Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, No.11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
BMC Complement Med Ther. 2024 Aug 14;24(1):300. doi: 10.1186/s12906-024-04561-8.
The fragility index (FI), which is the minimum number of changes in status from "event" to "non-event" resulting in a loss of statistical significance, serves as a significant supplementary indicator for clinical physicians in interpreting clinical trial results and aids in understanding the outcomes of randomized controlled trials (RCTs). In this systematic literature survey, we evaluated the FI for RCTs evaluating Chinese herbal medicine (CHM) for irritable bowel syndrome (IBS), and explored potential associations between study characteristics and the robustness of RCTs.
A comprehensive search was conducted in four databases in Chinese and four databases in English from their inception to January 1, 2023. RCTs encompassed 1:1 ratio into two parallel arms and reported at least one binary outcome that demonstrated statistical significance were included. FI was calculated by the iterative reduction of a target outcome event in the treatment group and concomitant subtraction of a non-target event from that group, until positive significance (defined as P < 0.05 by Fisher's exact test) is lost. The lower the FI (minimum 1) of a trial outcome, the more fragile the positive result of the outcome was. Linear regression models were adopted to explore influence factors of the value of FI.
A total of 30 trials from 2 4118 potentially relevant citations were finally included. The median FI of total trials included was 1.5 (interquartile range [IQR], 1-5), and half of the trials (n = 15) had a FI equal to 1. In 12 trials (40%), the total number of participants lost to follow-up surpassed the respective FI. The study also identified that increased FI was significantly associated with no TCM syndrome differentiation for inclusion criteria of the patients, larger total sample size, low risk of bias, and larger numbers of events.
The majority of CHM IBS RCTs with positive results were found to be fragile. Ensuring adequate sample size, scientifically rigorous study design, proper control of confounding factors, and a quality control calibration for consistency of TCM diagnostic results among clinicians should be addressed to increase the robustness of the RCTs. We recommend reporting the FI as one of the components of sensitivity analysis in future RCTs to facilitate the assessment of the fragility of trials.
脆弱指数（FI）是指从“事件”到“非事件”的状态最小变化数，导致统计意义丧失，它是临床医生解释临床试验结果的重要补充指标，有助于理解随机对照试验（RCT）的结果。在这项系统文献调查中，我们评估了评估中药治疗肠易激综合征（IBS）的 RCT 的 FI，并探讨了研究特征与 RCT 稳健性之间的潜在关联。
我们在中文的四个数据库和英文的四个数据库中进行了全面检索，检索时间从数据库建立到 2023 年 1 月 1 日。纳入 1:1 比例的两平行臂 RCT，且至少报告了一个具有统计学意义的二分类结局。FI 通过迭代减少治疗组的目标结局事件，并从该组中同时减去非目标事件来计算，直到阳性意义（Fisher 精确检验定义为 P < 0.05）丧失。试验结局的 FI 越低（最低 1），结局阳性结果越脆弱。采用线性回归模型探讨 FI 值的影响因素。
共纳入 24118 篇潜在相关文献中的 30 项试验。纳入试验的 FI 中位数为 1.5（四分位距 [IQR]，1-5），其中半数（n=15）的 FI 等于 1。在 12 项试验（40%）中，失访的总人数超过了各自的 FI。研究还发现，FI 增加与患者纳入标准无中医证候分类、总样本量较大、偏倚风险低以及事件数较多显著相关。
大多数具有阳性结果的中药 IBS RCT 被发现是脆弱的。为了提高 RCT 的稳健性，应确保足够的样本量、科学严谨的研究设计、适当控制混杂因素以及对中医诊断结果进行质量控制校准，以确保一致性。我们建议在未来的 RCT 中报告 FI 作为敏感性分析的一部分，以方便评估试验的脆弱性。
