Center for Clinical Epidemiology and Methodology (CCEM), Guangdong Second Provincial General Hospital, Guangzhou, China.
Department of Endocrinology, Guangdong Second Provincial General Hospital, Guangzhou, China.
Osteoporos Int. 2021 Sep;32(9):1713-1723. doi: 10.1007/s00198-021-05865-y. Epub 2021 Feb 17.
This is the first report on the fragility of results from randomized controlled trials (RCTs) for the treatment of osteoporosis. The results of aforementioned RCTs appear to depend on a small number of events and are generally statistically fragile.
Osteoporosis remains a health concern worldwide. Evidence-based guideline recommendations that are mainly based on results of clinical trials are important to clinical decision-making. The fragility index (FI) is a novel statistical metric to measure the fragility of results from an RCT. Our study aimed to analyze the fragility of the clinical trials referenced in the guidelines for the treatment of osteoporosis.
Trials were included if they investigated primary osteoporosis, randomized patients to treatment or control in a 1:1 design, and reported fracture outcome as the primary endpoint. The FI and fragility quotient (FQ) were calculated for assessing the robustness of results from the eligible RCTs. An FI was defined as the minimum number of events in the intervention group that needs to change from a non-event to an event in order to render a significant result non-significant (or vice versa). The FQ was calculated by dividing the FI by the sample size of the trial.
Of the 372 RCTs identified from the guidelines, 42 were eligible for analyses. Their median FI was 10 (25th-75th percentile [Q1-Q3]: 4-18), with a median FQ of 0.007 (Q1-Q3: 0.0017-0.019). Approximately one third of the RCTs had a FI of less than or equal to 5. There were 17 (40.5%) trials where the number of patients lost to follow-up was greater than the FI. The FI was significantly associated with sample size, journal impact factor, and the percent of patients lost to follow-up.
Results from some RCTs supporting guideline recommendations for the treatment of osteoporosis depend on a small number of events. The FI and FQ may provide additional, intuitive metrics to help interpret the robustness of trial results.
这是第一篇关于骨质疏松症治疗的随机对照试验（RCT）结果脆弱性的报告。上述 RCT 的结果似乎取决于少数事件，并且通常在统计学上很脆弱。
骨质疏松症仍然是全球关注的健康问题。主要基于临床试验结果的循证指南建议对于临床决策非常重要。脆弱性指数（FI）是一种新的统计指标，用于衡量 RCT 结果的脆弱性。我们的研究旨在分析指南中治疗骨质疏松症的临床试验的脆弱性。
如果试验调查原发性骨质疏松症，将患者以 1:1 的比例随机分配到治疗组或对照组，并将骨折结局报告为主要终点，则纳入试验。计算 FI 和脆弱性商数（FQ）以评估合格 RCT 结果的稳健性。FI 定义为需要从非事件变为事件的干预组中最小事件数，以使显著结果变为不显著（反之亦然）。FQ 通过将 FI 除以试验的样本量来计算。
从指南中确定的 372 项 RCT 中，有 42 项符合分析条件。它们的中位数 FI 为 10（25 百分位数-75 百分位数[Q1-Q3]：4-18），中位数 FQ 为 0.007（Q1-Q3：0.0017-0.019）。大约三分之一的 RCT 的 FI 小于或等于 5。有 17 项（40.5%）试验中，失访患者的数量大于 FI。FI 与样本量、期刊影响因子和失访患者的百分比显著相关。
支持骨质疏松症治疗指南建议的一些 RCT 结果取决于少数事件。FI 和 FQ 可以提供额外的直观指标，以帮助解释试验结果的稳健性。
