24 ms·

FDA statement on following the authorized dosing schedules for Covid-19 vaccines

111 points by simonpure 6y ago

usaar333 6y ago
> However, making such changes that are not supported by adequate scientific evidence may ultimately be counterproductive to public health. 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.
- Retric 6y ago
  Unlike stocks the risk here is vastly larger than the reward. 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.
  - paulmd 6y ago
    On what basis do you say that? Stocks could potentially involve you losing everything, and the "reward" of cutting the number of necessary doses in half is that we could potentially reach herd immunity much faster. 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.)
    - kingnothing 6y ago
      You're not going to die from bad stock advice. You may die from COVID.
    - cma 6y ago
      Why don't we start playing options? Everyone gets a tenth of a dose so we can get it done next week. Just start a whole new study, made up of everyone.
  - creddit 6y ago
    > COVID vaccines aren’t indefinitely effective Citation?
    - deleted 6y ago
      [deleted]
    - Retric 6y ago
      We don’t have specific data on covid, but it’s closely related to other diseases where immunity from contacting the disease tapered over time. 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.
      - creddit 6y ago
        > We don’t have specific data on covid 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?
        Retric 6y ago
        > So you’re making a super strong statement that’s not very justifiable 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 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.
  - standardUser 6y ago
    Vaccines generally do not eliminate a pathogen and they are not expected to eliminate this Coronavirus. Smallpox is the only human disease to ever be successfully eliminated.
    - Retric 6y ago
      Relatively few vaccines exist, and even fewer old ones, but on the whole they have been quite effective. https://www.vaccines.gov/diseases https://www.vaccines.gov/diseases In total both Smallpox (human) and Rinderpest(cattle) have been eliminated in the wild. Seasonal flu is kind of an interesting case as each year is arguably a different disease with the old one having been eradicated. That’s hopefully a model which will work for covid-19. 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.
- finnthehuman 6y ago
  > The question isn't whether this "may be" a harmful decision (of course it might); it is whether it is likely to be. 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.
  - enchiridion 6y ago
    This is why I am frustrated by the FDA. It seems like all they are willing to do is read statistics produced by others. 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.
    - finnthehuman 6y ago
      FDA is doing exactly what’s in their statutory responsibility and authority. ie: what congress told them to do. (See my edited addendum to the parent comment.)
      - fennecfoxen 6y ago
        When someone observes that a government agency which seems to be doing something nonsensical is actually just following the law perfectly, it always brings to mind H. L. Mencken: "Democracy is the theory that the common people know what they want, and deserve to get it good and hard."
- chadash 6y ago
  I think this is part of the overall issue with the handling of this pandemic. No one wants to take responsibility. 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.
  - busyant 6y ago
    > The FDA clearly has a goal of not tarnishing their reputation. 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.
- curiousllama 6y ago
  > This reads like a letter by someone who keeps all their money in CDs rather than stocks, because they might lose money 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.
  - lastofthemojito 6y ago
    I hear you about the path to end the pandemic, but there's also that scary thing about the virus mutating enough to render the current vaccines useless. That feels like a very compelling reason to at least consider whether a single dose or smaller doses might get more of us immunity more quickly. Apparently the variant seen in South Africa recently is "concerning" scientists: https://globalnews.ca/news/7553824/coronavirus-variant-south-africa-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?
    - vorpalhex 6y ago
      News is generally trustworthy, but it is in their interest to always make everything sound as dramatic as possible. "Potential new strain which may result in mild reduction in vaccine effectiveness" is not a headline you will ever read. It's a very boring headline. It's in the interest of an advertisement supported company to make the most inflammatory headlines possible. Let the science do it's work, don't try to be clever and cheat the system.
  - bobcostas55 6y ago
    Following the status quo path will likely result in significantly more people dying. It's a gamble either way, and if you want to argue that the risk of a first-doses-first approach is not worth the risk, then quantify your reasoning and explain exactly how many extra deaths you're willing to accept instead of these platitudes about paths.
- fabian2k 6y ago
  How much uncertainty we accept depends a lot on the potential downsides. For example there isn't much of a downside to wearing masks, so that is a measure you could defend on rather flimsy data if you had to. 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.
- JTbane 6y ago
  >This reads like a letter by someone who keeps all their money in CDs rather than stocks, because they might lose money. 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.
- deleted 6y ago
  [deleted]
- abecedarius 6y ago
  This post makes the same point at greater length and considers counterarguments: https://marginalrevolution.com/marginalrevolution/2021/01/first-doses-first-show-your-work.html https://marginalrevolution.com/marginalrevolution/2021/01/fi... What's the expectation in lives/disability of one course vs. the other? That's the first-order question. Added: https://www.acpjournals.org/doi/10.7326/m20-8137 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.
- hnrodey 6y ago
  step 1. do no harm.
- hcknwscommenter 6y ago
  It reads to me like a letter by someone who invests in target date retirement funds and index etfs by dollar cost averaging on an automated schedule, and avoids investing in tulip bulbs, because the available data shows that this is the most prudent approach.
- remote_phone 6y ago
  We have a known vaccine that works with 2 doses. We don’t know if 1 dose will work. We have single-dose vaccines with higher temperature tolerance from AstraZeneca and J&J ready to be approved. 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.
- foolmeonce 6y ago
  I think the FDA is dodging the obvious since the US doesn't want to alienate the UK: 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.
  - dcolkitt 6y ago
    All of the mRNA vaccines target the spike protein. Coronavirus spike protein mutations have only ever been observed to occur in bats- never humans. Therefore the number of vaccinated people will almost assuredly not increase the likelihood of a resistant strain.
    - foolmeonce 6y ago
      I would accept a similar kind of reasoning in an argument towards caution, but not in an argument for seeing what happens with prolonged partial but insufficient immunity. Aside from near certainty that a change to the target protein is game over, we have no idea what other mutations could render immune responses triggered by the vaccines worthless, and I don't see the ethics in an experiment to find these mutations.
  - JohnCohorn 6y ago
    From what I recall from Dr. John Campbell’s excellent daily videos, the UK strategy was not to give only one dose, but to simply delay the second dose a few weeks so that more people could get their first injection from the initial supply(presumably supply will increase over time). That sounds much lower risk. I think the single dose proposal was a US thing.
sradman 6y ago
Throughout this pandemic my impression is that nations generally failed on two fronts: 1. data sharing, and 2. scaling. You can't optimize what isn't measured and the vaccination programs that I know of are not sharing basic logistics data. In absence of hard data, people try to optimize systems based on hypothetical problems. 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.
SllX 6y ago
tl;dr FDA to Public Health authorities: don’t screw around. Administer these vaccines in the manner prescribed because it is proven to be effective. Glad to see it.
- bpodgursky 6y ago
  You're really missing that these prescribed regimes aren't some long-tested, optimized plan. The vaccine manufacturers literally had one chance to guess what the right application schedule was, and had one chance to do clinical trials on them. 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.
  - SllX 6y ago
    I’m not missing any point. They picked what they could initially prove and the FDA expands on this to say that yes, we could try some other variables in further clinical trials. 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.
  - ketamine__ 6y ago
    > The vaccine manufacturers literally had one chance to guess what the right application schedule was, and had one chance to do clinical trials on them. Couldn't they have done additional arms in the trial? Moderna could have had a trial arm with 1 mcg doses.
m3kw9 6y ago
For the people that is arguing for a delayed dose. The issue at hand is we have 80% of the stock pile unused, there is currently no point in even applying this tactic and taking unnecessary risk.
- dehrmann 6y ago
  While I think Trump botched the initial response to covid, it was so new and we had so little information that I'm not convinced Biden (or anyone else) would have done much better. 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.
  - curiousllama 6y ago
    It's just so variable across the board. Chicago is doing a _wonderful_ job; Florida is apparently botching it. 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.
    - ars 6y ago
      > 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.
  - blhack 6y ago
    How is it at all Trump's failure? The states have these doses, and it is the state health departments which are just refusing to give the vaccines to people out of "fairness". 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-global-distribution/ 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-wife-nm-nursing-home-amid-covid-pandemic/ 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?
SubiculumCode 6y ago
As a medical researcher, I received my first Moderna vaccine dose yesterday. I feel incredibly lucky, but also, a tiny bit guilty. I have very minimal patient contact, and I could not help but wonder if by taking the vaccine, I was depriving someone more needy of the vaccine. In the end, I decided that due to inevitable bureaucratic/managerial inefficiencies, any action I take would not materially affect when non-hospital employees begin to get vaccinated, and that by getting vaccinated could potentially prevent me from spreading the virus in the future. Who knows whether I made the most ethical choice, but at least, I tell myself, I considered the question. 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.
- dehrmann 6y ago
  > I could not help but wonder if by taking the vaccine, I was depriving someone more needy of the vaccine. (Assuming you're in the US) If it helps, vaccine distribution has been so poor that you're not depriving anyone of anything.
- jostmey 6y ago
  Yeah, I'm at a medical university and in a similar situation. However, I am hearing that far fewer eligible people are electing to receive the vaccine than hoped. The line to get the vaccine is far shorter than it was supposed to be. We need people to take the vaccine to make this go away, so I suppose anyone in line should just take the vaccine and not feel guilty.
  - driverdan 6y ago
    This depends on where you are. Some places are managing it well, some aren't. 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.
- SllX 6y ago
  You know what? Congrats. You got your first injection. This does make you less likely to be a vector for this particular virus, and more importantly, makes it less likely that you’re going to die or suffer long term effects from COVID. 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.
rossdavidh 6y ago
While I admit that this is a tough call, and I can see coherent arguments for either one, if the FDA was _trying_ to infuriate people who disagree with them, they could hardly have done a better job than this. 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.
hcknwscommenter 6y ago
In this thread, none of the comments seem to note a key issue here as stated in the FDA post: "Those participants who did not receive two vaccine doses at either a three-or four-week interval were generally only followed for a short period of time, such that we cannot conclude anything definitive about the depth or duration of protection after a single dose of vaccine from the single dose percentages reported by the companies. " 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.
- dcolkitt 6y ago
  > The most reasonable approach is to assume that there is little to no durable protection from a single dose 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.
  - s0rce 6y ago
    Propose to the companies to conduct a trial to test your hypothesis on the effectiveness of a single dose? Until then the FDA policy is clearly data based and they are saying to follow the tested dose schedule from the clinical trial and not to deviate.
    - dcolkitt 6y ago
      Hypothetical question. Imagine if for some reason everyone in the trial received the vaccine on a rainy day (maybe it occured in Seattle during a bad patch of weather). The vaccine shows immunity, but we can only be sure for a population that got it on a rainy day. 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.
csense 6y ago
How did they originally decide to do 2 doses, instead of 1 or 3? How did they originally decide to do 21 days, instead of 42 or 3? 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?
- cltby 6y ago
  Two (or more) doses are fairly standard for vaccines. The first to trigger seroconversion, the subsequent ones to exercise the secondary immune response (and for those relative few individuals who did not seroconvert after the first jab). The interval between them is typically quite long, often on the order of years [1]. From that pov, the 3-4 week booster interval for the COVID vaccines is tiny. It's likely the minimum possible interval given that seroconversion takes >= 14 days (I'd guess the short interval was chosen to get trial results as soon as possible). There are many reasons to think that alternative dosing schedules would be not only viable but better than the current default. [1] https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolesc...
  - csense 6y ago
    How did they decide on this years-apart schedule though? Presumably they had some data to say "we tried giving group A a booster after 90 days, group B after 365 days, group C after 2 years, group D after 3 years, group E after 7 years, and group D did best in terms of not catching the disease"? 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.
asdfadsfgfdda 6y ago
>If people do not truly know how protective a vaccine is, there is the potential for harm because they may assume that they are fully protected when they are not, and accordingly, alter their behavior to take unnecessary risks. Amazing, this statement could equally apply to recommending mask wearing. Seems like the prudent answer in both cases is "public education" on risk.
- chapium 6y ago
  Public education fails against people's psychological biases and social dynamics. Its part of the solution but not a replacement for other top down policies.
drewg123 6y ago
What was the reason that the researchers decided on a 2 dose regimen in the first place?
- Exmoor 6y ago
  They took essentially the approach most likely to be effective and deliver results as fast as possible. If you choose the overly conservative choice on dosage you might possibly end up with not meeting your efficacy goals and end up either having to rerun phase III. 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.
  - myself248 6y ago
    It's strange to me that they couldn't test several dosing regimens in parallel. 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?
    - pkaye 6y ago
      J&J is testing both a single and two dose regime so its possible.
    - Majromax 6y ago
      The phase 3 trials were already large: the Pfizer trial had over 40,000 enrolled patients. 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.
tibbydudeza 6y ago
I would go with what has been tested with in the clinical trials and manufacturer dosage recommendations. 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.
williesleg 6y ago
Trump cures the common cold and everybody has TDS. Good thing Biden is in his basement.
bsimpson 6y ago
These vaccines were invented a year ago. Especially given the emergency this virus has created, I can't help but wonder how life would have been different if the trials were open to anyone who wanted one. "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.
- cududa 6y ago
  Huh? Anyone could sign up for the trial, even after I participated in one I still got calls from countless trial recruiters from other manufacturers. It was quite easy to participate
  - matthewtoast 6y ago
    But if you just do the trial you don't know if you actually got the vaccine or placebo.
    - cududa 6y ago
      It’s pretty obvious if you got it or not. Also .... why would you want the trial to not be double blind??
      - Broken_Hippo 6y ago
        How is it obvious in a trial? 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-2795103#:~:text=A%20double%2Dblind%20study%20is,characteristics%20or%20the%20placebo%20effect https://www.verywellmind.com/what-is-a-double-blind-study-27....
jpdus 6y ago
The most important picture in this discussion in my opinion is this the cumulative incidence rates for both Biontech/Pfizer and Moderna vs Placebo: https://postimg.cc/NLQYYgDS https://postimg.cc/NLQYYgDS 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.
- mantap 6y ago
  Efficacy, like stock prices, can go down as well as up. We don't know what would happen to that chart if the second dose wasn't given. It could look like a bell curve for all we know.
zaroth 6y ago
Let’s take the Moderna trial for example, which doses on Day 1 and Day 29. I can’t find specific published data, but safe to assume that “Day 29” is not absolutely 28 days later in every case, but on average 28 days later. 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.
imchillyb 6y ago
o, is the vaccine effective? 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... --- War... War never changes... ::intro-music::

111 points by simonpure 6y ago

> However, making such changes that are not supported by adequate scientific evidence may ultimately be counterproductive to public health. 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.

Retric 6y ago
Unlike stocks the risk here is vastly larger than the reward. 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.
- paulmd 6y ago
  On what basis do you say that? Stocks could potentially involve you losing everything, and the "reward" of cutting the number of necessary doses in half is that we could potentially reach herd immunity much faster. 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.)
  - kingnothing 6y ago
    You're not going to die from bad stock advice. You may die from COVID.
  - cma 6y ago
    Why don't we start playing options? Everyone gets a tenth of a dose so we can get it done next week. Just start a whole new study, made up of everyone.
- creddit 6y ago
  > COVID vaccines aren’t indefinitely effective Citation?
  - deleted 6y ago
    [deleted]
  - Retric 6y ago
    We don’t have specific data on covid, but it’s closely related to other diseases where immunity from contacting the disease tapered over time. 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.
    - creddit 6y ago
      > We don’t have specific data on covid 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?
      - Retric 6y ago
        > So you’re making a super strong statement that’s not very justifiable 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 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.
- standardUser 6y ago
  Vaccines generally do not eliminate a pathogen and they are not expected to eliminate this Coronavirus. Smallpox is the only human disease to ever be successfully eliminated.
  - Retric 6y ago
    Relatively few vaccines exist, and even fewer old ones, but on the whole they have been quite effective. https://www.vaccines.gov/diseases https://www.vaccines.gov/diseases In total both Smallpox (human) and Rinderpest(cattle) have been eliminated in the wild. Seasonal flu is kind of an interesting case as each year is arguably a different disease with the old one having been eradicated. That’s hopefully a model which will work for covid-19. 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.
finnthehuman 6y ago
> The question isn't whether this "may be" a harmful decision (of course it might); it is whether it is likely to be. 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.
- enchiridion 6y ago
  This is why I am frustrated by the FDA. It seems like all they are willing to do is read statistics produced by others. 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.
  - finnthehuman 6y ago
    FDA is doing exactly what’s in their statutory responsibility and authority. ie: what congress told them to do. (See my edited addendum to the parent comment.)
    - fennecfoxen 6y ago
      When someone observes that a government agency which seems to be doing something nonsensical is actually just following the law perfectly, it always brings to mind H. L. Mencken: "Democracy is the theory that the common people know what they want, and deserve to get it good and hard."
chadash 6y ago
I think this is part of the overall issue with the handling of this pandemic. No one wants to take responsibility. 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.
- busyant 6y ago
  > The FDA clearly has a goal of not tarnishing their reputation. 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.
curiousllama 6y ago
> This reads like a letter by someone who keeps all their money in CDs rather than stocks, because they might lose money 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.
- lastofthemojito 6y ago
  I hear you about the path to end the pandemic, but there's also that scary thing about the virus mutating enough to render the current vaccines useless. That feels like a very compelling reason to at least consider whether a single dose or smaller doses might get more of us immunity more quickly. Apparently the variant seen in South Africa recently is "concerning" scientists: https://globalnews.ca/news/7553824/coronavirus-variant-south-africa-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?
  - vorpalhex 6y ago
    News is generally trustworthy, but it is in their interest to always make everything sound as dramatic as possible. "Potential new strain which may result in mild reduction in vaccine effectiveness" is not a headline you will ever read. It's a very boring headline. It's in the interest of an advertisement supported company to make the most inflammatory headlines possible. Let the science do it's work, don't try to be clever and cheat the system.
- bobcostas55 6y ago
  Following the status quo path will likely result in significantly more people dying. It's a gamble either way, and if you want to argue that the risk of a first-doses-first approach is not worth the risk, then quantify your reasoning and explain exactly how many extra deaths you're willing to accept instead of these platitudes about paths.
fabian2k 6y ago
How much uncertainty we accept depends a lot on the potential downsides. For example there isn't much of a downside to wearing masks, so that is a measure you could defend on rather flimsy data if you had to. 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.
JTbane 6y ago
>This reads like a letter by someone who keeps all their money in CDs rather than stocks, because they might lose money. 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.
deleted 6y ago
[deleted]
abecedarius 6y ago
This post makes the same point at greater length and considers counterarguments: https://marginalrevolution.com/marginalrevolution/2021/01/first-doses-first-show-your-work.html https://marginalrevolution.com/marginalrevolution/2021/01/fi... What's the expectation in lives/disability of one course vs. the other? That's the first-order question. Added: https://www.acpjournals.org/doi/10.7326/m20-8137 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.
hnrodey 6y ago
step 1. do no harm.
hcknwscommenter 6y ago
It reads to me like a letter by someone who invests in target date retirement funds and index etfs by dollar cost averaging on an automated schedule, and avoids investing in tulip bulbs, because the available data shows that this is the most prudent approach.
remote_phone 6y ago
We have a known vaccine that works with 2 doses. We don’t know if 1 dose will work. We have single-dose vaccines with higher temperature tolerance from AstraZeneca and J&J ready to be approved. 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.
foolmeonce 6y ago
I think the FDA is dodging the obvious since the US doesn't want to alienate the UK: 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.
- dcolkitt 6y ago
  All of the mRNA vaccines target the spike protein. Coronavirus spike protein mutations have only ever been observed to occur in bats- never humans. Therefore the number of vaccinated people will almost assuredly not increase the likelihood of a resistant strain.
  - foolmeonce 6y ago
    I would accept a similar kind of reasoning in an argument towards caution, but not in an argument for seeing what happens with prolonged partial but insufficient immunity. Aside from near certainty that a change to the target protein is game over, we have no idea what other mutations could render immune responses triggered by the vaccines worthless, and I don't see the ethics in an experiment to find these mutations.
- JohnCohorn 6y ago
  From what I recall from Dr. John Campbell’s excellent daily videos, the UK strategy was not to give only one dose, but to simply delay the second dose a few weeks so that more people could get their first injection from the initial supply(presumably supply will increase over time). That sounds much lower risk. I think the single dose proposal was a US thing.

sradman 6y ago

Throughout this pandemic my impression is that nations generally failed on two fronts: 1. data sharing, and 2. scaling. You can't optimize what isn't measured and the vaccination programs that I know of are not sharing basic logistics data. In absence of hard data, people try to optimize systems based on hypothetical problems. 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.

SllX 6y ago

tl;dr FDA to Public Health authorities: don’t screw around. Administer these vaccines in the manner prescribed because it is proven to be effective. Glad to see it.

bpodgursky 6y ago
You're really missing that these prescribed regimes aren't some long-tested, optimized plan. The vaccine manufacturers literally had one chance to guess what the right application schedule was, and had one chance to do clinical trials on them. 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.
- SllX 6y ago
  I’m not missing any point. They picked what they could initially prove and the FDA expands on this to say that yes, we could try some other variables in further clinical trials. 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.
- ketamine__ 6y ago
  > The vaccine manufacturers literally had one chance to guess what the right application schedule was, and had one chance to do clinical trials on them. Couldn't they have done additional arms in the trial? Moderna could have had a trial arm with 1 mcg doses.

m3kw9 6y ago

For the people that is arguing for a delayed dose. The issue at hand is we have 80% of the stock pile unused, there is currently no point in even applying this tactic and taking unnecessary risk.

dehrmann 6y ago
While I think Trump botched the initial response to covid, it was so new and we had so little information that I'm not convinced Biden (or anyone else) would have done much better. 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.
- curiousllama 6y ago
  It's just so variable across the board. Chicago is doing a _wonderful_ job; Florida is apparently botching it. 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.
  - ars 6y ago
    > 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.
- blhack 6y ago
  How is it at all Trump's failure? The states have these doses, and it is the state health departments which are just refusing to give the vaccines to people out of "fairness". 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-global-distribution/ 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-wife-nm-nursing-home-amid-covid-pandemic/ 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?

SubiculumCode 6y ago

As a medical researcher, I received my first Moderna vaccine dose yesterday. I feel incredibly lucky, but also, a tiny bit guilty. I have very minimal patient contact, and I could not help but wonder if by taking the vaccine, I was depriving someone more needy of the vaccine. In the end, I decided that due to inevitable bureaucratic/managerial inefficiencies, any action I take would not materially affect when non-hospital employees begin to get vaccinated, and that by getting vaccinated could potentially prevent me from spreading the virus in the future. Who knows whether I made the most ethical choice, but at least, I tell myself, I considered the question. 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.

dehrmann 6y ago
> I could not help but wonder if by taking the vaccine, I was depriving someone more needy of the vaccine. (Assuming you're in the US) If it helps, vaccine distribution has been so poor that you're not depriving anyone of anything.
jostmey 6y ago
Yeah, I'm at a medical university and in a similar situation. However, I am hearing that far fewer eligible people are electing to receive the vaccine than hoped. The line to get the vaccine is far shorter than it was supposed to be. We need people to take the vaccine to make this go away, so I suppose anyone in line should just take the vaccine and not feel guilty.
- driverdan 6y ago
  This depends on where you are. Some places are managing it well, some aren't. 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.
SllX 6y ago
You know what? Congrats. You got your first injection. This does make you less likely to be a vector for this particular virus, and more importantly, makes it less likely that you’re going to die or suffer long term effects from COVID. 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.

rossdavidh 6y ago

While I admit that this is a tough call, and I can see coherent arguments for either one, if the FDA was _trying_ to infuriate people who disagree with them, they could hardly have done a better job than this. 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.

hcknwscommenter 6y ago

In this thread, none of the comments seem to note a key issue here as stated in the FDA post: "Those participants who did not receive two vaccine doses at either a three-or four-week interval were generally only followed for a short period of time, such that we cannot conclude anything definitive about the depth or duration of protection after a single dose of vaccine from the single dose percentages reported by the companies. " 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.

dcolkitt 6y ago
> The most reasonable approach is to assume that there is little to no durable protection from a single dose 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.
- s0rce 6y ago
  Propose to the companies to conduct a trial to test your hypothesis on the effectiveness of a single dose? Until then the FDA policy is clearly data based and they are saying to follow the tested dose schedule from the clinical trial and not to deviate.
  - dcolkitt 6y ago
    Hypothetical question. Imagine if for some reason everyone in the trial received the vaccine on a rainy day (maybe it occured in Seattle during a bad patch of weather). The vaccine shows immunity, but we can only be sure for a population that got it on a rainy day. 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.

csense 6y ago

How did they originally decide to do 2 doses, instead of 1 or 3? How did they originally decide to do 21 days, instead of 42 or 3? 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?

cltby 6y ago
Two (or more) doses are fairly standard for vaccines. The first to trigger seroconversion, the subsequent ones to exercise the secondary immune response (and for those relative few individuals who did not seroconvert after the first jab). The interval between them is typically quite long, often on the order of years [1]. From that pov, the 3-4 week booster interval for the COVID vaccines is tiny. It's likely the minimum possible interval given that seroconversion takes >= 14 days (I'd guess the short interval was chosen to get trial results as soon as possible). There are many reasons to think that alternative dosing schedules would be not only viable but better than the current default. [1] https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolesc...
- csense 6y ago
  How did they decide on this years-apart schedule though? Presumably they had some data to say "we tried giving group A a booster after 90 days, group B after 365 days, group C after 2 years, group D after 3 years, group E after 7 years, and group D did best in terms of not catching the disease"? 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.

asdfadsfgfdda 6y ago

>If people do not truly know how protective a vaccine is, there is the potential for harm because they may assume that they are fully protected when they are not, and accordingly, alter their behavior to take unnecessary risks. Amazing, this statement could equally apply to recommending mask wearing. Seems like the prudent answer in both cases is "public education" on risk.

chapium 6y ago
Public education fails against people's psychological biases and social dynamics. Its part of the solution but not a replacement for other top down policies.

drewg123 6y ago

What was the reason that the researchers decided on a 2 dose regimen in the first place?

Exmoor 6y ago
They took essentially the approach most likely to be effective and deliver results as fast as possible. If you choose the overly conservative choice on dosage you might possibly end up with not meeting your efficacy goals and end up either having to rerun phase III. 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.
- myself248 6y ago
  It's strange to me that they couldn't test several dosing regimens in parallel. 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?
  - pkaye 6y ago
    J&J is testing both a single and two dose regime so its possible.
  - Majromax 6y ago
    The phase 3 trials were already large: the Pfizer trial had over 40,000 enrolled patients. 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.

tibbydudeza 6y ago

I would go with what has been tested with in the clinical trials and manufacturer dosage recommendations. 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.

williesleg 6y ago

Trump cures the common cold and everybody has TDS. Good thing Biden is in his basement.

bsimpson 6y ago

These vaccines were invented a year ago. Especially given the emergency this virus has created, I can't help but wonder how life would have been different if the trials were open to anyone who wanted one. "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.

cududa 6y ago
Huh? Anyone could sign up for the trial, even after I participated in one I still got calls from countless trial recruiters from other manufacturers. It was quite easy to participate
- matthewtoast 6y ago
  But if you just do the trial you don't know if you actually got the vaccine or placebo.
  - cududa 6y ago
    It’s pretty obvious if you got it or not. Also .... why would you want the trial to not be double blind??
    - Broken_Hippo 6y ago
      How is it obvious in a trial? 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-2795103#:~:text=A%20double%2Dblind%20study%20is,characteristics%20or%20the%20placebo%20effect https://www.verywellmind.com/what-is-a-double-blind-study-27....

jpdus 6y ago

The most important picture in this discussion in my opinion is this the cumulative incidence rates for both Biontech/Pfizer and Moderna vs Placebo: https://postimg.cc/NLQYYgDS https://postimg.cc/NLQYYgDS 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.

mantap 6y ago
Efficacy, like stock prices, can go down as well as up. We don't know what would happen to that chart if the second dose wasn't given. It could look like a bell curve for all we know.

zaroth 6y ago

Let’s take the Moderna trial for example, which doses on Day 1 and Day 29. I can’t find specific published data, but safe to assume that “Day 29” is not absolutely 28 days later in every case, but on average 28 days later. 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.

imchillyb 6y ago

o, is the vaccine effective? 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... --- War... War never changes... ::intro-music::