高危型人乳头瘤病毒核酸体外检测试剂盒临床功能验证的中美指导原则解读

Interpretation of guidance for establishing the performance characteristics of in vitro diagnostic devices for the detection or detection and differentiation of high-risk human papillomaviruses issued by Food and Drug Administration of United States and China

为促进人乳头瘤病毒（HPV）检测试剂盒临床功能验证设计的规范化，中国国家食品药品监督管理总局（CFDA）和美国国家食品药品监督管理总局（FDA）分别针对HPV检测试剂盒核酸检测的准确性验证和临床功能，包括不明意义非典型鳞状细胞（ASC－US）人群分流、联合筛查和初筛的有效性验证方面，从临床试验设计或评价等方面推荐了较为详细的指导原则。中美两国指导原则在研究设计、研究对象、样本量估计和统计分析等关键点的要求略有差异，但评价指标类似。按照CFDA指导原则要求，可采用横断面研究设计代替FDA建议的前瞻性设计进行ASC－US人群分流用途的验证；同时采用前瞻性研究设计，对同一个自然人群进行拟申报产品HPV和细胞学平行检测，通过至少3年细胞学随访，对初筛和联合筛查进行拟申报产品的临床有效性验证。

To establish the standardization of clinical verification designs for in vitro diagnostic devices（IVDs） of human papillomavirus, China Food and Drug Administration （CFDA） and United States Food and Drug Administration （FDA） issued guidelines of detailed study designs and effectiveness evaluation for accuracy validation and clinical performance of nucleic acid detection, respectively, including triage of a typical squamous cells of undetermined significance（ASC-US） patients and validation of combined screening and preliminary screening. The design, study population, sample size estimation and statistical analysis of guidelines were moderately different from America to China, however, the evaluation indication was similar. According to the guideline issued by CFDA, prospective design suggested by FDA could be replaced by cross sectional study design to validate the triage of ASC-US patients. Alternatively, prospective design could be used to conduct the HPV product declaration and cellular parallel detection for the same natural population, and the clinical effectiveness of declared products could be validated by at least 3 years follow-up of cytology.