TX Q&A

For some in vitro diagnostic reagents that currently lack a clear clinical diagnostic "gold standard" and have no comparable similar products on the market, clinical trial researchers should establish reasonable methods for comparative studies based on existing clinical practices and theoretical foundations. For some in vitro diagnostic reagents, in clinical trials, nucleic acid sequence determination, GC-MS/MS, and other laboratory detection reference methods are used as comparative methods for comparative studies. These methods are not routine clinical detection techniques, requiring specialized equipment and testing conditions, which clinical trial institutions may not have. In such cases, applicants should select clinical trial institutions with the necessary conditions as much as possible to conduct clinical trials. For clinical trial institutions without testing conditions, some testing can be outsourced to specialized sequencing institutions or laboratories with certain testing qualifications, and the test results should be recognized. Submit the delegation certificates between the clinical trial institution and the commissioned institution and evaluate the methodological research and overall quality of the comparative methods.

It is possible to select the typical model A for clinical trials. For model B, which has not undergone clinical trials, the similarities and differences between model B and model A should be detailed, evaluating whether the differences adversely affect the safety and effectiveness of the product.

Dental etchants are used for intraoral repair or orthodontic treatment, where the corrosive nature of the etchant is used to treat the surfaces of teeth, metals, ceramics, and other restorative materials to remove contamination layers, rough surfaces, and improve their surface performance. Products with different main chemical components should be divided into different registration units, for example, phosphoric acid etchants and citric acid etchants should be separate registration units.

1. Informational Content: When using sequencing methods, the clinical trial data should include relevant information about the sequencing method. 1.1 Information such as the principles of the sequencing method, the model of the sequencing instrument, and information about sequencing reagents and consumables should be provided. 1.2 Information related to the primers used in the sequencing method, such as gene segment selection, molecular weight, purity, functional experiments, etc., should be provided. The primer design should reasonably cover the target nucleic acid segments, sites for amplification of the test reagent, and all types of mutations. 2. Methodological Validation Information 2.1 Reasonable validation of the analytical performance of the selected sequencing method, especially confirmation of the lowest detection limit, is recommended. It is suggested to appropriately compare the selected sequencing method with the relevant performance of the test reagent. 2.2 A reasonable positive quality control and negative quality control should be established for the sequencing method to control the quality of the detection results of clinical samples. 3. Sequencing Result Information In addition to the sequencing results in the result data table, representative sample sequencing chromatograms and result analysis data should be submitted.

According to the "Technical Guidance Principles for Accepting Overseas Medical Device Clinical Trial Data," medical devices listed in the "Catalog of Class III Medical Devices Requiring Clinical Trial Approval" can submit overseas clinical trial data based on this guidance. Following ethical, legal, and scientific principles, if overseas clinical trial data meets China's registration-related technical requirements and is scientifically sound, complete, and sufficient, clinical trials do not need to be conducted in China.

When accepting overseas medical device clinical trial data, it is not always necessary for the data to include data from Chinese subjects. According to the "Guiding Principles for Accepting Overseas Medical Device Clinical Trial Data," factors that may affect the clinical trial results are not limited to ethnic differences. It is necessary to consider the impact of differences in the tested population and clinical trial conditions based on the product characteristics. Although these factors objectively exist and have a certain impact on clinical trials, the determination of the degree of influence of each factor should also consider the characteristics of the device to be applied for and the objectives of the clinical trial. In situations where it can be determined that the impact of certain factors on the clinical trial data of most medical devices is not clinically significant based on the current status of medical device development, clinical experience, and understanding of relevant diseases and treatment methods, individual verification may not be required. When it can be determined that certain factors have a clinically significant impact on the clinical trial data, or when it is difficult to determine whether certain factors have a clinically significant impact on the clinical trial data, the applicant should clarify the methods used to reduce or eliminate the impact of each difference, such as considering subgroup design for the tested population or conducting subgroup analysis on existing clinical trial data as needed.

Clinical trials conducted overseas may meet the technical evaluation requirements of the country (region) where the trial is conducted, but may not necessarily fully comply with the relevant evaluation requirements in China. For example, when designing clinical trials, some countries may only require the trial to conclude that the device's performance reaches a certain observational endpoint. However, in China, it may be necessary for the device's performance to meet multiple observational endpoints to confirm its effectiveness, with appropriate evidence supporting the device's safety. If the National Medical Products Administration issues specific technical evaluation guidance principles for a particular medical device that include requirements for its clinical trials, the overseas clinical trials of that device should consider these requirements. In case of any inconsistencies, sufficient and reasonable justifications and evidence should be provided.

When conducting parallel control clinical trials, if for valid reasons you cannot use an already marketed product of the same category as the control, you can consider various factors such as product design features, preclinical study results, risk-benefit analysis, clinical trial objectives, evaluation criteria, and follow-up time. Consider selecting a similar product that is clinically recognized for efficacy and safety, has the same scope of application as the investigational device, and has evaluation criteria set in the clinical trial that are comparable to the investigational device.

In single-arm designs comparing against target values, it is essential to pre-specify target values for clinically significant primary endpoints. By examining whether the results of the primary endpoints in a single-arm clinical trial fall within the specified target value range, the effectiveness/safety of the investigational device can be evaluated. Since there is no control group, single-arm target value design clinical trials cannot confirm the superiority, equivalence, or non-inferiority of the investigational device; they can only confirm that the device's effectiveness/safety meets the minimum standards recognized within the professional field. The target value represents the minimum standard that the effectiveness/safety evaluation indicator of a certain type of medical device should achieve within the professional field. This includes two types: Objective Performance Criteria (OPC) and Performance Goal (PG). Target values are typically binary (e.g., effective/ineffective) indicators but can also be quantitative, including target values and one-sided confidence interval limits (usually the 97.5% one-sided confidence interval limit). When performing statistical analysis on clinical trial results, it is necessary to calculate the point estimate and one-sided confidence interval limit of the primary endpoint and compare them with the target value. Constructing target values usually involves comprehensive collection of clinical research data with a certain level of quality and a considerable number of cases, followed by scientific analysis (such as Meta-analysis). As medical device technology and clinical skills advance, OPC may change, necessitating re-analysis of clinical data for confirmation.

For therapeutic products, when selecting a positive control, priority should be given to using already marketed products of the same category with clinically recognized efficacy and safety. If for valid reasons the marketed products of the same category cannot be used, a product as similar as possible can be chosen as the positive control, followed by considering standard treatment methods. Standard treatment methods encompass various situations, including drug therapies. In cases where there are no identical or similar marketed products or corresponding standard treatment methods for the experimental device, if the device's efficacy includes a placebo effect, the trial design should consider a placebo control, taking into account ethical considerations. If the efficacy of marketed products has not yet been clinically recognized, the trial design can, depending on the specific circumstances, consider a standard treatment method control or placebo control, and the applicant must provide sufficient justification for the selection of the control.