As long as the corresponding conditions are met, it is possible.
Technical Guide for Receiving Data from Overseas Clinical Trials of Medical Devices
In order to better meet the public's clinical demand for medical devices and promote the technological innovation of medical devices, these guiding principles are formulated according to the Opinions of the General Offices of the General Office of the Central Committee of the CPC and the State Council on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Medical Devices (No.42 [2017]) and the relevant requirements of China's medical device registration management.
The Guiding Principles aim to provide technical guidance for applicants to apply for overseas clinical trial data registration of medical devices and the regulatory authorities to review such clinical trial data, so as to avoid or reduce repeated clinical trials and speed up the listing process of medical devices in China.
I. Scope
These guiding principles are applicable to guiding medical devices (including in vitro diagnostic reagents) to apply for registration in China and accept overseas clinical trial data as clinical evaluation data.
The overseas clinical trial data referred to in these Guiding Principles refers to the research data generated during the process of confirming the safety and effectiveness of medical devices to be registered in China under normal use conditions by clinical trial institutions required by countries (regions) conducting clinical trials overseas.
Second, the basic principles of accepting overseas clinical trial data
ethical principle
Overseas clinical trials should follow the ethical standards stipulated in the Helsinki Declaration of the World Medical Congress. At the same time, the applicant shall explain the norms and standards formulated by the ethics, laws and regulations of the country (region) where the clinical trial is located, or the international norms and standards.
(2) legal principles
Overseas clinical trials should be conducted in countries (regions) with clinical trial quality management, and meet the regulatory requirements of clinical trials of medical devices (including in vitro diagnostic reagents) in China. If there are differences between the clinical trial quality management documents that clinical trials meet and the Good Practice for Clinical Trials of Medical Devices (GCP), the contents of the differences should be explained in detail, and it should be fully proved that the differences will not affect the authenticity, scientificity, reliability and traceability of the research results, and can protect the rights and interests of the subjects. Applicants and clinical trial institutions shall accept the supervision and inspection of China Food and Drug Administration.
(3) scientific principles
Overseas clinical trial data shall be true, scientific, reliable and traceable, and the applicant shall provide complete test data and shall not conduct screening.
The applicant shall ensure that the purpose of the clinical trial conducted abroad is appropriate, the design of the trial is scientific and reasonable, the conclusion of the trial is clear, the rights and interests of the subjects are protected, and the risks that others may suffer are guaranteed.
Three, overseas clinical trial data submission and acceptance requirements
The overseas clinical trial data submitted by the applicant shall at least include: clinical trial plan, ethical opinion and clinical trial report. The clinical trial report should include the analysis and conclusion of the complete clinical trial data.
According to the clinical evaluation path selected in the applicant's registration application, overseas clinical trial data can be used as clinical trial data and verification data, which proves that the difference with similar devices will not adversely affect the safety and effectiveness of products.
Among them, the generation process of the latter clinical trial data includes: (1) the data generated by foreign clinical trials for the differences of the same variety of devices; The applicant's existing overseas clinical trial data can cover the contents of the identification test that needs to be carried out after comparing the same variety of devices.
Overseas test data meet the requirements of China's registration, and the data is scientific, complete and sufficient, so it will be accepted. Overseas trial data meet the basic requirements stipulated in Article 2 of these Guiding Principles, but if some data need to be supplemented according to the technical requirements of registration in China, supplementary clinical trials can be conducted in China or abroad, and the supplementary experimental data and the original experimental data abroad can be accepted after comprehensive evaluation meets the technical requirements of registration in China.
If the applicant uses the data of multi-center clinical trials conducted simultaneously in China and abroad as the application materials for registration, it should also clarify the distribution basis of the number of cases undertaken in China, so as to further evaluate whether it meets the relevant requirements for registration in China.
Medical devices listed in the third category of medical devices approved by clinical trials may also submit overseas clinical trial data in accordance with these guiding principles.
Four, to accept the overseas clinical trial data matters needing attention and technical requirements.
(a) Differences in technical review requirements
Clinical trials conducted overseas may meet the technical review requirements of the countries (regions) where the trials are conducted, but they may not completely meet the relevant review requirements of China.
For example, when designing clinical trials, some countries only require that clinical trials can conclude that the performance of the device has reached a certain observation end point; However, when applying for registration in China, it may be required that the performance of the device reaches multiple observation endpoints to confirm its effectiveness, and the safety of the medical device is supported by appropriate evidence.
If the technical review guidelines for specific medical devices issued by China Food and Drug Administration contain relevant requirements for clinical trials, the relevant requirements shall be considered in overseas clinical trials of the devices. If there is any inconsistency, sufficient and reasonable reasons and basis shall be provided.
(2) Differences between subjects
Because the mechanism of medical devices acting on human body, the way and time of contact with human body and the expected clinical effect are different, the safety impact and intervention degree of some devices used in different groups of people are also different. The applicant should confirm that the population data studied can be extrapolated to the user population in China.
Due to the difference of subjects, the factors that may affect the clinical trial data include:
1. Internal cause: refers to the influencing factors based on human genetic characteristics or demographic characteristics, including race, race, age, gender, etc.
2. External factors: refers to the influencing factors based on social environment, natural environment and culture, including eating habits, religious beliefs, exposure to the environment, smoking, drinking, disease incidence, rare or regional diseases, obesity, treatment concept, socio-economic status, education level, medical compliance, etc.
Some of the above factors can be based on internal and external factors, such as ethnic differences.
(3) Differences in clinical trial conditions
Overseas clinical trials need to consider the influence of the differences between experimental conditions and domestic ones on the correlation between experimental data and domestic expected users. The differences of experimental conditions include: medical environment, medical facilities, researcher's ability (learning curve), diagnosis and treatment concept or standard, etc.
Some factors may have a significant impact on the test results. For example, due to different diagnosis and treatment concepts or standards, the clinical operation methods may not meet the relevant clinical operation guidelines in China.
In addition, the differences in medical facilities and the level of researchers will also have an impact on the test data. For instruments with high operability requirements, the ability of researchers to use instruments may have a direct and obvious impact on the test conclusions.
The influencing factors caused by the differences in the above three aspects may exist alone or in multiple ways in the process of generating clinical trial data of medical devices. Although it is known that these factors exist objectively and will have certain influence on clinical trials, the determination of the influence degree of each factor should also be combined with the characteristics of the devices to be declared and the purpose of clinical trials.
According to the development status of medical devices, clinical experience, and understanding of related diseases and diagnosis and treatment methods, if it can be judged that the influence of most clinical trial data of medical devices has no practical clinical significance, it is not required to prove them one by one.
When it can be determined that some factors have a clinically significant impact on the clinical trial data, or it is difficult to determine whether some factors have a clinically significant impact on the clinical trial data, the applicant should specify the methods to reduce or eliminate the impact of various differences, such as subgroup design of the trial population or subgroup analysis of the existing clinical trial data as needed.
For the factors that can be clearly defined and have a clinical impact on the test data, the applicant can conduct supplementary tests in China according to different factors, and combine the original overseas clinical trial data to confirm the safety and effectiveness of the device under normal domestic use conditions.
It is suggested that the applicant should fully communicate with the medical device evaluation department before submitting the overseas clinical trial data, so as to facilitate a scientific, complete and full understanding of the clinical evaluation data of medical devices to be declared.
Examples of products that can be defined by different factors that have a clinically significant impact on clinical data are as follows:
Example 1: Pulse oximeter is used for noninvasive measurement of pulse oxygen saturation (SpO2) and pulse rate (PR) through the interaction between optical signals and tissues and the change of optical characteristics of tissues with time caused by pulsating blood flow. Because the working principle involves the interaction between light signals and tissues, the problem of skin melanin deposition should be considered. There are differences in skin color between overseas Chinese and China people, and corresponding clinical research should be conducted.
Example 2: In vitro diagnostic reagents for detecting genetic diseases. If the genetic genes of different races are different, the detection genes selected by overseas products based on overseas populations may be different from those of China population. Therefore, we should consider the influencing factors such as mutation sites and mutation frequencies of related disease genes in China population and conduct corresponding clinical research.
Example 3: In vitro diagnostic reagents for pathogen detection have different genotypes at home and abroad. For example, the genotype distribution of hepatitis B virus is different around the world. There are common types B, C and D in China, and there are 9 genotypes A-I * * * in the world. Hepatitis B virus genotyping detection reagent should prove its genotyping coverage and detection ability through clinical evaluation.