The testing is so maddening. The FDA could say: “we are going to provisionally authorize for sale any test that has been approved by the EU, UK, Japanese or South Korean authorities.” This isn’t thalidomide- the worst possible outcome is somewhat higher error rates. Big deal.
The Biden administration’s passivity on COVID has been so frustrating. There are so many things they could be doing - none of which require approval from Republicans and/or Sinema/Manchin. To pull in another stream from “the discourse” - this would be a perfect job for Kamala Harris. She could be the COVID czar- running around and pushing end runs around these dumb regulatory barriers. It would be great the country and even better for her!
Imagine it- here’s Harris at the FDA announcing that they are now authorizing foreign rapid tests, with the expectation that they will be significantly cheaper. Two weeks later - here’s Harris again at a Walmart, where they have started putting foreign tests on the shelves and they’ll cost $3 each. Here’s Harris at a big research university where they are beginning human challenge trials of a new super-targeted Omicron booster (check out the footage of the super wholesome photogenic young volunteers). Here’s Harris at a Moderna manufacturing plant, 3 weeks later the day after the successful completion of the trial where they are starting up production of the new Omicron booster. Here’s Harris at an airport - at a new TSA lane where travelers can voluntarily prove their vax status and take a rapid test - but then they get a tamper proof bracelet that lets them fly that day without a mask.
There so much they could be doing - every two weeks or so we could see Harris on TV and we’d love seeing her because each time she’d be doing something that is making the pandemic just a little bit easier to deal with.
The CDC seems to have a weird inverted pyramid of evidence where “any study conducted by the CDC” is at the top, “double blind study conducted by a fancy drug company” appears somewhere in the middle, and “anything out of Israel or Great Britain” is at the bottom. That’s how we end up with essentially all guidance determined by a couple observational studies of Provincetown Bear Week and some incident in a Marin county school while the high quality studies conducted by nationalised health care systems go seemingly ignored.
There's a really fascinating how-the-other-side-lives angle to this article, somewhat orthogonal to its main thrust.
Away from the Coastal Elites (TM), in my lefty, 85%-of-adults-vaccinated MSA, I've gotten one covid test ever (got violently sick from some bad chicken--practice safe refrigeration, folks!). Regular testing as policy, beyond definite exposure to someone who is confirmed positive, isn't a culture-war flashpoint--it's unheard-of, not discussed as even a theory. Aside from pretending masks matter when we're standing in the restaurant and not when we're sitting, the 'rona is over, and our death rate last month was about 1/100,000.
¯\_(ツ)_/¯
I'm not yet bought into the idea that there's a segment of the population that adopted the pandemic as a part of their identity and refuses to let it go, but I'm no longer able to casually dismiss that idea. The local paper sure has figured out what types of coronavirus get clicks, though. The vaccines "may" offer "somewhat less" protection against a new variant, and other technically-correct weasel language of that nature.
Chickens always come home to roost. As an old guy I well remember when governments had a hard time finding manufacturers of vaccines at all. The margins were low, even the best produced rare serious and occasionally lethal side effects so the absolutely insane American tort laws made this a very risky business to do. The intelligent thing was done and a kind of insurance pool was created to assist people with the consequences of rare adverse side effects and legal recourse was limited. I note that this was universally excoriated on the left, as was all product liability tort reform. They wanted vaccines but also the power to sue the vaccine manufacturers out of existence.
I will add, as an interesting side point, that before Covid exploded into our world, the largest manufacturer of N95 masks in the United States, 3M, was successfully sued by exactly two coal miners for about thirty million dollars. The theory here being that defective masks resulted in their getting black lung. Do I believe this? Nope. But a jury did.
With regard to test kits for Covid one has to ask, why would any sane manufacturer rush to invest in making tests of dubious reliability (thereby creating a low margin high risk business model) when they are virtually certain to face class action suits related to false positives or false negatives. Is someone planning on addressing this issue? I can't find anyone doing so. And I am willing to bet that various members of the ABA are salivating at the prospects.
Are there any good articles or definitive explanation about why the FDA has been so slow to approve covid tests that Europe has? Is it regulatory capture by incumbents who want to jack up prices? Slow bureaucracy, somehow less efficient than European states?
"But is it actually true that the Moderna vaccine is “more effective,” or are they just giving you triple the dose? An ibuprofen gel tab is no more effective than a normal ibuprofen pill, but if you take 3x the dosage of the gel tab that will have a stronger effect."
This is a terrible analogy! It's like observing that pressing down on the gas peddle makes your car go faster, so logically, pouring gasoline all over the engine and lighting on fire will make it go even faster.
Ibuprofen circulates in the bloodstream. It binds receptors (on cyclo-oxygenase) antagonistically, meaning it is inhibitory. The higher the concentration of ibuprofen, the further the equilibrium shifts towards bound ligand-protein, i.e., the greater the effect. Fluvoxamine is an agonist towards a receptor that leads to the up-regulation of a an anti-inflammatory. In both cases, higher doses lead to higher concentrations in the bloodstream, which lead to greater (side)effects.
The Pfizer and Moderna vaccines are suspensions of lipid nanoparticles containing messenger RNA. They are injected locally in to muscle tissue specifically so that they do not enter the blood stream. Their efficacy is unrelated to binding constants; once a strand of m-RNA makes it into the cytoplasm, it is actively transported into the ribosome where its sequence is transcribed into a protein. That protein is then released, but since it is exogenous, the immune system identifies it as such, generates antibodies to attack it and then retains a record of the antibodies for later use. Higher doses may elicit stronger immune responses by producing proteins in more cells (with the upper-bounds being full-blown COVID-19 symptoms), but they might also cause necrosis.
Moreover, the Moderna and Pfizer vaccines encode different sequences, so they are not even producing the same proteins. It could just as easily be the case that higher Pfizer doses would lead to worse immune responses because they interact with antibodies differently from the Moderna-instantiated proteins.
It's easy to armchair quarterback vaccine development and testing with bad analogies, easier still to assume a profit motive behind Pfizer's vaccine schedule. But the reality is that these things are not arbitrary and people far more knowledgeable about mRNA vaccines, epidemiology and clinical trials than any of us were intimately involved in planning and executing the vaccine trials.
I'm not arguing against more testing, but I see stupid analogies like this everywhere, usually in the context of trying to make the CDC or FDA or scientists look lazy or stupid. Worse, this is the same faulty reasoning that is used to attack epidemiology; it is common sense that higher doses work better than lower doses, so clearly there is a conspiracy theory and/or these hacks with their fancy degrees do not know what they are doing.
"For example, the folks at Pfizer decided they wanted to test a 30-microgram dose, while Moderna scientists decided to test a 100-microgram dose. We learned from those experiments that 30-micrograms of Pfizer work but 100-micrograms of Moderna work better. But is it actually true that the Moderna vaccine is “more effective,” or are they just giving you triple the dose?"
That's not an apples-to-apples comparison though; they're different vaccines. Drug makers do a lot of calculations to try to predict the proper human dose and then adjust as they start running the trials. For example, you wouldn't assume to take the same amount of acetaminophen or ibuprofen to treat a headache, even though people use those for similar purposes.
For at home rapid testing, I agree in principle that we should be doing for more of that, but this article in the Atlantic gave me pause: https://www.theatlantic.com/health/archive/2021/12/jen-psaki-free-rapid-covid-testing-sarcastic/620925/. Germany and the UK have been doing widespread rapid testing and have still faced large numbers of COVID cases lately. The article does note the objection that perhaps we should be doing even higher levels of testing than they're already doing but then glosses over it without really addressing whether that would make a difference, so I'm not 100% convinced either way on this.
As for molnupiravir, I saw Zeynep Tufecki flagged the potential for viral mutations from non-compliance the other day... not sure how much of concern that is, but it's certainly not zero. But the bigger thing is, Pfizer already demonstrated that Paxlovid is far more effective! It's a protease inhibitor and the mechanism of action (MoA) is such that it should attack all variants of COVID. So there's no need to take the risk on molnupiravir unless someone is going to run a trial for a combination therapy (but molnupiravir is a Merck drug, so the companies would have to iron out the legal details with that).
The government healthcare community picked sides in the culture wars. Once they did that conservatives shut them out. The scientist need to say “I don’t do culture wars, I just do science. I follow facts wherever they lead”. Fauci should step down and Biden should appoint someone who takes this approach. That would be better for the country. Fair or not fair, Fauci is viewed as a partisan.
"So everyone is following procedure and doing things by the book."
Of course they are. Because if the school does one thing that hasn't been government approved and one child gets sick, they are going to get sued. Until the longer dosing regime is approved by the government, no school or other entity is even going to entertain the thought of doing it differently.
Even if they really, really wanted to go with the best evidence and change the dose timing, their lawyers would advise them not to and get signed statements saying this was our advise and they are acting against our advise.
If you read the SEC filings, earnings conference calls, etc. from Quidel, maker of the QuickVue rapid test and a smaller competitor to Abbott, it is absolutely clear that the limiting factor in Quidel rolling out more tests is production capacity. And on top of that, the US government itself has tied up a lot of Quidel's output with a large DoD contract to buy QuickVue tests. But nowhere is the government subsidizing increases to the production capacity.
Meanwhile, a company like Quidel is beholden to shareholders and cannot reasonably justify building out crisis-level capacity when it may not be needed in 2 or 5 years. At the same time, such capacity - if created with government help - could be an element of a government-led quick-response program for future pandemics.
Also on masking. LA Public health is still handing out CLOTH masks at vaccine centers, with public health logos on them. This suggests that LA Public Health thinks cloth is just as good as N95 (which is widely available in Los Angeles), which is clearly not the case.
The challenge for the intelligent generalist pundit, like Matt, is to be read up enough on a subject and fast enough to be able to say something interesting and meaningful. The problem is that you don't know as much as the people on the inside and often don't really have the professional background to discern what is a screwup and what is driven by concrete obstacles.
For all I know, the FDA and the CDC have been and continue to screw up in unforgiveable ways (Scott Gottlieb's new book, "Uncontrolled Spread" is very good on this, though I note that he's a lot more unforgiving to the CDC than the FDA, which he had headed). But what I also know from professional experience is that it's often the things you don't know that are really meaningful and can refute what you think is the truth and the path forward. Life is complicated.
An example of this is congestion at the LA/Long Beach port. Bad problem, and people who know very little instantly opined on how to fix it. But as you dig deeper into the details, you realize that we're facing a series of bottlenecks, and each one needs to be resolved sequentially, after doing due diligence. It's usually never "one weird trick."
So Matt may be way off base here -- though none of us is expert or informed enough to know. That said, we need people like Matt out there asking interesting questions and trying to inform the public, even when he doesn't know enough to give us the full truth.
Another issue is with respect to quarantines. It does not seem that the PHA at large have adjusted their quarantine requirement other than to reduce it from 14 to 10 days. Most of this guidance preceded the onset of vaccines.
Here in Ohio, I'm able to stop by the local rec center and pick up a free Binax Now test. They have a weird layer of bureaucracy where the box doesn't include instructions and they want you to use an online proctor, but apparently that is just so that the results can be "officially" used for school, travel, etc. https://coronavirus.ohio.gov/wps/portal/gov/covid-19/resources/general-resources/rapid-covid-19-test
The testing is so maddening. The FDA could say: “we are going to provisionally authorize for sale any test that has been approved by the EU, UK, Japanese or South Korean authorities.” This isn’t thalidomide- the worst possible outcome is somewhat higher error rates. Big deal.
The Biden administration’s passivity on COVID has been so frustrating. There are so many things they could be doing - none of which require approval from Republicans and/or Sinema/Manchin. To pull in another stream from “the discourse” - this would be a perfect job for Kamala Harris. She could be the COVID czar- running around and pushing end runs around these dumb regulatory barriers. It would be great the country and even better for her!
Imagine it- here’s Harris at the FDA announcing that they are now authorizing foreign rapid tests, with the expectation that they will be significantly cheaper. Two weeks later - here’s Harris again at a Walmart, where they have started putting foreign tests on the shelves and they’ll cost $3 each. Here’s Harris at a big research university where they are beginning human challenge trials of a new super-targeted Omicron booster (check out the footage of the super wholesome photogenic young volunteers). Here’s Harris at a Moderna manufacturing plant, 3 weeks later the day after the successful completion of the trial where they are starting up production of the new Omicron booster. Here’s Harris at an airport - at a new TSA lane where travelers can voluntarily prove their vax status and take a rapid test - but then they get a tamper proof bracelet that lets them fly that day without a mask.
There so much they could be doing - every two weeks or so we could see Harris on TV and we’d love seeing her because each time she’d be doing something that is making the pandemic just a little bit easier to deal with.
<sigh> I’ll go back to dreaming again.
The CDC seems to have a weird inverted pyramid of evidence where “any study conducted by the CDC” is at the top, “double blind study conducted by a fancy drug company” appears somewhere in the middle, and “anything out of Israel or Great Britain” is at the bottom. That’s how we end up with essentially all guidance determined by a couple observational studies of Provincetown Bear Week and some incident in a Marin county school while the high quality studies conducted by nationalised health care systems go seemingly ignored.
There's a really fascinating how-the-other-side-lives angle to this article, somewhat orthogonal to its main thrust.
Away from the Coastal Elites (TM), in my lefty, 85%-of-adults-vaccinated MSA, I've gotten one covid test ever (got violently sick from some bad chicken--practice safe refrigeration, folks!). Regular testing as policy, beyond definite exposure to someone who is confirmed positive, isn't a culture-war flashpoint--it's unheard-of, not discussed as even a theory. Aside from pretending masks matter when we're standing in the restaurant and not when we're sitting, the 'rona is over, and our death rate last month was about 1/100,000.
¯\_(ツ)_/¯
I'm not yet bought into the idea that there's a segment of the population that adopted the pandemic as a part of their identity and refuses to let it go, but I'm no longer able to casually dismiss that idea. The local paper sure has figured out what types of coronavirus get clicks, though. The vaccines "may" offer "somewhat less" protection against a new variant, and other technically-correct weasel language of that nature.
Chickens always come home to roost. As an old guy I well remember when governments had a hard time finding manufacturers of vaccines at all. The margins were low, even the best produced rare serious and occasionally lethal side effects so the absolutely insane American tort laws made this a very risky business to do. The intelligent thing was done and a kind of insurance pool was created to assist people with the consequences of rare adverse side effects and legal recourse was limited. I note that this was universally excoriated on the left, as was all product liability tort reform. They wanted vaccines but also the power to sue the vaccine manufacturers out of existence.
I will add, as an interesting side point, that before Covid exploded into our world, the largest manufacturer of N95 masks in the United States, 3M, was successfully sued by exactly two coal miners for about thirty million dollars. The theory here being that defective masks resulted in their getting black lung. Do I believe this? Nope. But a jury did.
With regard to test kits for Covid one has to ask, why would any sane manufacturer rush to invest in making tests of dubious reliability (thereby creating a low margin high risk business model) when they are virtually certain to face class action suits related to false positives or false negatives. Is someone planning on addressing this issue? I can't find anyone doing so. And I am willing to bet that various members of the ABA are salivating at the prospects.
Are there any good articles or definitive explanation about why the FDA has been so slow to approve covid tests that Europe has? Is it regulatory capture by incumbents who want to jack up prices? Slow bureaucracy, somehow less efficient than European states?
"But is it actually true that the Moderna vaccine is “more effective,” or are they just giving you triple the dose? An ibuprofen gel tab is no more effective than a normal ibuprofen pill, but if you take 3x the dosage of the gel tab that will have a stronger effect."
This is a terrible analogy! It's like observing that pressing down on the gas peddle makes your car go faster, so logically, pouring gasoline all over the engine and lighting on fire will make it go even faster.
Ibuprofen circulates in the bloodstream. It binds receptors (on cyclo-oxygenase) antagonistically, meaning it is inhibitory. The higher the concentration of ibuprofen, the further the equilibrium shifts towards bound ligand-protein, i.e., the greater the effect. Fluvoxamine is an agonist towards a receptor that leads to the up-regulation of a an anti-inflammatory. In both cases, higher doses lead to higher concentrations in the bloodstream, which lead to greater (side)effects.
The Pfizer and Moderna vaccines are suspensions of lipid nanoparticles containing messenger RNA. They are injected locally in to muscle tissue specifically so that they do not enter the blood stream. Their efficacy is unrelated to binding constants; once a strand of m-RNA makes it into the cytoplasm, it is actively transported into the ribosome where its sequence is transcribed into a protein. That protein is then released, but since it is exogenous, the immune system identifies it as such, generates antibodies to attack it and then retains a record of the antibodies for later use. Higher doses may elicit stronger immune responses by producing proteins in more cells (with the upper-bounds being full-blown COVID-19 symptoms), but they might also cause necrosis.
Moreover, the Moderna and Pfizer vaccines encode different sequences, so they are not even producing the same proteins. It could just as easily be the case that higher Pfizer doses would lead to worse immune responses because they interact with antibodies differently from the Moderna-instantiated proteins.
It's easy to armchair quarterback vaccine development and testing with bad analogies, easier still to assume a profit motive behind Pfizer's vaccine schedule. But the reality is that these things are not arbitrary and people far more knowledgeable about mRNA vaccines, epidemiology and clinical trials than any of us were intimately involved in planning and executing the vaccine trials.
I'm not arguing against more testing, but I see stupid analogies like this everywhere, usually in the context of trying to make the CDC or FDA or scientists look lazy or stupid. Worse, this is the same faulty reasoning that is used to attack epidemiology; it is common sense that higher doses work better than lower doses, so clearly there is a conspiracy theory and/or these hacks with their fancy degrees do not know what they are doing.
"For example, the folks at Pfizer decided they wanted to test a 30-microgram dose, while Moderna scientists decided to test a 100-microgram dose. We learned from those experiments that 30-micrograms of Pfizer work but 100-micrograms of Moderna work better. But is it actually true that the Moderna vaccine is “more effective,” or are they just giving you triple the dose?"
That's not an apples-to-apples comparison though; they're different vaccines. Drug makers do a lot of calculations to try to predict the proper human dose and then adjust as they start running the trials. For example, you wouldn't assume to take the same amount of acetaminophen or ibuprofen to treat a headache, even though people use those for similar purposes.
For at home rapid testing, I agree in principle that we should be doing for more of that, but this article in the Atlantic gave me pause: https://www.theatlantic.com/health/archive/2021/12/jen-psaki-free-rapid-covid-testing-sarcastic/620925/. Germany and the UK have been doing widespread rapid testing and have still faced large numbers of COVID cases lately. The article does note the objection that perhaps we should be doing even higher levels of testing than they're already doing but then glosses over it without really addressing whether that would make a difference, so I'm not 100% convinced either way on this.
As for molnupiravir, I saw Zeynep Tufecki flagged the potential for viral mutations from non-compliance the other day... not sure how much of concern that is, but it's certainly not zero. But the bigger thing is, Pfizer already demonstrated that Paxlovid is far more effective! It's a protease inhibitor and the mechanism of action (MoA) is such that it should attack all variants of COVID. So there's no need to take the risk on molnupiravir unless someone is going to run a trial for a combination therapy (but molnupiravir is a Merck drug, so the companies would have to iron out the legal details with that).
The government healthcare community picked sides in the culture wars. Once they did that conservatives shut them out. The scientist need to say “I don’t do culture wars, I just do science. I follow facts wherever they lead”. Fauci should step down and Biden should appoint someone who takes this approach. That would be better for the country. Fair or not fair, Fauci is viewed as a partisan.
Welcome to American public "discourse:"
All culture war, all the time. Every facet of life is a new front in the culture war.
"So everyone is following procedure and doing things by the book."
Of course they are. Because if the school does one thing that hasn't been government approved and one child gets sick, they are going to get sued. Until the longer dosing regime is approved by the government, no school or other entity is even going to entertain the thought of doing it differently.
Even if they really, really wanted to go with the best evidence and change the dose timing, their lawyers would advise them not to and get signed statements saying this was our advise and they are acting against our advise.
It is a giant CYA.
If you read the SEC filings, earnings conference calls, etc. from Quidel, maker of the QuickVue rapid test and a smaller competitor to Abbott, it is absolutely clear that the limiting factor in Quidel rolling out more tests is production capacity. And on top of that, the US government itself has tied up a lot of Quidel's output with a large DoD contract to buy QuickVue tests. But nowhere is the government subsidizing increases to the production capacity.
Meanwhile, a company like Quidel is beholden to shareholders and cannot reasonably justify building out crisis-level capacity when it may not be needed in 2 or 5 years. At the same time, such capacity - if created with government help - could be an element of a government-led quick-response program for future pandemics.
Here's some detail on the DoD contracts: https://www.nsmedicaldevices.com/news/four-firms-win-647m-contracts-from-us-dod-to-supply-covid-19-test-kits/
Also on masking. LA Public health is still handing out CLOTH masks at vaccine centers, with public health logos on them. This suggests that LA Public Health thinks cloth is just as good as N95 (which is widely available in Los Angeles), which is clearly not the case.
The challenge for the intelligent generalist pundit, like Matt, is to be read up enough on a subject and fast enough to be able to say something interesting and meaningful. The problem is that you don't know as much as the people on the inside and often don't really have the professional background to discern what is a screwup and what is driven by concrete obstacles.
For all I know, the FDA and the CDC have been and continue to screw up in unforgiveable ways (Scott Gottlieb's new book, "Uncontrolled Spread" is very good on this, though I note that he's a lot more unforgiving to the CDC than the FDA, which he had headed). But what I also know from professional experience is that it's often the things you don't know that are really meaningful and can refute what you think is the truth and the path forward. Life is complicated.
An example of this is congestion at the LA/Long Beach port. Bad problem, and people who know very little instantly opined on how to fix it. But as you dig deeper into the details, you realize that we're facing a series of bottlenecks, and each one needs to be resolved sequentially, after doing due diligence. It's usually never "one weird trick."
So Matt may be way off base here -- though none of us is expert or informed enough to know. That said, we need people like Matt out there asking interesting questions and trying to inform the public, even when he doesn't know enough to give us the full truth.
Looking at Publix discourse at this point, I’m unsure whether we’re supposed to follow the science, or Follow The Science (TM).
These are two very different things.
Another issue is with respect to quarantines. It does not seem that the PHA at large have adjusted their quarantine requirement other than to reduce it from 14 to 10 days. Most of this guidance preceded the onset of vaccines.
https://www.theatlantic.com/science/archive/2021/12/fully-vaccinated-covid-isolation-breakthrough-transmission/620919/
Here in Ohio, I'm able to stop by the local rec center and pick up a free Binax Now test. They have a weird layer of bureaucracy where the box doesn't include instructions and they want you to use an online proctor, but apparently that is just so that the results can be "officially" used for school, travel, etc. https://coronavirus.ohio.gov/wps/portal/gov/covid-19/resources/general-resources/rapid-covid-19-test