The placebo group didn't need to become unblinded. Assume they were in the study to receive free ivermectin. Due to wide use in Brazil they know that ivermectin works and works fairly rapidly. As soon as they are several days into the study and are getting worse they are going to go elsewhere for their ivermectin.
The question that they could easily answer is “How many deaths were there in the Per Protocol Placebo arm?”
It’s a mystery to me why they didn’t use this as the primary metric anyway, it simply makes no sense to mix and match the results from one cohort (Per Protocol) and another.
Even then, this would not explain why so many of the other totals don’t add up. A peer-reviewed paper should already have undergone such scrutiny.
Asking patients for the estimate as to days of symptoms is not a scientifically precise measurement that can be relied upon.
Also, the important start date is not when they enrolled but how many days after first symptom did they receive the first pill?
The qualification process, before getting a pill, appears quite lengthy:
Inclusion criteria and steps to approval :
Patient says yes "within 7 days after symptom onset"
Meets standard of "at least one high-risk criterion for progression of Covid-19"
Then "trial personnel obtained written in-person informed consent and performed a rapid antigen test for SARS-CoV-2..."
Then. "Before randomization, trial personnel obtained data on ..."
Then "Participants also completed the Patient-Reported Outcomes Measurement Information System Global-10 health scale..".
Then "Patients underwent randomization by means of a block randomization procedure...:
The active-drug and placebo pills were packaged in identically shaped bottles and labeled...
Then "Patients were shown a welcome video with information on the trial, ivermectin, adverse events, and follow-up procedures... "
Then obtained medication ?
Why not list the number of days after first symptom that they took the first dose, rather than the number of days after first symptom that they applied for inclusion?
It appears that the per-protocol numbers are placebo patients who completed a 3-day placebo, as opposed to 1,7,10,14 day placebo. So the others didn't drop off, they're just a non-protocol placebo.
Suspected the Together Trial would be rigged to show ivermectin failure. And…no surprise. Really appreciate your analysis Phil. It’s a shame that those who follow mainstream media will never see this.
However, the insurance industry just might be the financial and political powerhouse needed to expose pharmaceutical and public healthcare agencies corruption. Reports like this just might go into their quiver.
Phil, there were 3 different analyses done: per protocol, intention to treat, and a modified per protocol. Per protocol was the one that was supposed to omit everyone who did not (by their own admission which may not be accurate) comply with the study.
You are amazing Phil - I took one look at the pdf and decided this was too complex for me to sort out - I also support Dr. Mobeen Syed on Patreon. It sounds like he is also going to do a deep dive video review on either Odysee or Rumble. - Do you know if John Campbell is also going to do a review?
About 24 mins in he discusses the exclusion criteria showing a slide where they excluded those taking the study medications. This is misleading because, as I mentioned in another comment, as late as Nov. 2021 in a report they wrote on the trial protocol, there STILL was no mention of excluding those already taking the trial medications. This is a full two months AFTER they already submitted for publication.
It has been discussed that the six month delay in NEJM finally publishing it is unusually long. I think there is little doubt that the journal reviewers required them to go back and interview subjects to insure none of them were taking the IVM.
It’s difficult to believe, as the authors imply, none of them had taken IVM outside the trial since it was widely promoted and taken for COVID in Brazil, being sold in Brazil over-the-counter(no prescription required), especially since the large number of placebo subjects only getting one dose, would KNOW they were in the placebo group.
The placebo group didn't need to become unblinded. Assume they were in the study to receive free ivermectin. Due to wide use in Brazil they know that ivermectin works and works fairly rapidly. As soon as they are several days into the study and are getting worse they are going to go elsewhere for their ivermectin.
So well explained, even I could understand it. A new happy monthly subscriber!
So, using the numbers for patients who completed the study...
Ivermectin, deaths, 21/624 = 3.4%
Placebo, deaths, 25/288 = 8.7%
Ivermectin reduced deaths by 61% , or said the opposite way, not taking Ivermectin increased the chances of death by 2.6 times.
As a retired scientist I find the sloppy work in these tables unacceptable. Obviously they were not well vetted. Thank you for this review.
The question that they could easily answer is “How many deaths were there in the Per Protocol Placebo arm?”
It’s a mystery to me why they didn’t use this as the primary metric anyway, it simply makes no sense to mix and match the results from one cohort (Per Protocol) and another.
Even then, this would not explain why so many of the other totals don’t add up. A peer-reviewed paper should already have undergone such scrutiny.
This stinks.
Asking patients for the estimate as to days of symptoms is not a scientifically precise measurement that can be relied upon.
Also, the important start date is not when they enrolled but how many days after first symptom did they receive the first pill?
The qualification process, before getting a pill, appears quite lengthy:
Inclusion criteria and steps to approval :
Patient says yes "within 7 days after symptom onset"
Meets standard of "at least one high-risk criterion for progression of Covid-19"
Then "trial personnel obtained written in-person informed consent and performed a rapid antigen test for SARS-CoV-2..."
Then. "Before randomization, trial personnel obtained data on ..."
Then "Participants also completed the Patient-Reported Outcomes Measurement Information System Global-10 health scale..".
Then "Patients underwent randomization by means of a block randomization procedure...:
The active-drug and placebo pills were packaged in identically shaped bottles and labeled...
Then "Patients were shown a welcome video with information on the trial, ivermectin, adverse events, and follow-up procedures... "
Then obtained medication ?
Why not list the number of days after first symptom that they took the first dose, rather than the number of days after first symptom that they applied for inclusion?
It appears that the per-protocol numbers are placebo patients who completed a 3-day placebo, as opposed to 1,7,10,14 day placebo. So the others didn't drop off, they're just a non-protocol placebo.
Suspected the Together Trial would be rigged to show ivermectin failure. And…no surprise. Really appreciate your analysis Phil. It’s a shame that those who follow mainstream media will never see this.
However, the insurance industry just might be the financial and political powerhouse needed to expose pharmaceutical and public healthcare agencies corruption. Reports like this just might go into their quiver.
Thanks Phil for your thorough analysis. Its so needed.
Indeed, another attempt to fool people with sloppy “science”. Thanks for all the digging!
Phil, there were 3 different analyses done: per protocol, intention to treat, and a modified per protocol. Per protocol was the one that was supposed to omit everyone who did not (by their own admission which may not be accurate) comply with the study.
You are amazing Phil - I took one look at the pdf and decided this was too complex for me to sort out - I also support Dr. Mobeen Syed on Patreon. It sounds like he is also going to do a deep dive video review on either Odysee or Rumble. - Do you know if John Campbell is also going to do a review?
Thanks for all you do!!
Ed Mills discusses the TOGETHER trial in this video conference call from March 18, 2022:
Grand Rounds Rethinking Clinical Trials 03-18-2022.
https://vimeo.com/690426154
About 24 mins in he discusses the exclusion criteria showing a slide where they excluded those taking the study medications. This is misleading because, as I mentioned in another comment, as late as Nov. 2021 in a report they wrote on the trial protocol, there STILL was no mention of excluding those already taking the trial medications. This is a full two months AFTER they already submitted for publication.
It has been discussed that the six month delay in NEJM finally publishing it is unusually long. I think there is little doubt that the journal reviewers required them to go back and interview subjects to insure none of them were taking the IVM.
It’s difficult to believe, as the authors imply, none of them had taken IVM outside the trial since it was widely promoted and taken for COVID in Brazil, being sold in Brazil over-the-counter(no prescription required), especially since the large number of placebo subjects only getting one dose, would KNOW they were in the placebo group.
Robert Clark
Another odd aspect of the TOGETHER trial is they did not exclude for prior OR EVEN CURRENT IVM USE:
Robert Clark
@RGregoryClark
Replying to
@omnichord
and
@boulware_dr
As late as Nov., 2021 the trial authors *still* said no exclusions for prior IVM use: 2 mos. AFTER it was already submitted for publication!
https://gatesopenresearch.org/articles/5-117
Only now *after* it’s published are they claiming they excluded on IVM use. MUST do INDEPENDENT review on prior use
https://twitter.com/rgregoryclark/status/1510731349476401160?s=21&t=XAZw5fMpMAnfW9ww5xxftg
From the study protocol published Nov. 2021, two months after submission to NEJM:
===================================================
Patients who meet any of the following criteria are excluded:
1. Patients with acute respiratory condition compatible with COVID-19 treated in the primary care and with hospitalization need.
2. Patients with acute respiratory condition due to other causes.
3. Severe terminal illness irrespective of type or etiology.
4. Acute flu showing at least ONE of the criteria below:
I. Respiratory Rate > 28 / min
II. SaO2 < 90% or < 93% on nasal oxygen therapy at 10 L / min;
III. PaO2 / FIO2 < 300 mmHg
5. Use of the following medications in the last 14 days:
Monoamine Oxide Inhibitors (MAOIs): Phenelzine, Tranylcypromine, Selegiline, Isocarboxazide, moclobemide
Alpha-1 antagonists, Sotalol, Clonidine, Phosphodiesterase 5 inhibitors, Methyldopa, Prazosin, terasozin, Doxazosin)
Use of antiretroviral agents
6. Patients using serotonin reception inhibitors (Donepezil, Sertraline).
7. Pregnant or breastfeeding patients.
8. Surgical procedure or use of contrast planned to occur during treatment or up to 05 days after the last dose of the study medication.
9. Inability of the patient or representative to give informed consent or adhere to the procedures proposed in the protocol.
10. Known hypersensitivity and / or intolerance to IPs, or taking medications contraindicated by IPs.
11. Inability to follow protocol-related procedures.
===================================================
https://gatesopenresearch.org/articles/5-117
Robert Clark
Thank you Phil!