TOGETHER Leaks, Part 1: Were More Patients Deleted?

This article is part of a series on the TOGETHER trial. More articles from this series here.

Today, I’m starting to dig into the stack of emails released by Pierre Kory in his latest Substack. I was planning to do a single article with the emails and minimal commentary—and I still might—but as I looked at the first email in the post, I realized it implied something that I had not considered so far.

Did the TOGETHER trial principal investigator admit to dosing patients with high-dose ivermectin before official ethics approval was secured, and did those patients get removed from the published paper?

Ed Mills, TOGETHER trial’s principal investigator, Mar 6, 2021 on IVM dosing:

(email addresses redacted & emphasis mine)

From: Edward Mills
Sent: Saturday, March 6, 2021 4:48 PM
To: Steve Kirsch
Cc: filipe rafaeli Pierre Kory Patrick Collison
Subject: Re: IVM under dosing in Brazil trial

We are doing three days of dosing. The original protocol had one day of dosing, which was used back in January, when we submitted this for approvals at the ethics and national bodies. It then changed to three days of dosing after an amendment based on emerging trials from Andrew Hill’s synthesis. I have already explained that on several occasions.  Thats what is being administered. Clinicaltrials.gov  needs to be updated. Clinicaltrials.gov is not a protocol, it’s a registry. Gates funded the first part of this trial, when we evaluated HCQ and lopinavir vs placebo.

Thats why they are on the website. Again, this has been clearly explained in the past.

We will do an interim analysis after 800 patients. We aren’t making any changes until then.

Ed

In this email, Mills unambiguously says that at that time (March 6, 2021) TOGETHER was administering ivermectin with three days of dosing, which is the high-dose regimen.

And yet, the published study in the New England Journal of Medicine, has this to say about the dates:

The evaluation that is reported here involved patients who had been randomly assigned to receive either ivermectin or placebo between March 23, 2021, and August 6, 2021. The initial trial protocol specified single-day administration of ivermectin, and we recruited 77 patients to this dose group. On the basis of feedback from advocacy groups, we modified the protocol to specify 3 days of administration of ivermectin. Here, we present data only on the patients who had been assigned to receive ivermectin for 3 days or placebo during the same time period.

The supplementary appendix expands on this with the following:

This posology (400 mcg/kg) of the ivermectin evaluation versus placebo received Brazilian national ethics committee-CONEP approval on March 21, 2021, and the first patient enrolled on this posology was March 23, 2021. This evaluation of the trial was registered on clinicaltrials.gov on March 21, 2021. No patients included in this analysis were recruited prior to this date.

Obviously, what was said in the email cannot be true if the published paper is true, and vice versa.

You might remember that I had already concluded that the three-dose placebo (the specific placebo subgroup that was administered to match the high-dose ivermectin arm) had to have started around March 4, 2021:

TOGETHER Trial: Solving the 3-Day Placebo Subgroup Riddle

Mills' newly released email (which I saw on Pierre Kory's Substack) was written right after that change. In it, he claims that three-day dosing was already being given to patients on March 6th, noting the fact that this was despite clinicaltrials.gov not being updated. His email acts as confirmation of my conclusion that placebo had started recruitment earlier, but implies something even darker: That patients had been recruited into the treatment arm as well, who were actually getting their dose administered already on March 6th. We have no record of such patients.

This sounds like a serious allegation, so what motive would the authors have to obscure patients recruited before March 23rd? The appendix quote we saw above states that the local ethics approval came on March 21, 2021. The actual document from the regulator is dated March 15, 2021. Whichever one of those we believe, March 6th is earlier. Any patients reported on at that time would have been given the increased dose without approval of the local regulator. It’s a pretty compelling reason to make those patients go away.

In fact, this isn't the first time we've seen exactly this pattern. The fluvoxamine study also seems to have deleted a patient recruited before the ethics approval arrived.

Alexandros Marinos @alexandrosM

Wait - was there an extra patient recruited between Jan 15 and Jan 20th? We don't have to wonder. If we go back to the August 6 slides, it's right there. 3 patients recruited to fluvoxamine treatment on the week starting January 18th. One must have been before the 20th.

May 17th 2022

6 Retweets33 Likes

To add insult to injury, in his email, Mills says that the dose was changed based on Andrew Hills' meta-analysis. This makes sense and the dates fit. Yet the paper says nothing about Hill’s meta-analysis and instead talks about "advocacy groups.” Those groups have never been clearly specified. Which is it?

This is yet another reason for a full investigation into what happened with the TOGETHER trial. My analysis has been out for over a month, and the silence is deafening; the "fraud busting data detectives" that have been parading every bad ivermectin study like a trophy have had no curiosity about any of this, or the lack of raw data from the investigators, despite their prior pronouncements:

Health Nerd @GidMK

When people running clinical trials refuse to share anonymized raw data, it is a giant red flag without a very good excuse

August 3rd 2021

9 Retweets101 Likes

I sure hope someone, somewhere, starts asking questions the investigators can’t ignore, and soon.

This article is part of a series on the TOGETHER trial. More articles from this series here.