The problem of community use of ivermectin in Brazil at the time the TOGETHER trial was trialing high-dose ivermectin has been discussed to no end. And yet, I don’t think I’ve ever brought all the collected evidence together. This article aims to be a straightforward aggregation of all the clues we have, hopefully pointing the way to an answer.
I personally know four people (two couples) in Estado do Rio de Janeiro who were prescribed ivermectin for post-exposure prophylaxis (exposure to different individuals) and for routine prophylaxis. BTW none became infected even though one couple had close contact with someone who was hospitalized shortly after meeting with them. I don't believe Mills' claim that ivermectin was not widely used in Minas Gerais when his data were being collected. If that claim is so crucial to the Together trial, why haven't the investigators done a poll in Minas asking people whether they took ivermectin during the period of the trial?
have you ever talked with David Wiseman about the Lopez trial? If not, you may want to reach out to David who spent time wading through the differences in the AEs between the three different weeks as the protocol changed and changed again during the trial. I took notes back when he told me about it, and planned to write an article, but was too focused on the N other HCQ analyses/articles I was working on. I've since let the finer details drain from my head, but David knows them intimately.
Did you know that if you DON"T Take ivermectin, you are much better off than if you DON't TAKE hydroxycloroquinine.
That's what the TOGETHER TRIAL results say.
If that doesn't make any sense to you, you are starting to see that the Together Trial doesn't make sense.
In particular, experiment control group placebo treatments have to be at the same timeframe as the drug patients. In multi-arm trials they sometimes "chose" who was in the control group afterwards. Balancing things they want to be even, such as sex, wieight... But they didn't balance the time frame.
And the virus changed. on them.
So the control group had a different virus than the drug group.
Sloppy work. They should retract the paper and go in to TimeOut.
Unequal randomization, significant confounding by time. The trial reports 1:1:1:1 randomization, however independent analysis shows much higher enrollment in the ivermectin treatment arm towards the start of the trial [c19ivermectin.com (D), longhaulwiki.com]. This introduces very significant confounding by time due to the major change in the distribution of variants. [Zavascki] show dramatically higher mortality for Gamma vs non-Gamma variants (28 day mortality from symptom onset aHR 4.73 [1.15-19.41]). Many more patients were randomized to ivermectin vs. placebo in the first few weeks, for example the first week shows 82 ivermectin vs. 28 placebo patients, 2.9x higher. The period of excess ivermectin enrollment coincides closely with a period of significantly higher deaths and CFR in Brazil.
So if Ivermectin use has been high in South America shouldn't those countries have better case fatality rates? Brazill is the 2nd highest country listed in observed case fatality ratio per Johns Hopkins? https://coronavirus.jhu.edu/data/mortality Back in the day just eye balling Africa's numbers figured it served as evidence to support the notion HCQ and Ivermectin at least helped. That should hold wherever early treatment is in play.
If you deliberately set out to undermine the use of Ivermectin as a treatment for Covid, then all of the above makes sense does it not?
I personally know four people (two couples) in Estado do Rio de Janeiro who were prescribed ivermectin for post-exposure prophylaxis (exposure to different individuals) and for routine prophylaxis. BTW none became infected even though one couple had close contact with someone who was hospitalized shortly after meeting with them. I don't believe Mills' claim that ivermectin was not widely used in Minas Gerais when his data were being collected. If that claim is so crucial to the Together trial, why haven't the investigators done a poll in Minas asking people whether they took ivermectin during the period of the trial?
Could the "or were likely to have taken it" be a reference to multiple imputation?
This would then be a crazy post hoc exclusion based on some likelihood the case might have taken ivm?
have you ever talked with David Wiseman about the Lopez trial? If not, you may want to reach out to David who spent time wading through the differences in the AEs between the three different weeks as the protocol changed and changed again during the trial. I took notes back when he told me about it, and planned to write an article, but was too focused on the N other HCQ analyses/articles I was working on. I've since let the finer details drain from my head, but David knows them intimately.
Did you know that if you DON"T Take ivermectin, you are much better off than if you DON't TAKE hydroxycloroquinine.
That's what the TOGETHER TRIAL results say.
If that doesn't make any sense to you, you are starting to see that the Together Trial doesn't make sense.
In particular, experiment control group placebo treatments have to be at the same timeframe as the drug patients. In multi-arm trials they sometimes "chose" who was in the control group afterwards. Balancing things they want to be even, such as sex, wieight... But they didn't balance the time frame.
And the virus changed. on them.
So the control group had a different virus than the drug group.
Sloppy work. They should retract the paper and go in to TimeOut.
from: ivnmeta.com
Unequal randomization, significant confounding by time. The trial reports 1:1:1:1 randomization, however independent analysis shows much higher enrollment in the ivermectin treatment arm towards the start of the trial [c19ivermectin.com (D), longhaulwiki.com]. This introduces very significant confounding by time due to the major change in the distribution of variants. [Zavascki] show dramatically higher mortality for Gamma vs non-Gamma variants (28 day mortality from symptom onset aHR 4.73 [1.15-19.41]). Many more patients were randomized to ivermectin vs. placebo in the first few weeks, for example the first week shows 82 ivermectin vs. 28 placebo patients, 2.9x higher. The period of excess ivermectin enrollment coincides closely with a period of significantly higher deaths and CFR in Brazil.
Good article from Robert Clancy
https://quadrant.org.au/opinion/public-health/2022/08/the-suppression-of-useful-covid-19-treatments/
So if Ivermectin use has been high in South America shouldn't those countries have better case fatality rates? Brazill is the 2nd highest country listed in observed case fatality ratio per Johns Hopkins? https://coronavirus.jhu.edu/data/mortality Back in the day just eye balling Africa's numbers figured it served as evidence to support the notion HCQ and Ivermectin at least helped. That should hold wherever early treatment is in play.