Technical Guidance On Clinical Evaluation Of Medical Devices Part 2 Clinical Evaluation (Draft)
2021-06-22
Technical Guidance on Clinical Evaluation of Medical Devices Part Two: Clinical Evaluation (Draft) I Introduction (I) Definition of Clinical Evaluation The clinical evaluation in this guidance refers to the activities using scientific and reasonable methods to evaluate and analyze clinical data to confirm the safety, clinical performance and / or effectiveness are in the scope of the application of the medical devices. (II) Entire Life-span Clinical Evaluation Clinical evaluation should be carried out continuously throughout the entire life-span of medical devices. In the design and development phase, clinical evaluation should determine the clinical data required for pre-market product evaluation and whether clinical trials are needed and the clinical outcomes to be observed. When the product is on the market, the product needs periodic clinical evaluation as the product safety, clinical performance and/or effectiveness information is constantly updated. The above updated information will be entered into the risk management process and may cause changes in risk assessments, clinical trial documents, operating instructions, and post-market activities. 16 (III) The Importance of Clinical Evaluation At the time of product registration, the registration applicant should use appropriate conformity assessment procedures to demonstrate that the product complies with the Essential Principles of Safety and Performance of Medical Devices. The registration applicant needs to prove that the product has achieved the expected performance under the applicable scope; compared with the benefit, the known and foreseeable risks have been minimized and are acceptable. Any claims regarding the safety, clinical performance and / or effectiveness of the medical device may be supported by appropriate evidence. Registration applicant need to implement and maintain a post-market surveillance program for routinely monitoring the product safety, clinical performance, and / or effectiveness as part of a quality management system. The scope and nature of post-market surveillance should be compatible with the product and its applicable scope. The registration applicant needs to use the data generated by the surveillance program (such as adverse event reports, post-market clinical trials, clinical literature data, etc.) to conduct clinical evaluations, product performance and safety periodically review and risk-benefit assessments, and update clinical evidence. Ongoing clinical evaluation allows the registration applicant to report significant changes in product risk and benefit, or changes in 17 contraindications, warnings, precautions or instructions, as required by regulations to regulatory agencies. (IV) The Process of Clinical Evaluation
Identify basic principles of safety and effectiveness that require clinical data;
Identify available clinical data related to the device and its applicable scope;
Evaluate the applicability and contribution of clinical data according to the need to demonstrate the safety, clinical performance and / or effectiveness of the product under its applicable scope;
Based on the above process, new clinical data is generated based on the need to resolve remaining issues of safety, clinical performance and / or effectiveness;
Aggregate all clinical data and draw conclusions about product safety, clinical performance and / or effectiveness. The results of the above processes should be documented and filed in the clinical evaluation report. The clinical evaluation report and the underlying clinical data will be used as clinical evidence to support the device on the market. The registration applicant uses clinical evidence, as well as other design verification and confirmation documents, device descriptions, 18 labels, risk analysis, and production information, to demonstrate the product comply with the basic principles of safety and effectiveness. The above information and documents are part of the medical device technical document. (V) Detailed Grade of Clinical Evaluation The clinical evaluations should be thorough and objective (including both favorable and unfavorable data) for effectively proving the product safety, clinical performance and / or effectiveness. However, the types, history, and risks of technologies applied in products vary widely. Many products are developed or improved through incremental innovation and are not completely new. Such products can often use clinical experience and literature reports that compare device safety, clinical performance, and / or effectiveness as their clinical evidence, thereby reducing the need for declared products conducting clinical trials to collect data. Similarly, if the product is based on technology whose safety, clinical performance, and / or effectiveness have been fully validated, it can meet the requirements for clinical evidence by meeting accepted acceptance criteria. The depth and breadth of the clinical evaluation need to comply with the nature, applicable scope, and risks of the product. Therefore, this guidance will not address specific requirements for clinical evaluation. II Scope 19 This document is intended to guide registration applicants on how to conduct and document clinical evaluations before and after the product is on the market and take it as part of the compliance assessment process. At the same time, this document is intended to guide regulatory agencies on how to evaluate clinical evidence submitted by registration applicants. This document includes: 1. Basic principles of clinical evaluation; 2. How to identify relevant clinical data; 3. How to evaluate and summarize clinical data; 4. How to document clinical evaluation to form a clinical evaluation report. This guidance applies to medical devices and not to IVD devices. III Basic Principles of Clinical Evaluation (I) Scope of Clinical Evaluation The clinical evaluation comprehensively analyzes the pre-market and post-market clinical data (including safety, clinical performance and / or effectiveness data) under the applicable scope of products, including data on declared products and Predicate data selected by the registration applicant. The evaluation must confirm the adequacy of the device-related clinical claims, product labeling and product information (especially contraindications, precautions / warnings), and the suitability of the instructions for use. Define the scope of clinical evaluation based on the basic principles 20 of safety and effectiveness that need to be confirmed from a clinical perspective, considerations including:
Whether are there design features or target audiences that require special attention. The clinical evaluation shall cover all design features (such as drug coated devices, human or animal-derived components) that may cause special performance or safety concerns, the intended purpose and use of the device (such as target population and diseases, warnings, contraindications, and methods of use ) and the product safety, clinical performance and / or effectiveness declared by the registration application. The scope of clinical evaluation shall be determined based on risk management documents, and the two can refer to each other. Risk management documents identify product risks and how to deal with them. However, the clinical evaluation shall address the residual risks after risk control from the design level.
Whether data from Predicates can be used to support the safety, clinical performance and / or effectiveness of the declared product. Determining whether the information of Predicates can be used for the clinical evaluation of declared products shall be considered from relevant aspects such as the applicable scope, technical and / or biological characteristics, etc. The applicable scope, technical and / or biological characteristics shall have broad similarities, but the impact of differences 21 on product safety, clinical performance and / or effectiveness must be considered. In some cases, the similarity of these characteristics should preclude significant clinical differences in safety, clinical performance, and / or effectiveness between devices. The applicable scope of the devices includes the clinical status of the treatment, the severity and stage of the disease, the location of the human body and the patient population; the technical characteristics include design, technical parameters, physical and chemical properties (including energy intensity), configuration methods, key performance requirements and working principles; the biological characteristics include the biocompatibility of the material in contact with human body fluids / tissues. Annex 1 presents additional considerations to demonstrate the comparability. Registration applicants shall evaluate non-clinical supportive information, summarize it and include it in a clinical evaluation report. (Note: The clinical evaluation does not comprehensively evaluate the technical characteristics and biological characteristics).
Be applied in data sources and data types of clinical evaluation Registration applicants may use data from one or more sources specified in Section 5. When choosing a data type, factors to be considered shall include product design, applicable scope and risks, development background of device technology (new or mature technology) and clinical application of mature technology. If a product is 22 based on an existing mature technology and is expected to be applied in a mature application of that technology, its clinical evaluation is most likely to be accomplished through compliance with recognized standards and / or literature review and / or clinical experience with Predicates. High-risk products based on new technologies or extended applicable scope are more likely to require clinical trial data. Registration applicants shall consider the advantages and limitations of each data type. (II) How to Identify Relevant Clinical Data? When the evaluation scope is determined, the clinical evaluation includes three stages (see Figure 1):
Identify relevant clinical data;
Assess the relevance, applicability, quality, and clinical significance of each data set;
Analyze each data set to draw conclusions about product safety, clinical performance and / or effectiveness, and product information (labels, patient instructions, and instructions for use). The above stages are contained in different chapters of this document. In the final stage of clinical evaluation, a clinical evaluation report shall be drafted to forms clinical evidence with relevant clinical data. If clinical evidence is not sufficient to demonstrate that the product comply with the basic principles of safety and performance, the registration 23 applicant shall generate new data (such as conducting clinical trials and expanding the scope of literature searches). Therefore, clinical evaluation may need to be repeated. (III) Clinical Evaluator Clinical evaluations are carried out by personnel with appropriate experience. The registration applicant shall prove the rationality of its selection of the evaluator, and may refer to the qualifications and experience of the evaluator. Evaluators generally need to have the following knowledge:
Device technology and its use;
Methodology (clinical trial design and biostatistics); and
Diagnosing and managing the expected diseases’ diagnosis and treatment of medical devices.
