the requirements of the country (region) where the clinical trial is conducted.
2. Basic principles for accepting overseas clinical trial data
2.1 Ethical principles
Overseas trials should follow the ethical guidelines of the Helsinki Declaration of the World Medical Congress.
2.2 Principles of law
(1) Overseas clinical trials should be conducted in countries (regions) with Good Clinical Practices (GCP) management;
(2) In line with the regulatory requirements for clinical trials of Chinese medical devices, if the clinical trial quality management documents that the clinical trials meet are different from the Medical Device GCP, the differences should be specified and the differences should be fully demonstrated. Does not affect the authenticity, scientificity, reliability and traceability of the research results, and can protect the rights of the subjects;
(3) Applicants and clinical testing institutions shall be subject to supervision and inspection by NMPA.
2.3 Scientific principles
The data of overseas clinical trials should be true, scientific, reliable and traceable. Applicants should provide complete the data and should not screen.
Applicants should ensure that the clinical trials conducted outside the country are appropriate, the test design is scientific and reasonable, the test conclusions are clear, the rights of the subjects are protected, and the risks that other personnel may be exposed to are prevented.
3. Submission of overseas clinical trial data and acceptance requirements
The overseas clinical trial data submitted by the applicant shall include at least:
(1) Clinical trial plan
(2) Ethical opinions
(3) Clinical trial report
The clinical trial report should include an analysis of the complete clinical trial data and conclusions:
a. The overseas clinical trial data is in compliance with the relevant requirements of Chinese registration regulations, and the data is scientific, complete and sufficient, and acceptable.
b. The overseas clinical trial data is in line with the basic requirements of the “Technical Guidelines for Accepting Overseas Clinical Trial Data of Medical Devices”. However, when some information needs to be supplemented according to the relevant technical requirements for registration in China, supplementary clinical trials may be carried out within or outside China. After the comprehensive evaluation of the original data and the supplementary data meets the relevant technical requirements of the Chinese registration, it will be accepted.
If the applicant uses the multi-center clinical trial data carried out in China and abroad as the registration application data, it should also clarify the allocation basis of the number of cases undertaken in China, so as to further evaluate whether it meets the requirements for registration in China.
4. Considerations and technical requirements when accepting overseas clinical trial data
4.1 Differences in technical review requirements
Clinical trials conducted abroad may be in line with the technical review requirements of the country (region) where the trial is conducted, but may not fully comply with the relevant Chinese review requirements.
For example, when designing a clinical trial, some countries only require clinical trials to conclude that the performance of the device has reached a certain end point; however, when registering in China, the performance of the device may be required to reach multiple observation endpoints to confirm its validity. And the safety of medical devices is supported by appropriate evidence.
If NMPA issues the technical review guidelines for specific medical devices that contain relevant requirements for clinical trials, the overseas clinical trials of the device should consider the relevant requirements. When there are inconsistencies, sufficient and reasonable reasons and basis should be provided.
4.2 Differences in the test population
Because the mechanism of the medical device acting on the human body, the way and time of contact with the human body, and the expected clinical effects are different, some devices are used for different populations with different safety effects and intervention levels. Applicants should confirm that the population data can be represented for the Chinese population (ethnic differences).
4.3 Differences in clinical trial conditions
Overseas clinical trials need to consider the impact of differences in clinical trial conditions in China on the trial data and the relevance of the intended population in China.
Differences in trial conditions include: medical environment, medical facilities, researcher capabilities (learning curve), differences in diagnosis and treatment guidelines, and criterion.
Some factors may have a significant impact on the trial results. For example, due to different medical concepts or standards, clinical methods may not meet the relevant clinical guidelines in China. In addition, differences in the level of medical facilities and researchers will also have an impact on the clinical data. For devices with higher operational requirements, the ability of the researcher to use the device may directly affect the conclusion of the trials.
If it is possible to determine whether certain factors have clinically meaningful effects on clinical trial data, or if it is difficult to determine whether certain factors have clinically meaningful effects on clinical trial data, the applicant should clarify the method of reducing or eliminating the effects of differences, such as subgroup design of the test population can be considered, or subgroup analysis of existing clinical trial data.
For factors that have a clear clinical impact on the clinical data, the applicant may conduct supplementary trials in China for different factors, and combine the original overseas clinical trial data to confirm that the device is safe and effective under normal use conditions in China.
Applicants are advised to fully communicate with the medical device review department before submitting the overseas clinical trial data, in order to facilitate the scientific, complete and full consensus on the clinical evaluation data of the medical device to be declared.
Examples of products that can be defined by different factors that have clinically meaningful effects on clinical data are as follows:
Example 1: Pulse oximeter device, through the interaction of light signals with tissue, uses pulsed blood flow to cause time-dependent changes in tissue optical properties, for non-invasive measurement of pulse oximetry (SpO2) and pulse rate. Because the working principle involves the interaction of light signals and tissues, the problem of skin melanin precipitation should be considered. There is a difference in the skin color between the overseas population and the Chinese population, and corresponding clinical research should be carried out.
Example 2: In vitro diagnostic reagents for genetic testing of genetic diseases. If there are differences in the genetics of different ethnic groups, the detection genes selected by overseas products based on the overseas population may be different from the genetics of the Chinese population. The genetics of related diseases in the Chinese population should be considered. The influencing factors such as the mutation site and the mutation frequency are carried out in the corresponding clinical trials.