Would like to add that the adcom meeting that happened yesterday wasn't unanimous even though efficacy data was strong because of they were asked to approve it for 17 and 16 year olds as well even though the data for these age groups was lackluster.
This likely didn't matter much to FDA because 16 and 17 year olds aren't likely to receive any doses before the full throated approval because they by and large aren't in the people first in line for the vax (1st line workers, vulnerable groups, old people).
Interestingly, this seems to also be the case with pregnant women (unless I’m missing something). I’m guessing they’ll be ahead of teens but still low enough in the priority scheme to mostly not receive it?
Pregnancy is a "generic" risk factor for any medical intervention, as is young age. There is no reason to believe the vaccine is particular harmful in these groups. But since it's eminently possible to avoid the risk by vaccinating most people around them, that option is (slightly) more attractive.
The Society for Maternal-Fetal Medicine advocates for the inclusion of pregnant women in vaccine trials and just released a statement applauding FDA’s decision to allow pregnant women access to the vaccine. [1] [2] US FDA’s decision deviates from UK MHRA’s decision to hold off on finalizing their advice for women who are pregnant. [3]
And the concerns about 16-17 weren't that it wasn't effective or safe, but that given that age group has a very low incidence of serious symptoms or death that the bar for risks needed to be much higher since they compromised a relatively small part of the study group.
Considering this going to be the strategy all over the world,
I think children should get the vaccines ASAP provided the vaccine is proven safe as missing a year of school is going to have profound impact on their life and society. Many students from marginalized society, especially from poor countries might never go to school again as they have been employed by their parents for meager sum.
But I think definition of who's 'vulnerable' is what going to be contentious, apart from obvious front-line workers and elderly whom would you decide are vulnerable? Immunity compromised individuals? I'm myself house ridden for over 2 years now due to spine surgery and so likely immunity compromised but there's no way that could be informed to the Govt. I just hope my elderly parents get their vaccine.
The virus goes after the ace2 receptor, which is activated by puberty. Children under 14 can get it, but they get a very mild case because they don't have the receptors.
"Children have increased concentration of ACE2 receptors in lung pneumocytes that may have a protective effect on severe clinical manifestations due to SARS-CoV-2 infection."
I'm not telling children are getting COVID-19, but schools haven't opened in several countries due to COVID-19 unfortunately replies have glossed over that.
Children are low on the priority list because they get severe symptoms at a much, much lower rate than adults and especially older adults.
And the schools are not closed right now because of the fear that younger children are going to get the virus. Schools are closed because teachers are (rightly) concerned about getting the virus, and families are (rightly) concerned that their children might pick up the virus at school and bring it home with them and infect more at-risk individuals. If the teachers and family members are vaccinated, then I think it is pretty clear the risk/benefit analysis would highly suggest sending children back to school, even if they aren't vaccinated yet.
Schools in the US have already opened in many places before there is a vaccine, so I don't doubt schools are going to be opening ASAP, and that is almost certainly before most children are vaccinated.
> And the schools are not closed right now because of the fear that younger children are going to get the virus. Schools are closed because teachers are (rightly) concerned about getting the virus
Schools in the UK have been open since September. Typically if there's a positive case then they isolate and typically their closest contacts isolate, if there's more than one then the entire class isolates.
There's no evidence that teachers are any more likely to die from covid than many other essential workers who aren't working from home.
There's no evidence that these vaccines stop spread, so there's little point in prioritising vaccination of children who - even if they did catch covid - are practically immune. Same with the majority of teachers. Makes far more sense to vaccinate older people who are at serious risk (with IFR in the 5, 10, 15% range) - then they don't need to worry about the kids bringing the virus home.
>There's no evidence that teachers are any more likely to die from covid than many other essential workers who aren't working from home.
What's the death rate for teachers been since September compared to other occupations like nurses? Is there "no evidence" because the evidence shows they're less likely to die, or is there no evidence because no one is bothering to keep track?
>There's no evidence that these vaccines stop spread
Nothing is 100%, but my understanding is that the AstraZeneca has results showing that it significantly reduces the chance that someone who has the vaccine will spread the disease
Someone at the CDC disagreed with the strategy of vaccinating people in long-term care facilities first because their weaker immune systems might not have an effective response to the vaccine. I'm not even sure if vaccinating front-line heathcare workers first makes sense because they've probably been exposed already (or not; this is easily checked with antibody tests).
You want to vaccinate people most likely to spread it. Who that is, I'm not sure.
I think along the lines you're thinking, you would actually want to come up with an expected cost of an infection of an individual ("cost" being in a misery-illness-utility sense, not financial). This would presumably include the average expected illness severity of the person infected but also the average illness burden in others indirectly attributable to that person being infected.
So you'd want to give it first to people who are very likely to become severely ill themselves, and whose infection would cause others to become severely ill, directly or indirectly (eg through disease spread or through lost resources, as if an ER doc in an understaffed area became severely ill).
Only 42% of RNs having ever been tested is pretty solidly "We don't test health care workers in America". I would expect close to 100% of them to be tested on a regular basis.
The trouble with vaccinating people most likely to spread it, at least as I've seen it explained, is that you have to vaccinate a lot of people in order to have an impact compared to vaccinating the most at risk groups and there's only a limited supply of vaccine and limited capacity to administer it right now. (Also, technically there's probably more evidence of it working to protect at-risk people from severe disease and death than for it stopping anyone spreading it, but that's mostly just an artifact of what's been tested so far.)
I'd be worried creating a viral reservoir in schools even if the adult population were completely vaccinated. It'd be an excellent environment for the virus to mutate and become endemic.
I'm not a virus expert, but my understanding is this type of virus is very unlikely to mutate in a way where the vaccine will not work against it, and it is going to become endemic regardless of what we do. So I don't think either of those concerns would merit not opening schools.
Covid-19 is a new disease that requires continued study before we can make definitive statements about its evolutionary possibility frontier. Having said that, we currently have extremely effective vaccines (far more effective than our flu vaccines), so we have an excellent chance of nipping this thing in the bud before it becomes endemic if we act swiftly.
It'll probably be at least a year before enough vaccine is produced that low-risk groups like children become eligible, so modified education in one form or another will have to continue till that point. This doesn't mean they can't go to school, but things like pods, wearing of PPE, social distancing, and other such things will need to continue till herd immunity can be achieved through vaccination.
You'd need to vaccinate most of 7B people, and this sickness is low priority in most places due to more pressing concerns, once vulnerable groups are protected.
As far as we know young children don’t spread COVID. There aren’t any confirmed cases of children under ten spreading it to other people. It’s super odd, but that’s what the evidence suggests at this point.
The latest evidence indicates that young children are about half as likely to get infected and half as likely to spread the virus. That's great, but the Covid-19 is incredibly contagious, so it can still spread like wildfire in children.
That article states that the risk starts to increase between 10-12 tears of age and between the ages 10 and 15 children are half as infectious as adults. I doesn't really dig into details about children under 10.
It was likely due to disapproval over the inclusion of people age 16 and 17. At least two of the four dissenting votes have confirmed that this was their reason and they would otherwise have given their wholehearted approval. [1] As GP points out few in that age group will be in line to get the vaccine early anyway.
What was the point in waiting? What was under the consideration for so long that the FDA needed to wait weeks or months after all of the data has been released?
To be fair, this was an extremely basic analysis on a relatively minuscule amount of data, where the form and format of data and the method of analysis has been prescribed months ago.
There was no decision that shouldn’t have been made ahead of time. Either it met the predefined criteria or it didn’t.
The only thing that couldn’t be verified until the last minute was the unblinded results.
Everything else should have been a continuous process of pre-verification up to the point the 128 positive confirmed COVID cases were unblinded.
Assume the unblinded results will be good enough, and verify everything else you would normally verify ahead of time. The only thing that remains is to verify the unblinded cases the day they are announced.
And not just that but your approval thresholds should already be preset and preregistered, the doses already distributed to point-of-care, and nurses start administering shots the very next day.
Yes it’s a big waste of money if it turns out not to work. That’s the whole point.
Turns out the vaccine is highly effective 10 days after the first dose. We could have been doing at least a million doses a day since November 19th. Realistically even long before then.
I’m not in the drug industry, but in mine you can never turn the full decision process into a push button. Its trivial to turn the tests on your main metrics (is it effective) into push button, but you also have to look to make sure nothing else concerning is present, and it’s muuuch harder to formalize “nothing else here to make you worry” independent of the data.
Ahhh... the old HN post of “I work in tech so I know more about how to approve an experimental vaccine than the FDA which is comprised of thousands of scientists and has been approving drugs for over 70 years.”
Remember when the CDC was considered the world’s absolutely top infectious disease center? Remember when they couldn’t even ship COVID test kits with uncontaminated distilled water?
Remember when the FDA wouldn’t let public or private labs run their own COVID tests and everything was being shipped to CDC headquarters to PCR?
The CDC and the FDA essentially guaranteed through extraordinary ineptitude that the US would not fend off COVID back in January/February. They deserve zero benefit of the doubt.
The FDA’s 70 years of process likely worked against them here. What I can say for certain is that there was a t-minus one, the day before the results were unblinded, and there was a t-zero, the day results were unblinded. On that day t-zero they uncovered which of the patient IDs got the vaccine versus which got placebo.
No expense should have been spared in preloading the analysis, verification, whatever could have been done, it should have been done up until t-minus-1. On day t-zero you get 15,000 patient IDs in column A and 15,000 in column B, that’s the only new thing you learn that day. There should be nothing new to talk about or discuss, the approval criteria should already be set in stone. Check the IDs and launch.
I'm sorry you're being downvoted. The testing disaster killed far more than this vaccine approval delay has killed and it's infuriating that nobody seems to care.
They spent far too long before approving any kind of at-home testing and to this day have not approved most rapid testing.
Three weeks ago the EUA was submitted, so three weeks ago there was an entire team of people at pfizer who had reviewed all the data and were confident FDA would approve the application, but somehow nobody at FDA was part of that set of people. In any reasonable process that application would have contained no new information, if it contained any new information they were not communicating closely enough.
I understand spending a few days doing some final checks on the data before approving. Three weeks, however, is suspiciously long. It's possible they were in fact doing important work which could not possibly have been done before the application was submitted, but nobody seems able to articulate what that important work actually was.
A shitty test with 60% accuracy can make things worse than they already are.. People are making decisions based on results that are right barely half the time. I don’t blame the FDA for saying “no”.
I love HN who is normally vehemently anti-business (with good reason) suddenly flips and says “well Pfizer said the vaccine was ok, isn’t that good enough?”
No. It’s not good enough. The reason we spend billions per year on the FDA is because we want an independent, critical and evidence based body making decisions on drugs given to hundreds of millions of Americans.
I mean, hell, Trump was bullying the FDA (which was stupid) and HN seems to be arguing for that exact thing.
There probably exist universes where a shitty test would make things worse. How are you so sure we're in that universe? And how are you so sure that the unapproved tests are so shitty that you're not at all curious whether the FDA made the right choice?
Nowhere in my comment did I say the FDA should just take Pfizer's word for anything.
I'm also not sure why you're trying to use Trump's actions as evidence here. "Trump did a thing and therefore doing that thing was the correct action" is an argument which requires some justification.
>The incentives to hide or falsify data can be enormous.
Highly doubtful. Pushing out an unsafe vaccine would be disastrous to Pfizer. They have every incentive in the world to be as absolutely certain as possible that the data is solid.
What kind of computation do you think it is they are doing on this data? Seriously, it takes at MOST a week to do an extremely deep code review of this. It's not like this is some brand new testing methodology developed ad hoc for this.
How is it you think the UK was able to approve it already???
The link provides some arguments and maybe FDA should've/could've rolled with the process. Long times do not provide safety, only double blind tests and verifications do.
Are Gov jobs granted overtime work by ruling party, and how was this important work prioritized and coordinated by top leader?
It's probably the fastest a new vaccine has ever been developed, using a technique never before used for this purpose, for something that will quickly be given to millions upon millions of people. Maybe it shouldn't have taken 3 weeks, but there was certainly a non-zero period of time during which the FDA should seriously scrutinize and not just take Pfizer's word on things.
I was wondering as well... the data was submitted about 3 weeks ago...
I understand that it is extensive data (for about 44,000 patients), but taking 3 weeks to compile/analyze seems excessive. They should have put in an army of analyzers into it...
There are about 3,000 people dying every day.... it is like 9/11 every day, or 9 jumbo jets falling....
The FDA should be treating this as a war effort, and not drag their feet into pointless bureaucratic 'safety' theater.
> There are about 3,000 people dying every day.... it is like 9/11 every day, or 9 jumbo jets falling
This is wrong. Median expected remaining healthy lifespan of a 9/11 deceased was ~35 years, whereas for a COVID decease it's ~3.5 years. So 9/11 is still 10x worse.
Don't get me wrong, COVID is still terrible, but it is not a "9/11 every day".
My figure is correct, the 11.7yr is wrong. It's a pretty good paper, but 2 major flaws that I think should be corrected.
From the paper:
> Both of the above calculations may overstate the loss of remaining life in that they assign the remaining life expectancy based only on age, without taking into account that COVID-19 deaths are disproportionately occurring among those with compromised health status.
So their 11.7 average years remaining ignores the critical bit of information that we know this person died of COVID. It is extremely unlikely that if you took 2 80 year olds, one who died of COVID and one who did not, that if neither got COVID they would live to be the same age. I wouldn't be surprised if it was a 10x difference. While they do mention this and add some caveats (a good thing), I think because it completely changes the conclusions of the paper, they should have gone with a range and not a 11.7 number, which seems very improbable.
> Avoiding 1.75 million deaths or 20.5 trillion person years of life lost would be valued at $10.2 to $17.5 trillion
Then they take the 11.7 figure from above and multiply it by the estimated average value of a year of life. Again, there is at least an order of magnitude difference between a year of life at age 90 and a year of life at age 30, for most people.
Finally, although my ~3.5 number is much closer to the truth than 11.7, there is a difference between life expectancy and "healthy lifespan", aka "healthspan" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136295/). Healthspan is a newer concept but I expect will be the primary term in a decade or two.
> I wouldn't be surprised if it was a 10x difference
The next sentence:
> Hanlon et al. (10) estimate that those dying from COVID-19 have only about 1 y less of remaining life on average than those at the same age in the general population, which would mean that the overstatement is not very large, around 8%.
Your own link states that healthspan is not quantifiable, so your claim that it is 3.5y doesn't make a whole lot of sense.
I saw Hanlon, and again a pretty good paper (http://eprints.gla.ac.uk/215598/1/215598.pdf), but far off. First, it came out in April, when CFR in the USA was 6.2%, not 1.9%. So that alone would be enough to drive YLL of fatalities down close to my number.
> "used to construct a plausible scenario for the prevalence of combinations of LTCs among people who died from COVID-19 for the modelling presented here."
Second, the dataset used at the time to generate their synthetic data was weak. You can see it immediately in their bar charts, where they have mostly healthy 50-69 y.o. dying in their synthetic data, skewing their YLL to the right.
> Your own link states that healthspan is not quantifiable, so your claim that it is 3.5y doesn't make a whole lot of sense.
I provided a link to a "conservative" description of healthspan, but in the field people are more optimistic about it.
Very good questions you brought up though, thanks!
That is taken out of context. The prior sentence pointed out, "we calculate that the 2020 American population of 330 million people has on average..."
The calculation you reference was done using all people in the US. Just two sentences later they wrote, "... would on average lose about 0.2 y of remaining life ..." You need to compare to the groups of affected people, which is generally not 100% of people in the US.
The calculation I reference is the average remaining lifespan for people who die of COVID-19. The additional context doesn't make any difference, it just provides two additional (different) calculations:
average remaining lifespan across the entire population:
> we calculate that the 2020 American population of 330 million people has on average 45.8 y of remaining life expectancy, totaling 14.9 billion person years.
reduction in remaining lifespan in the 70-89 age group:
> Older individuals ages 70 to 89 y, taking those who die and those who survive together, would on average lose about 0.2 y of remaining life, and younger individuals would lose far less.
I did not include these calculations because they are not comparable to the number to which I was responding.
Also the sooner a vaccine is released, the sooner you can dampen the exponential growth, potentially compounding the lives saved. Not sure how significant of an effect this might be, though.
We don’t have gold-standard proof that it prevents transmission, because studying that has not been a priory. There’s no reason to think that it doesn’t prevent transmission when you look at the mechanism involved. It would be very surprising.
I didn’t know that, thanks! I guess I need to learn more about how vaccines work. I thought that vaccine implied immunity which implied that transmission is prevented.
No we didn't. :P The US has 6.4 million doses of the Pfizer vaccine now. Projections of up to 50M delivered worldwide by the end of the year. We're on a crazy ramp.
If you want to complain about a misallocation, a key complaint would be that they're holding slightly more than half the doses back to ensure everyone dosed can get a second dose... but with rolling production such a large holdback isn't necessary.
> What could matter is if delay increases the speed at which you can ramp up.
All the jurisdictions I know will blow through the entire supply of existing doses allocated to them very quickly. It doesn't go on a slow distribution ramp gated by approval like your ridiculous source suggests. What governs the ramp is production rates, which have been running flat-out irrespective of this decision.
> All the jurisdictions I know will blow through the entire supply of existing doses allocated to them very quickly. It doesn't go on a slow distribution ramp gated by approval like your ridiculous source suggests.
You misunderstand. "Blowing through entire supply" and being left with nothing is exactly the "slow distribution" Alex Tabarrok, a professor at GMU, talks about in the link I gave. He contrasts it with vaccinating entire population on day 1. Read it carefully.
> What governs the ramp is production rates, which have been running flat-out irrespective of this decision.
I consider the vaccine production regulation people to be just as incapable at cost-benefit analysis as vaccine approval people, so I assume that most production constraints are just as artificial as the approval constraints.
>You misunderstand. "Blowing through entire supply" and being left with nothing is exactly the "slow distribution" Alex Tabarrok, a professor at GMU, talks about in the link I gave. He contrasts it with vaccinating entire population on day 1. Read it carefully.
Vs.
"Now assume that the vaccine can’t roll out to everyone immediately. For the sake of this simple model let’s assume that on day one you can only vaccinate half the population. By doing so you save 1000 lives on day 1 and 2000 lives every day thereafter for the length of the pandemic. That’s the fourth panel. Now suppose we delay the vaccine rollout by one day. 2000 people die on Day 1 but you save 1000 on Day 2 and 2000 on Day 3 and every day thereafter for the length of the pandemic. How many people were killed by the delay? Compare the 4th and 5th panels. 2000 exactly as before! "
This compares vaccinating 50% on day 1, and the remaining 50% on day 2, to vaccinating 50% on day 2 and the remaining 50% on day 3.
But in blowing through the supply, we're comparing vaccinating 1% on day 1 and another 1% on day 7 and another 1% on day 15 to vaccinating 1% on day 7 and 1% on day 8 and 1% on day 15. Not at all the same scenario.
There are many people (like me) who argued for exactly that. We should have had general distribution and ramp up of production as soon as the Phase I studies were done. This could have prevented the second wave we are in, and saved hundreds of thousands of lives.
It's also the case that if you were to screw up on the first approval, if the first vaccine actually wasn't as safe as it needs to be, then most people will be scared of vaccine #2 or #3, regardless of their safety, regardless of how they were produced. And that would cause a huge setback and prolong all the stupidity for years, potentially.
After the Phase 1 data was back, arguably it wouldn’t have been a bad call to give doses for free and gamble on the efficacy even if it turned out to be below 50%.
> From an ethical viewpoint, this is incredibly wrong, as vaccines given to healthy people which cause problems later are very very dangerous.
The first two phases are the safety tests, the third one is efficacy (so we knew the vaccine was "safe" after phase 2, we just didn't know the efficacy - that's what the poster above is alluding to).
With many millions of people intentionally disregarding simple low-cost precautions and unecessarily exposing themselves now, the population doesn't seem a good case for rolling out an experimental vaccine en masse.
"extensive data" is 44K patients!? Wait until I tell you about the extremely extensive data that tech companies at scale deal with every day. I run a large data science organization at a major tech company. If someone told me that it was going to take 3wks to analyze an experiment of this type, I would probably have to start firing people.
If someone wanted to take three weeks to analyze an experiment with these kinds of stakes, you’d fire them?! I have to assume you’re being hyperbolic.
And are you suggesting that it’s easier because the data isn’t as extensive as what the rest of us deal with? That only makes it harder.
Sure if it’s some random A/B test with data from your own systems from an experiment you designed, but this is a vaccine the whole fucking world has been waiting for for most of the year. God forbid people treat it a little more carefully.
> If someone wanted to take three weeks to analyze an experiment with these kinds of stakes, you’d fire them?!
I would absolutely need to start a performance improvement process. They are definitionally 1/3 as productive as they should be. Also in terms of stakes, please show me even a modicum of work that suggests the downside risk of approval is greater than the delayed vaccinations. What reason have I to believe there is great risk in approval? Again, the UK approved this over a week ago.
> And are you suggesting that it’s easier because the data isn’t as extensive as what the rest of us deal with? That only makes it harder.
No, I'm mocking the idea of it being extensive data. It's not.
> but this is a vaccine the whole fucking world has been waiting for for most of the year.
> Also in terms of stakes, please show me even a modicum of work that suggests the downside risk of approval is greater than the delayed vaccinations. What reason have I to believe there is great risk in approval?
As I understand it, medical ethics isn’t about utilitarianism, or else we’d skip the rats and monkeys and just go straight to testing on the poor for money. They don’t seem to prioritize minimizing the opportunity cost of avoiding bad outcomes. Their guiding principle seems to be avoiding giving harmful treatment.
Meanwhile some healthcare workers at my partner’s facility are skeptical about whether the vaccine was rushed (I think they’re crazy, for the record). But there’s real risk if enough of the public doesn’t trust the vaccine. I’d bet that kind of angle is part of why they focus on “do no harm” instead of “minimize cumulative regret.”
But like even all of that being the case, that’s still no justification for taking 3wks to validate the data. The actual testing process is no different, the only difference is in how quickly approval comes. The same evidence is considered regardless. So what is the ethical justification for taking longer to consider the exact same evidence? Now if your point were that they should consider more evidence, then that’s fine and I can understand that but that’s not what’s at question here. The question is the speed at which the evidence is considered. What is the medical ethics justification that the UK was able to use to get this out over a week ago that is invalid in the US?
I bring up the ethics question because a strict utilitarian analysis would be primarily answer the question of whether the drug is effective, looking for any red flags secondarily. A do no harm analysis (in the ethics sense, not the experimental design sense) has to look for any harms as a primary goal, maybe even equally to the question of efficacy.
Answering the question of whether the experiment harmed anything important is always much harder, as I’m sure you know. You see some metric is way down, but after a multiple comparisons correction it might just as well be noise, so then you have to start digging, doing a bespoke analysis for the fact that these non iid metrics point in these particular directions. You can’t pre-automate it because with N metrics that are practically significantly up/flat/down, that’s at least 3^N possible investigations to convince yourself whether it’s enough to stop rollout.
That’s the part that takes time, in any analysis I’ve ever done. Maybe literally zero time to check efficacy because that part is automated, then sometimes days to check whether there’s anything else worrisome in the probably-just-noise on other metrics, spending time proportional to the cost of getting the harm part wrong. Some of the hard questions aren’t statistical. You see some KPIs definitely up and some KPIs definitely down and deciding whether to roll out becomes a bitter fight between competing interests. Maybe you don’t roll it out yet for client segment X (like this trial and kids and pregnant women, as I understand it).
Re US vs UK, no idea. I’m not saying 3 weeks is necessarily the right amount of time here. I’m just so taken aback at the idea that 3 weeks is necessarily too long to the point you “would probably have to start firing people” and would “absolutely” have to start putting them on PIPs.
Where you think processing the data just means loading up an excel table (or running a CSV through R) and that's the only data relating to the studies. Patient data is not the only thing being analyzed and it includes things like manufacturing, transport, etc
> Where is this MD, MPH from Johns Hopkins wrong?
He's not wrong but his worries as a clinical trial expert are a subset of the worries of an agency like the FDA. And I'm sure his workflow as clinical study expert is more fine tuned for that.
Or as in a developer analogy: making a code change is a 5 minute job. Actually making the change, testing, deploying, etc may take a whole day.
> Why is the UK able to approve it over a week ago but the FDA needs longer?
Pfizer sent the last info to the FDA on 22th of November. The MHRA had started a rolling review and received the last batch of info they needed on the 23rd of November.
I am certainly frustrated with the speed as well, but I don't think it's too much of a difference. Yes, maybe it could be faster.
So I work in public health, with public health colleagues. I came up with analyses pieced together from the publicly reported information and think that piece is a little disturbing.
Sure, you can come up with some standard numbers in an hour. But it wouldn't be the most thoughtful analysis, and the decision isn't really about a single efficacy estimate anyway.
I guess I figure if you're going to go down this route of pissing matches over how fast you can do an analysis on how big of a dataset, why the hell even have an FDA anyway? Just require the company post all their information and get rid of the regulation entirely. I actually think this isn't an unreasonable argument, even if I don't necessarily agree or disagree with it. It certainly seems more reasonable to me than "we should have a regulator that just rubber stamps things."
I'm fine with the FDA taking their time. The problem with risk in decisions is people forget in high stakes high risk decision making, it's about the process. This whole discussion about the FDA taking too long will look a lot different if a year from now the vaccine turns out to have some horrible long term effects (which it could, even though I think it's unlikely, just, you know, 'cause).
> Sure, you can come up with some standard numbers in an hour. But it wouldn't be the most thoughtful analysis, and the decision isn't really about a single efficacy estimate anyway.
No one is saying don't be thorough. What I'm saying and Makary is saying and the UK is saying is that the required thoroughness shouldn't take this long and when it does, real human lives are lost and sustained invasive measures in the freedoms of individuals are required.
> I guess I figure if you're going to go down this route of pissing matches over how fast you can do an analysis on how big of a dataset, why the hell even have an FDA anyway?
What a ridiculous leap. That's so many logical steps away from "the FDA moves way too slow" it's an absurdity. Who is arguing against the FDA's existence other than I guess you now sort of???
I know nothing about what goes into approving a vaccine, but I am genuinely curious how come the US FDA was a whole 10 days behind the UK in approving this, and were also beaten by Bahrain and Canada.
Is it because they're genuinely more careful? Or is it just bureaucracy?
The UK was unusually aggressive in getting everything in place to roll out this vaccine early - not just the approval process, but other logistics as well. The FDA, on the other hand, was under pressure to delay approval for partisan election-related reasons; the press created the perception that approving the vaccine early would be an evil plot by Trump to win the election. If the trials had reached enough cases to return results earlier, the difference could've been really dramatic because those delaying tactics essentially imposed a minimum length of time the trial had to run for in a slightly stupid way.
I’d question what was the point of rushing this out?
The vaccines are gonna be supply constrained for a while. The same number of people will be vaccinated on Jan 31 (or the day before the next batch of vaccines become available) whether we start today or a few weeks from now.
At this point the more important consideration should be not doing anything that might even slightly reduce public faith in the vaccine.
> The same number of people will be vaccinated on Jan 31
That could still mean a big difference in the number of deaths. Some of those people may die/become seriously ill before Jan 31 before the vaccine gets to them
Not a big difference. A few thousand. A drop in the bucket compared to the 250K and any more ahead killed because many Americans are making a religion of intentionally refusing to limit their spreading of the virus.
The first batch of Pfizer vaccine is enough to vaccinate a substantial portion of the vulnerable elderly (after vaccinating healthcare workers). Given that they are the ones that are dying at the highest rates, getting it deployed as fast as possible is likely to extend quite a few lives.
It's not like they've executed well on your last point in the meantime.
They needed to wait months to see if the people who received vaccine did not get the virus, and that they also were not harmed by the vaccine. This isn't some binary instantaneous outcome.
They’re arguing about analyzing the data more quickly rather than spending three weeks analyzing it. There’s no additional data gleamed in that time period.
I highly doubt it's related to the election, but there is a "conspiracy theory" that is entirely plausible to me which is that the paternalistic leaders of the FDA/CDC believe that by taking longer to "validate" the data they are going to be better at convincing anti-vaxxers of the safety of the vaccine. The data analysis here is comically straightforward! This doesn't take 3wks! There's a reason the UK has already approved it!
From a personal perspective, I want a safe and effective vaccine as soon as anyone would. I do not want to be propagandized into taking something potentially dangerous just because it lets the business community make money. What I want is a careful, rigorous, and non-politicized decision making process before I can trust the output of an experimental process. This has clearly not happened.
The FDA announced early this morning that they were definitively going to authorize it[1], but they didn't actually issue the authorization at that point, with people telling the press that authorization would come "in the next few days".
If someone called up the FDA after that and said "hey, you've already told everyone you're going to approve this, so just sign the papers and make it official today rather than going home for the weekend and finishing it up on Monday", I have no problem with that. That's not pressure to prematurely authorize it (since they already confirmed they would), that's just cutting through the red tape/BS and making it official faster (IMO).
Put it into a tech perspective - if your company's cloud product went down and you were losing $millions every hour, and the devs found the bug and fixed it, but the product manager said "hey great, we'll fill out the release paperwork in the next few days and maybe approve pushing the change to prod on Monday", would anyone go for that? No way - they'd say we're not going home until this is fixed and released. Replace $millions with actual human lives and that's basically what we have here, isn't it?
No need to worry in this case. They were going to hold their meeting to give final approval on Saturday. All Trump's blustering did was move that to late Friday.
It did not change any deliberations or analysis, nor did it change when the vaccine will actually go into use.
I hate Trump's bullying tactics as much as the next person, but let's be clear - the FDA had completed its data analysis and released it a few days ago, and then the advisory panel yesterday supported its endorsement. At this point it was clear the vaccine was safe and effective, and an EUA should be rapidly announced by the FDA, whether the Trump would pressure them or not.
I mean obviously this was not the case, since they announced they would definitely approve it but not for a few more days. We are talking about government bureaucrats here after all.
Actually prior to the threat they stated that they would approve it as fast as possible and were targeting Saturday morning. Trumps bullying sped things up by about 12 hours.
Note that the approval date has absolutely nothing to do with the production schedule, which is the real limiting factor here. Having a few hundred people get their shots on Saturday instead of Tuesday or whatever isn't realistically going to move the needle. Every dose we can get is going into a patient somewhere.
Yes, and every dose produced so far is ready to go into a patient immediately, they don't have a stockpile for the whole society, not remotely. Two days or whatever isn't going to matter that much. The timing of the first few thousand doses will change, the timing of the first ten million doses has to do with production and shipping, not approval.
I saw on the news today that the vaccine was sitting waiting for the approval to ship. So yeah, getting approval sooner will get the vaccine shipping sooner.
It is possible he was just pissed at any delay at all. I am just feeling extremely skeptical about believing any of these people as their goal is to get us to forget about the pandemic and get back to work at maximum productivity regardless of whether this thing works.
What's the point in rushing? Production is already going at full speed and they're not yet ready to begin the vaccination programme. Rolling this thing out is going to be a massive operation given the delicate conditions it must be stored under and the coordination across thousands of health systems required. All the preparation work is well under way and the timing of this approval doesn't impact it in the slightest.
My point was that none of the work required to prepare to begin the vaccinations was held up by the work of reviewing the studies and granting approval.
Furthermore, how many lives would be lost if society didn't have confidence in the approval process and declined vaccination? Russia is suffering this exact problem at the moment.
I know these threads tend to get bogged down with the various things all COVID related threads do these days, but let's just take a second to savor this moment. The mRNA vaccines were developed in days[0], using only the genetic sequence of the virus. Yes, testing took many months, but science solved what is typically the hard part of the problem overnight.
Personally I'm hoping I get the mRNA vaccine not so much because they're currently the most effective, but because it will make me some small part of one of the most impactful scientific works of our lifetimes.
We should be seeing another announcement in a week for the Moderna mRNA vaccine as well as their committee review is scheduled for 12/17.
Pretty incredible and pretty surreal. I honestly wasn't sure how the utterly incompetent federal response of the US would ever dig itself out of this and I guess the answer is here.
It’s worth highlighting that a ton of basic science work went into mRNA vaccine development, starting in the early 1990s:
- developing the lipid nanoparticles that the mRNA is delivered in, so your cells could actually take it up intact
- figuring out how to get the mRNA to evade the immune system
Do you (or anyone else on HN) know why mRNA vaccines haven't been used before COVID? Are they more useful against coronavirii? Or is it just that existing vaccines are good enough, so no one has bothered releasing an mRNA vaccine for the mumps or whatever?
Fun fact: most professionals and all official FDA documents use "FDA" and never "The FDA". It's a neat little shibboleth because it is so counterintuitive to omit "the". Use ctrl-f to find the pros in this thread ;)
This isn’t as reliable of a signal as you might hope. It’s also context dependent. Here’s an example: I’ve presented my research to FDA researchers, and one of my dissertation committee members worked at the FDA twice in her career before coming back to academia. Note that in one sentence I managed to use both options, and I am certainly a pro in this context. And even if you won’t accept that I’m a pro for some reason, the previously mentioned dissertation committee member happens to be the dean of a school of public health and she inserts “the“ or not however she damn well pleases, and she’s a stickler for proper style is most cases. Here’s an example from the FDA itself that uses both options: https://www.fda.gov/safety/fdas-sentinel-initiative
I actually completely agree. If anything it's a one-way shibboleth: if people use "FDA" they likely have industry experience. The other way doesn't signal much.
I don't know, but am really curious to find out the rationale! I just noticed it as I started working on FDA approval of a medical device this year and thought it was really odd.
Very interesting! I don't think that grammar is the issue here. "FDA" and "the FDA" are apparently used interchangeably no matter the sentence. With NASA, the difference is that no one spells out N.A.S.A., you say it as one word. With FDA, you spell it out. Please correct me if I'm wrong :)
I didn't mean using the acronym adjectivally, that would be ridiculous as your examples show ;) When expanding the examples and using the acronym as a noun you can indeed use both forms:
Taxol gains quick approval of FDA.
Taxol gains quick approval of the FDA.
Or others: FDA has approved... vs. The FDA has approved...
To most lay persons, omitting "the" will look a bit weird.
Now the interesting part is that NASA has become a proper noun (probably because it is an acronym that can be pronounced). No one will say "I work at the NASA". With FDA you will see people use both forms, even though the final A in both NASA and FDA stands for Administration. I'm not sure about other government organizations. I don't think anyone says "I work at CIA" or FBI for that matter.
Ok, but I don't think it's different from so many three-letter agencies.
People say that they were "investigated by (the) IRS" or "got a letter from (the) DMV" all the time. One reads in the press about companies being "fined by (the) EPA" or people being "detained by (the) FBI". Dropping the "the" doesn't look that weird.
Looking at https://www.cia.gov they use both forms "work at the CIA" and "work at CIA" (google returns twice as many results for the former than for the latter).
The development of a vaccine of this apparent efficacy at this speed is an astonishing scientific achievement, and if it is as good as it appears to be, it is an immense moment for medical science. Plus, the way this vaccine works is absolutely fascinating:
In technical terms, it seems to me they're almost like unit testing for the body: You take out everything except the bit you care about most, and subject it to intense scrutiny until you develop a correct response.
It took roughly 48 hours to develop the vaccine once China published the genetic sequence. The actual study design was nothing particularly impressive. This was by no means a “entire world” effort.
I think the untold story of production and distribution could be interesting, but most of that is yet to be written.
Agreed, we’ve never produced a vaccine of this type at scale nor managed the required supply chain considerations. Making 10K efficacious non-harmful vaccines for a trial may be much easier than making 100M or 1B. Some processes don’t scale easily.
While popular films often depict a vaccine that’s effective enough and soon enough to stop an epidemic (Contagion, I Am Legend, World War Z) in real life many epidemics are fought without the help of vaccines (Ebola, HIV, SARS). The combination of speed, effectiveness, and new technology in COVID vaccines is “astonishing” indeed.
I do believe we have a 36-hour to vaccine protocol for pandemic flu (one of my coworkers ran a real run of the protocol against a novel flu strain almost a decade ago [0]), estimated weeks to first responders/highly vulnerables and maybe a month or two for general population.
This is really at the limit of what is physically possible (at best some sort of highly flexible distributed manufacturing network maybe down to weeks for general population?): Flu vaccines are very precedented, and though this protocol had many "new bits" efficacy, infra, and scaleup are kind of more "well known".
[0] it was considered to be a dry run in case of a real pandemic; he was told that he would get a phone call during the week, and was emailed the flu virus sequence one morning, built the vaccine over the course of a day, and fed-exed the vaccine seequence to the scaleup and testing facility and by 36 hours they had validation that the vaccine caused a positive antigen response. That year's flu did not become a pandemic, well by luck so far we really haven't had a major flu pandemic since that year.
Speaking of flu vaccines reminds me of this Pfizer press release from November 2018 [1] that described “a collaboration with German biotech BioNTech to develop new RNA vaccine technology to create a better flu shot”. The press release concluded with optimism but cautioned that “the technology is several years away from being tested in the US”.
I could be wrong, but it's difficult to believe that the BioNTech technology provides much of an advantage over the flu, the proposed scaleup for a (traditional) emergency flu vaccine is "take over existing chicken egg infrastructure and hijack a big chunk of it for a week". I'm glad it found a use in the COVID vaccines, because coronaviruses are resistant to other vaccination techniques iirc.
This is good news for everyone. Countries which can’t afford to or don’t have the expertise to thoroughly test and review multiple vaccines can take a cue from the ones that have approved them. Supply is a different issue of course.
Generally, health care workers and those most at risk are being granted early access.
From a public safety perspective, I wonder if perhaps those most likely to spread the disease should be the first to be innoculated rather than those most likely to have a bad outcome.
I’ve heard this argument before, I’m still convinced that covering at-risk groups first is the best idea. Even if it still continues to spread for months, we can bring the deaths way down, and give our isolated elderly generation a much-needed opportunity to see family and friends.
>From a public safety perspective, I wonder if perhaps those most likely to spread the disease should be the first to be innoculated rather than those most likely to have a bad outcome.
The argument is that the vaccine has not been proven to prevent infection and spread. Only to prevent severe disease in those who do get infected. So administering it to those with comorbidities, for now, is the most effective means of reducing overall mortality based on known evidence.
That's technically true, but I'd be really surprised if vaccinated people didn't spread it less...so surprised that I'd argue it's a risk worth taking.
The US has currently purchased enough vaccine for 50 million people (100 million doses). Further doses from Pfizer are not expected until around June because of obligations Pfizer has to other countries.
Within the US, each state will be allocated vaccines in proportion to their population. Each state is then responsible for deciding how to allocate them. You can look for your state here [0]
Logisticly speaking, the plan [1] is for Pfizer to ship vaccines directly to the point of use, using custom containers featuring dryice, thermal sensors, and GPS. These containers can passively maintain temperature for up to 10 days.
Once at the point of use, the vaccine can be stored for up to 6 months if a suitable freezer is available.
Without a ultra low temperature freezer, the vaccine can be stored in the Pfizer container used for shipping for up to 30 days, provided the dry ice is replaced regularly.
Standard refrigerators can store the vaccine for up to 5 days.
The US passed on an opportunity to secure up to 500 million additional doses despite warnings from Pfizer. [1]
> Accounts differ over the timing of the discussions between Pfizer and federal officials about locking in extra doses. Several people said that during late summer or early fall, Pfizer officials repeatedly warned the Trump administration that demand could vastly outstrip supply and urged it to pre-order more doses, but were turned down.
The US also has at least a couple hundred million doses lined up of Moderna's vaccine. Their request for an emergency use authorization was submitted 10 days after Pfizer's so hopefully will be approved before Christmas.
Also the antibody test, at least the one I did, involves sticking a needle in you and paying money. If you are going to get stuck you may as well just stick vaccine in I figure.
Have any of the vaccines been tested on those actually dying of COVID-19? Would they be likely to have any effect on survival? Seems like those who are actively dying could potentially benefit the most from a vaccine rather than frontline medical workers and the elderly and should be given priority (if it helps). If a vaccine could prevent death then even with few doses available initially it seems possible that no more people would have to die at all (or many fewer).
Thinking about this perhaps those who have already experienced organ damage may not be helped much. But perhaps if everyone who was hospitalized was immediately vaccinated the death rate would drop drastically. My guess (and it's just a guess) is that the phase III trials did not try to answer this question directly, and in fact may have excluded anyone who already had a COVID-19 diagnosis (the drug companies want to show maximum effectiveness which would mean vaccinating before being exposed to the disease). That does not mean it would not help prevent deaths in hospitalized cases though. If none of the early doses are given to those hospitalized then it could be a long time before we know the answer to this question. Probably as the vaccines become more widely distributed someone will try it. But trying it early could potentially save the most lives (again, if it works).
However, maybe there are good reasons you don't vaccinate someone who already has a disease. Maybe it's a large burden on the body to ramp up the immune system in a different way when the body is already fighting off the infection? I don't know, but I'd like to see more public discussion of this. Here's one article I was able to find that suggests adverse reactions at least are unlikely (seems it's actually been tried a few times):
"COVID-19 patients, those with antibodies too may be vaccinated, says Health Ministry"
Another thing I don't see being discussed much is that while the phase III trials involved tens of thousands of people, only a few hundred people who received the placebo exhibited COVID-19 as far as we know. It would seem that means the vaccines have really only been tried against the disease itself just a few hundred times (and found not to work for about ten of those few hundred). Even if you assume that 10x more people caught COVID-19 but had no symptoms or mild symptoms, that still means very few actual challenges of the vaccine against the disease. It does show that the vaccines are fairly safe since there were few adverse events in the tens of thousands vaccinated, but it does not really seem to show that the vaccines are actually widely effective. The NY Times has a good article about this:
"2 Companies Say Their Vaccines Are 95% Effective. What Does That Mean?"
So it seems possible the vaccines may be much less effective , we won't really know until many, many people are vaccinated. That's no reason not to get vaccinated since the safety seems good from the trials. But it could affect the future dramatically. I guess since we can't know until lots of people have been vaccinated, we just have to wait to find out, nothing more can be done. Presumably data will be being collected so someone (maybe not the public) will have an ongoing readout of effectiveness.
This is great news! I'll definitely be in line to get it whenever my turn comes.
A thing that keeps worrying me is the amount of people I've seen/chatted with (empirical evidence) that don't trust these vaccines. The most common comments they make are: "I don't want to be guinea pig", "How do I know the government won't control me", and more conspiracy theories. All of these fears seem to come from misinformation on the internet, friends and family get a ton of memes/fake news through WhatsApp highlighting the unproven negative effects of the vaccine.
Is there any effective way to control the propagation of misinformation on these platforms?
How would one even get started to tackle that problem?
No problem. All that's needed to get people wanting it is to tell them they can't have it. Just announce that it will be distributed last to places that don't require masks, and watch the screams.
Some people think emotionally, not logically. Figuring that out took me way longer in life than it should have.
Logical thinkers will be able to do the risk/benefit analysis with “good enough” fidelity so long as data is available, so you don’t really have to worry about convincing them.
For the emotional thinkers, whom I am assuming have a large intersection with the people that believe misinformation (that assumption may need to be checked, but I ... just don’t have that data), perhaps we would have had better luck by pushing a message like “we are all soldiers in a war now, and soldiers take risks to protect each other.” Complete with an advertising campaign featuring a frontline combat veteran recounting how she walked out under enemy fire to rescue her comrades, and subtly or not-so-subtly shaming people who are unwilling to take tiny risks to protect their fellow soldier-citizens.
It isn't entirely the typical anti-vax nonsense or outlandish conspiracy theories, though. mRNA vaccines are entirely new and I don't believe we've had even traditional vaccines start getting used outside of trials so quickly before. This is new ground, and not without its own potential risks.
It's important to understand that antivaxxers are wrong not because they make a risk analysis of vaccines, but because they make that analysis based on flawed data. They severely undervalue the risks of the various diseases, and severely overvalue the risks of the vaccines, and land in the wrong conclusion that every single vaccine therefore is bad for you.
But they're not wrong in making that risk analysis in the first place.
I do not belong to a risk group for covid-19. I don't live with anyone in a risk group, I don't hang out with people in a risk group or even meet with them. So I don't mind being at the back of the line for this vaccine, the risk of the disease is negligible to me, while the risk of the vaccine is unknown. I don't mind waiting and seeing what happens after millions of people have gotten the vaccine before I get it myself. That minimizes the risk to me.
But my dad belongs to a risk group, so for him the same risk analysis gets a different result, because his risk of dying is a hundred times greater than my risk of dying. So he will try to get vaccinated as soon as he can, as he should.
> They severely undervalue the risks of the various diseases, and severely overvalue the risks of the vaccines, and land in the wrong conclusion that every single vaccine therefore is bad for you.
What's the data look like for long-term effects of an mRNA vaccine?
What are the long-term effects of vaccines everyone is talking about? This is not a loaded question, I'm asking in good faith.
And I ask because even the rarest documented effects occur within 3-4 months of administration, which is hardly long-term.
There may be a case for a specific Lyme disease vaccine, but thanks to the anti-vaxxers, the whole thing was withdrawn (against FDA recommendation) before the actual reason could be found.
I think the bigger concern in this case is that we don't know. And the overwhelmingly strong historical case for vaccines that exist doesn't really apply that well here since it's a pretty new approach of essentially doing gene therapy to get your own body to produce the protein that triggers the immune response. And as far as I know (and admittedly, my slightly more-than-average time spent researching this still rounds down to nothing) that technique has only been used in humans on a fairly rare disease so far. I'm definitely optimistic from the data so far. I'm more likely to get it since I know I'm done having children anyway. If I was high risk I would probably get it. But I'm not high risk. I'm also optimistic I could survive a COVID-19 infection. I'm not rushing out the door to get my hands on either to be honest.
Exactly. This is a new type of vaccine that was rushed through testing being deployed widely for a disease that kills less than 1% of people who get it.
I think the best we can do is lead by example in the short term, and in the long term investigate the failure of education systems that bring this about
This is what I think too. I try to do my best to talk to these people and alleviate their fears. But as well, I predict that as their family and friends and millions of people in general in front of them receive the vaccine, and end up fine, that it will change their mind. The vaccine will go from being spooky to no big deal.
Disinformation and the rise of computer generated audio, video, and images is going to make this problem even more challenging. I think we may need to come up with ways to sign audio, video, and images that guarantee that the media is captured naturally (or that the media hasn't been tampered with since it was spread by a certain entity).
I also think we need to build back the public's trust in institutions. Once they deserve that trust. When anyone with any motive can spread content online that reaches thousands or millions without much of an editorial process, well... it's proven to be disrupting.
These are very challenging problems.. I'm counting on Tristan Harris to bring us something.
> A thing that keeps worrying me is the amount of people I've seen/chatted with (empirical evidence) that don't trust these vaccines. The most common comments they make are: "I don't want to be guinea pig", "How do I know the government won't control me", and more conspiracy theories. All of these fears seem to come from misinformation on the internet, friends and family get a ton of memes/fake news through WhatsApp highlighting the unproven negative effects of the vaccine. Is there any effective way to control the propagation of misinformation on these platforms? How would one even get started to tackle that problem?
Whether or not you agree with their opinions or the sources they derived them from, what you're advocating is dangerous. Who should have that authority to determine what is and is not misinformation?
Well it sure doesn't help people gain trust in the institution when the large cooperations like Facebook Google and Twitter censor wrong speak with the blessing of many political leaders. eg. YouTube will censor videos about election fraud (in the 2020 presidential election not the 2018 Georgia senator election) or anything against the WHO (even though they corrected themselves a few times).
Misinformation? This is literally a very untested vaccine. There are literally no longitudinal studies. You should be weary of this vaccine. I am not an unintelligent person. I have a bachelors and masters and I am very weary of something that has been spread through its trials this quickly.
The people who you hear say "I don't want to be guinea pig" ... they're not wrong. This vaccine could be perfectly safe .. or we could see a lot of edge cases when you start injection a million people at a time with it. On top of all of that, you can be sure hospital will be sure to force front line workers to take it first.
Please, let's be honest about this. Why are we suddenly trusting drug companies after disasters like viox. I'm not against vaccines in general. I've had all my MMRs, took my Typhoid, Meningitis, Hep B for certain overseas trips. But those took time to go through trials and were vetted for safety in a way this simply hasn't had the time to.
People are going to be weary and that's not wrong. That's not "anti-science." This is legitimately going to be an experiment which, if they get wrong, can potentially harm a lot of people. You only need to look back to the 70s and the Swine Flu vaccine disaster.
There's some value to their fear. I share some of it too.
These are some of the fastest-to-market vaccines ever produced. Some were also developed with technology never used before at this scale.
There's some nuance to the fear though - for example, once frontline, health workers and people like Dr Fauci are vaccinated, and it becomes clear that these are at least as safe as flu vaccines, I'll also likely take one, if only for the sole reason that I sorely miss travel.
It's won't though, not for at least 1~5 years. All the long term studies are being skipped. So long as this vaccine is a choice, I'm okay with it. But if it becomes required for certain jobs, or to be able to enter a store or venue ... I dunno. The speed that this has been rushed through just does not feel right.
I would rather wait 5 years. I prefer that risk for myself over the risk of a rushed to market vaccine. The trouble is, everyone will yell that you not getting the shot can hurt everyone else.
This gets into the dangerous game of personal agency, liberty and autonomy vs what the State is telling you is mandatory for the safety of all. There won't be enough doses for this to matter for a while, but when it does, we'll see some big ethical concerns and court cases.
There are no long term studies. The reason vaccines take so much in "regular" circumstances are:
- Actually finding money to run the trials
- Run Phase 1, 2, 3 trials one after another
- (longest) Waiting for the events (infections) to accrue: if it's not in a pandemic, and with relatively low incidence, this takes years to happen
- Regulatory approval (if not in emergency, that's two years)
- Production scale-up (at least one year)
The fact that vaccines takes years to develop for safety is a myth. It is mostly a matter of time, and the fact that we were used to them taking years. Let's not forget smallpox and rabies vaccinations took far less to be invented, and people devising them didn't even know what viruses were. And also because most of the easy targets are now done. What's left are the harder ones (HIV). SARS-CoV-2 might have been hard, or one of the easy pickings. Luckily, it fell into the "easy" camp.
In this specific case, production was started during the trials, events, due to the fact that the virus is spreading like wildfire in the USA, took a matter of weeks to accrue (from 35 in October to 94 two weeks later, according to the Pfizer data), and the fact that an obscene amount of money was spent meant that most trials were started as soon as possible.
But, even looking at the protocols, you might notice that it ticks all the good boxes for proper clinical research.
I hope they learned some lessons here and seek to accelerate lifting the ban on the Johnson & Johnson and Astrazeneca vaccines. Work they can do to get those approved in the next few weeks are what can end the pandemic in Q1.
In the US, given by Feb, there will have been about 100M infected, It really only takes about 100M vaccines to hit herd immunity. Between Pfizer, Moderna, J&J and Astrazeneca it's reasonable to expect/demand 100M out by Feb.
The FDA's approach of "moving slow to give confidence" cost lives and does not actually build confidence. Allowing this vaccine to be taken by the willing was among the easiest decisions ever made, and their pretending otherwise was absurd. It would have built more confidence if they said within 24 hours of the EUA filing "hey public, this was an easy call. We already looked at all this data over months, cut no corners. This isn't a borderline approval, this looks amazing."
How are you arriving at 100M infected by February? The current case count is at around ~15M with ~250,000 cases being reported yesterday. To reach 100M by February you would need close to ~2M cases a day for every day between today (Dec 11th) and February 1st.
> The actual number of coronavirus infections in the U.S. reached nearly 53 million at the end of September and could be approaching 100 million now, according to a model developed by government researchers.
> The model, created by scientists at the Centers for Disease Control and Prevention, calculated that the true number of infections is about eight times the reported number, which includes only the cases confirmed by a laboratory test.
Infection count is a lot higher than case count. If you divide the number of deaths by an IFR of 1% you get 30 million infected so far, while with an IFR of 0.5% you get 60 million. There are probably half a million infections every day right now, so 100 million by February doesn't seem that far fetched.
Though I see no reason to complain about the FDA dragging its feet, given that the bottleneck to vaccinating the populace is manufacturing, not authorization.
Enrollment of people into the studies had been paused after some people in the respective studies had suffered health issues that needed to be investigated to determine whether they were adverse reactions or not.
As I understand it, both pauses ended over a month ago, and there hasn't been any "ban".
As someone who just received a J&J vaccine or a placebo, I can definitively say that at least the one is not banned currently.
Both studies were paused, as is customary, due to medical complications from someone in the study. Upon investigation it was deemed in both cases to likely have not come from the vaccine, and the trials were resumed.
Your and likely most people's interpretation when they hear "ban" is that the FDA took some active step to specifically ban the J&J and AstraZeneca vaccines.
The other interpretation is that all pharmaceutical drugs are banned by default and that approving a drug is actually removing that ban. I suspect the original commenter was using "ban" in this context.
I'm very weary of this approval. This is the first messenger RNA .. thing (this isn't a vaccine; not like any attenuated or inactivated virus vaccines that have come before it. This is something very different in the way it works). There are no Longitudinal studies. This will be a significant increased risk for people under 40.
We shouldn't see to fast track any drug, vaccine or treatment outside of the normal process. I wish the inhaled steroid controlled studies had completed because I was curious of that would have been a useful treatment (a lot of doctors are using them off label) and we wouldn't need something this untested.
Fast tracking medications is how mistakes are made. Let's be critical of how these emergency powers are used.
No mRNA vaccine has been approved before, but from clinical trials of mRNA vaccines dating back to 2008 [1] there’s evidence of short-term side effects but no reason to suspect long-term safety concerns. mRNA vaccines don’t present the risk that attenuated vaccines pose to immunocompromised individuals or pregnant women, and they don’t stay in the body long enough to be a long-term threat. We can’t guarantee 100% because our bodies are complex, but I wouldn’t characterize it as “significant increased risk” for people under (or over) 40.
70% is the kind of "default" number. It's based on 1-1/R0. If R0 is 3, then you need 66.7% to no longer be susceptible before cases start to decay. If the vaccine is 95% effective, then you need about 70% vaccinated to get 66.7% no longer susceptible.
But: 1-1/R0 assumes universal, uniform susceptibility and uniform contact graph, which aren't true-- so it's pessimistic. And some people have caught the virus already and are no longer susceptible through that means.
Many computational models put it at about `25% of people infected will result in herd immunity with normal behavior, and the US is presently at about 16%. Unfortunately, getting the "right" additional 9% of people will require vaccinating much more than 9% of the population (we're not as good at selecting the most susceptible and most involved in spreading as the virus itself), but substantially less than 70%.
Further, R0 is based on baseline behavior. I suspect a decent chunk of us will be much more careful for some time, which effectively changes the required decrease in susceptibility to cause a case count decay.
Sure, there may be 53M infections, but how many of those untested positives will go on to get a vaccine? This will actually hinder herd immunity, wasting limited vaccines.
> Sure, there may be 53M infections, but how many of those untested positives will go on to get a vaccine? This will actually hinder herd immunity, wasting limited vaccines.
Oh, ideally you wouldn't vaccinate people who are already immune, but saying it hinders herd immunity is a bit silly.
I find it's always helpful to do thought experiments at the limit.
Do you think reaching herd immunity requires more doses A) in a population that is 99% of the way to herd immunity, but that 25% of doses will be wasted because they'll be given to people who are already immune, or B) in a population that is 1% of the way to herd immunity, but only 4% of doses will be wasted in this way?
> Oh, ideally you wouldn't vaccinate people who are already immune, but saying it hinders herd immunity is a bit silly.
If you only have 100M doses and you waste half on undetected positives, that definitely hinders achieving herd immunity. Unless you are saying uncontrolled spread helps develop herd immunity. It does, but it isn't a desirable method.
Nobody said it was a desirable method. But I did assert that past infections does reduce the doses you need to give to reach herd immunity, which is a point you seemed to argue with.
We'll likely be at >70M natural infections before vaccination efforts hit full steam in mid-January. This is pretty close to the lower end of where models predict herd immunity effects (not ~60% because of non-uniform contact graphs and susceptibility). You don't need a whole lot of vaccination tacked on top of this to start to tamp things down, even though A) some of the vaccinations will be wasted, and B) the vaccinations will not be as "on-target" to break important links in the graph as infection itself is.
> But I did assert that past infections does reduce the doses you need to give to reach herd immunity, which is a point you seemed to argue with.
Sorry for the misunderstanding. I wasn't arguing that past infections change the needed doses, I was arguing that undiagnosed positives waste limited doses. Hope that's clarified.
They can't be added up like that though, since some of the previously infected will still be vaccinated. So it'll be more like 170 million total with 100 million vaccinated.
100M doses brings us closer to 17%. We need 400M doses to innoculate 200M people, which is what we need to achieve 70%, counting the 16M people that have been diagnosed with the disease.
This likely didn't matter much to FDA because 16 and 17 year olds aren't likely to receive any doses before the full throated approval because they by and large aren't in the people first in line for the vax (1st line workers, vulnerable groups, old people).