Biostatistics Unit, St Joseph's Healthcare-Hamilton, Canada.
Biostatistics Unit, St Joseph's Healthcare-Hamilton, Canada.
Contemp Clin Trials. 2020 Oct;97:106151. doi: 10.1016/j.cct.2020.106151. Epub 2020 Sep 15.
BACKGROUND: Randomized controlled trials (RCTs) are often used to inform clinical practice and it is desirable that their results be robust. A fragility index (FI), defined as the smallest number of participants in whom an outcome change from non-event to event would turn a statistically significant result to a non-significant result, can be computed to measure robustness. We sought to determine the distribution of fragility indices across various research areas and summarized the factors associated with fragility. METHODS: We searched PubMed between February 2014 and May 2019 and included reviews that reported on fragility indices and the associated factors. Two investigators independently screened articles for eligibility and extracted all relevant data from each review. Fragility indices were pooled using random effects meta-analysis. RESULTS: Twenty-four (24) reviews met the inclusion criteria. They contained a median of 41 trials (first quartile [Q1]-third quartile [Q3]: 17-120). The overall mean FI across different fields of research was 4 (95% confidence interval [CI] 3-5), indicating a high level of fragility. Higher journal impact factor, larger sample size, bigger effect size, more outcome events, a lower p-value, and adequate allocation concealment were reported to be associated with the higher FI. The ecological correlation between median FI and median sample size (22 studies) was 0.95 (95% CI 0.58-0.99). CONCLUSION: Trials across various fields of research are frequently fragile. We also identified some factors associated with fragility. Researchers should consider strategies to enhance the robustness of studies and minimize fragility.
背景:随机对照试验(RCT)常用于为临床实践提供信息,其结果的稳健性是理想的。脆弱性指数(FI)定义为使结果从无事件变为事件的参与者数量最小,可用于衡量稳健性。我们旨在确定各种研究领域的脆弱性指数分布,并总结与脆弱性相关的因素。
方法:我们于 2014 年 2 月至 2019 年 5 月在 PubMed 上进行了检索,纳入了报告脆弱性指数和相关因素的综述。两名调查员独立筛选文章的入选标准,并从每篇综述中提取所有相关数据。使用随机效应荟萃分析对脆弱性指数进行汇总。
结果:24 篇综述符合纳入标准。它们包含中位数为 41 项试验(第一四分位数[Q1]-第三四分位数[Q3]:17-120)。不同研究领域的总体平均 FI 为 4(95%置信区间[CI] 3-5),表明脆弱性较高。更高的期刊影响因子、更大的样本量、更大的效应量、更多的结局事件、更低的 P 值和充分的分配隐藏被报道与更高的 FI 相关。22 项研究中中位数 FI 与中位数样本量之间的生态相关性为 0.95(95%CI 0.58-0.99)。
结论:各个研究领域的试验都经常存在脆弱性。我们还确定了一些与脆弱性相关的因素。研究人员应考虑采用策略来增强研究的稳健性并尽量减少脆弱性。
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