2/n The study is here, and has an objectively large impact with nearly a dozen news stories and an Altmetric of 2750https://www.medrxiv.org/content/10.1101/2021.05.31.21258081v1 …
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3/n The study is pretty simple - 116 people with Covid-19, randomized to either receive ivermectin or a placebo Reported results were viral load, and more specifically proportion of people with Ct>30 at various time points on PCRpic.twitter.com/ozXyxZwAOj
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4/n The authors report a marginally significant benefit at various days using an uncorrected logistic regression, and from this the massive attention sprangpic.twitter.com/5xk5vLDkrH
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5/n One of the first things I do when I read randomized trials like this is look at their pre-registration. This is basically what the authors SAID they would do registered BEFORE they did it Here's the pre-reg for this trial:https://clinicaltrials.gov/ct2/show/NCT04429711?term=NCT04429711&draw=2&rank=1 …
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6/n Immediately on looking at the pre-registration, there is a HUGE discrepancy with the published results Here's what the authors pre-registered as their exclusion and the flow chart from the study. Notice the difference?pic.twitter.com/eMFPtwG9Y6
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7/n It appears that the authors have added an extra exclusion criteria that is applied AFTER randomization and treatment. This is "tested Ct>35" in the first two testspic.twitter.com/V5ZfCZWhv7
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8/n Based on the protocol, that implies the sequence of events went like this: 1. patient tests positive, randomized and started treatment 2. Day 2, patient tests Ct>35 3. Day 4, patient tests Ct>35
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9/n This is an issue for two reasons - firstly, it's not what the authors said they'd do. Secondly, it means that they are excluding people WHO MEET THEIR PRIMARY OUTCOME (i.e. Ct>30) after randomization and treatment has started
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10/n This makes absolutely no sense to me. These people were randomized and treated, and they met the inclusion criteria pre-registered by the authors. Why were they excluded?
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11/n If you add these people back in, the results of the study entirely lose their significance At day 10, this would be 87% of the ivm and 77% of the control reaching the primary endpoint, p=0.16pic.twitter.com/UjgaGpjYFw
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12/n In addition, the authors pre-registered 3 primary outcomes. I can only see one (viral clearance) properly assessed in the paper (shedding is somewhat assessed, but it looks like they didn't get enough samples to statistically analyse this)pic.twitter.com/wv4hnBhNNE
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13/n Anyway, the main issue is that, if you use the pre-registered protocol, the study appears to have null results And yet, reported as positive to massive worldwide acclaim
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14/n This has nothing to do with fraud, takes literally minutes to check, and I encourage everyone to do so. Please let me know if I've made an error somewhere
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15/n Also, to be clear - I'm not accusing the authors of any research misconduct, this is just very basic due diligence that everyone should do for any trial that they read
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16/n Also worth noting that it is entirely possible the study still has some positive results when you add these patients back in - the point is their primary outcome, which is the main thing reported, seems to change substantially when these people are included!
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