If the declared product does not meet the requirements of the Exempted Catalog or is not listed in the Exempted Catalog, but its working principle is clear, the production process is mature, the clinical application is widely used and the risk is low and there are mature similar products, the same species pathway is often a good choice. It should be noted that when conducting clinical evaluation of the same species pathway, the substantial equivalence between the declared product and the comparative product is quite important, because theoretically, any difference between the two products may affect their clinical risks and benefits. The difficulties in clinical evaluation of the same-species pathway are mainly the following 3:
1. Obtaining information on same-species medical devices
According to the requirements of the Guiding Principles, to determine the substantial equivalence between the declared product and the same-species product, it is necessary to determine from the basic principles, structural composition, manufacturing materials, production processes, performance indicators, scope of application, etc. In most cases, the above information on other same-species products is commercial confidentiality, and it is generally difficult to obtain.
The path is more applicable to the declaration of product upgrading, the use of the previous generation of products as the same varieties of products.
If the applicant for registration adopts another manufacturer's product as the same variety of medical devices, then the information access needs to be legally authorized by the manufacturer of the product. It is worth mentioning that, for the product performance indicators, some of the drug regulatory authorities have public information available (such as the Guangdong Provincial Bureau of some of the products), even if the selected performance indicators of the same varieties of products without public information, the applicant for registration can also try to the same varieties of products registered in the location of the provincial drug regulatory authorities to apply for disclosure.
2. Argumentation of the differences between the products
As mentioned earlier, theoretically any differences between the declared product and the same variety of products may affect its clinical risk and benefit, so the differences between the declared product and the same variety of products will be the focus of the review of the key part of the concern, but also the core content of the clinical evaluation report. In writing this part of the content, should identify all the differences between the declared product and the same variety of products, and all the differences should be provided with the corresponding basis for discussion, for example, the declared product and the same variety of products with different manufacturing materials, then the discussion should pay attention to the key points of the difference between the manufacturing materials, the declared product materials and the same varieties of different whether it affects the function of the relevant components, whether it affects the key performance parameters, whether it affects the performance of the whole machine and the long-term performance of the product. Whether the performance of the machine and long-term storage impact and so on. Should not use a "one-off", "fuzzy expression" and other ways to write, because this is often a higher risk of hair repair.
When making the argument for differences, the argument can be made in the order of "the magnitude of the impact on clinical use". For example, for some active products, its basic principles, key technical parameters (performance indicators), the use of the product has a greater impact on the clinical application of the product should be prioritized in the demonstration of the difference, and the product's production process (non-sterile products) on the clinical application of the impact of the difference is often small and can be compared to the key technical parameters of the difference in the demonstration, so this time, the production process can be simple to compare or even not compared! (e.g. ultrasound probe). For products containing software, if the software of the declared product and the software of the same variety of products are different, the software should also be compared and analyzed. Including software functions, core algorithms, methods of use and so on. For example, an image acquisition equipment with an image of the analysis function, the same variety of comparison needs to be embedded in the image analysis software to carry out a detailed comparison, including the analysis of the image of the process, the process of each step of the processing method and core algorithms, etc., for the existence of differences in the part, the relevant functional verification should be provided, such as the consideration of the same measurement object, the two algorithms whether to output the same results.
3. Collection of relevant clinical data
According to the requirements of the Guiding Principles, clinical literature data and clinical experience data of the same variety of medical devices should be collected, and these data collected should be analyzed and demonstrated. Clinical literature data refers to published scientific literature and legally obtained data within and/or outside China, and clinical experience data includes completed clinical studies and related adverse event data. In general, completed clinical study data is often difficult to obtain, therefore, in the collection of relevant clinical data, more often than not, the collection of clinical literature data and adverse event data of the same variety of products.
According to the requirements of the Guiding Principles, the clinical literature to be searched should be the clinical literature of "the same variety of medical devices", so in the process of clinical literature search, it is necessary to carry out literature search on the same variety of products that have been selected as a comparison product. In the process of clinical literature search, it is the basic requirement to ensure "complete" and "accurate" search, so the search can be carried out for the selected product characteristics of the comparison product, such as manufacturer, model number, etc. as the keywords, which can quickly realize the "complete" and "accurate" search. "Check all", "check accurate" purpose. It should be noted that the literature search needs to be based on the requirements of the Guiding Principles to develop a reasonable literature search program, after the completion of the search, the need to prepare a literature search report, while the need to export the literature search directory to ensure that the results of the search can be reproducible.
It is worth mentioning that some applicants for registration have declared that there is a relaxation of the scope of application of the product relative to the product of the same species when conducting clinical evaluations of the same species. As the relaxation of the scope of application will have a significant impact on the clinical application of the product, the difference is often difficult to demonstrate through non-clinical studies, at the same time, even if the same varieties of products have been reported in the literature can be used for the relaxation of the indications, but due to the fact that at this time the indications have not been approved by the drug regulatory authorities, so the review may not be recognized by the literature results, so the applicant of the registration in the same varieties of the process of clinical evaluation on the Therefore, the applicant for registration should be particularly cautious when relaxing the indications during the clinical evaluation of the same product.
After completing the collection of clinical literature data, the next step is to evaluate the quality of the literature data and analyze the results reported in the literature. For data that cannot be combined (e.g., different studies with different endpoints), descriptive analysis can be used to qualitatively analyze the results of the literature reports. It should be noted that the analysis of the results of the literature should focus on the reports of adverse events and the differences between the results of the literature reports (e.g., one literature reported no adverse events, another literature reported more relevant adverse events, and then focus on analyzing the possible reasons for adverse events); for those who can be combined, the results of the literature reports can be analyzed with caution. For data that can be combined, "exploratory" meta-analysis can be performed to improve the quality of the evidence. For simple Meta-analysis, it is recommended to use Review Manager software, which is easy to use and free of charge to meet the general Meta-analysis needs. If accurate statistical test results are needed, sata software is a good choice, especially in the evaluation of publication bias, in addition to outputting funnel plots, sata software can also carry out the relevant statistical tests, and sata software can use "cut-and-patch" software to analyze the results. At the same time, sata software can analyze the publication bias of the literature quantitatively by using the "cut-and-patch method".
Conclusion - emergo
The clinical evaluation of medical devices is a systematic work, because its clinical application is often in the design and development stage has been finalized, so the clinical evaluation of medical devices should be from the perspective of the design and development of medical devices to enter and think about the development of the product according to the characteristics of the product to formulate the appropriate evaluation strategy and the direction of the argumentation, is the key to writing the report of the clinical evaluation of medical devices. This is the key to writing a clinical evaluation report for medical devices.