How To Choose A Comparator Product/method In The Clinical Trial Of An IVD Reagent?

 In order to confirm the clinical significance and testing performance of an IVD reagent, and to provide sufficient supporting evidence for the intended use of the product, ideally, in a clinical trial, the investigational IVD reagent should be compared with clinical reference standards for performance evaluation of the correlation between the test results of the in vitro diagnostic reagent and the target status of the subjects.

A clinical reference standard should be the best available method for establishing a subject’s true status with respect to a target condition. Generally, the recognized, reliable and authoritative disease diagnosis standards under the existing conditions (e.g., the pathological result of a biopsy sample, imaging examination result, bacterial isolation and identification, conclusions from long-term follow-up, etc.) should be adopted. In the case of new detection indicators or other circumstances where there is no clear disease diagnosis standard that can be referred to, the disease diagnosis method specified in the disease diagnosis and treatment guidelines, or the consensus of experts in the industry or the clinically recognized and reasonable reference method, etc., can also be considered.

For clinical trials of IVD reagents with similar products already approved to be marketed in China (comparator product), the method of comparative study between the investigational reagent and another NMPA-approved similar product on the market can also be used to evaluate the agreement of the two methods. For the choosing of the similar reagent, which is used as the comparator, it should be considered that the comparator should have good comparability with the investigational IVD reagent in terms of intended use, expected population, sample type, test methodology, test result reporting method, traceability of calibrator value, expected value or reference interval, and analytical performance, etc.

For a new biomarker or other situations where a clinical reference standard does not exist or is not available, and5 at the same time, there is still not any similar product approved in China, when designing a clinical trial, the product’s clinical significance should be demonstrated first. At the same time, a comparative study should be carried out and a comparator that is not a clinical reference standard may be specified and used, for example, a widely accepted and reasonably used laboratory reference methods. For the choosing of the comparator, it should be considered in several aspects: the method should have been widely accepted clinically; it should have good comparability with the new marker test; the method should have been scientifically designed, fully evaluated for analytical performance and be able to achieve good quality control.