Of course surrogate endpoints are used in cancer clinical trials all the time (generally progression-free survival). This has been pointed out as a troubling trend.
Yes, much beloved by industry as it’s much quicker, cheaper and easier to demonstrate success in surrogate endpoints - and regulators may even accept this.
Labs allow for control not possible outside of labs.
"How the Laws of Physics Lie" by Nancy Cartwright discusses this problem.
Furthermore, having RCTs at the top of the evidence-based pyramid only gives more power to those who can run adequately-powered RCTs and ignores the problem of test-design bias.
I always got why the overriding narrative early on discouraged the idea of immunity from natural infection - it was a policy that seemed to be born of the fear that huge numbers of people would, for some reason, rush to seek infection as quickly as possible. But I also always had issues with it.
1) it denied all established research into immune health up to that point (and would inevitably blow back as a consequence at some point)
2) it treated people like children who couldn't work out what was best for them (like much of the 'official' messaging over the last two years)
3) it allowed countries like Italy where I've been living to treat recovered but unvaccinated people like second class citizens regardless of their actual immune status
4) it seemed to miss the point that those who caught and recovered from the virus really COULD return to normal life at any point particularly when it was understood that there was no silver bullet against infectivity. (Did anywhere end up staffing COVID wards with people who'd already had the disease/virus?)
Other than my original suggestion was there ANY other good reason to label the recovered as likely to have less or no immunity (to disease at the very least) than the vaccinated? Hmmm ahhhh, OK, not going there. There was a time before Sars Cov2 vaccines however. The original weeks of "We know nothing, we MUST throw the baby out with the bath water" reaction cannot justify all the weirdness that has followed, surely? I sometimes wonder how different things would have been if the default starting point had been to build on what was already known, moving on to calm, well designed investigations to confirm it.
Thanks for stating the obvious so well, Alasdair. Thanks for standing up for the clinically unwell and what their needs really are. Thanks for holding onto the bath water along with the baby and not pandering to the toddlers throwing their toys out of the pram*
Well done. Even Pfizer admitted that they were uncertain of the Cora relation between antibody levels and protection. But we could have had better data on this had the rcts not been prematurely ended. Sure I know the argument that it was unethical to continue them and that's fallacious since we really didn't have evidence that severe outcomes were worse in the unvaccinated group.
Point of fact all cause mortality was worse in the vaccinated group when the trials were terminated
"For Covid-19 immunity, these show that immunity following infection is comparable to that following vaccination."
But shouldn't infection produce antibodies to various viral proteins which should hinder/prevent immune escape, which has been a major problem for jabs? So, theoretically, shouldn't we _expect_ natural immunity to be superior to jabs?
Indeed, the immune system is complicated. Do you have any correlates that you use?
Pardon my ramblings about the immune system.
Zinc and selenium deficiency can undermine the immune system, and, of course, deficiencies in vits. A, C, D, and the B complex will do so as well. D deficiency is a mine worth mining to improve immune competence for all sorts of reasons--correlations between risk of severe covid and D-deficient groups and D deficiency/insufficiency being a common occurrence in almost all populations--especially in winter in extreme latitudes.
D deficiency is implicated strongly in covid ARDS and sepsis because vit. D is needed for the normal immune process of inflammation reduction of previously infected tissues after the virus has been cleared. I think that some form of prednisone may be prescribed in case of vit. D deficiency and high inflammation markers, but that's only my non-medical opinion.
Supplementation with D3 is dilatory compared with calcifediol supplementation, but a large dose (300k units) of D3 can take effect in a few days, from what I am reading. I don't know if it will work in ICU, but maybe it will in non-intensive covid wards. Certainly, D3 is worth a go in cases of mild covid in community care in case it may prevent progression and shorten symptoms and perhaps prevent long covid. Risk is negligible and there may be benefit.
Groups at risk for D3 deficiency include the elderly, the obese, the dark-complected, and those with liver dysfunction. Coincidentally, these groups are also at elevated risk for severe covid.
Thank you for patiently explaining this! Having serious discussion on Twitter is pretty tough.
Of course surrogate endpoints are used in cancer clinical trials all the time (generally progression-free survival). This has been pointed out as a troubling trend.
Yes, much beloved by industry as it’s much quicker, cheaper and easier to demonstrate success in surrogate endpoints - and regulators may even accept this.
Philosophical/epistemological observations...
Labs allow for control not possible outside of labs.
"How the Laws of Physics Lie" by Nancy Cartwright discusses this problem.
Furthermore, having RCTs at the top of the evidence-based pyramid only gives more power to those who can run adequately-powered RCTs and ignores the problem of test-design bias.
I always got why the overriding narrative early on discouraged the idea of immunity from natural infection - it was a policy that seemed to be born of the fear that huge numbers of people would, for some reason, rush to seek infection as quickly as possible. But I also always had issues with it.
1) it denied all established research into immune health up to that point (and would inevitably blow back as a consequence at some point)
2) it treated people like children who couldn't work out what was best for them (like much of the 'official' messaging over the last two years)
3) it allowed countries like Italy where I've been living to treat recovered but unvaccinated people like second class citizens regardless of their actual immune status
4) it seemed to miss the point that those who caught and recovered from the virus really COULD return to normal life at any point particularly when it was understood that there was no silver bullet against infectivity. (Did anywhere end up staffing COVID wards with people who'd already had the disease/virus?)
Other than my original suggestion was there ANY other good reason to label the recovered as likely to have less or no immunity (to disease at the very least) than the vaccinated? Hmmm ahhhh, OK, not going there. There was a time before Sars Cov2 vaccines however. The original weeks of "We know nothing, we MUST throw the baby out with the bath water" reaction cannot justify all the weirdness that has followed, surely? I sometimes wonder how different things would have been if the default starting point had been to build on what was already known, moving on to calm, well designed investigations to confirm it.
Thanks for stating the obvious so well, Alasdair. Thanks for standing up for the clinically unwell and what their needs really are. Thanks for holding onto the bath water along with the baby and not pandering to the toddlers throwing their toys out of the pram*
*Child analogies blatantly intended
Well done. Even Pfizer admitted that they were uncertain of the Cora relation between antibody levels and protection. But we could have had better data on this had the rcts not been prematurely ended. Sure I know the argument that it was unethical to continue them and that's fallacious since we really didn't have evidence that severe outcomes were worse in the unvaccinated group.
Point of fact all cause mortality was worse in the vaccinated group when the trials were terminated
"For Covid-19 immunity, these show that immunity following infection is comparable to that following vaccination."
But shouldn't infection produce antibodies to various viral proteins which should hinder/prevent immune escape, which has been a major problem for jabs? So, theoretically, shouldn't we _expect_ natural immunity to be superior to jabs?
It often is but not always.
The immune system is a complicated thing, and finding reliable correlates of protection is one of its biggest challenges!
That’s why the clinical data is so important.
Indeed, the immune system is complicated. Do you have any correlates that you use?
Pardon my ramblings about the immune system.
Zinc and selenium deficiency can undermine the immune system, and, of course, deficiencies in vits. A, C, D, and the B complex will do so as well. D deficiency is a mine worth mining to improve immune competence for all sorts of reasons--correlations between risk of severe covid and D-deficient groups and D deficiency/insufficiency being a common occurrence in almost all populations--especially in winter in extreme latitudes.
D deficiency is implicated strongly in covid ARDS and sepsis because vit. D is needed for the normal immune process of inflammation reduction of previously infected tissues after the virus has been cleared. I think that some form of prednisone may be prescribed in case of vit. D deficiency and high inflammation markers, but that's only my non-medical opinion.
Supplementation with D3 is dilatory compared with calcifediol supplementation, but a large dose (300k units) of D3 can take effect in a few days, from what I am reading. I don't know if it will work in ICU, but maybe it will in non-intensive covid wards. Certainly, D3 is worth a go in cases of mild covid in community care in case it may prevent progression and shorten symptoms and perhaps prevent long covid. Risk is negligible and there may be benefit.
Groups at risk for D3 deficiency include the elderly, the obese, the dark-complected, and those with liver dysfunction. Coincidentally, these groups are also at elevated risk for severe covid.
I guess we can quote Rob Hughes again.