中国内地脑卒中治疗多中心随机对照试验方法学质量现状报告

An assessment of methodological quality of multi-center randomized controlled trials of stroke treatments conducted in Chinese Mainland

目的了解中国内地脑卒中临床治疗多中心随机对照试验方法学质量现状与发展趋势,为未来国内临床试验设计及指南制定提供参考依据。方法电子检索PubMed、Embase、Cochrane临床试验登记数据库、中国生物医学文献数据库、中国期刊全文数据库、万方数据库、中国科技期刊全文数据库,纳入2000年1月-2019年12月国内外发表的中国内地关于脑卒中(缺血性脑卒中、脑出血、蛛网膜下腔出血)治疗的多中心随机对照试验(randomized controlled trial,RCT),对所纳入的RCT进行基本情况、方法学质量及结局指标的评价。结果共纳入脑卒中治疗多中心RCT 90个。2000年-2009年发表多中心RCT 39个,2010年-2019年发表多中心RCT 51个;2010年-2019年发表的多中心RCT数量是2000年-2009年发表数量的1.31倍。以缺血性脑卒中为研究对象的研究占58.9%(53/90),以脑出血为研究对象的研究占14.4%(13/90),共同纳入缺血性和出血性脑卒中的研究占26.7%(24/90)。药物试验占总纳入试验的55.6%(50/90),非药物试验占44.4%(40/90)。与2000年-2009年比较,2010年-2019年发表的多中心RCT在报告失访情况(P=0.005)、明确报告主次要结局指标(P=0.027)以及不良反应报告(P=0.007)方面差异有统计学意义;两个时间段发表的多中心RCT在正确使用随机方法(P=0.341)、分组隐藏(P=0.611)、盲法(P=0.551)、报告使用意向性分析(P=0.573)以及随访时间(P=0.061)方面比较,差异均无统计学意义。结论近20年来,中国内地脑卒中治疗多中心RCT质量改善进步依旧缓慢,提高急性脑卒中治疗试验的设计与实施质量需引起更多重视。

Objective To evaluate the current status and trend of methodological quality of multi-center randomized controlled trials(RCTs)of stroke treatments in Chinese Mainland.Methods Multi-center RCTs of stroke treatments conducted in Chinese Mainland published in Chinese or English language from January 2000 to December 2019 were retrieved from seven databases including PubMed,Cochrane Central Registry of Controlled Trials,Embase,China Biology Medicine,China National Knowledge Infrastructure,Chinese Science and Technique Journals Database,and Wanfang Database.The basic information was collected.Methodological items were referred to the Cochrane Collaboration’s tool for assessing risk of bias.The definitions of Wade were used to assess the outcome measure.Results A total of 90 multi-center RCTs were included,of which 39 were published from 2000 to 2009,and 51 were published from 2010 to 2019.The total number of trials published from 2010 to 2019 was 1.31 times of that published from 2000 to 2009.The research subjects were ischemic stroke patients in 58.9%(53/90)of the RCTs,intracerebral hemorrhage patients in 14.4%(13/90)of the RCTs,and ischemic stroke patients as well as hemorrhagic stroke patients in 26.7%(24/90)of the RCTs.There were 55.6%(50/90)drug trials,and 44.4%(40/90)non-drug trials.There were statistically significant differences in the loss of visit report(P=0.005),primary and secondary outcome indicators report(P=0.027),and adverse reaction report(P=0.007)between the two periods;there was no statistically significant difference in reported adequate randomized methods(P=0.341),allocation concealment(P=0.611),blindness(P=0.551),used intentionality analysis(P=0.573),or follow-up time(P=0.061)between the two periods.Conclusion In the past 20 years in Chinese Mainland,the quality of stroke treatment RCTs improves slowly,and more attention should be paid to develop the RCTs of true randomization,blinding,and better patient outcome measures.