I’m a housewife and a dog rescuer but even I know to dose dogs according to weight! I would not expect mange mites to die or intestinal worms to die if I gave a reduced dose.
I think what your trying to achieve is an estimate of the number of patients who received less than 400mcg/kg.
I don’t think it is worth pursuing this unless you have the raw data. It is too speculative, could easily be out by 5 patients either way and irrespective, the authors will not respond nor change their paper based on this speculation.
However, all hope is not lost. If a patient is 100kg or greater then they would have received 360mcg/kg or less.
Even without knowing the exact weights of the patients, it is almost certain that at least 1 patient was greater than 100kg (although likely many more). I chose 100kg because this represents a 10% reduction in the stated dose that was supposedly being assessed for effect. As I mentioned previously, you could pick any number under 400mcg/kg but a 10% reduction becomes clearly significant
The mere fact that even a single underdosed patient was included in the study results without mention anywhere in the paper renders the study invalid and requires at the very least a retraction and rewrite.
With raw data you can then start to exclude underdosed patients and reassess the results.
I think the time is right to escalate and insist the NEJM retract the paper and/or grant access to raw data.
Lastly, I know you’re doing it but keep a close eye on the original paper, there is every chance that they’ll change the manuscript again in regards to the dosing regime and its potential failings
Urban Minas Gerais has a population that is typical of Brazil in general. Any BMI distribution data from Brazil could be reasonably extrapolated to the IVM study region. Or if you can't get a Brazilian BMI distribution, how about finding BMI distribution data from Europe or North America and then assume that the Brazilian BMI distribution is of similar shape. You would only need to rescale the distribution to have a mean equal to that of the Brazilian distribution; the Brazilian mean BMI is available; around 26, I believe. Brazilians have an average BMI only slightly lower than the USA, in other words, they are pretty overweight.
Assuming that you don't have the raw data, you could estimate the underdosing by using a Monte Carlo simulation, i.e. drawing a sample of 100,000 heights and weights from data of Central Brazil, and randomly pairing them to generate the probable BMI distribution along with its mean and variance, from which you could determine what portion of the patients likely weighed over 90 kg and so were underdosed.
90 kg is a low cutoff point. I am 76 kg (160 lbs), 5.11", BMI of 22.3. If I weighed 200 lbs (=90.7 kg), I would have a BMI of 27.9, about the middle of the overweight category. I have lived in Brazil and can say that BMIs over 28 are quite common there.
All I know is that the outcome was likely decided and the study designed to match that desired end. Everything I've read about this confirms this, at least for me.
Honestly this adherence to scientific principles and examination of the trial for methodological flaws seems almost besides the point, now. They could not allow any readily-available therapeutic to appear to work because that would invalidate the EUA. That's it. There was some pretence at testing pharmaceuticals for show purposes, but everyone knew an engineered outcome was essential to prop up mandates and, especially, to frighten people into wanting the vax for their children.
I admire your stamina here and I want every bit of fraud exposed. But, again, we know why it happened, right?
I can't see how to calculate questions 1 and 2. They screwed up and I don't see how you can go back and get anything meaningful without knowing everyone's weight. The 2 biggest problems to me were that #1. it wasn't early treatment and #2. the IVM was used during the gamma variant whereas the placebo group used had an earlier, less severe variant. The 2 groups were not run concurrently. The problem with RCTs is that in order to do it right for IVM, you need the right dose and to have your cut off for early treatment be early, like Day1 or 2 and that takes tremendous diligence, which these guys don't have because it is in their best interest to have the results be neutral or negative. This is why I find population studies more accurate.
You could possibly then exclude anyone who received less than 350mcg/kg from the results. Or maybe be more strict and exclude anyone who received less than 375mcg/kg.
If you wanted to go crazy you could also exclude anyone who received their first dose after day 5.
Eventually you would be left with only those who had >375mcg/kg with first dose within 5 days of symptoms versus placebo.
Might give that 17% reduction in hospitalisations that leg up it needs to reach statistical significance
Run it by John Abramson who used to analyze clinical trials for a living. He is an MD and in February, 2022, published "Sickening: How Big Pharma Broke American Health Care and How We Can Repair It." He was interviewed on Tucker Carlson Today on Feb. 14, 2022 in an episode titled, "Exposing Big Pharma."
I know your questions are not specifically addressed to this, but the limitation is likely based on the quantity of 3 mg tablets available. 75 kg would be ten (10) 3 mg tablets. They rationed the tablets out.
it is incomprehensible to me why anybody would calculate BMI when in fact a far better indicator of proportion of fat is abdominal circumference. Much of the cytokine (IL 6)storm happens in the belly fat.
I’m a housewife and a dog rescuer but even I know to dose dogs according to weight! I would not expect mange mites to die or intestinal worms to die if I gave a reduced dose.
I think what your trying to achieve is an estimate of the number of patients who received less than 400mcg/kg.
I don’t think it is worth pursuing this unless you have the raw data. It is too speculative, could easily be out by 5 patients either way and irrespective, the authors will not respond nor change their paper based on this speculation.
However, all hope is not lost. If a patient is 100kg or greater then they would have received 360mcg/kg or less.
Even without knowing the exact weights of the patients, it is almost certain that at least 1 patient was greater than 100kg (although likely many more). I chose 100kg because this represents a 10% reduction in the stated dose that was supposedly being assessed for effect. As I mentioned previously, you could pick any number under 400mcg/kg but a 10% reduction becomes clearly significant
The mere fact that even a single underdosed patient was included in the study results without mention anywhere in the paper renders the study invalid and requires at the very least a retraction and rewrite.
With raw data you can then start to exclude underdosed patients and reassess the results.
I think the time is right to escalate and insist the NEJM retract the paper and/or grant access to raw data.
Lastly, I know you’re doing it but keep a close eye on the original paper, there is every chance that they’ll change the manuscript again in regards to the dosing regime and its potential failings
Urban Minas Gerais has a population that is typical of Brazil in general. Any BMI distribution data from Brazil could be reasonably extrapolated to the IVM study region. Or if you can't get a Brazilian BMI distribution, how about finding BMI distribution data from Europe or North America and then assume that the Brazilian BMI distribution is of similar shape. You would only need to rescale the distribution to have a mean equal to that of the Brazilian distribution; the Brazilian mean BMI is available; around 26, I believe. Brazilians have an average BMI only slightly lower than the USA, in other words, they are pretty overweight.
Assuming that you don't have the raw data, you could estimate the underdosing by using a Monte Carlo simulation, i.e. drawing a sample of 100,000 heights and weights from data of Central Brazil, and randomly pairing them to generate the probable BMI distribution along with its mean and variance, from which you could determine what portion of the patients likely weighed over 90 kg and so were underdosed.
90 kg is a low cutoff point. I am 76 kg (160 lbs), 5.11", BMI of 22.3. If I weighed 200 lbs (=90.7 kg), I would have a BMI of 27.9, about the middle of the overweight category. I have lived in Brazil and can say that BMIs over 28 are quite common there.
All I know is that the outcome was likely decided and the study designed to match that desired end. Everything I've read about this confirms this, at least for me.
Honestly this adherence to scientific principles and examination of the trial for methodological flaws seems almost besides the point, now. They could not allow any readily-available therapeutic to appear to work because that would invalidate the EUA. That's it. There was some pretence at testing pharmaceuticals for show purposes, but everyone knew an engineered outcome was essential to prop up mandates and, especially, to frighten people into wanting the vax for their children.
I admire your stamina here and I want every bit of fraud exposed. But, again, we know why it happened, right?
I can't see how to calculate questions 1 and 2. They screwed up and I don't see how you can go back and get anything meaningful without knowing everyone's weight. The 2 biggest problems to me were that #1. it wasn't early treatment and #2. the IVM was used during the gamma variant whereas the placebo group used had an earlier, less severe variant. The 2 groups were not run concurrently. The problem with RCTs is that in order to do it right for IVM, you need the right dose and to have your cut off for early treatment be early, like Day1 or 2 and that takes tremendous diligence, which these guys don't have because it is in their best interest to have the results be neutral or negative. This is why I find population studies more accurate.
I think you need access to the raw data, all of it.
Hopefully they documented the weight of each patient, not just BMI.
Then you can work out the exact mcg/kg dose each participant received.
Then, once known, you can examine outcomes from each subgroup of dosing.
In other words you could divide the Ivermectin arm into groups based on dosing
Ie <200mcg/kg, 201-250mcg/kg, 251-300mcg/kg, 301-350mcg/kg, 351-400mcg/kg.
You could possibly then exclude anyone who received less than 350mcg/kg from the results. Or maybe be more strict and exclude anyone who received less than 375mcg/kg.
If you wanted to go crazy you could also exclude anyone who received their first dose after day 5.
Eventually you would be left with only those who had >375mcg/kg with first dose within 5 days of symptoms versus placebo.
Might give that 17% reduction in hospitalisations that leg up it needs to reach statistical significance
Run it by John Abramson who used to analyze clinical trials for a living. He is an MD and in February, 2022, published "Sickening: How Big Pharma Broke American Health Care and How We Can Repair It." He was interviewed on Tucker Carlson Today on Feb. 14, 2022 in an episode titled, "Exposing Big Pharma."
I know your questions are not specifically addressed to this, but the limitation is likely based on the quantity of 3 mg tablets available. 75 kg would be ten (10) 3 mg tablets. They rationed the tablets out.
it is incomprehensible to me why anybody would calculate BMI when in fact a far better indicator of proportion of fat is abdominal circumference. Much of the cytokine (IL 6)storm happens in the belly fat.
The under-dosing and PK no meal gaffe are inexcusable . Does anyone seriously think this is good science?
Very subtle, but there.
Poorly designed, with an apathetic PI more concerned about hurt feelings than achieving success 💰🤦♀️