Also relevant: My half-joke to my friend earlier this month that if Omicron really is super-duper-mild and gives immunity against worse variants, maybe we should just rebrand it as a vaccine.
Yep, and I'd say it as more than a half-joke. At some degree of mildness (perhaps Omicron is close to this level) surely we'd actually choose, if we could, for it to be more infectious rather than less. That's the way we can help the vaccine-alarmed.
May I say how much I appreciate the fairness: criticism when the FDA seems to be doing harm, praise when it seems to be improving. Neither all-regulation-is-always-bad nor all-regulation-is-always-good. Calling balls and strikes.
One problem with all of this is that it is hard to see how to do the incentives right. In the future, not too many people are going to care/remember extra efficiency (say a two week sooner approval of the vaccine) but all of us are going to remember if people grew two noses after they got a shot. The people in charge are way more scared of making a mistake in the direction of not enough caution...but that is probably correctly mirroring public opinion. This particular pandemic is showing how bad public opinion can be for this kind of thing. Seems like an unavoidable problem with an adversary based political system.
It's important to remember that the FDA is still shit overall even if they've accidentally managed to get a few things (these two issues and opposing boosters for the general population) correct recently.
Great news about Paxlovid! Does anyone know what the availability timeline will be? Will it be prescribed to people who get sick in the next week in the US? Or is it going to be a few weeks to months before it's generally available?
Generally available? Paxlovid is never going to be generally available - it's 550 dollars per person! Do you not see the carnage and grief this is going to cause?
$550 is much less than the cost of a day in the hospital. For insured people, this will absolutely be generally available. The US government has made promises to pay substantially more than this for uninsured people to receive monoclonal antibodies for the past several months, so I expect them to cover this too.
Apologies for my misunderstanding. I guess you were thinking about general availability to Americans and I was thinking about the wider world. Seeing as you mentioned "in the US" your meaning should have been clear to me.
I've heard they expect to have a few hundred thousand doses available before the end of the month. Given that there are about 150,000 positive test results in the USA per day right now, it'll take a lot more before it is "generally available".
It does sound like they expect to have several hundred million doses manufactured in the next year. It looks like there have been fewer than 300 million total positive tests worldwide since the start of the pandemic, so it does seem likely that in a few months it should be "generally available" in the places where people have access to moderately expensive cutting-edge medications.
Where did you hear "several hundred million doses"? This is from the Washington Post article on the approval today:
> Pfizer has been working to scale up to produce 120 million pill packs in 2022, but those doses will not be available all at once. Mike McDermott, Pfizer’s president of global supply, said that the current goal is to have about 30 million treatments available by the middle of next year but that the company is looking for ways to speed up and increase production.
That's a much less optimistic take on speed of availability.
It won’t be available to everyone. It will be prescribed to people deemed high risk. I have not seen info about what criteria will be used for assessing someone’s risk, but it’s a drug intended to be started within 5 days of diagnosis, so it seems like risk assessment will be based on things like age and pre-existing conditions, not on clinical course. Of course vaccination status is a major determinant of risk, but I have yet to see any mention in the press of this issue (which is one guaranteed to give many people an immediate case of Rage Virus).
Am I the only person seeing problems with the whole "people deemed high risk"? In particularly litigious countries I can see lawyers making hay (and a good living) from saying "my client pleaded to be given Paxlovid and is now stone cold dead as a result of a clinicians refusal"
This is over and above the problems of unvaccinated people automatically being high risk and there being a very limited supply of the drug.
I'm generally speaking an vociferous anti-doomer, but I can see a whole heap of problemos following the approval of Paxlovid, along with the obvious good things.
FWIW, I was triple vaccinated (two of Pfizer and the booster as soon as I was eligible), just tested positive for COVID last night. The authorities would characterize my case as "mild" since I'm not on a ventilator, but it doesn't necessarily feel "mild." Even taking a hospital-grade cough suppressant, I have coughing fits so severe that my neck hurts afterwards and I have to lie down. High temperature, aches, sinus congestion, can't sleep through the night, etc. It's certainly the sickest I've been in many years, perhaps a decade.
My doctor at Mt. Sinai in NYC told me they aren't offering any ambulatory treatment to vaccinated patients, because they consider breakthrough infections to be low risk. You have to be unvaccinated to qualify for the scarce treatments like the GSK monoclonal antibodies. My doctor there also refused to prescribe fluvoxamine. He initially equated it to ivermectin and didn't seem to know there had been a big study suggesting some more meaningful effectiveness. After I pointed him to the Scott Alexander post and the Johns Hopkins protocol, he quickly Googled fluvoxamine and then said he still would not prescribe because the study said no evidence of a reduction of mortality and he thinks SSRIs carry a risk of suicidal ideation.
So . . . my experience, at least, is that vaccine + booster shot doesn't help too much against Omicron. And if you get it, you won't get any treatments.
Maybe the mechanism is neurolinguistic or kotodamaic - after all fluvoxamine sounds remarkably like flu vaccine. Perhaps this is merely a case of the True Name principle. Differential studies must be carried out immediately.
The paxlovid thing is interesting since it seems like nearly all the delay was the pharma company sending them the study data,the approval came about a week after that. Actually decreased my pessimism about the FDA a decent bit after learning that.
Nice to hear about some big wins today!
Approved COVID —> Approved Luvox :-)
Relevant to the typo'd version: https://twitter.com/slatestarcodex/status/1465211423168995328
Also relevant: My half-joke to my friend earlier this month that if Omicron really is super-duper-mild and gives immunity against worse variants, maybe we should just rebrand it as a vaccine.
I’m waiting for the Omicron passports.
After all, the original 'vaccine', cowpox/vaccinia, is a very mild disease related to smallpox, which gives immunity against the latter.
Yep, and I'd say it as more than a half-joke. At some degree of mildness (perhaps Omicron is close to this level) surely we'd actually choose, if we could, for it to be more infectious rather than less. That's the way we can help the vaccine-alarmed.
Also: https://apnews.com/article/coronavirus-pandemic-business-health-boeing-co-66f15a491da89f5037502a7c4a3b2e41
May I say how much I appreciate the fairness: criticism when the FDA seems to be doing harm, praise when it seems to be improving. Neither all-regulation-is-always-bad nor all-regulation-is-always-good. Calling balls and strikes.
It is an improvement by reducing the harm done.
It's a Christmas miracle!
This is proof the FDA can do an EUA without waiting 4 weeks to convene an advisory panel, if they want to.
I signed the letter of support for the fluvoxamine EUA!(https://docs.google.com/forms/d/e/1FAIpQLSc7TATp80UcJiNns1tufyl8G36TQCnib7Sw0vtE2KQ6gAwgmA/viewform)
Great news. Thank you for the update.
One problem with all of this is that it is hard to see how to do the incentives right. In the future, not too many people are going to care/remember extra efficiency (say a two week sooner approval of the vaccine) but all of us are going to remember if people grew two noses after they got a shot. The people in charge are way more scared of making a mistake in the direction of not enough caution...but that is probably correctly mirroring public opinion. This particular pandemic is showing how bad public opinion can be for this kind of thing. Seems like an unavoidable problem with an adversary based political system.
It's important to remember that the FDA is still shit overall even if they've accidentally managed to get a few things (these two issues and opposing boosters for the general population) correct recently.
I really think Paxlovid will finally end this horseshit.
Totally agree. It will eliminate fear of getting infected. We are on our way to normal.
Hope so.
When Scott complains, things get done, man.
Great news about Paxlovid! Does anyone know what the availability timeline will be? Will it be prescribed to people who get sick in the next week in the US? Or is it going to be a few weeks to months before it's generally available?
Generally available? Paxlovid is never going to be generally available - it's 550 dollars per person! Do you not see the carnage and grief this is going to cause?
$550 is much less than the cost of a day in the hospital. For insured people, this will absolutely be generally available. The US government has made promises to pay substantially more than this for uninsured people to receive monoclonal antibodies for the past several months, so I expect them to cover this too.
I meant available in the sense that they will be physically available at pharmacies or hospitals for people who need them.
Apologies for my misunderstanding. I guess you were thinking about general availability to Americans and I was thinking about the wider world. Seeing as you mentioned "in the US" your meaning should have been clear to me.
I've heard they expect to have a few hundred thousand doses available before the end of the month. Given that there are about 150,000 positive test results in the USA per day right now, it'll take a lot more before it is "generally available".
It does sound like they expect to have several hundred million doses manufactured in the next year. It looks like there have been fewer than 300 million total positive tests worldwide since the start of the pandemic, so it does seem likely that in a few months it should be "generally available" in the places where people have access to moderately expensive cutting-edge medications.
Where did you hear "several hundred million doses"? This is from the Washington Post article on the approval today:
> Pfizer has been working to scale up to produce 120 million pill packs in 2022, but those doses will not be available all at once. Mike McDermott, Pfizer’s president of global supply, said that the current goal is to have about 30 million treatments available by the middle of next year but that the company is looking for ways to speed up and increase production.
That's a much less optimistic take on speed of availability.
I think I had mis-remembered that "120 million" number as "200 million".
Thank you!
It won’t be available to everyone. It will be prescribed to people deemed high risk. I have not seen info about what criteria will be used for assessing someone’s risk, but it’s a drug intended to be started within 5 days of diagnosis, so it seems like risk assessment will be based on things like age and pre-existing conditions, not on clinical course. Of course vaccination status is a major determinant of risk, but I have yet to see any mention in the press of this issue (which is one guaranteed to give many people an immediate case of Rage Virus).
Am I the only person seeing problems with the whole "people deemed high risk"? In particularly litigious countries I can see lawyers making hay (and a good living) from saying "my client pleaded to be given Paxlovid and is now stone cold dead as a result of a clinicians refusal"
This is over and above the problems of unvaccinated people automatically being high risk and there being a very limited supply of the drug.
I'm generally speaking an vociferous anti-doomer, but I can see a whole heap of problemos following the approval of Paxlovid, along with the obvious good things.
Awesome, Well done FDA. Boosted Monday, (flexes muscles), bring on Omicron, I'm ready. (as I'll ever be.)
FWIW, I was triple vaccinated (two of Pfizer and the booster as soon as I was eligible), just tested positive for COVID last night. The authorities would characterize my case as "mild" since I'm not on a ventilator, but it doesn't necessarily feel "mild." Even taking a hospital-grade cough suppressant, I have coughing fits so severe that my neck hurts afterwards and I have to lie down. High temperature, aches, sinus congestion, can't sleep through the night, etc. It's certainly the sickest I've been in many years, perhaps a decade.
My doctor at Mt. Sinai in NYC told me they aren't offering any ambulatory treatment to vaccinated patients, because they consider breakthrough infections to be low risk. You have to be unvaccinated to qualify for the scarce treatments like the GSK monoclonal antibodies. My doctor there also refused to prescribe fluvoxamine. He initially equated it to ivermectin and didn't seem to know there had been a big study suggesting some more meaningful effectiveness. After I pointed him to the Scott Alexander post and the Johns Hopkins protocol, he quickly Googled fluvoxamine and then said he still would not prescribe because the study said no evidence of a reduction of mortality and he thinks SSRIs carry a risk of suicidal ideation.
So . . . my experience, at least, is that vaccine + booster shot doesn't help too much against Omicron. And if you get it, you won't get any treatments.
Mr. Alexander—
You have surely convinced all your readership that the FDA kind of sucks.
Perhaps next you could study what exactly makes it suck, and what policy changes would improve it.
Maybe the mechanism is neurolinguistic or kotodamaic - after all fluvoxamine sounds remarkably like flu vaccine. Perhaps this is merely a case of the True Name principle. Differential studies must be carried out immediately.
Scott, keep pushing for ketamine approval for depression and suicidality. It is ridiculous that it isn't approved for that.
> According to Metaculus, there was only a 6% chance we would get Paxlovid approved this quickly.
There's a bias in this number: At the time of Metaculus' opinion, it had already updated on Paxlovid having not been approved in the past.
To quote Scott:
"Here’s my pitch for fluvoxamine (Luvox) for COVID.
In the midst of all the hype about ivermectin and hydroxychloroquine, scientists put together the giant
4,000-person TOGETHER trial, intended to test all these exciting COVID early treatments. You know what
happened next: ivermectin and hydroxychloroquine crashed and burned.
But a different drug, the SSRI antidepressant fluvoxamine, actually did really well!
It decreased COVID hospitalizations by about 30% "
OK. Let's actually look at the report from the TOGETHER trial:
https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00448-4/fulltext
This trial had a primary endpoint of hospitalisation.
"Our primary outcome was a composite endpoint of hospitalisation defined as either
retention in a COVID-19 emergency setting or transfer to tertiary hospital due to COVID-19
up to 28 days postrandom assignment on the basis of intention to treat."
The result was about a 30% improvement in this metric with treatment with fluvoxamine. This is encouraging,
but look at the secondary findings:
"Table 3 presents findings from secondary outcome
analyses. There were no significant differences between
fluvoxamine and placebo for viral clearance at day 7
(p=0·090) and hospitalisations due to COVID (p=0·10),
all-cause hospitalisations (p=0·09), time to hospitalisation
(p=0·11), number of days in hospital (p=0·06), mortality
(p=0·24), time to death (p=0·49), number of days on
mechanical ventilation (p=0·90), time to recovery
(p=0·79) or the PROMIS Global Physical (p=0·55) or
Mental Scale (p=0·32; appendix 2 p 8)."
>>>No Difference<<< in
hospitalisations due to COVID (p=0·10)
mortality (p=0·24)
time to death (p=0·49)
Why does anyone care about the primary endpoint when you're going to die just as fast?
So what is the rational argument for approving a drug that has shown no improvement in hospitalisation or death?
I certainly wouldn't fault FDA for not approving a drug on this sort of evidence.
Thanks for the heads up. I just signed it.
And what was your rational for signing it?
The paxlovid thing is interesting since it seems like nearly all the delay was the pharma company sending them the study data,the approval came about a week after that. Actually decreased my pessimism about the FDA a decent bit after learning that.