摘要
目的:通过文献检索和Meta分析方法为上市前药物洗脱球囊(DEB)导管治疗冠状动脉分支病变相关临床试验提供样本量依据。方法:目前仅有辽宁垠艺生物科技股份有限公司生产的轻舟®(Bingo®)DEB导管被国家药品监督管理局(NMPA)批准用于分支病变治疗,故可采用随机对照试验的非劣效性设计,主要评价指标为术后9个月随访时基于造影获得的分支血管靶病变节段内直径狭窄百分比(DS%)。根据产品和适应证等设定关键词检索组合,对同品种产品开展文献检索和筛选,用Meta分析方法整合已上市同类产品结果,为上市前DEB导管随机对照试验的样本量计算提供效应值、非劣效界值等依据。结果:共计筛选106篇文献,最终符合入排标准共计10篇文献(含9项研究),其中报告术后9个月DS%的5项研究,结合临床实际和Meta分析合并同品种产品研究的结果,假设两组DEB导管能够达到同样的DS%水平,即Meta合并效应值点估计27.74%,并基于所有单项研究报道结果保守估计标准差设置为±18.00%,结合4项DEB导管与普通球囊相比较的术后DS%均差Meta结果为-9.61%(95%CI:-15.29%~-3.93%),再结合临床考虑设定非劣效界值在7.00%,并以此为基础计算出最终每组需入选140例,两组共计280例。结论:以DEB导管治疗冠状动脉分支病变为例,采用文献检索和Meta分析方法可为临床试验的样本量估算提供更为稳妥的文献支持。
Objectives:To provide the evidences for sample size design in pre-marketing clinical trials of drug eluting balloon(DEB)catheter for the treatment of coronary bifurcation lesions through literature searching and meta-analyses.Methods:Non-inferiority design could be used for these clinical trials.The primary efficacy endpoint was angiographic target lesion percentage diameter stenosis(DS%)at 9 months.Literature searching and screening for equivalent products were performed based on key word combination of products and indications.Endpoint results of equivalent products on global markets were analyzed using meta-analyses,which could provide evidences for effect sizes and non-inferiority margin of sample size design in pre-marketing randomized controlled trials of DEB catheter.Results:106 articles were screened,and ten articles were eligible,including nine studies,five of which reported DS%at 9-month follow-ups.Combined with clinical experiences and meta-analysis results from equivalent products,the same DS%levels could be presumed in two DEB catheter groups as 27.74%from meta-analysis for single-arm DEB catheter results.A conservative estimate of the standard deviance was set as±18.00%according to the results of all individual studies.In metaanalyses of four clinical trials for DEB catheter vs.plain old balloon angioplasty(POBA),weight mean difference(WMD)of DS%after surgery was obtained as-9.61%(95%CI:-15.29%to-3.93%).Combined with clinical consideration,noninferiority margin was defined as 7.00%.Finally,140 patients should be included in each arm,and the total sample size was set as 280 in two arms trials.Conclusions:DEB catheter was taken as an example for treatment of coronary bifurcation lesions,literature searching and meta-analyses could be used to provide more reliable literature supports for sample size designing in clinical trials.
作者
尹潞
韩国亮
丁丽娟
李思冬
刘小云
赵延延
李卫
王杨
YIN Lu;HAN Guoliang;DING Lijuan;LI Sidong;LIU Xiaoyun;ZHAO Yanyan;LI Wei;WANG Yang(Medical Research and Biometrics Center,National Center for Cadriovascular Diseases and Fuwai Hospital,CAMS and PUMC,Beijin(g102308),China)
出处
《中国循环杂志》
CSCD
北大核心
2021年第5期494-500,共7页
Chinese Circulation Journal
基金
中国医学科学院医学与健康科技创新工程经费(2016-I2M-2-004)。
关键词
药物洗脱球囊导管
冠状动脉分叉病变
样本量计算
文献检索
Meta分析
drug eluting balloon catheter
coronary bifurcation lesions
sample size calculation
literature searching
metaanalyses
