生物与医学2021nature.com
伊维菌素的教训：仅基于汇总数据的 meta 分析不可靠
Lesson of ivermectin: meta-analyses based on summary data alone are unreliable
入门 · 约 30 分钟读完前置知识：荟萃分析基础、循证医学基本概念
导读
这篇 Nature Medicine 文章以伊维菌素治疗新冠的争议为例，指出仅基于汇总数据（summary data）的荟萃分析不可靠：纳入的原始研究本身质量低下甚至存在造假（如被撤稿的 Elgazzar 预印本），导致荟萃分析得出站不住脚的结论。文章强调荟萃分析必须评估原始研究的科学严谨性，而不能只做形式上的汇总。
HN 关注点：伊维菌素是疫情期间最具争议的药物之一，HN 读者借此讨论荟萃分析方法的系统性缺陷、预印本滥用和同行评审失效的问题。
后来怎么样
伊维菌素荟萃分析争议成为循证方法学中被广泛引用的案例，推动了荟萃分析中对原始研究质量评估和预印本可信度问题的讨论
HN 评论精选
这几条评论里：支持 1 质疑 1 补充 2
支持大多数荟萃分析因不评估原始研究质量而不可靠
我要说一个可能有争议的观点：以我的经验，大多数荟萃分析都是垃圾。荟萃分析的前提是纳入的多项研究本身科学严谨，但实际情况几乎从来不是这样。临床文献中虽然形成了控制偏倚、控制变异等标准，却很少真正评估纳入研究的科学质量，因为这难以标准化。结果就是大量荟萃分析得出根本站不住脚的结论——伊维菌素的情况正是如此，也正是这篇 Nature 文章的要点。
gwerbret查看英文原文
I'm going to make what is probably a controversial statement, which is that, in my experience, most meta-analyses are trash. A meta-analysis is usually grounded on the assumption that an aggregation of multiple, well-conducted studies can provide significant information that may not be evident by taking each study individually. Essential to this assumption is the premise that those studies included in the meta-analysis be scientifically rigorous in themselves. Unfortunately, this is almost never the case. The great utility of the meta-analysis in the clinical literature is such that there have emerged a series of standards for how to conduct such analyses, such as controlling for bias, controlling for variability, etc. These seldom include actual assessment of the scientific quality of the studies, as this is harder to standardize. Consequently, there is a preponderance of meta-analyzes that come to conclusions that are simply not justified, because the studies themselves were not scientifically rigorous. I believe this applies to the situation of ivermectin, and it just so happens that this is the thrust of the point raised in the Nature article cited here.
补充预印本传播助长了造假论文的扩散
另一个教训是预印本发布渠道极易被滥用。推动这整场风波的主要论文及其荟萃分析看起来是彻头彻尾的造假，但它作为预印本被大量传播给分不清预印本和同行评审论文的人。如果预印本传播更受限，这一切或许可以避免。
ashtonkem查看英文原文
The other takeaway is that preprint publication is a pathway ripe for abuse. The major paper that drove most of this situation, and the meta analysis, appears to have been a straight up fraud. But it got circulated a lot as a preprint to people who didn’t understand the difference between a preprint and a peer reviewed paper. If the preprint had been more private, this might have been averted.
质疑剔除撤稿论文后仍有荟萃分析显示有效，需等大型对照试验定论
这个领域的研究质量确实很差，抢发和无效的同行评审比比皆是。Marik 和 Kory 医生在剔除被撤稿的 Elgazzar 论文后更新了他们的荟萃分析，仍然发现显著效果。我不是背书他们的结论，只是指出 Nature 文章没提这件事。最终需要真正的大规模对照试验来定论，我期待 NIH ACTIV-6 的结果。
nradov查看英文原文
Yes the quality of scientific research in this area has been rather bad with rushes to publish and ineffective peer review. Drs. Paul Marik and Pierre Kory recently updated their meta analysis to remove the retracted Elgazzar paper, and still found a significant effect. I'm not endorsing their letter, just pointing out that it exists and isn't mentioned in this Nature article. https://journals.lww.com/americantherapeutics/fulltext/2021/10000/ivermectin,_a_reanalysis_of_the_data.9.aspx Ultimately we need a real large scale controlled trial to settle the issue so I'm looking forward to seeing results from NIH ACTIV-6. https://www.nih.gov/research-training/medical-research-initiatives/activ/covid-19-therapeutics-prioritized-testing-clinical-trials#activ6
补充中毒控制中心来电数据存在官方说法与媒体报道的矛盾
关于伊维菌素是否真的导致中毒控制中心来电显著增加，存在很多混淆。密西西比州官方文件说'至少 70% 的近期来电与摄入牲畜用伊维菌素制剂有关'，但美联社随后更正称：州流行病学家表示关于伊维菌素的来电只占约 2%，其中 70% 是摄入了兽用版本。有人有进一步的澄清吗？
cyounkins查看英文原文
There is a lot of confusion on whether there actually was a significant increase in calls to poison control centers due to ingestion of ivermectin. This [1] official Mississippi government document says, "At least 70% of the recent calls have been related to ingestion of livestock or animal formulations of ivermectin purchased at livestock supply centers." But then the AP [2] seemed to say that was incorrect: "The Associated Press erroneously reported based on information provided by the Mississippi Department of Health that 70% of recent calls to the Mississippi Poison Control Center were from people who had ingested ivermectin to try to treat COVID-19. State Epidemiologist Dr. Paul Byers said Wednesday the number of calls to poison control about ivermectin was about 2%. He said of the calls that were about ivermectin, 70% were by people who had ingested the veterinary version of the medicine." Does anyone have additional clarification? [1] https://msdh.ms.gov/msdhsite/_static/resources/15400.pdf [2] https://www.sfgate.com/news/amp/Health-Dept-Stop-taking-livestock-medicine-to-16405982.php
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