Decree 14 Principles Of Technical Guidance On Clinical Evaluation Of Medical Devices
2021-06-22
Attachment Technical Guidance on Clinical Evaluation of Medical Devices I. Purpose The clinical evaluation of medical devices is the assessment procedure conducted by registration applicants to validate whether the application requirements or intended use of the target medical device(s) can be achieved based on a comprehensive analysis of clinical literatures, clinical experience data and information gathered from the clinical trial(s). This guidance is intended for providing technical guidance to registration applicants for conducting clinical evaluation and to food and drug administrative authorities for reviewing the clinical evaluation report and related data. II. Legal Basis (1) “Regulations for the Supervision and Administration of Medical Devices” (State Council Decree No. 650) (2) “Provisions for Medical Device Registration” (Decree No. 4 by China Food and Drug Administration) (3) Relevant provisions on clinical trial quality control of medical devices III. Scope of Application This guidance is applicable to the clinical evaluation for registration application of Class II and Class III medical devices, and is not applicable to the clinical evaluation of in-vitro diagnostics administrated as medical devices. If there is technical guidance on clinical evaluation of specific medical device product available, the specific guideline should be followed for the clinical evaluation of the corresponding product. IV. Basic Principles The clinical evaluations should be thorough and objective. Corresponding data should be collected by multiple means including clinical trial(s). Clinical performance and safety data collected during clinical evaluation (including both favorable and unfavorable data) should be included in the analysis. The depth and extent of clinical evaluation, and required data type and volume should be flexible and appropriate to the product design features, critical technologies, intended use, and risks of the device as well as the depth and extent of the non-clinical studies. A clinical evaluation should verify the clinical claims made about the device, such as intended purpose and application of the device (e.g., target treatment group, the site of application to/in the body, method of contact with human body, indications, severity and state of the disease, application requirements and operation environment, etc.), method of deployment, contraindications, precautions, and warnings. The registration applicant should be able to reach the following conclusions through clinical evaluation: the product can achieve the expected performance in normal use conditions; the product risks are acceptable balanced with expected benefits; clinical performance and safety of the product are both supported by sufficient evidence. V. The Requirements of Clinical Evaluation for the Products Listed in “The 2 Catalogue of Medical Devices Exempted from Clinical Trial” For the clinical evaluation of products listed in “The Catalogue of Medical Devices Exempted from Clinical Trial” (hereinafter referred to as “the Catalogue”), the registration applicant should submit the comparison summary of relevant information of the device under application with the corresponding information in the Catalogue, and the comparison description of the device under registration to the equivalent product listed in the Catalogue which has already obtained domestic registration approval. The clinical evaluation to be submitted should include the following information: (1) Comparison between the device under application and corresponding information in the Catalogue. (2) Comparison between the device under application and an equivalent device in the Catalogue which has obtained domestic registration approval. The comparison description should include ‘comparison table between the device under application and an equivalent device which has obtained domestic registration approval’ (see Annex 1) and relevant supporting documents. The above submissions should be able to prove equivalence between the device under application and the corresponding device listed in the Catalogue. If this is not the case, the application procedures should be followed according to other relevant requirements defined in this guidance. VI. Requirements for Clinical Analysis and Evaluation Based on Data from Clinical Application or Clinical Trial(s) of the Equivalent Medical Device (I) Equivalent Medical Devices
Definition of Equivalent Medical Device The equivalent medical device refers to the device product which has obtained domestic registration approval and is substantially equivalent to the registration device in aspects of basic principle, structure composition, manufacturing material (manufacturing material in contact with the human body for active device), manufacturing process, performance requirements, safety evaluation, conformed national /industry standards and intended use. The registration device could be viewed as substantially equivalent with the equivalent device in case that the differences between the two devices do not cause any negative impact on the safety and effectiveness of the device.
Determination of Equivalent Medical Device If the registration applicant would like to prove the safety and effectiveness of the registration device utilizing the data from the clinical application experience or clinical trial(s) of the equivalent device, the applicant needs to compare the registration device with one or more equivalent device(s) and prove the substantial equivalence between the devices The comparison items with the equivalent device shall include, but be not limited to the items listed in Annex 2, including the qualitative and quantitative data, the verification and validation results. The similarities and differences between the two products should be described in details. Whether the differences will result in any negative impact on the safety or effectiveness of the registration device should be verified and/or confirmed based on the data of the registration device, such as data 3 obtained from its non-clinical study, clinical literature, clinical experience, and clinical trials conducted in China to address any difference. Collection, analysis, and evaluation of the relevant data should meet the requirements defined in sections (III) and (IV) and corresponding annexes. The clinical trials should meet clinical trial quality management regulations. The registration applicant should provide comparative information in tabular form (see Annex 3 for the format). For specific products with inapplicable items, the justification should be provided. (II) Evaluation Path See Annex 4 for the details of evaluation path. (III) Collection of Data from Clinical Experience or Clinical Trial(s) of Equivalent Medical Device The clinical experience or trial(s) data (hereinafter abbreviated as clinical data) can be obtained from public scientific literature released in China and/or overseas and legally obtained data, including clinical literature data and clinical experience data. The registration applicant can select the appropriate data sources and collection methods based on the specific requirements of the products.
Collection of Clinical Literature Data When collecting the literature data for clinical evaluation, the reliability, comprehensiveness of the literature search should be guaranteed. The recommended literature search and screening elements are in Annex 5. Before literature search, the literature search and screening protocol should be formulated (the content and format are in Annex 6). After the literature search and screening, the report on literature search and screening must be prepared (the content and format are in Annex 7). The clinical literature search and screening should have repeatability. The personnel in charge of literature search and screening should have appropriate professional knowledge and practical experience.
Collection of Clinical Experience Data Collection of clinical experience data should include collection of data from completed clinical trials, adverse events, and corrective measures related to clinical risks. (1) Collection of Data from Completed Clinical Trials According to the design of the clinical study, clinical studies can be divided into prospective study, retrospective study, random control study, nonrandom control study, single arm study and case report. The registration applicant should collect and provide the opinion of Ethics Committee (if applicable), clinical study protocol and clinical study report. (2) Collection of Adverse Events Data The registration applicant should collect the corresponding adverse event data from the complaints and adverse events database established by the applicant, and the adverse events database issued by the regulatory authorities of various countries, such as the “Medical Device Adverse Events Bulletin” and “Alert Newsletter of Medical Devices” issued by China Food and Drug Administration, the Manufacturer and User 4 Facility Device Experience Database (MAUDE) of U.S. Food and Drug Administration and the British Medical Device Alert (MDA). The registration applicant should provide the following information related to the equivalent device: number of complaints and adverse events, classified reasons of complaints and adverse events, number of complaints and adverse events in different classified reasons, the relationship of the adverse events with the product. For serious adverse events, the specific information such as event description, cause analysis, and corrective action should be summarized in tabular form. For the product under application, specific information such as the time on market in different countries, accumulated sales and outcome of serious adverse events should also be provided. (3) Data Collection of Corrective Measures Associated with Clinical Risks The specific information of corrective measures associated with clinical risks (such as recall, announcements, warnings, etc.) of the equivalent device and adopted risk control measures should be collected and provided by the registration applicant. (IV) Analysis and Evaluation of Clinical Data from Equivalent Medical Device
Quality Evaluation of Data The registration applicant should classify the data to be analyzed in accordance with generally accepted evaluation criteria of clinical evidence level (such as the evaluation criteria of clinical evidence level developed by the Oxford Center of Evidence Based Medicine). For some clinical data that are not applicable for product performance evaluation, if applicable they may be still applied to the safety evaluation of the product.
Establishment of Data Sets The collected clinical data can be grouped into several data sets according to their different data type and data quality. The registration applicant may also establish data sets according to different evaluation purposes, for example, if the clinical performance and/or safety of certain products have ethnic differences, the Chinese subgroup data sets can be established for evaluating the safety and /or efficacy of the product in Chinese population.
Statistical Analysis of Data The appropriate data analysis methods should be adopted to conduct statistical analysis in different data sets. For the data sets with multiple study results, the analysis method should include the qualitative analysis and quantitative analysis.
Data Evaluation Based on the analysis results of different data sets, the applicant should evaluate whether the registration device could reach the expected performance in normal conditions of use, and whether the risks are acceptable balanced with the expected benefits.
