31 Comments
May 16, 2022Liked by Alexandros Marinos

Did this abomination really just win an annual best study award?

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May 16, 2022Liked by Alexandros Marinos

Thank you! very helpful and very shareable with others!

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Jun 4, 2022Liked by Alexandros Marinos

Alex it looks like this study was indeed poorly conducted - however can you please address the criticism of the Itajai study where it was revealed 94% of participants didn't continue to take the treatment after the third dose. I have yet to see a explanation of this and if it's true it may render the entire Itajai study as worthless as the TOGETHER trial.

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May 17, 2022Liked by Alexandros Marinos

A couple more questions off the top of my head:

(1) Was the exclusion criterion for vaccination changed mid-trial, as it appears to have been? If so, can the authors speak to why this change was made, the numbers of vaccinated people throughout the trial (it appears this information was collected?), and the effects this might have had on the results?

(2) What were the results for the 1-dose IVM arm? This would be a great mini data set to include in the supporting information, because presumably this data is otherwise going to remain unpublished.

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May 17, 2022Liked by Alexandros Marinos

TOGETHER obviously did not get their act - or fraud - together.

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Questions are good, avoid inferences about their motivations and absolutely avoid accusations.

Consider adding: “How many patients received less than 400mcg/kg of Ivermectin?

If these patients are excluded from the analysis does it change the results of the study? If so, how?”

Are you planning to send those questions to the authors or the NEJM?

The authors almost certainly won’t respond to you, even if you get it co-signed by some heavy hitters such as the editor(s) of the BMJ.

The authors will respond to the NEJM however, although if the NEJM take ownership of the questions then they’re not obliged to pass on the results. They can simply say “We’ve received a reply from the authors and are happy with the responses”.

So you’re efforts may be entirely futile, be prepared for that.

However, you are doing great work and may be on the verge of something extraordinary.

But even if you achieve nothing you have been honest, and that is the ultimate victory

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My understanding is that administration of ivermectin was on and empty stomach, which is would cause lesser bioavailability for a fat soluble active ingredient. If one were treating stomach or intestinal parasites, this would be the correct method of administration, however for antiviral, this approach will further compound the underdosing. I have not had a chance to reconfirm this as I’m travelling.

Great work. Keep it up.

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Why no question about confounding due to allowing vaccinated participants?

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Many of these points are addressed in the article. For example point 4 with the placebos the paper clearly states the different groups "corresponded with that of a comparable active-treatment group in the trial". So there is not "no theoretical justification" as you say, but a very pragmatic and clearly stated justification. I believe you did not fully understand the paper.

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If we change the endpoint to focus just on mortality, Treatment arm was 21 deaths (3.1% of N=679) and Placebo arm was 24 deaths (3.5% of N=679). The national death rate in Brazil between March-August 2021 was between 2.69-2.88% (source: worldometer, case-positive death rate)

If we follow the theory that both the treatment and control groups had use of ivermectin, then it explains why the results between the two groups were similar, but it doesn't explain why the death rate of these groups was worse than the Brazil national average during that period.

Surely we would expect that if the treatment works, you would still get some kind of favourable outcome compared to the national average, right?

The caveats that I think might change this statistic would be

- removing the BMI>30 deaths from both groups to get a more fair comparison. I don't have the data to do this.

- consider that inclusion to the trial was dependant on the patient having at least one high-risk criterion. Which would make the expected fatality rate higher than the national avg.

Let me know if you have any thoughts on the above. Thank you.

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Great investigative work overall. And good summary. I think you can probably scratch off the question of “why did the authors adopt this novel endpoint?“ Unless I’m misunderstanding the nature of your question, they do touch on the reason for the composite endpoint in the paper

and further elaborate on the change to a 6 hour threshold in the Supplemental Appendix, specifically the Section titled “Description of Prolonged ER Visits and Modification of Primary Endpoint” on page 8. I think your other critiques about that topic in your linked article are still valid though.

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