[HN Gopher] FDA statement on following the authorized dosing sch...
___________________________________________________________________
FDA statement on following the authorized dosing schedules for
Covid-19 vaccines
Author : simonpure
Score : 81 points
Date : 2021-01-05 14:38 UTC (8 hours ago)
(HTM) web link (www.fda.gov)
(TXT) w3m dump (www.fda.gov)
| SubiculumCode wrote:
| 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.
| eplanit wrote:
| Here in Southern California, 20-40% (!) of front-line medical
| workers are refusing the vaccine[1]. I wouldn't feel guilty, if
| I were you.
|
| [1]
| https://www.sandiegouniontribune.com/news/california/story/2...
| SubiculumCode wrote:
| That is outrageous.
| jostmey wrote:
| 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 wrote:
| 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.
| dehrmann wrote:
| > 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.
| bluGill wrote:
| We need as many people as possible to get a vaccine. High risk
| is secondary and only worth thinking about at all because of
| limited supply.
| SllX wrote:
| 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.
| malkia wrote:
| I've felt the same about a friend (he works in a hospital).
| Rather than feeling jelaous, we all felt something good is
| happening, lots of folks are still afraid to take it, so this
| taken by medical personnel is uplifting.
| jquery wrote:
| You did the right thing, in my opinion. I am in a cohort that
| has no hope of getting the vaccine before May... from where I'm
| sitting, it's very frustrating seeing vaccine doses just
| sitting there, not being taken because of bureaucratic
| inefficiency. I'd infinitely rather the vaccines went to some
| of the "wrong" people than sit unused. In fairly short order, I
| think the main problem is going to be people refusing to take
| the vaccine, making it difficult to achieve herd immunity.
| bsimpson wrote:
| 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 wrote:
| 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 wrote:
| But if you just do the trial you don't know if you actually
| got the vaccine or placebo.
| cududa wrote:
| It's pretty obvious if you got it or not. Also .... why
| would you want the trial to not be double blind??
| drewg123 wrote:
| What was the reason that the researchers decided on a 2 dose
| regimen in the first place?
| Exmoor wrote:
| 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 wrote:
| 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?
| Majromax wrote:
| 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.
| jonahrd wrote:
| I think the idea is to run multiple trials, each _still_
| with 40,000 patients. That way we could have approved a
| 2-week dosing schedule and started giving out the first
| doses, and by the time the first patients are ready for
| their 2-week dose, the results of the 4-week dosing
| schedule would be ready, etc, etc. So we could push back
| the 2nd dose "indefinitely", preventing this issue in the
| first place. (Assuming by the time the 2nd dose is really
| worth getting, we have already made enough vaccines that
| the scheduling details are less important)
| clankyclanker wrote:
| You're neglecting the time it takes to recruit 40,000
| patients. It's not fast or easy to identify those folks,
| as a significant number of people have disqualifiers
| (like comorbidities e.g., obesity). Once they're
| identified as candidates, you still need to go through
| the task of recruiting them, likely through their
| healthcare network. You can't just use automated calls
| for that because nobody's going to trust a recording that
| promises "Free Vaccine Fast, Act Now!"
|
| 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).
| pkaye wrote:
| J&J is testing both a single and two dose regime so its
| possible.
| usaar333 wrote:
| > 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.
| abecedarius wrote:
| This post makes the same point at greater length and considers
| counterarguments:
| 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
|
| > 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.
| curiousllama wrote:
| > 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.
| bobcostas55 wrote:
| 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.
| curiousllama wrote:
| You can't ask me to quantify my reasoning and then throw
| out wild unsubstantiated claims out like:
|
| > 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
| mhb wrote:
| No. But we can ask the FDA to justify its reasoning by
| sharing their modeling of the expected value of QALY for
| different courses of actions. It's ridiculous for them to
| spit out a proclamation like this without providing a
| framework for the decision other than "has not been
| tested".
| lastofthemojito wrote:
| 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...
|
| 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 wrote:
| 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.
| fabian2k wrote:
| 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.
| hnrodey wrote:
| step 1. do no harm.
| [deleted]
| hcknwscommenter wrote:
| 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.
| Retric wrote:
| 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.
| standardUser wrote:
| 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 wrote:
| Relatively few vaccines exist, and even fewer old ones, but
| on the whole they have been quite effective.
| 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.
| creddit wrote:
| > COVID vaccines aren't indefinitely effective
|
| Citation?
| Retric wrote:
| 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.
| [deleted]
| paulmd wrote:
| 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 wrote:
| You're not going to die from bad stock advice.
|
| You may die from COVID.
| cma wrote:
| 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.
| finnthehuman wrote:
| > 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 wrote:
| 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 wrote:
| 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 wrote:
| 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."
| s1artibartfast wrote:
| 1) The FDA does not run clinical trials.
|
| 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.
| bluGill wrote:
| Running trials takes time. It isn't worth it.
| mikem170 wrote:
| > politician with the balls
|
| 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.
| hcknwscommenter wrote:
| It is not about who has "balls." You seem to think this is
| just a balancing of risks. It is not. It is a balancing of
| "what do we actually have data to support" versus "what do we
| hope to be the case but have no actual evidence to suggest it
| is so."
| beisner wrote:
| Sure, but we do have prior probabilities based on other
| vaccination campaigns and studies. We also have some
| understanding of the causal mechanism of this vaccine, so
| there is other evidence. It's just not a direct randomized
| control. People fixate on statistical testing under
| randomized control, but there's a lot more information out
| there that can be used to assess probabilities.
| jschwartzi wrote:
| Given that we've never before studied an mRNA vaccine,
| how do any of the numerous other studies apply to either
| the Moderna or Pfizer vaccine?
| finnthehuman wrote:
| > You seem to think this is just a balancing of risks.
|
| 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.
| chadash wrote:
| 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 wrote:
| > 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.
| JTbane wrote:
| >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.
| remote_phone wrote:
| 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 wrote:
| 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.
| JohnCohorn wrote:
| 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.
| dcolkitt wrote:
| 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.
| hcknwscommenter wrote:
| 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 wrote:
| > 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.
| jzwinck wrote:
| It's not only about minimizing total infections. If it were,
| priority would be given based on social sphere sizes, eg
| priests and postmen before old people.
|
| 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.
| s0rce wrote:
| 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 wrote:
| 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.
| s0rce wrote:
| I think the analogy to your example is to have conducted
| a larger trial where the dose was given under different
| weather conditions, or in the case of the real vaccine
| vary the timing of the 2nd dose. I agree, if experts
| agree the likelihood that 1 dose is effective and the
| likelihood of it being ineffective is low, we should do
| what will save the most lives. This is an emergency.
| hcknwscommenter wrote:
| " if experts agree the likelihood that 1 dose is
| effective and the likelihood of it being ineffective is
| low"
|
| Experts do not agree.
| abduhl wrote:
| > Yet doctors, scientists and public health experts use
| judgement and empirical priors to determine when and
| where we can relax the requirements.
|
| 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?
| dcolkitt wrote:
| Considering that the FDA let thousands of Americans
| needlessly die because they delayed the approval hearing
| to enjoy a relaxing Thanksgiving weekend... Yes, I don't
| trust their judgement.
|
| As for more general critiques, there's mountains of
| evidence that the FDA is too risk averse, even before
| Covid.
|
| https://www.hoover.org/research/fdas-risky-risk-aversion
| jschwartzi wrote:
| Setting aside my deep visceral reaction to what you're
| suggesting, how is it safe or productive to conduct a
| review on a Friday evening at the end of a long week and
| not sleep or eat until it is done? Do you have any reason
| to believe they would make more or fewer mistakes doing
| so? And what's your personal policy on making really
| important decisions while sleep deprived? Would you, for
| example, get some sleep before signing a contract on a
| house?
| dcolkitt wrote:
| The application was submitted on November 22 and the
| review meeting was not scheduled until December 10. The
| UK, not exactly a country known for taking reckless
| medical risks, approved the Pfizer vaccine eight days
| earlier than the US despite receiving the application at
| the same time.
|
| While nearly ten thousand Americans died, I guess the FDA
| was "catching up on its sleep". Eight long days of
| glorious sleep!
| 1stcity3rdcoast wrote:
| If anyone only ever made decisions while they were
| perfectly fed and rested, this would be a sad, slow,
| boring world, because nothing would ever get done or
| decided. There is such a thing as urgency, and people do
| work beyond a 35 hour work week with evenly spaced meals,
| and especially during a global pandemic.
|
| 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.
| abduhl wrote:
| And yet, regardless of your own personal feelings and
| beliefs, here we sit, locked in our little worlds which
| have been shrunk down to the space inside the walls of
| our homes, with a government mandated two dose regimen as
| you scream helplessly into the wind like an obese turtle
| on its back screeching for help. Because we're going to
| Follow the Science that the government and experts have
| decided is Correct. So stop complaining, stay the fuck
| inside, and quit questioning the science because you
| half-dosers are really starting to sound like antivaxxers
| and antimaskers all of a sudden.
| dcolkitt wrote:
| A lot of ad hominem and hysterics, for someone who
| continuously dances around the very simple question. What
| is your prediction for the effectiveness of a single dose
| regime?
|
| 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.
| spoonjim wrote:
| Now replace "FDA" with "FAA" and "two doses is the
| regimen" with "the 737 MAX is safe."
| [deleted]
| rpedela wrote:
| We have no data for mRNA vaccines except those trials. We
| don't know if the historical data on traditional vaccines are
| applicable here. As such, it is also possible that a single
| dose isn't good enough or a single dose is good enough but
| only for a couple months. 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.
| panda-giddiness wrote:
| > How is that the most reasonable approach?
|
| The reasonable approach is to be overly cautious. A false
| sense of security is worse than no security at all.
| dhnajsjdnd wrote:
| The cautious thing to do is vaccinate the entire population
| with two doses. Oops, we don't have enough doses for that.
| nl wrote:
| > 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).
| hcknwscommenter wrote:
| "Virtually every vaccine ever discovered provides more
| immunity on first dose, than the incremental gain on
| subsequent boosters."
|
| Citation needed.
| mchusma wrote:
| "No data" is wildly incorrect. We have priors from other
| vaccines and vaccine candidates, and the data from these
| trials. All data about the first dose suggests strongly that 1
| dose provides very strong protection against severe disease,
| and solid protection against mild disease.
|
| 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.
| feralimal wrote:
| we have also not had animal trials - there is very little data
| at all. We will get that in 2 years, once the live trials are
| completed.
| paxswill wrote:
| There were animal trials. Here's an overview post of various
| vaccine's primate trials: https://blogs.sciencemag.org/pipeli
| ne/archives/2020/07/30/co...
|
| And as linked in that post, Moderna's primate study: https://
| www.nejm.org/doi/full/10.1056/NEJMoa2024671?query=fe...
| mikem170 wrote:
| > we basically have NO DATA on single dose schedules for
| Moderna/Pfizer vaccines
|
| 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.
| excerionsforte wrote:
| Agreed. Taking a conservative approach to something you don't
| yet understand is the best approach on a mass scale. There
| isn't any significant data for the one dose approach. These
| vaccines are only authorized on an EUA on a specific way to
| apply the dosage and it would be foolhardly to experiment now
| with different approaches on health care workers who are high
| risk on the front line.
|
| 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.
| Animats wrote:
| Yes. At this phase, it's best to stick to what's known to
| work.
|
| 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...
| cltby wrote:
| It's simply pathological to claim that we have NO DATA just
| because a large scale RCT wasn't performed.
|
| 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...
| jschwartzi wrote:
| We have data, but no information. We have to synthesize the
| data into information using analytical techniques or it is
| meaningless.
| jfengel wrote:
| _There is no "partial immunity"--you're immune or you're
| not._
|
| 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.
| hcknwscommenter wrote:
| The OP's categorical statement on partial immunity is
| entirely false. Look at the Astrazeneca data in the Lancet.
| No hospitalizations in the treatment arm. That is evidence
| of "partial immunity."
| jfengel wrote:
| Thank you.
| nl wrote:
| Note that this isn't a "booster shot" in the sense of the
| boosters you are linking.
|
| 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.
| m3kw9 wrote:
| 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.
| amanaplanacanal wrote:
| Should we eventually reach the point where there is a shortage
| of vaccine stocks it might make sense to revisit. As things are
| going it doesn't seem likely though.
| dehrmann wrote:
| 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.
| blhack wrote:
| 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-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?
| standardUser wrote:
| States need money to establish and run a new and fast
| operation, money that was finally approved by Congress long
| after it should have been. Trump wasn't even involved in
| negotiations (too busy contesting the election with no
| evidence and/or golfing) and then he refused to sign the
| bill for several days because of surprise, last minute
| demands he decided to make (and then go back on, gaining
| nothing but losing us all time). A competent leader would
| have been all-in on the entire process.
|
| 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.
| salmon30salmon wrote:
| Thank you so much for saying this! I am beyond upset at my
| state for fucking this up so badly. We can't open schools
| but we can take time off and worry about equity over
| expediency?
|
| 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
| curiousllama wrote:
| 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 wrote:
| > 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.
| jsight wrote:
| Yes, this false choice is confusing the issue. The rules for
| who gets the vaccine and when are poorly thought out and are
| leading to us using 1/6 of the available doses.
|
| That's the thing that needs to be fixed.
| usaar333 wrote:
| That's a separate problem that needs to be debugged. [It sounds
| like there's distribution problems that may be temporary or may
| require vastly simplifying our distribution rules - e.g. just
| set up drive-thrus and tell any elderly person they can come
| because rules restricting access slow down vaccinations --
| fwiw, we discovered the similar problems when we initially
| tried to restrict testing]
|
| However, once we fix that, we still have a problem of
| insufficient vaccine.
| sradman wrote:
| 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 wrote:
| 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 wrote:
| 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 wrote:
| 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__ wrote:
| > 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.
| meddlepal wrote:
| This is what I don't understand... why didn't we run
| several parallel studies for different dosages and time
| frames? I highly doubt there was a shortage in the pool of
| people willing to sacrifice themselves.
| tibbydudeza wrote:
| 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.
| rossdavidh wrote:
| 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.
| csense wrote:
| 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 wrote:
| 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-
| adolesc...
| williesleg wrote:
| Trump cures the common cold and everybody has TDS. Good thing
| Biden is in his basement.
| asdfadsfgfdda wrote:
| >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.
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