FDA statement on following the authorized dosing schedules for Covid-19 vaccines
fda.gov
fda.gov
In other words, we basically have NO DATA on single dose schedules for Moderna/Pfizer vaccines. There's too few of them anyway to gain any statistically meaningful insight even if we did follow up on these study participant washouts. This is hydroxychloroquine all over again. When you are looking at inadequate data, you can find all sorts of patterns. It is very rare that such patterns turn out to be real. The most reasonable approach is to assume that there is little to no durable protection from a single dose, just like most prime/boost vaccines.
How is that the most reasonable approach? Virtually every vaccine ever discovered provides more immunity on first dose, than the incremental gain on subsequent boosters.
You certainly can't be sure of this, but pre-existing evidence would strongly suggest that this vaccine is subject to the law of diminishing returns. At the end of the day, we're just trying to maximize infections prevented. If the two-dose schedule confers 95% immunity, then as long as we expect over 50% immunity from a single dose, then First Dose First is best policy.
Now we're distributing the vaccine, but the bottleneck is that we have to keep waiting for rainy days. It's especially bad in Arizona and Nevada. Is your contention that we keep the rainy day requirement? Even when all are scientific and empirical priors tell us that the effect is de minims.
The example is kind of silly, but it makes my point. There's literally countless number of factors that go into any trial. There's no possible way that the way treatment is deployed in the field will exactly match the way it was tested. Yet doctors, scientists and public health experts use judgement and empirical priors to determine when and where we can relax the requirements.
Experts do not agree.
They certainly do. And the FDA, a collection of the leading doctors, scientists, and public health experts, just told you that two doses is the regimen. Is there something that you know that these experts don't?
As for more general critiques, there’s mountains of evidence that the FDA is too risk averse, even before Covid.
Specific to this instance, this FDA meeting was a formality -- they had already had the data for two weeks to review. The efficacy was well-known. They chose to take a 4-day holiday (Thursday, Friday, Saturday, Sunday).
People don't all of a sudden sign house contracts. They've germinated the idea, spent weeks or months working through the pros and cons, talking to their life partners and family and agent and mortgage broker. The decision is made well in advance of the actual contract signing, and all the red lines are done before you get to the actual meeting to sign on the line. Similarly with the FDA regulators, they weren't meeting to review the data for the first time and come up with a decision on the spot. This was one final step in a very long process.
While nearly ten thousand Americans died, I guess the FDA was “catching up on its sleep”. Eight long days of glorious sleep!
Because if it's over 50%, then the math is very simple. First doses must go first. Here's my simple proposal: I bet you $500 that the first peer-reviewed study to specifically test one-dose mRNA Covid-19 vaccines finds at least 50% effectiveness.
Talk is cheap, and I'm sure you get a lot of upvotes on Reddit and Twitter by sprouting some "Follow the Science" hashtag. But actual people's lives are on the line, so if you won't even risk a little bit of money on your beliefs, stop risking people's lives.
3-4 weeks are quite short intervals for booster shots, picked because of the urgency of getting results, not because it's optimal from a medical standpoint.
> FDA, a collection of the leading doctors, scientists, and public health experts
FDA is primarily a regulatory bureaucracy, tasked with enforcing federal law in this area. The incentives it is under do not always align with optimizing public health.
I'm not sure I would describe the FDA as optimistically as you do - they are a collection of federal employees, leaning heavily on private industry expertise to navigate the demands of politicians, the expectations of the public, and needs of businesses.
The reasonable approach is to be overly cautious. A false sense of security is worse than no security at all.
True. But that isn't what is happening here.
This is more "some level of security which is less than absolute, and unclear what sense of security people will assume they have"
We've seen "false sense of security" arguments used time and time again to oppose partial, imperfect safety interventions (seat belts in cars is a great example).
This is not how decision making under uncertainty works. When you don't have rigorous proof of whether something works or doesn't work you have to make educated guesses based on various priors and make the percentage play. You can't refuse to incorporate priors into your decision making just because you don't have a peer reviewed p<0.05 study validating it.
Uncertainty about the result cuts both ways. You can't claim that we can't do X over Y because we don't have rigorous proof that X is better than Y, when we don't have rigorous proof that Y is better than X either. Regardless of what you do you're taking a leap of faith.
> We just don't know and it would be way worse if it turns out we have to re-vaccinate everyone because we were impatient.
If there's probability p that it doesn't work and we have to spend X extra months re-vaccinating everyone that's an expected delay of p * X. But if it does work then not pursuing the single dose strategy will delay the vaccination schedule by X' months also.
If p * X < (1-p) * X' then the former is a perfectly acceptable risk.
Sure, there could be some odd unforeseen effect. If so we'd learn as we go.
> it would be way worse if it turns out we have to re-vaccinate everyone
Worse than 3000 people dying every day? Because of the extra expense of making more doses?
The cardiologist says, “Well, I’ve identified drugs that have saved the lives of millions of people.” Impressed, the kidnappers turn to the immunologist. “What have you done?” they ask.
The immunologist says, “The thing is, the immune system is very complicated …”
And the cardiologist says, “Just shoot me now.”
From https://www.theatlantic.com/health/archive/2020/08/covid-19-... :)
As someone who is an active researcher in this field, I can tell you that this is just not true. The immune system is VERY complex and we know very little about it. We have only had the tools to begin to systematically probe it for a few years.
But I don't think they apply to these rather basic questions about how these mRNA vaccines work.
The theory for how they work is clear, and strongly confirmed by the studies showing 95% effectiveness.
Is there really any reason to think that a booster shot that provides 95% protection when given after 21 days will be damaging after 12 weeks?
Or that when two shots gives 95% immunity, 1 shot might give negative immunity?
This what's being implied by the "you never now, so let's do NOTHING" crowd here!
It's also about giving people a vaccine they can believe in, which allows them to return to some of their normal activities. If everyone is 50% safe, no one has any real expectation that they can take any risks without being infected. If half the people are 95% safe, that half can do more things (travel long distances, go to school) while the unvacccinated half can continue to avoid risks until more vaccine is available.
Exactly how it is rolled out here in Moscow. It has never occurred to me that it's not the one and obvious way.
But yes, the "Sputnik" vaccine has huge problems with giving people something they can believe in. Rolling it out in a "rational" order, as if they actually believe it works, is probably the most city government can do to raise confidence.
Citation needed.
And as linked in that post, Moderna's primate study: https://www.nejm.org/doi/full/10.1056/NEJMoa2024671?query=fe...
For starters, we have profound differences in the attack curves between treatment and control group, starting about 14 days after administration of the first dose [1]. I don't have the numbers in front of me, but I'm going to guess the trial size is more than adequately powered to detect differences 27 days out.
All this is exactly as theory would predict. Seroconversion typically takes about two weeks. Once seroconversion happens, immunity lasts years (if not decades), which is why most booster doses are given years apart [2]. And any talk of "full efficacy" is confusing population statistics with individual outcomes. To say that Moderna is ~85% effective after one dose, as it appears to be, is to say that 85% of the population will produce antibodies after a single dose. There is no "partial immunity"--you're immune or you're not.
[1] https://www.ft.com/content/7cebed90-3267-4651-a249-56f5a9ae7...
[2] https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolesc...
These are rDNA Prime/Boost vaccines, which is completely different to the conventional vaccines with the multi-year booster regime.
I agree that the 14 and 27 day attack curves should provide some efficiency data though.
Is that true? (I'm not an immunologist; I genuinely have no idea.)
I'd have thought that it was all a statistics game: how many antibodies you have and how fast your white cells can respond to the threat before the virus got a foothold. In that model there is partial immunity: some people would win that race, and some wouldn't.
If I'm wrong about that I'd appreciate a better model. Thanks.
It simply isn't workable to reason from lighter symptoms to "partial immunity." Let's pretend the vaccine didn't exist. Take someone with a mild case of covid. Would you say this person is partially immune? Or consider someone with no symptoms at all--are they completely immune? Since the vast majority of cases are mild or asymptomatic, are you prepared to argue that "immunity" is actually very widespread?
Again, your "some people win the race, some lose" analogy is on the mark. It's pointless to talk about "partial victory"
You've basically answered your own question. At the population level, immunity is probabilistic. At the individual level, it's ~deterministic. Those who are challenged but stay healthy are immune. Those who are challenged but get sick are not immune. If we were to repeat the experiment, the individuals who stay healthy/get sick would largely remain the same. In this ex-post view of things, there's no "in-between." You got sick or you didn't, you're immune or you're not.
From an ex-ante perspective, we would instead try to predict whether a person will get sick or not. The answer to this largely depends on whether the body can generate a response to previously recognized antigens. This again is binary. You have memory B-cells due to primary response or you don't; you're immune or you're not.
I wonder if anything can be deduced given knowledge of the mechanisms these vaccines use compared to other vaccines against other viruses.
I know there are vaccines like for HEP-A that confer immunity for at least 10 years given a single shot, and a 20+ years of immunity if a booster is given in six months.
It appears that the FDA doesn't want to offer any information outside of the studies. This cut in half the number of people who can be protected during this winter's covid season.
Most vaccines have increased efficacy when spreading out the doses, so the same is likely true here, which means this is most likely to increase efficacy.
We don't have data on lots of things, like what if we vaccinated people in cars instead of indoors? We can't run RCTs for everything in this world.
People are also not advocating for 1 dose only, rather spreading the doses out more to get more people vaccinated faster.
1 dose first, followed by another 12 weeks later is almost certainly going to be highly effective and it's almost certainly going to be safe.
This is also not a binary decision. To let you to 10M people try this regime while watching the data has as close to "only upside" as you can get in medicine.
If the FDA approved Astrazeneca now, and the states focused on getting first doses, we could be done with this pandemic in like 45 days. It's worth taking a tiny amount of risk that this group of 10M might not have effective immunity and need to be revaccinated.
EUA means Emergency Use Authorization. Emergency, yes, that's what Covid is. As such, leadership means taking some calculated risks. What FDA essentially does is "you can't get fired for buying IBM". They stick to "we don't have any data for this and that", "this is what the science shows", and people out there are dying. A perfect demonstration of lack of leadership.
1) For how long
2) How it impacts future vaccination efforts
(As well as a slew of other things)
If it was just #1, I'd be with you. If we give a big chunk of the population a vaccine which lasts 6 months and makes them unimmunizable, we've changed a serious problem into a serious, serious problem.
Is there any scientific basis for this hypothetical?
One mechanism: If you have a vaccine designed to deliver a spike protein (without a virus) surrounded by a carrier. The body learns to destroy the carrier. On future doses, the body recognizes the carrier, and the vaccine is destroyed before the body can react.
Of course, a vaccine with a different carrier won't be affected by this mechanisms, but there are many other mechanisms as well. I'm not an expert, and I don't know all of them. I'm not sure science knows all of them either, for that matter.
There have even been instances of vaccines making diseases worse too (actually, viruses not too dissimilar to COVID19). And there are a bunch of other possibilities.
I'd buy the basic premise of giving each person one dose for giving everyone imperfect immunity if not for these sorts of complications. I'd rather just wait a few more months than risk a small (but definitely non-zero) chance of something really, really bad.
Definitely need more data on the single dose approach and if that proves safe enough then providers can go that route. Playing with people's health because we want to go cowboy and extract many doses as possible is irresponsible.
What happens if the single dose approach doesn't work as well as hoped? I wouldn't want to be that guinea pig who thought "I'm protected". How long will it be that all hospitals get the information to go back to the two dose approach. Consistent messaging is key during this pandemic. That alone has been hard enough.
Besides, right now most countries are having more problems getting immunizations done than getting vaccine supplies.
Broward County, FL just put vaccinations on Eventbrite, as a fast way to get appointments set up.[1]
[1] https://www.theverge.com/2021/1/4/22213307/covid-vaccine-flo...
"240 Israelis found with COVID after vaccination, underscoring need for vigilance"
https://www.timesofisrael.com/240-israelis-diagnosed-after-v...
If you give more people a single dose you may be gambling that those people receive sufficient uncertainty, but if you give fewer people two doses you are ALSO GAMBLING with the lives of people who do not receive a vaccine. There is no "safe" option here. You just have to make educated guesses about the probabilities and risks involved instead of pretending that one approach is the "safe, conservative" one.
The same is true for vaccines; we have lots of them and we can make an educated guesses about how new ones work, even if new vaccines may not always behave the same as old ones. When you have to make decisions under uncertainty you can't refuse to incorporate educated guesses just because you don't have rigorous p<0.05 peer-reviewed proof confirming those hypotheses.
I remain sympathetic to the argument that we're maintaining too high of a standard of evidence during a rapidly moving pandemic. The question isn't whether this "may be" a harmful decision (of course it might); it is whether it is likely to be. The FDA's memo fails to convince me the expectation is worse taking the single dose strategy.
This reads like a letter by someone who keeps all their money in CDs rather than stocks, because they might lose money.
COVID vaccines aren’t believed to be indefinitely effective, so it’s very possible that less effective large scale vaccination effort would cycle through and fail to stop the spread long term. However, a sufficient vaccination effort could completely eliminate the disease globally.
Citation?
The best estimate we can make on the vaccine is. "From what we know of the duration thus far of immunity, I would be surprised if it turns out to be a 20-year duration, but I would also be surprised if it was less than a year,"
We don’t have the capacity to make enough vaccines for global herd immunity in under a year. Which is why reduced long term efficiency is a significant concern over a faster rollout schedule.
So you're making a super strong statement that's not very justifiable.
> but it’s closely related to other diseases where immunity from contacting the disease tapered over time.
I mean, maybe? Let me know when there's more then extremely minimal evidence of reinfection. We are at the point now where we are coming up on a year of significant spread and it's still missing. Additionally, have we ever seen an mRNA vaccine for a coronavirus? Nope. Evidence here is at best uncertain.
> We don’t have the capacity to make enough vaccines for global herd immunity in under a year. Which is why reduced long term efficiency is a significant concern over a faster rollout schedule.
Would we have enough if we split doses? Why does the US need global herd immunity?
We don’t think of each annual flu as it’s own disease, but they are caused by closely related strains not a single virus. Similarly, COVID-19 was originally named SARS-Cov-2 due to it’s close relationship with SARS-CoV also known as SARS. https://www.cdc.gov/coronavirus/types.html
Which is why the vaccine could both be developed so quickly in the first place and we can make reasonable predictions about the vaccine. They didn’t create a successful vaccine in under a week from scratch without a lot of knowledge of closely related diseases. It’s that same knowledge which is behind the dosing schedule, and why it was tested like that.
> Why does the US need global herd immunity?
Ending the vast social and economic harm from social distancing efforts. With local herd immunity things go back to normal even if the rest of the world is dealing with the disease.
PS: The demographics of the developing world even support a staggered approach. First a focus on vaccinations for the elderly and medical workers globally then local herd immunity based on population demographics. Local herd immunity protects those who the vaccine can’t, but evenly spreading out vaccinations to the younger population accomplishes little.
No, it wasn't. The disease and the virus that causes it were originally referred to as “the 2019 novel coronavirus” (or, 2019-nCoV for short.)
SARS-CoV-2 was announced as the name of the virus by the International Committee on Taxonomy of Viruses on 11 February 2020; COVID-19 was announced as the name of the disease by WHO also on 11 February 2020.
But yes, the disease was named COVID-19 thus the overlap, and current confusion over the viruses name.
Makes all you're saying have even less sense.
> They didn’t create a successful vaccine in under a week from scratch without a lot of knowledge of closely related diseases. It’s that same knowledge which is behind the dosing schedule, and why it was tested like that.
Was there a SARS vaccine? What same knowledge would give the current dosing schedule then? Why does it trump the new knowledge gained from an actual RCT of the vaccines?
> With local herd immunity things go back to normal even if the rest of the world is dealing with the disease.
Huh? So then the US doesn't need the global herd immunity like I was suggesting?
> PS: The demographics of the developing world even support a staggered approach. First a focus on vaccinations for the elderly and medical workers globally then local herd immunity based on population demographics. Local herd immunity protects those who the vaccine can’t, but evenly spreading out vaccinations to the younger population accomplishes little.
Okay, how is this relevant to whether or not there should be a longer time between initial dose and booster? It's totally irrelevant.
Bear in mind that the expectation is only about 1.9 billion doses total will be produced in 2021 - so we are talking about the difference between maybe 1/3 or 1/2 of the first world being immunized, and hitting herd immunity this year.
I'm not saying we should, the FDA is probably correct that we should follow the dosing schedule we know works rather than throwing away a whole year of vaccination efforts, but it's obviously desirable.
(it's unfair but I'm sure that most of the doses are going to end up in the US, Europe, and other western-aligned countries first, then China and Southeast Asia, and the developing world is going to get the shit end of the stick, the developed world is going to hit herd immunity long before let's say India or Africa.)
You may die from COVID.
Polio is very close to being eliminated, with only 125 known cases in 2019, which was a spike. Rubella dropped from 670 thousand in 2000 to under 15 thousand in 2018.
Ovine rinderpest elimination is considered a reasonable goal, but still 15+ years off.
The statement said there was insufficient data to make that calculation definitively. If you want to take a course of action not borne out by the study, the FDA doesn’t go after you or your doctor for off label use. The FDA is clarifying that the unproven route is, well, unproven.
The FDA is all about medical risk vs provable results. They can’t intelligently comment on the uncontrolled unknown beyond saying that that you’re entering that territory. If you want odds on rolling the dice outside that space, they’re irrelevant to you. So stop looking there.
edit: what you want is a politician with the balls to say whether we should do it anyway and convince other politicians that they should own making that decision even if they turn out to be wrong. But Washington is full of cowards too cowardly to even go to bat for sticking to the studied regime beyond milktoast deference to science so you’re here expecting the FDA to start exceeding their role.
The suggested dosing is obviously unproven because it has not had a nice large scale study done. Shouldn't this be where they conduct a few rapid small scale experiments?
That data, the existing trials, along with a deep bench of knowledge should be enough to make a well justified determination.
2) Trials must be large to see results because Covid is rare. The Moderna trial took 30,000 patients 3 months to get to 90 covid cases.
3) This could be a an interesting opportunity for challenge trials, but unfortunately, the key metric for vaccines is reduction in severe cases. Subjecting people likely to have a severe case is unethical when there chance of normally catching it is very low.
This is part of my complaint. Why is a large trial, or even a challenge trial (which I also support), the only way to get results here?
There is more to science than reading statistics from trials. They should be able to ask and answer very specific questions based on the working model proven far. Then scale those results to the broader problem.
No I don’t. I was saying that the kind of balancing you mention is out of scope for FDA to answer. The fact you can’t find anyone to answer the question you want answered is not the FDA’s problem.
I said go off-label if you want to (although off-label might be slightly the wrong word in this case). Good luck finding a politician that wants to tie themselves to recommending that, in case it turns out wrong.
I wish that these decisions wouldn't need to be deferred to politicians. So many of them are selfish idiots.
I'd more trust the vote of relevant medical specialists. I'd rather that these specialist provide the public the best/concise information they have and let people make informed decisions for themselves, or even have a referendum on one dose versus two, and prioritizing.
Politicians have already turned the world upside down for something that looks like it will kill two out of a thousand people when all is said and done, mostly older. Half the population is dumbfounded by their lack of perspective, the other half is scared shitless.
The FDA's job is not to decide which lives are more valuable than others, or what our society's risk tolerance is. Their job is to keep people safe and to present the data and the options to political leaders.
The FDA clearly has a goal of not tarnishing their reputation. If they make the wrong decision here, then they lose credibility with approvals for future drugs that come out to treat Alzheimer's or diabetes or whatever else.
Ultimately, I think we look to our scientists to make many decisions that aren't really their place to decide. A scientist can tell me that vaccine X is this effective based on their data. Or even that they have a hunch that treatment X will do Y. But ultimately, I think it's on our elected leaders' shoulders to hear the scientists out about what the various risks are and then make a decision. Unfortunately, I don't have faith that our current elected leaders can adequately listen to our scientists counsel and then make wise decisions accordingly.
I agree with this statement, but I think there is more to it. The FDA is not only concerned about its reputation, but also public trust.
Don't get me wrong, my _gut_ tells me that a single dose of the vaccine would be beneficial to achieving "herd immunity" more quickly.
But if the FDA goes down that route and they are wrong, then they will have demolished the trust associated with many future decisions.
If there were a clear delta in expected value, then we'd do it. But you can't compare a speculative change to requirements with asymmetrical costs/rewards in a policy context during a pandemic to CDs vs stocks.
Don't give in to the temptation to be like the business guys who change requirements the day of launch. We have a path to end the pandemic. Let's take it.
Apparently the variant seen in South Africa recently is "concerning" scientists: https://globalnews.ca/news/7553824/coronavirus-variant-south...
Sure, Moderna and Pfizer could whip up a new vaccine to tackle this ... but how much does the new variant spread and further mutate while we're testing new vaccines?
Let the science do it's work, don't try to be clever and cheat the system.
> Following the status quo path will likely result in significantly more people dying
Besides, the clinical trials _are_ quantified. The issue is we don't have data for the potential changes.
Armchair speculation of "maybe half will work" != data
The potential downside here is very large, it could mean that the vaccine loses a lot of efficacy if the delay to the second dose is too large. It also could create circumstances that favor mutations that escape the vaccine, because you have a lot of people with a weaker vaccination response while the virus is circulating widely.
That's a good thing in medicine and science- it's called the "precautionary principle". We have what we know (two does in the trials) working, so trying something new like a one dose regimen is risky.
Added: https://www.acpjournals.org/doi/10.7326/m20-8137
> We find that under most plausible scenarios, a more balanced approach that withholds fewer doses during early distribution in order to vaccinate more people as soon as possible could substantially increase the benefits of vaccines, while enabling most recipients to receive second doses on schedule.
I've only read the abstract, but this is an example of the kind of analysis you want to see behind a decision, as opposed to "we cannot conclude anything definitive" which is true but a deflection from actual decision-making.
Let’s not snatch defeat from the Jaws of victory. Let’s let the 2 dose vaccines goes to those who need it the most and the most at risk. They need more care and monitoring to entire they get both doses.
In a few months when the other vaccines come online then we have unimaginable more flexiblity.
Now is not the time to confuse Americans who apparently are easily confused. Take two doses now. Splitting them up and then some getting Moderna and some getting Pfizer is just a clusterfuck.
R-Value with UK mutation: 3?
Effectiveness with 1 dose: 66%?
Probability of breeding a new mutation if you gradually vaccinate everyone in the UK up to only 1 dose:
99.9%?
Once 2/3 of people have 1 dose, mutations that make the vaccines worthless should dominate given the available pool, and then the available pool is back to everyone again.
"This vaccine probably works. We won't know for sure until December. If you want to try it anyway, come get one. Otherwise, we'll let you know when the trials are completed."
It's heartbreaking to think about all of the irreplaceable experiences people missed this year, especially for those who didn't live to see the end of this pandemic. Of course I'm glad for all the people who didn't catch the virus, but the costs are too infrequently considered. Our regulatory bureaucracy was insanely expensive this year in terms of our most valuable resource: quality time. Nobody even questions it; we just accept that this is how it's supposed to work, because it's all we've ever experienced.
I mean, take the flu shot. The times I've gotten it I've not had any reaction or one so mild I don't remember. Maybe a sore arm? Slightly tired, though that could have been work. I wouldn't personally know until they do blood tests.
Even if you have side effects - outside of a possible sore arm, you wouldn't know it was the vaccine or just unfortunate timing for a virus or something.
You want the trial to be double blind because it means there is less bias: https://www.verywellmind.com/what-is-a-double-blind-study-27....
I don't know what the poster above was talking about, getting calls to participate in a study. Nobody contacted my wife or I with such offers. I suspect that the poster was lucky to live right in a city where the test was being conducted; those outside of major cities are probably not included in his claim that anyone could participate in the trials.
Sometimes it just doesn't work to have double blind: LSD trials, for example, make things pretty obvious. It isn't the case for the flue, though.
You are correct on the trials: most folks don't get called. That said, living outside the city doesn't exclude you from trials in general because they generally need participants with x and/or y. Often, they will pay for expenses to travel, especially if your disease is uncommon or they have trouble finding participants.
What if, at any time, you could walk into your doctor's office and say "I'm ready for that experimental vaccine?" You could contribute your data to the pool that increases our confidence in its efficacy. As confidence gets stronger, more people volunteer. Eventually, third party labs (maybe regulators like the FDA - maybe NGOs like the UL) certify that they believe a vaccine is safe and effective, which makes even more people comfortable getting it.
If we had done that, how would life be different now? Could we have closed fewer things? Would more people have led a more normal/less stressful lives? Would we be closer to being done with this mess? How many fewer long-term ramifications (health, financial, social, developmental, psychological, mortal) would people have to deal with?
We reconsidered, reenvisioned, and reinvented so many things this year. Why can't we apply that same mindset here too?
Back in the summer, supplies were much smaller than the current shortage. So it wouldn't have made much difference.
That said, I support drug legalization of all kinds.
mRNA vaccines should become very fast to ramp up production of, since it's an industrial process, not a biological one, but this is the very first time it's done.
A single scientist at Pfizer created 10 vaccine candidates in a day. Most worked, but some were less 'tolerated' than others. It's ok to do that in a lab setting, with health care standing by. There are limited resources for trials, you can't easily scale to millions.
Here’s a list of examples that shows why the FDA must be deliberate in their testing. People can die or be permanently crippled when we screw it up. Just imagine if we rushed a coronavirus vaccine with a similar safety concern and ended up hurting millions of people before we realized it: https://www.cdc.gov/vaccinesafety/concerns/concerns-history....
The FDA already does have compassionate use exemptions for people that are on death’s door and there are no downsides to taking an experimental drug- they’re dying anyway if it doesn’t work out. I think that’s about the right level threshold for deciding whether to give people unproven drugs and we should not have rushed the vaccines any faster- hindsight may show us that the vaccines are safe but we couldn’t have known that a few months ago. We have to do the testing.
Yet it appears that the FDA makes no attempt to understand the downside risk associated with NOT taking the vaccine. I don't see them talking to economists trying to understand what damage will be done to our businesses, and how people will suffer as a result of that; or even of what lockdowns are doing to our mental health. The ONLY risks they're considering are on the side of taking the vaccination.
And this is always how it works for them, both in normal times and during the pandemic. Consider last March, when the CDC's covid-19 test was defective. Despite the fact that the assay is a simple matter that any decent hospital can do in their own lab, the FDA would not allow anyone to do it. That set America's pandemic fight back by a couple of weeks. If we could shift the spread backwards by two weeks, how many thousands of lives would we be saving? The FDA's hidebound refusal to look at both sides is responsible for this.
(I should amend that a bit. They've clearly done a lot to streamline their processes for this. But as far as I can tell, they haven't done anything to balance different kinds of risk in their standards.)
It essentially implies that other nations, most prominently the U.K., that decide to gamble the other way, are foolish or unaware that there are risks. This is manifestly not the case. It is a gamble, and there are certainly risks, but no one who is advocating changing the dose regimen on the fly is suggesting otherwise, that I know of.
The motivation for going with one dose for twice as many people (in a given period of time), is that currently we seem on track to have the vaccine show up just barely too late to do much good. The virus is getting better at spreading all the time, and at the current rate of production, even if everything were distributed more or less instantly (which it isn't), we won't get a vaccine to most people before they get exposed to the virus anyway.
Now, there are still certainly arguments to be made that sticking with the tested regimen is the least bad option. None of them were present in this statement, which more or less attacks a straw-man argument that changing the dose regimen is without risk. If they were trying to make people angry with them, they could hardly have done a better job.
edit: I would add that telling friends and family that I got vaccinated actually uplifted their spirits: It seemed to give them hope that this would all end. Its different when people you know get it, versus hearing about it on the news.
There was a huge mess in Chattanooga with people waiting in line for 6h, being told there weren't enough doses and to leave, and then there being plenty so they gave them to friends and family.
(Assuming you're in the US) If it helps, vaccine distribution has been so poor that you're not depriving anyone of anything.
You shouldn’t discount that.
Sincerely, a member of the public.
EDIT: the type of typo that is the exact opposite of what I meant to say. Goddamnit.
[1] https://www.sandiegouniontribune.com/news/california/story/2...
Presumably these choices weren't picked out of thin air, or made up by some businessperson based on business considerations -- "We think we can get paid twice if we put it in two doses, but if we try to go to three doses it'll be impossible to market" -- hopefully that's not what happened.
Hopefully instead this decision was made based on actual data -- for example in animals or a small group in Phase I or for some similar vaccine, they did actually try N-day dose separations for all 1 < N < 50 and then made some actual measurements of how fast white blood cells attacked the COVID virus in a lab dish or whatever. The lab test maybe wouldn't be as ironclad as the Phase 2 which actually sends the subjects back into the wild and sees how many got COVID in the next 3 months, but it's some concrete data.
Where is that data? Couldn't you use whatever data was used to decide on the dosing schedule in the first place to quantifiably answer how much worse were the alternative dosing schedules that weren't chosen?
[1] https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolesc...
Or maybe they said "we measured secondary immune response with a lab test, and group D had the highest number"?
If these weren't done for the COVID vaccine specifically, but some other vaccine, couldn't you still put some rough ballpark quantitative guesses on the COVID vaccine to help guide public policy better than "shrug, we have no clue what will happen if you do anything other than 21 days"?
Something like "We think 40% will be protected with one shot, 90% will be protected with two separated by 21 days, and we can fit a curve to these two data points which has the same shape as curves for other decades-old vaccines that have tons of data and is supported by biological theory [paper1] [paper2] [paper3] [paper4] [paper5], and that curve continues to monotonically increase, so waiting 5 weeks instead of 3 should be no problem, in fact we think you'd be 91% immune instead of only 90% immune (provided you don't actually get the disease in the extra intervening 2 weeks), r^2 = whatever, but waiting 1 week instead of 3 is probably super bad, you only get up to 50% based on the shape of the curve and what's known from other vaccines, [paper6] [paper7] r^2 = whatever.
Disclaimer: This assumes COVID-19 vaccine acts like the vaccines in [paper8] [paper9] [paper10] which collectively cover 80% of known vaccines, but it's always possible since it's MRNA the curve will be something super weird and there's absolutely no reason to think it'll be like that, but it'll take us 10 years to definitively rule it out, but if you need to make public policy and you don't have 10 years to wait, a policy based on a tentative analysis with a 20% chance of being wrong, which 20% we got by polling experts' Bayesian priors of the probability that a new vaccine will have a totally different curve, is probably better than a policy based on a completely random guess [paper11] [paper12] [paper13]."
Based on that you could do an expected-value calculation of how many less people will get sick under policies of holding back various percentages of vaccine for second doses (the factor you control), vs some distribution of possible random future production hiccups (the factor you don't). You might find it's better to get shots in arms now to have as many people as possible 50% protected as long as possible if you know it's implausible that it's going to be a disaster if those people wait 5 weeks instead of 3 for the second shot due to a manufacturing hiccup.
You definitely could (and this is exactly what many people are trying to do!) But this approach relies on many assumptions, and the FDA is hesitant to let assumptions (no matter how well-grounded) enter into its evaluations. Thus its near exclusive reliance on RCTs. This is mostly reasonable, but it causes confusion amongst people who don't understand evidentiary standards. Thus all the braying about "no data" or "no evidence."
It's very important to note that Phase 3 was about COVID19 disease and less about Sars-Cov2 infection. They do have some infection information, but the vaccine is licensed to prevent disease, not infection.
If there was more time, there would be more answers, but you can only run so many trials when people are dying from a pandemic.
0. https://www.fda.gov/media/144434/download page 53
* Take all of the above with a huge grain of salt, I am not a doctor, immunologist, public health professional, epidemiologist, etc
Vaccine distribution is another matter. We knew this was coming, we knew we'd need cold storage, and there were only a few reasonable scenarios for who would be prioritized. Not getting out doses is the real failure, and not just Trump's; governors aren't doing great, either.
The other failure was not preparing for a winter surge.
I'm legit surprised Trump didn't hand the whole thing to the military. If there's one thing the military is good at, it's freaking logistics.
He did. Gen. Gustave Perna is in charge of vaccine distribution.
In my state, Arizona, the injection sites are open from 8-5 every day, and were closed on New Years Day.
This is so far past frustrating to me that I don't have words for it. Get the fucking vaccines into people's arms YESTERDAY. Don't take one minute of rest until you have to as you wait to get resupplied.
Here's a tracker: https://www.bloomberg.com/graphics/covid-vaccine-tracker-glo...
We were giving 400,000 vaccine doses. So far we have used 1/4 of them. 75% of our supply is sitting on a shelf while people go home every day at 5:00, or take a day off to celebrate the new year.
Not acceptable.
I just absolutely do not understand why these state health departments won't get going. For the love of god this is NOT the time to be taking vacation days. I just cannot even wrap my head around that. This pandemic is so awful that we are locking people in their homes, doing who knows what sort of damage to an entire generation of children, locking the elderly in nursing homes isolated from the world, destroying businesses, neglecting cancer treatments and screenings, and sprinting as fast as we can towards a collapsing economy.
We have the solution sitting in a freezer. Instead of putting it into practice, people are going on vacation.
Is this a catastrophic global pandemic or not? Why are people seriously taking VACATION time during something which is causing the collapse of our society?
Here's a story from 5 days ago where a New Mexico man has had to sue for the ability to touch his wife (https://www.fox19.com/2020/12/31/husband-sues-right-touch-wi...). And people are going on vacation instead of solving this? They're going home at 5:00?
This is how my state views the vaccine: "OHA considers the planningfor COVID-19 vaccine to be an opportunity to reimagine how the agency engages communities in co-creating the work of public health. This vaccine plan, as mentioned above, is a starting point for this journey."
Fuck this all. Get shots in the arms right fucking now
EDIT: It's also worth noting that these healthcare professionals you are attacking have been working under difficult conditions and at significant risk for most of a year and probably deserve either a) a bunch of extra pay that states cant afford on their own or b) some damn time off.
In fact, I think I'm doing the exact opposite here. It's not healthcare workers who are holding these vaccines back.
Those "people" are the healthcare workers.
However, once we fix that, we still have a problem of insufficient vaccine.
That's the thing that needs to be fixed.
The U.S. seems unable to distribute their existing supply, Canada seems unable to acquire enough supply, the EU was slow to approve, and Israel seems to be firing on all cylinders. If we had better data perhaps we could do more than speculate about the emergent bottlenecks and best practices of each process chain.
It is like me saying if I put 24V on the 12V rail of my PC power supply it in theory should go much faster since there is more power.
So the “fail safe” method would be to have a 100% reserve of second doses at all times. No first dose can be given if a second dose is not reserved.
Alternatively, you give out all your doses as fast as they come in, and you have a separate queue for 2nd-dosers who get priority when they schedule their time slot. Some days your whole supply could go to 2nd shots.
But unless you’re willing to actually delay the second dose for several months, the total number of people vaccinated in the first 3 months doesn’t really change all that much between the two scenarios.
In either case you shouldn’t literally be locking up doses for 30 days. The smart thing to do logistically is you have tracking on doses throughout the delivery pipeline, probably knowing your specific scheduled deliveries at least 14 days out. The second dose for a person dosed today doesn’t have to sit in the freezer from Day 1, it just needs to be reserved from the delivery expected on Day 24.
If a shipment gets behind and someone gets their second shot on Day 30 or 31, obviously this is perfectly fine. The only issue with getting ahead of yourself would be a major unexpected supply chain interruption that could leave people waiting a couple weeks longer, but then we have much bigger issues.
Amazing, this statement could equally apply to recommending mask wearing. Seems like the prudent answer in both cases is "public education" on risk.
I got downvoted in another thread for this opinion, but given the very obvious efficacy BEFORE the second dose (in fact the effect of the second dose is not observable at all in the incidence rate data), I find it ethically very challenging to accept thousands of additional, preventable deaths just to stick to the protocol and because nobody wants to take responsibility for a unprecedented decision.
The duration between doses was chosen because it was the minimum plausible time that the second dose was likely to provide significant additional benefit, and therefore the fastest to test. It's entirely plausible given what we know about other vaccines, that delaying the second dose 8-12 weeks may actually have been more effective long-term, but if they'd done that the end of the testing (and therefore approval) would have been delayed another 4-8 weeks.
Surely this would present no more moral dilemma than having a control group in the first place. It's just a question of numbers and resources, and if there's ever been a vaccine trial in history that could afford to throw numbers and resources at the problem, this is it.
Was there some legal or regulatory reason not to do this obvious thing?
However, they were still optimizing for speed: they presented results to regulatory agencies as soon as they reached a threshold number of covid infections in the group, which allowed them to demonstrate efficacy.
If instead they ran a split-dose trial, the results from each arm would have less statistical power, so the trial could not conclude until it sees more covid patients, taking longer overall.
They likely ran the trial with 40,000 patients because that was all the qualified patients they were able to quickly contact reliably enough to include them in the study (otherwise you have study dropouts, as mentioned in other comments above).
Glad to see it.
Because they NEEDED the vaccine to work, they chose very conservative numbers. Multiple doses, high loads, super cold temperatures, etc. Those trials have produced a lot of strong corollary evidence that partial vaccinations work, but it will take a very long time to do a full set of clinical trials on those doses.
And in the interim, a lot of people will die, who probably would have lived had we proceeded with 1-shot vaccinations. There's a lot of risk here either way, and choosing and never modifying the original dose schedule is not "safer" -- it's just a bias towards inaction.
It’s time to start injecting people, and to stop bullshitting around it. The vaccine is not effective immediately, we’re still going to have to continue social distancing and practicing better than usual hygiene and masking for most of us. You want to save lives? Be responsible instead of advocating for reckless changes to vaccine dosages. Continue to wear your mask, continue to practice good hygiene, continue to keep your distance until such a time as herd immunity is achieved. These aren’t even the only vaccines in the pipeline, just the two authorized by the FDA thus far and Pfizer, Moderna and FDA can continue clinical trials to see if they can lighten up on the dosage requirements down the line.
Couldn't they have done additional arms in the trial? Moderna could have had a trial arm with 1 mcg doses.
How long would that delay trial results you think?
And if they just delayed the other dosing arms, we’d be in the same spot we are now anyways - waiting for more data.
Yes! Most certainly. It'll definitely help with (our pocketbooks) the Covid Pandemic!
Okay. So, what's the dose, and how many boosters are required and at what intervals?
Uh, well. You see... It's complicated.
Cut the crap Pfizer. We know how many boosters are necessary for mumps, measles, rubella, pneumonia, shingles, chicken-pox, and tetanus....
Yes. Well, you see...
Cut the crap Pfizer. Out with it.
Okay. Well the thing is, it works for at least 6 months in our trials. Our models show effective immune response at over a year though!
Models? You mean you don't really know?
Yes. Well, you see...
Damn it Pfizer! Do you have any idea how far over the line my ass is on this one?! Do you?!?!
Yes. Well, you see...
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War... War never changes... ::intro-music::