3/n I should say that my position on ivermectin previously has been that there is some interesting evidence but that most of the studies are low quality so it's hard to say much (even the one or two high-quality studies aren't very conclusive)
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14/n I could go on. Suffice to say that my assessment of this study would place it at moderate to high risk of bias, especially considering that it's really quite short and there's a fair bit of important information missing
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15/n Worth noting that I don't disagree with the assessment for every study - I had a detailed read of Mahmud (2020) and it looks like a very well-done piece of research at a low risk of biaspic.twitter.com/Esr9s7DnC9
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16/n Another weird one is Niaee - on the risk of bias table, it looks pretty decent, but there are some really odd holes in the studypic.twitter.com/g0woK9ZPmF
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17/n For example, this was a randomized study of ivermectin for COVID-19, but they included people who were clinically positive and PCR-negative And somehow, the proportion of PCR negatives in the control group was far higher than in the intervention (47% vs 20%)

pic.twitter.com/MtZGuumDpP
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18/n If the study had a MUCH bigger proportion of people who had PCR +ve COVID-19 receiving the intervention, that's not a great sign wrt the allocation concealment procedures (which aren't that well described either)
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19/n This sort of finicky examination is where it gets really, really tough, because like I said, it's a bit subjective. I don't really care either way about the studies included, but people can (and probably will) disagree
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20/n That being said, I quickly redid the meta-analysis excluding these two quite weird studies, and the results completely change, with no significance at all (RR 0.72, 0.41-1.25) Make of that what you willpic.twitter.com/8ucUe40gq3
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21/n Even if you ignore my opinions, limiting the analysis to only studies rated BY THE AUTHORS as "low" risk of bias gives you a completely inconclusive result (RR 0.65, 0.12-3.59)
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22/n So I don't really have an issue with the methodology or the results of the study, except to say that I think the risk of bias here is generally quite high and publication bias is likely The conclusions however...
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23/n I don't think this is justified at all to be honest. Even if we ignore the issues that I mentioned in this thread, most of these studies are really short (probably because they're all preprints) containing only a fraction of the information you need to properly assess thempic.twitter.com/8tX77GMESA
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24/n There's a good reason the risk of bias for so many regions here is 'unclear' - the studies simply don't include enough information! Often the methods sections are 3-4 paragraphs long (v. short for an RCT)pic.twitter.com/8AP18DKtD2
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25/n Moreover, publication bias looks to be a bit of an issue, and it's not really addressed. Quite likely to be some null findings that are floating around but will be published eventually!
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26/n On top of this, if you only look at studies that the authors have rated as having a low risk of bias for all domains, the evidence is pretty much squarely null, although this is limited by the fact that there are only 3 good studies
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27/n I don't think that this study really supports the use of ivermectin as a treatment for COVID-19 outside of a clinical trial, which is a shame because it'd be fantastic to have another effective drug for the disease
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28/n The depressing thing is that 100s of millions of people, mostly in developing countries, have had ivermectin for COVID-19, and yet we've only got 3 low-risk studies with <700 participants total to use as good evidence


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29/n Oh, one other point is that the authors considered the Fonseca study an "outlier" because exclusion lowered the I^2, which I don't understand because excluding the Elgazzar study lowers the I^2 a lot as well
pic.twitter.com/49WMIzgXWe
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30/n Also, I should reiterate that while I disagree with the conclusions, the study itself is pretty strong. The methodology was well constructed, I have few if any criticisms of the actual research the authors conducted
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End of conversation
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