基于高通量测序的伴随诊断试剂临床评价方法及运用

Clinical evaluation methods and using of companion diagnostic reagents based on next-generation sequencing

随着分子生物学技术的发展,靶向治疗药物已经在临床广泛应用,但药物的治疗效果存在着较大的个体差异,需要伴随诊断试对可获益患者进行区分.与此同时,高通量测序作为高通量测序具有速度快、准确性高、报告位点多、所需样本量小等等优势,将高通量测序作为伴随诊断试剂指导用药有着强烈的需求.但如何对高通量测序可同时报告多个位点的性能进行临床评价是研究人员还是监管者都面临的巨大挑战.美国FDA提出了Follow-on临床评价方法,通过外部等效性研究评价二者的临床性能的一致性.本文基于在美国使用该临床评价方法已上市的产品对基于高通量测序的伴随诊断试剂的评价方法进行阐述,以期为我国研究人员和生产企业在该类产品研发、申报时提供参考.

With the development of molecular biology technology,targeted therapeutic drugs have been widely used in clinical practice. Still,there are significant individual differences in the therapeutic effects of drugs,and it is necessary to distinguish between patients who can benefit from a diagnostic test. At the same time,second-generation sequencing as a high-throughput sequencing has the advantages of fast speed,high accuracy,many reporting sites,small sample size,etc. There is a strong demand for second-generation sequencing as a guide for companion diagnostic reagents. But how to conduct a clinical evaluation of the performance of second-generation sequencing that can report multiple sites at the same time is a huge challenge for researchers and regulators. The US FDA has proposed a Follow-on clinical evaluation method to evaluate the consistency of the clinical performance of the two through external equivalence studies. In this article,based on the products that have been marketed in the United States using this clinical evaluation method,the evaluation method of companion diagnostic reagents based on Next-generation sequencing technology is described in order to provide reference for Chinese researchers and manufacturers in the development and application of such products.