国际目标值法临床研究的文献和方法学特征分析

Characteristics of the international clinical studies using objective performance criteria

目的分析运用目标值法进行临床研究的英文文献特征,为临床试验研究者设计临床试验确定外部对照提供参考。方法计算机检索PubMed、The Cochrane Library和EMbase数据库,获取自建库至2019年2月20日发表的所有运用目标值法进行临床研究的英文文献。由2名研究者独立筛选文献、提取资料,并进行统计分析。结果共纳入英文文献51篇,发表时间除2001年发表1篇外,其余文献发表在2010~2018年。2017~2018年发表文献最多(27/51,52.9%),最新累计影响因子为411分。在提及了使用目标值法原因的文献中,8篇(8/11,72.7%)认为无法随机化和设置对照组是促使其使用目标值法的主要原因。已发表的文献中,心血管系统疾病及外周血管疾病占86%,医疗器械的有效性或安全性评价占76.5%。共涉及单臂试验(40篇)、随机对照试验(2篇)、病例-对照研究(2篇)、病例系列(5篇)和诊断试验(2篇)。大部分纳入研究主要用于安全性(43/51)和有效性评价(34/51)。目标值的选取来源于干预性临床试验(29/51,56.9%)、国家标准、Meta分析及专科学会标准4种。其结局指标同目标值比较方法中使用假设检验法进行比较的文献有27篇(27/51,52.9%),而使用可信区间法进行比较的文献有24篇(24/51,47.1%)。结论目标值法主要用于干预措施安全性和有效性评价。其发展迅速,特别是心血管研究领域。其方法学信息报告相对完善。使用目标值法的主要原因大多因随机化和对照上的实施困难。使用目标值法应考虑目标值的选择来源、样本量和比较方法等因素。目标值法的应用不仅可解决诸多临床科研具体实施的困难,也可为解决真实世界中的临床研究实际困难提供新思路和新方法。

Objectives To explore the characteristics of the international clinical studies using objective performance criteria(OPC) and provide a reference to design clinical trials and determine external controls.Methods PubMed, The Cochrane Library and EMbase databases were searched for all clinical studies which used OPC.Two reviewers independently screened literature, extracted data and descriptive analysis was then performed. Results A total of 51 English language articles were included. Merely one was published in 2001, and others were published between2010 and 2018. Twenty-seven articles(27/51, 52.9%) were published between 2017 and 2018, with accumulated impact factors of 411. In the article referring to the reasons for using the objective performance criteria, reasons for using OPC study was primarily the difficulties of randomization and comparison(8/11, 72.7%). Articles with cardiovascular disease and peripheral vascular disease accounted for 86%, and articles on the effectiveness or safety of medical devices accounted for 76.5%. Single-arm trial(40), randomized controlled trials(2), case-control studies(2), case series(5) and diagnostic tests(2) were included. OPCs were mostly derived from the data of clinical trials of other similar products, national standards, specialist association standard and meta-analysis of multiple clinical studies. A total of 27 articles(27/51, 52.9%)used hypothesis testing to compare research results with objective performance goal, and 24 articles(24/51, 47.1%) used the confidence interval method. Conclusions OPC studies are primarily used for safety intervention and effect evaluation. OPC studies are developing very rapidly, especially in the field of cardiovascular studies. Methodological details are reported reasonably sufficient. Reasons for using OPC study are primarily the difficulties of randomization and comparison. Factors such as source of the OPC, sample size, and comparison method should be taken into account. The application of the OPC can not only solve the difficulties of the implementation of numerous clinical research, but also provide new insights for solving the practical difficulties of clinical research in the real-world.