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
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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
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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
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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.
