On April 3rd, 2022, the principal investigator of the TOGETHER trial, Edward Mills, was responding to some questions. Medical researchers weren’t happy with a growing list of issues in the trial’s published data. Those problems haven’t gone away, but that’s a story for another day. For now, I want to look closely at what Mills said when
Phil, thanks for covering this. A couple of weeks ago I watched the video (and read the news coverage) and noticed the same points you covered in your post. I was planning on trying to pass it on to somebody (perhaps Jimmy Dore, who just dropped a video discussing this TOGETHER trial a few days ago. A while back, he ripped into Andrew Hill for his hypocrisy. I'd love it if he ripped into Ed Mills as well!).
Here's the link to Ed Mills discussing the TOGETHER trial (Grand Rounds Rethinking Clinical Trials 03-18-2022), and my rough notes with time stamps (includes some other points not covered in your post). Mills was a bit disingenuous when discussing funding & why the study was stopped early:
??:?? Discussed theory used to set low IVM dosage. Acknowledges that more effective with meals, but gave fasting so matches label? [Why not use higher does & duration practitioner's were using for Gamma?]
28:36 Wondered what would have happened if had kept randomizing? Changed things? I don't know. Waiting for other trials.
29:31 If more randomized; hospitalization changed to significant? Entirely possible.
29:45 IVM not a safety concern
30:44 Cannot rule out small treatment effect. Answer not yet conclusive. Subgroup within trial possibly antiparasitic [see other March '22 JAMA paper] which responsible for effect.
From Q & A:
32:50 “No significant effect. Doesn't mean anything. Low confidence interval, Stopped too early? “ : I totally agree.
I don't call shots when to stop trial [really?] The DSMV decides [later hes says they make recommendation to the steering committee that Mills is on!] ]
Funding issue; 32 year old [billionaire!] was funding, limited resources [? With Billionaire?]. We were being abused by community, I lost interest because of attacks receiving.
35:50 Lessons. $4M, little money. $500B NIH trials ACTIV. Maybe IVM had 10% effect, no better than Fluvoxamine 30%. How much genuine interest in using repurposed drugs? Didn't get picked up by [IDSA,NIH,CDC/WHO] guidelines, why is that?
38:20 “Dosing? Want to take best shot using a high dose with a 1-arm treatment. Avoids the 'wasn't enough' question.”: Mills doesn't answer question.
45:40 DSMV parameters for stopping?: Rules in plan published. They followed the plan [really?] provided to them. Public pressure. If not for pressure, would have discontinued IVM. They can do what they like in making recommendations to the steering committee [of which Mills was a member; this committee makes the decision?].
56:54 Political. Zealots, opposite too, making fun. Nobody was right about that. How come back together?
Thank you, Phil. You are generous in ascribing the title of “Journalists” to those “engaged weeks prior to ‘launch’“. Complicit shills doing the bidding of their pimps. Can remember the Pentagon Papers and the Watergate Scandal. Apparently many professing independent journalism have found the bottom of the slippery slope and morphed into corporate media.
Thank you for this. I saw similar press regarding Hydroxychloroquine, but then read the studies, and found that either the study did not follow the protocol that treating physicians were using or that the trial was conducted in already hospitalized (and likely very sick patients) or it showed that actually, the drug was quite effective at reducing hospitalizations. Reading one such study and a critique of it, I learned that Dr. Boulware, at about the same time as the study began, had accepted a position as a Scientific Advisor for Revive Therapeutics, which was rumored to be working on 'one of those other therapies' that Dr. Boulware would like doctors to steer their patients to try. This conflict of interest was not disclosed in the trial info.
I also heard him in an interview speak about his being involved in an (at the time) upcoming study of Ivermectin, so I am not at all surprised at his stance. I did not realize that THIS is the study of which he spoke.
listening to the "collaborative" vimeo conference there's a discussion about halfway through: Ed Mills mentions that the study had become difficult because of deteriorating relations with the community... such that he "lost interest in it".
He had several opportunities to also mention otherwise: talked about the close interaction with the community, how they dealt with them with "respect", and how well they engaged them, and recruited them for the study.
So what happened?- M Robert Weiss, MD
So what happened? what kind of pressure and malcontent did they experience, such that he 'lost interest' in pursuing the trial?
P.S. Here's some notes taken from news coverage of the Together Trial. As in Phil's post, the "negative press campaign" is evident. However, some of the quotes also address other topics mentioned in my first comment on the NIH video:
Trial was funded by “young” billionaires (in video, Ed Mills claimed limited funding was a factor that led to stopping trial early).
Mills admits that trial actually showed a “small” (17%) benefit in reduction of hospitalization (but not “statistically significant”).
Craig Rayner (also in video) advised against using IVM in early trials because he claimed dose needed was 20x approved dose (and in video, from about 5:00 to 17:00, he explains his rationale for both using a low dose and giving it fasting even though he knew it was more effective with meals!).
Mills claims the 17% benefit was not from IVM treating Covid, but was “actually treating the underlying parasitic infections”.
. . .
New Covid trial results may point toward better ways to study medicines
Mills said the budget for TOGETHER was also $10 million. And it didn’t come from the National Institutes of Health, a big drug company, or a major charity. Instead, one of the major funders of the trial so far has been Patrick Collison, co-founder of payments firm Stripe, who Forbes estimates to have a $9.5 billion fortune. New funds are coming from the charitable foundation FTX, a cryptocurrency exchange, and its founder Sam Bankman-Fried, who is worth $24 billion, also per Forbes. [Note: in 3/18/22 video, Mill said 32-year old funding. Collison? Bankman-Fried? Billionaires with limited resources so couldn't fund the IVM trial a bit longer?].
Largest Study of Ivermectin Shows No Protection Against COVID-19 Hospitalizations Valerie DeBenedette
"Our clinical trial is the largest one yet of ivermectin for the early treatment of COVID. It did not show a statistically significant benefit," Edward Mills, PhD, study author and a professor at McMaster University in Hamilton, Ontario, told Verywell. "I think it will influence those who were uncertain about whether or not further research might provide more precise answers. I do not think it will influence people whose minds have already been made up about whether or not it works."
This study did not completely rule out a potential for a small [17%?] benefit from treatment with ivermectin, Mills said. "But given that there are other interventions out there that have some statistical significance [Fluvoxamine?], then a topic like ivermectin, where the finding is still uncertain after many, many trials, leads one to believe that it's just not a drug worth pursuing any further,” he said.
Jury’s in for ivermectin: “No clinical [?] significance.”
The trial found that ivermectin given in the first seven days after symptoms had no significant effect.
Ivermectin was not included in the initial line-up of repurposed drugs. TOGETHER team member Craig Rayner, a clinical pharmacologist affiliated with the US-based company Certara that provides scientific advice to drug developers, modelled the effective drug doses for the trial. Since the ivermectin dose required to kill the virus was more than 20 times the maximum approved dose, he advised against it. [Note: Rayner is also in the NIH video (5:00 -- 17:00) and rationalizes why he used such a low dose in the trial and gave it on an empty stomach, despite knowing it would reduced the effect!].
By the beginning of August 2021, the researchers had their results. Ivermectin did not reduce the risk of hospitalization [17%?]. By contrast the cheap antidepressant drug fluvoxamine did, reducing the risk of hospitalization by 30%.
And here [Brazil] they ran up against the problem of finding people who weren’t already self-medicating with ivermectin. [that might be a confounder!] That was partly circumvented by running the trial in Minas Gerais, a state in southeast Brazil where the use was not as widespread, says Rayner [really?!].
However, once the TOGETHER group overcame all these obstacles, why did they not publish a preprint like RECOVERY? Mills says they decided to go the route of publishing in a major journal and that they did ‘air’ the data in talks. [8 months before publication]
[LAST PARAGRAPH!] Because TOGETHER did actually find a small [17%!], but not statistically significant effect, of ivermectin on hospitalisation. Could it be a true but tiny signal in the noise? [Doesn't exactly match the headline "No Clinical Significance"!]
Mills suspects that in some Brazilian patients, ivermectin was actually treating the underlying parasitic infections – and that improved the person’s ability to fight COVID. That’s a theory suggested by this recent analysis.* If that’s the case, this tiny [17%] effect of ivermectin would be restricted to people who are fighting parasitic infections.
But we will have to wait –again– for the PRINCIPLE and NIH trials to be sure [I can't want for the results of more BS "official three-letter agency" trials. I think we already know what they will conclude].
*Comparison of Trials Using Ivermectin for COVID-19 Between Regions With High and Low Prevalence of StrongyloidiasisA Meta-analysis (March 21, 2022)
Ivermectin has been a controversial topic for much of the pandemic. The anti-parasitic drug has been touted by some as a treatment for COVID-19, but a new clinical trial finds no evidence to support that claim. … It could improve outcomes in COVID-19 patients who are fighting certain parasitic diseases, which is what ivermectin is primarily used for, but based on the findings it doesn’t have any effect on COVID-19 itself, Mills said.
I asked my sister ,when visiting Suva, Fiji recently to try and buy ivermectin over the counter.(She didn't know the story) She was told 'Only available on prescription as charlatan doctors have been selling it as a Covid cure.'
Phil, thanks for covering this. A couple of weeks ago I watched the video (and read the news coverage) and noticed the same points you covered in your post. I was planning on trying to pass it on to somebody (perhaps Jimmy Dore, who just dropped a video discussing this TOGETHER trial a few days ago. A while back, he ripped into Andrew Hill for his hypocrisy. I'd love it if he ripped into Ed Mills as well!).
Here's the link to Ed Mills discussing the TOGETHER trial (Grand Rounds Rethinking Clinical Trials 03-18-2022), and my rough notes with time stamps (includes some other points not covered in your post). Mills was a bit disingenuous when discussing funding & why the study was stopped early:
https://rethinkingclinicaltrials.org/news/grand-rounds-march-18-early-treatment-of-covid-19-the-together-adaptive-platform-trial-edward-mills-phd-frcp-craig-rayner-pharmd/
From Ed Mills Presentation:
??:?? Discussed theory used to set low IVM dosage. Acknowledges that more effective with meals, but gave fasting so matches label? [Why not use higher does & duration practitioner's were using for Gamma?]
28:36 Wondered what would have happened if had kept randomizing? Changed things? I don't know. Waiting for other trials.
29:31 If more randomized; hospitalization changed to significant? Entirely possible.
29:45 IVM not a safety concern
30:44 Cannot rule out small treatment effect. Answer not yet conclusive. Subgroup within trial possibly antiparasitic [see other March '22 JAMA paper] which responsible for effect.
From Q & A:
32:50 “No significant effect. Doesn't mean anything. Low confidence interval, Stopped too early? “ : I totally agree.
I don't call shots when to stop trial [really?] The DSMV decides [later hes says they make recommendation to the steering committee that Mills is on!] ]
Funding issue; 32 year old [billionaire!] was funding, limited resources [? With Billionaire?]. We were being abused by community, I lost interest because of attacks receiving.
35:50 Lessons. $4M, little money. $500B NIH trials ACTIV. Maybe IVM had 10% effect, no better than Fluvoxamine 30%. How much genuine interest in using repurposed drugs? Didn't get picked up by [IDSA,NIH,CDC/WHO] guidelines, why is that?
38:20 “Dosing? Want to take best shot using a high dose with a 1-arm treatment. Avoids the 'wasn't enough' question.”: Mills doesn't answer question.
45:40 DSMV parameters for stopping?: Rules in plan published. They followed the plan [really?] provided to them. Public pressure. If not for pressure, would have discontinued IVM. They can do what they like in making recommendations to the steering committee [of which Mills was a member; this committee makes the decision?].
56:54 Political. Zealots, opposite too, making fun. Nobody was right about that. How come back together?
Thank you, Phil. You are generous in ascribing the title of “Journalists” to those “engaged weeks prior to ‘launch’“. Complicit shills doing the bidding of their pimps. Can remember the Pentagon Papers and the Watergate Scandal. Apparently many professing independent journalism have found the bottom of the slippery slope and morphed into corporate media.
It’s very bizarre that Ed Mills’ ‘the jury is still out’ private messaging didn’t match the very definitive ‘it doesn’t work’ public message.
Or perhaps not bizarre at all, when one considers all the evidence of his multiple conflicts of interest.
Thank you for this. I saw similar press regarding Hydroxychloroquine, but then read the studies, and found that either the study did not follow the protocol that treating physicians were using or that the trial was conducted in already hospitalized (and likely very sick patients) or it showed that actually, the drug was quite effective at reducing hospitalizations. Reading one such study and a critique of it, I learned that Dr. Boulware, at about the same time as the study began, had accepted a position as a Scientific Advisor for Revive Therapeutics, which was rumored to be working on 'one of those other therapies' that Dr. Boulware would like doctors to steer their patients to try. This conflict of interest was not disclosed in the trial info.
https://revivethera.com/2020/03/revive-therapeutics-appoints-dr-david-boulware-md-as-scientific-advisor-for-infectious-diseases-including-covid-19/
I also heard him in an interview speak about his being involved in an (at the time) upcoming study of Ivermectin, so I am not at all surprised at his stance. I did not realize that THIS is the study of which he spoke.
Phil- something odd in that video :
listening to the "collaborative" vimeo conference there's a discussion about halfway through: Ed Mills mentions that the study had become difficult because of deteriorating relations with the community... such that he "lost interest in it".
He had several opportunities to also mention otherwise: talked about the close interaction with the community, how they dealt with them with "respect", and how well they engaged them, and recruited them for the study.
So what happened?- M Robert Weiss, MD
So what happened? what kind of pressure and malcontent did they experience, such that he 'lost interest' in pursuing the trial?
P.S. Here's some notes taken from news coverage of the Together Trial. As in Phil's post, the "negative press campaign" is evident. However, some of the quotes also address other topics mentioned in my first comment on the NIH video:
Trial was funded by “young” billionaires (in video, Ed Mills claimed limited funding was a factor that led to stopping trial early).
Mills admits that trial actually showed a “small” (17%) benefit in reduction of hospitalization (but not “statistically significant”).
Craig Rayner (also in video) advised against using IVM in early trials because he claimed dose needed was 20x approved dose (and in video, from about 5:00 to 17:00, he explains his rationale for both using a low dose and giving it fasting even though he knew it was more effective with meals!).
Mills claims the 17% benefit was not from IVM treating Covid, but was “actually treating the underlying parasitic infections”.
. . .
New Covid trial results may point toward better ways to study medicines
Matthew Herper March 23, 2022
https://www.statnews.com/2022/03/23/new-covid-trial-results-may-point-toward-better-ways-study-medicines/
Mills said the budget for TOGETHER was also $10 million. And it didn’t come from the National Institutes of Health, a big drug company, or a major charity. Instead, one of the major funders of the trial so far has been Patrick Collison, co-founder of payments firm Stripe, who Forbes estimates to have a $9.5 billion fortune. New funds are coming from the charitable foundation FTX, a cryptocurrency exchange, and its founder Sam Bankman-Fried, who is worth $24 billion, also per Forbes. [Note: in 3/18/22 video, Mill said 32-year old funding. Collison? Bankman-Fried? Billionaires with limited resources so couldn't fund the IVM trial a bit longer?].
Largest Study of Ivermectin Shows No Protection Against COVID-19 Hospitalizations Valerie DeBenedette
https://www.verywellhealth.com/largest-ivermectin-study-no-covid-benefit-5224499
"Our clinical trial is the largest one yet of ivermectin for the early treatment of COVID. It did not show a statistically significant benefit," Edward Mills, PhD, study author and a professor at McMaster University in Hamilton, Ontario, told Verywell. "I think it will influence those who were uncertain about whether or not further research might provide more precise answers. I do not think it will influence people whose minds have already been made up about whether or not it works."
This study did not completely rule out a potential for a small [17%?] benefit from treatment with ivermectin, Mills said. "But given that there are other interventions out there that have some statistical significance [Fluvoxamine?], then a topic like ivermectin, where the finding is still uncertain after many, many trials, leads one to believe that it's just not a drug worth pursuing any further,” he said.
Jury’s in for ivermectin: “No clinical [?] significance.”
1 April 2022/ Elizabeth Finkel Cosmos
https://cosmosmagazine.com/health/covid/jurys-in-for-ivermectin-no-clinical-significance/
The trial found that ivermectin given in the first seven days after symptoms had no significant effect.
Ivermectin was not included in the initial line-up of repurposed drugs. TOGETHER team member Craig Rayner, a clinical pharmacologist affiliated with the US-based company Certara that provides scientific advice to drug developers, modelled the effective drug doses for the trial. Since the ivermectin dose required to kill the virus was more than 20 times the maximum approved dose, he advised against it. [Note: Rayner is also in the NIH video (5:00 -- 17:00) and rationalizes why he used such a low dose in the trial and gave it on an empty stomach, despite knowing it would reduced the effect!].
By the beginning of August 2021, the researchers had their results. Ivermectin did not reduce the risk of hospitalization [17%?]. By contrast the cheap antidepressant drug fluvoxamine did, reducing the risk of hospitalization by 30%.
And here [Brazil] they ran up against the problem of finding people who weren’t already self-medicating with ivermectin. [that might be a confounder!] That was partly circumvented by running the trial in Minas Gerais, a state in southeast Brazil where the use was not as widespread, says Rayner [really?!].
However, once the TOGETHER group overcame all these obstacles, why did they not publish a preprint like RECOVERY? Mills says they decided to go the route of publishing in a major journal and that they did ‘air’ the data in talks. [8 months before publication]
[LAST PARAGRAPH!] Because TOGETHER did actually find a small [17%!], but not statistically significant effect, of ivermectin on hospitalisation. Could it be a true but tiny signal in the noise? [Doesn't exactly match the headline "No Clinical Significance"!]
Mills suspects that in some Brazilian patients, ivermectin was actually treating the underlying parasitic infections – and that improved the person’s ability to fight COVID. That’s a theory suggested by this recent analysis.* If that’s the case, this tiny [17%] effect of ivermectin would be restricted to people who are fighting parasitic infections.
But we will have to wait –again– for the PRINCIPLE and NIH trials to be sure [I can't want for the results of more BS "official three-letter agency" trials. I think we already know what they will conclude].
*Comparison of Trials Using Ivermectin for COVID-19 Between Regions With High and Low Prevalence of StrongyloidiasisA Meta-analysis (March 21, 2022)
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2790173
In the news: Edward Mills on study showing no indication Ivermectin is useful in treating COVID-19
https://brighterworld.mcmaster.ca/articles/in-the-news-no-indication-ivermectin-clinically-useful-in-treating-covid-19-says-edward-mills/
Ivermectin has been a controversial topic for much of the pandemic. The anti-parasitic drug has been touted by some as a treatment for COVID-19, but a new clinical trial finds no evidence to support that claim. … It could improve outcomes in COVID-19 patients who are fighting certain parasitic diseases, which is what ivermectin is primarily used for, but based on the findings it doesn’t have any effect on COVID-19 itself, Mills said.
I asked my sister ,when visiting Suva, Fiji recently to try and buy ivermectin over the counter.(She didn't know the story) She was told 'Only available on prescription as charlatan doctors have been selling it as a Covid cure.'