You may have heard that a new NIH-funded Randomized Controlled Trial was published recently. This one most definitely proves ivermectin doesn’t work for COVID-19—at least if the headlines are to be believed:
I was on oxygen for a year after covid (no preexisting conditions) went to specialist pulmonary in 3 cites even to University utah specialust all told me nithing they could do i have to wait they do not have any knowledge about covid!! When does a doctors tell you they cant do anything before covid if you went to the doctor with a cold they wound give antibiotics like candy!!
Well finally i found a doctor that followed the hippocratic oath “do no harm” who care about their patients !who knew what they were doing and were not led by politicians! That doctor prescribed Ivermectin and within a week i was off oxygen after a year of my life wasted for no
Another brilliant analysis. You are one of my favorite writers on substack. I would love to have a friend like you to analyze medical journals with on the regular. You are so sharp. Nothing gets past you, you are a true detective. Thank you for showing us what charlatans these NIH sponsored authors are. Keep up the good work. We need minds like yours to shine a bright light on the fraudsters in the NIH, FDA and tte CDC who are making a mockery of true science. They give “science” a bad name.
Yeah, I'd like to see Alexandros in a nice suit in an expensive TV studio giving his perspective on one questionable study after another. That'd be some great TV, for me.
Which means it ain't gonna happen until I move to the universe next door.
Oct 28, 2022·edited Oct 30, 2022Liked by Alexandros Marinos
Our study is NOT showing that IVM is bad, because we are angry about that we decided to instead test if it helps you lose weight so we can at least claim it fails at something.
Nice work. In case you weren't already aware, Kowa put out a press release of its IVM RCT in Japan which the press jumped on to claim IVM isn't effective, complete with photo of veterinary IVM. The results in the actual press release suggests the trial participants were so low risk no treatment would've shown an effect.
You say: <<the authors of this study found part-way through the trial that their original endpoint did not have sufficient statistical power to produce a useful result. At that point, they were faced with a choice of which of the secondary endpoints to promote to primary.>> NO. You are giving them too much credit. From what you showed us, as well as from my knowledge of other such trials, the actual reason for switching endpoint is more pernicious. They saw that their original endpoint was giving results that are too positive for IVM, and THAT is why they changed it. Because by day 28, many of those who were not taking IVM and failed to recover quickly would have had time to recover, and to catch up to the IVM group -- reducing the difference.
And we haven’t even got to what is likely to be the grand daddy of clusterfucks, the Principle trial.
I’ll put $1 that it shows a trend towards a positive effect yet falls just short of statistical significance. Despite this it is subsequently trumpeted as another nail in the coffin of Ivermectin…but on even superficial analysis is laughably flawed.
Also apparently the article I read stated that, The median duration from symptom onset and study drug administration was six days. Six days on average which means some started taking it maybe 7, 8 or 9 days after having symptoms? Six days is very late to start taking and antiviral isn't it. Plus seems they underdosed and they only gave for 3 days. What a waste of time. It's almost as if...they wanted it to fail?!
> What’s more, the statistical analysis plan that is shared with the trial, including many key details, is dated after the end of the trial, opening up the possibility that post-hoc decisions were made.
eFigure 3 shows treatment dates from Oct 2021 to Feb 2022. The statistical plan (v. 4.0) is dated Dec. 20, 2021, in the middle of treatment (not after the end).
I would like to understand better the reasons for covariate adjustment in an RCT. Are the variables pre-specified at the beginning of the study?
At the bottom of Table 2 the authors show 99% efficacy for Ivermectin to reduce "Time unwell" (although the benefit is small). Footnote d indicates that no covariate adjustment was done due to "low event rate". In my mind, this lack of adjustment actually makes the result more rigorous and stronger.
Did anyone notice under “Conflict of Interest Disclosures” in the JAMA paper the huge amount of pharmaceutical company and NIH funding received by many of the authors? This underscores what a longtime editor of the NEJM stated: "It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor of The New England Journal of Medicine.”- Marcia Angell, M.D.
Drug Companies & Doctors: A Story of Corruption | Marcia Angell
And from the British Medical Journal: "Evidence based medicine has been corrupted by corporate interests, failed regulation, and commercialisation of academia. The release into the public domain of previously confidential pharmaceutical industry documents has given the medical community valuable insight into the degree to which industry sponsored clinical trials are misrepresented. Until this problem is corrected, evidence based medicine will remain an illusion."
You give the authors too much credit when you BELIEVE their "explanation" that they moved the timeframe from 14 to 28 days to "rescue the study", because there was not enough data. I believe that the earlier timeframe actually showed IVM to be effective beyond the 95% margin, so it was shifted to "rescue" their plan to FAIL IVM. This makes sense -- IVM speeds up recovery, but waiting longer gives placebo patients a chance to catch up. And think about it -- why hide the results with the earlier timeframe, if not because they show this kind of outcome?
I was on oxygen for a year after covid (no preexisting conditions) went to specialist pulmonary in 3 cites even to University utah specialust all told me nithing they could do i have to wait they do not have any knowledge about covid!! When does a doctors tell you they cant do anything before covid if you went to the doctor with a cold they wound give antibiotics like candy!!
Well finally i found a doctor that followed the hippocratic oath “do no harm” who care about their patients !who knew what they were doing and were not led by politicians! That doctor prescribed Ivermectin and within a week i was off oxygen after a year of my life wasted for no
reason!!
Kinda makes sense https://twitter.com/SabinehazanMD/status/1567323466902437888 https://www.mdpi.com/2673-8449/2/3/15/htm
Another brilliant analysis. You are one of my favorite writers on substack. I would love to have a friend like you to analyze medical journals with on the regular. You are so sharp. Nothing gets past you, you are a true detective. Thank you for showing us what charlatans these NIH sponsored authors are. Keep up the good work. We need minds like yours to shine a bright light on the fraudsters in the NIH, FDA and tte CDC who are making a mockery of true science. They give “science” a bad name.
Yeah, I'd like to see Alexandros in a nice suit in an expensive TV studio giving his perspective on one questionable study after another. That'd be some great TV, for me.
Which means it ain't gonna happen until I move to the universe next door.
"The drugs were sent to the patients by mail, so that some patients took them 13 or 14 days after symptom onset."
My own experience of COVID (Omicron) was being 100% better by day 8 after symptom onset. Any drug given to me in the second week would have "failed".
Thus, this seems a peculiar new form of medical investigation in which we try to cure an illness patients might no longer be sick from.
You are the Minister of Health in the people's shadow cabinet.
Our study is NOT showing that IVM is bad, because we are angry about that we decided to instead test if it helps you lose weight so we can at least claim it fails at something.
Nice work. In case you weren't already aware, Kowa put out a press release of its IVM RCT in Japan which the press jumped on to claim IVM isn't effective, complete with photo of veterinary IVM. The results in the actual press release suggests the trial participants were so low risk no treatment would've shown an effect.
https://guygin.substack.com/p/a-tale-of-two-pills-media-bias-in
You say: <<the authors of this study found part-way through the trial that their original endpoint did not have sufficient statistical power to produce a useful result. At that point, they were faced with a choice of which of the secondary endpoints to promote to primary.>> NO. You are giving them too much credit. From what you showed us, as well as from my knowledge of other such trials, the actual reason for switching endpoint is more pernicious. They saw that their original endpoint was giving results that are too positive for IVM, and THAT is why they changed it. Because by day 28, many of those who were not taking IVM and failed to recover quickly would have had time to recover, and to catch up to the IVM group -- reducing the difference.
Paxlovid clinical trial: 5 days of treatment * 2 doses per day, given at a median of 3 days after symptom onset
ACTIV-6 ivermectin clinical trial: 3 days of treatment * 1 dose per day, given at a median of 6 days after symptom onset
And we haven’t even got to what is likely to be the grand daddy of clusterfucks, the Principle trial.
I’ll put $1 that it shows a trend towards a positive effect yet falls just short of statistical significance. Despite this it is subsequently trumpeted as another nail in the coffin of Ivermectin…but on even superficial analysis is laughably flawed.
Any takers?
Also apparently the article I read stated that, The median duration from symptom onset and study drug administration was six days. Six days on average which means some started taking it maybe 7, 8 or 9 days after having symptoms? Six days is very late to start taking and antiviral isn't it. Plus seems they underdosed and they only gave for 3 days. What a waste of time. It's almost as if...they wanted it to fail?!
Some took it as late as 13 or 14 days after symptom onset.
Ridiculous
Not "almost as if", I am willing to bet my last dollar, they DID want it to fail.
Thanks for the detailed analysis.
> What’s more, the statistical analysis plan that is shared with the trial, including many key details, is dated after the end of the trial, opening up the possibility that post-hoc decisions were made.
eFigure 3 shows treatment dates from Oct 2021 to Feb 2022. The statistical plan (v. 4.0) is dated Dec. 20, 2021, in the middle of treatment (not after the end).
Well done.
Their disclosure information guarantees bad behavior.
I would like to understand better the reasons for covariate adjustment in an RCT. Are the variables pre-specified at the beginning of the study?
At the bottom of Table 2 the authors show 99% efficacy for Ivermectin to reduce "Time unwell" (although the benefit is small). Footnote d indicates that no covariate adjustment was done due to "low event rate". In my mind, this lack of adjustment actually makes the result more rigorous and stronger.
Did anyone notice under “Conflict of Interest Disclosures” in the JAMA paper the huge amount of pharmaceutical company and NIH funding received by many of the authors? This underscores what a longtime editor of the NEJM stated: "It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor of The New England Journal of Medicine.”- Marcia Angell, M.D.
Drug Companies & Doctors: A Story of Corruption | Marcia Angell
And from the British Medical Journal: "Evidence based medicine has been corrupted by corporate interests, failed regulation, and commercialisation of academia. The release into the public domain of previously confidential pharmaceutical industry documents has given the medical community valuable insight into the degree to which industry sponsored clinical trials are misrepresented. Until this problem is corrected, evidence based medicine will remain an illusion."
The illusion of evidence based medicine
You give the authors too much credit when you BELIEVE their "explanation" that they moved the timeframe from 14 to 28 days to "rescue the study", because there was not enough data. I believe that the earlier timeframe actually showed IVM to be effective beyond the 95% margin, so it was shifted to "rescue" their plan to FAIL IVM. This makes sense -- IVM speeds up recovery, but waiting longer gives placebo patients a chance to catch up. And think about it -- why hide the results with the earlier timeframe, if not because they show this kind of outcome?