Operative Unit of Anesthesia and Intensive Care, S. Martino Hospital, Belluno, Italy.
Department of Medicine and Surgery, Università degli Studi Milano Bicocca, Milan, Italy.
Pulmonology. 2024 Nov-Dec;30(6):529-536. doi: 10.1016/j.pulmoe.2022.12.005. Epub 2023 Jan 25.
Researchers have tried unsuccessfully for many years using randomized controlled trials to show the efficacy of prone ventilation in treating ARDS. These failed attempts were of use in designing the successful PROSEVA trial, published in 2013. However, the evidence provided by meta-analyses in support of prone ventilation for ARDS was too low to be conclusive. The present study shows that meta-analysis is indeed not the best approach for the assessment of evidence as to the efficacy of prone ventilation.
We performed a cumulative meta-analysis to prove that only the PROSEVA trial, due to its strong protective effect, has substantially impacted on the outcome. We also replicated nine published meta-analyses including the PROSEVA trial. We performed leave-one-out analyses, removing one trial at a time from each meta-analysis, measuring p values for effect size, and also the Cochran's Q test for heterogeneity assessment. We represented these analyses in a scatter plot to identify outlier studies influencing heterogeneity or overall effect size. We used interaction tests to formally identify and evaluate differences with the PROSEVA trial.
The positive effect of the PROSEVA trial accounted for most of the heterogeneity and for the reduction of overall effect size in the meta-analyses. The interaction tests we conducted on the nine meta-analyses formally confirmed the difference in the effectiveness of prone ventilation between the PROSEVA trial the other studies.
The clinical lack of homogeneity between the PROSEVA trial design and the other studies should have discouraged the use of meta-analysis. Statistical considerations support this hypothesis, suggesting that the PROSEVA trial is an independent source of evidence.
多年来，研究人员一直试图通过随机对照试验来证明俯卧位通气治疗 ARDS 的疗效，但均未成功。这些失败的尝试为 2013 年发表的成功的 PROSEVA 试验的设计提供了有用的参考。然而，荟萃分析提供的支持俯卧位通气治疗 ARDS 的证据太低，无法得出结论。本研究表明，荟萃分析确实不是评估俯卧位通气疗效证据的最佳方法。
我们进行了累积荟萃分析，以证明只有 PROSEVA 试验因其强大的保护作用，对结果产生了实质性影响。我们还复制了包括 PROSEVA 试验在内的 9 项已发表的荟萃分析。我们进行了逐一剔除分析，从每次荟萃分析中剔除一个试验，测量效应大小的 p 值，以及 Cochran's Q 检验用于异质性评估。我们将这些分析表示在散点图中，以识别影响异质性或整体效应大小的异常值研究。我们使用交互检验正式识别和评估与 PROSEVA 试验的差异。
PROSEVA 试验的积极影响解释了荟萃分析中大部分的异质性和整体效应大小的降低。我们对 9 项荟萃分析进行的交互检验正式证实了 PROSEVA 试验与其他研究之间俯卧位通气有效性的差异。
PROSEVA 试验设计与其他研究之间临床缺乏同质性，这应该阻止使用荟萃分析。统计学考虑支持这一假设，表明 PROSEVA 试验是一个独立的证据来源。
