Thank you, thank you for this critical look at early treatments. If AI was used for treatment decision making, it is hard to imagine the advice from AI would be to stay home til your lips turn blue, then come into hospital where you will receive remdesivir and mechanical ventilation. Boy, have the medical community f’d up.
“at the outset of the pandemic, the broader part of the Mathematics community (not every individual, but enough that it matters) threw its head in the sand. Sadly, they are now largely a combination of bought, threatened, or wholly lacking in courage. When they do speak up, they are silenced—which can only take place when too few of them speak up.” Something I’ve been lamenting from the outset. But this is due to the culture in mathematics and that mathematicians are loathe to speak up in areas where uncertainty dominates. Modelers and Actuaries should have been at the front of the discussion, but sadly, the food on their tables is paid for by the guv’mint and/or big corporations with financial benefits from the hysteria.
I very much appreciate your analysis, but most of it is way over my head. Here is a simple anecdote from my past. I once had a father-in-law who was a world renowned MD and PhD (old school), and even though he usually talked way over my head, sometimes he would say something profoundly simple. In relation to respiratory infections he said "treat it with whatever you like and you will be better in 7 to 10 days; or, don't do anything, and you will be better in 7 to 10 days". I often think of this in relation to "studies" and "treatments". I decided to try it on myself when I got covid. I did cheat because I took 3,000 mg of Vitamin C per day, and used Ibuprofen as needed for muscle aches and headache. I also regularly take a multi one a day vitamin/mineral./trace element tablet. I got over it in 7 to 10 days. I have had it three times, and did the same thing, and got the same results. I am 70 and not obese. I also get plenty of rest and try to stay hydrated. I don't go to doctors or take any medications. I haven't been tested for covid or had any of the shots. So, in my case we can eliminate all of those confounding variables that they don't bother with in their "studies". I just thought you might like to chew on that.
I was always kind of frustrated that nobody ever disaggregated by protocol to compare different protocols using any particular drug, throwing all the studies using a particular drug into a big melting pot of sorts makes about as much sense as throwing all the drugs used into one big meta study analyzing "treatment" and claiming that it produces any sort of useful data at all, it's as foolish to weigh down optimally timed/dosed HCQ with stupidly (and dangerously even) dosed/timed HCQ as it would be to weigh Ivermectin down with Paxlovid.
This is another on my list of favorites because fancy math and common sense intersect.. close enough to swapping denominators in meish math to be fully confident in your process and conclusion. Good thing I agree, betcha you were sweating over my fact check! *smirk*
Let me express the post's message this way. "Much of the "early" treatment data simply adds noise, not signal." Noise dilutes signal strength. It's better to filter out the noise when refining the data.
Quantity of data from relevant protocols is a mountain in terms of scientific value. Researcher bias is a mole hill, relatively speaking.
Castillo, et. al., showed that 72 hours from symptom onset was the limit for time to treatment with HCQ to prevent mortality.
Didier Raoult, et. al., showed that viral load maxxed in mild cases at three days post symptom onset.
A Hopkins survey showed that PCR false negatives reached a nadir at three days post symptom onset.
The consilience of evidence is that time to treatment should begin within the first 72 hours post symptom onset.
Studies which begin treatment >72 hours after symptom onset add noise and the data must be adjusted to minimize the noise. This is not to say that there may not be some benefit to some people by treating late, but we should expect some mortality when people are treated late.
Very true. While c19early has limits and flaws it is one of the most comprehensive and less biased evaluations of the data available. I believe that if you and your learned colleagues were to each draft and submit a feedback on their site they might very easily add better sited graphs to document reality. Having these graphs one click away from the main page would show that they conform to alternate analysis styles and are not 'accepted' broadly by the entrenched establishment but it would also highlight how the advanced display of the same data conforms better with real world experience.
I would be very encouraged if you could get them to generate a set of results that have data removed that is part of the conflicted researcher or study tree removed and then be able to se the optimistic results compare them with the conservative results and even better to place them side by side with the results that the mainstream is trying to pass off as reality. I tell people that the WHO and mainstream media is trying to imply that all the results for generic cures are on the right side of the unity line and only vaccines and patent medicines are on the left while research obviously does not support that viewpoint.
I am unjabbed and have not caught covid yet. I feel like a unicorn here in Canada. I know I will get sick eventually so I armed myself with IVM, vitamins C and D, zinc, and quercetin. I'm ready once the bioweapon hits me.
In this study berberine was more effective than Ivermectin at reducing high viral loads when first administered late in the course of the disease. I keep some on hand in my antiviral emergency response kit:
Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses,
Why are the tallest columns of dots (all roughly uniform in size) with the narrowest confidence intervals? I see that there are more studies there, but the spreads are enough to make me doubt the band thicknesses there. In short, way too many dots are outside the band? Seems counterintuitive to what you might expect.
Thank you, thank you for this critical look at early treatments. If AI was used for treatment decision making, it is hard to imagine the advice from AI would be to stay home til your lips turn blue, then come into hospital where you will receive remdesivir and mechanical ventilation. Boy, have the medical community f’d up.
B"H" I dedicate this comment to the memory of Zev ben Aaron
re RCT fetishism (and specifically HCQ) see April / May 2020 from all places Harvard
Unleash the Data on COVID-19 Maryaline Catillon and Richard Zeckhauser
https://web.archive.org/web/20200505112045/https://twitter.com/daniel_bilar/status/1255193716459003904
""RCTs [..] only ethically acceptable when the safety & perf of a treatment is unknown. When ample data exists, as now, that criterion is not met"
"Analyzing real world data on actual outcomes [..] offers an alternative approach to learn almost immediately"
"High quality case control studies based on 1000s of cases [..] are immensely faster than RCTs"
“at the outset of the pandemic, the broader part of the Mathematics community (not every individual, but enough that it matters) threw its head in the sand. Sadly, they are now largely a combination of bought, threatened, or wholly lacking in courage. When they do speak up, they are silenced—which can only take place when too few of them speak up.” Something I’ve been lamenting from the outset. But this is due to the culture in mathematics and that mathematicians are loathe to speak up in areas where uncertainty dominates. Modelers and Actuaries should have been at the front of the discussion, but sadly, the food on their tables is paid for by the guv’mint and/or big corporations with financial benefits from the hysteria.
I very much appreciate your analysis, but most of it is way over my head. Here is a simple anecdote from my past. I once had a father-in-law who was a world renowned MD and PhD (old school), and even though he usually talked way over my head, sometimes he would say something profoundly simple. In relation to respiratory infections he said "treat it with whatever you like and you will be better in 7 to 10 days; or, don't do anything, and you will be better in 7 to 10 days". I often think of this in relation to "studies" and "treatments". I decided to try it on myself when I got covid. I did cheat because I took 3,000 mg of Vitamin C per day, and used Ibuprofen as needed for muscle aches and headache. I also regularly take a multi one a day vitamin/mineral./trace element tablet. I got over it in 7 to 10 days. I have had it three times, and did the same thing, and got the same results. I am 70 and not obese. I also get plenty of rest and try to stay hydrated. I don't go to doctors or take any medications. I haven't been tested for covid or had any of the shots. So, in my case we can eliminate all of those confounding variables that they don't bother with in their "studies". I just thought you might like to chew on that.
I was always kind of frustrated that nobody ever disaggregated by protocol to compare different protocols using any particular drug, throwing all the studies using a particular drug into a big melting pot of sorts makes about as much sense as throwing all the drugs used into one big meta study analyzing "treatment" and claiming that it produces any sort of useful data at all, it's as foolish to weigh down optimally timed/dosed HCQ with stupidly (and dangerously even) dosed/timed HCQ as it would be to weigh Ivermectin down with Paxlovid.
Brilliant analysis as always :)
This is another on my list of favorites because fancy math and common sense intersect.. close enough to swapping denominators in meish math to be fully confident in your process and conclusion. Good thing I agree, betcha you were sweating over my fact check! *smirk*
Interesting post.
Let me express the post's message this way. "Much of the "early" treatment data simply adds noise, not signal." Noise dilutes signal strength. It's better to filter out the noise when refining the data.
Quantity of data from relevant protocols is a mountain in terms of scientific value. Researcher bias is a mole hill, relatively speaking.
Castillo, et. al., showed that 72 hours from symptom onset was the limit for time to treatment with HCQ to prevent mortality.
Didier Raoult, et. al., showed that viral load maxxed in mild cases at three days post symptom onset.
A Hopkins survey showed that PCR false negatives reached a nadir at three days post symptom onset.
The consilience of evidence is that time to treatment should begin within the first 72 hours post symptom onset.
Studies which begin treatment >72 hours after symptom onset add noise and the data must be adjusted to minimize the noise. This is not to say that there may not be some benefit to some people by treating late, but we should expect some mortality when people are treated late.
"home* (not "hone") in on those studies
Very true. While c19early has limits and flaws it is one of the most comprehensive and less biased evaluations of the data available. I believe that if you and your learned colleagues were to each draft and submit a feedback on their site they might very easily add better sited graphs to document reality. Having these graphs one click away from the main page would show that they conform to alternate analysis styles and are not 'accepted' broadly by the entrenched establishment but it would also highlight how the advanced display of the same data conforms better with real world experience.
I would be very encouraged if you could get them to generate a set of results that have data removed that is part of the conflicted researcher or study tree removed and then be able to se the optimistic results compare them with the conservative results and even better to place them side by side with the results that the mainstream is trying to pass off as reality. I tell people that the WHO and mainstream media is trying to imply that all the results for generic cures are on the right side of the unity line and only vaccines and patent medicines are on the left while research obviously does not support that viewpoint.
I am unjabbed and have not caught covid yet. I feel like a unicorn here in Canada. I know I will get sick eventually so I armed myself with IVM, vitamins C and D, zinc, and quercetin. I'm ready once the bioweapon hits me.
In this study berberine was more effective than Ivermectin at reducing high viral loads when first administered late in the course of the disease. I keep some on hand in my antiviral emergency response kit:
Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses,
https://www.sciencedirect.com/science/article/pii/S0166354215300516
Therapeutic properties of Berberine
https://doorlesscarp953.substack.com/p/therapeutic-properties-of-berberine#footnote-11
Thank you! Awesome breakdown of optimized treatment.
Why are the tallest columns of dots (all roughly uniform in size) with the narrowest confidence intervals? I see that there are more studies there, but the spreads are enough to make me doubt the band thicknesses there. In short, way too many dots are outside the band? Seems counterintuitive to what you might expect.