I just wanted to see if anyone would take the under. Is there any combination of answers that would lead you to do so?
If shooter needs >= 1 kill for it to count along with some of the other restrctions, then I think about the under. But even then, itâs not clear.
I could be convinced to take the under if it was based on the mediaâs interpretation of the motive. Was it a disgruntled anti-vaxxer or just a white dude having a bad day??
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That is specifically why I asked for a list of cops who actually quit, not just telling the media theyâre going to quit. I suspect the ratio of blusterers vs actual quitters is going to be huge everywhere.
The deplorables couldnât even stick to their guns with their BOYCOTT of Coca Cola, theyâre not resigning en masse to protest shit.
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This is my thing. They are currently accepting info from people gritting money as reliable sources so I donât know how easy it is going to get them to believe actual science.
There has been plenty of pure science pleas to get vaccinated. Hopefully he can get his friend to see the light.
Hereâs a study on side effects from the vaccine:
https://www.nejm.org/doi/full/10.1056/NEJMoa2110475
Hereâs a video from Johns Hopkins about how the mRNA vaccines work and why they canât infect you with the virus:
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Kinda underwhelmed by this result. From the press release:
The Companies announced positive topline results from the pivotal trial on September 20, 2021. In the trial, which included 2,268 participants 5 to <12 years of age, the vaccine demonstrated a favorable safety profile and elicited robust neutralizing antibody responses using a two-dose regimen of 10 Îźg doses.
It seems like not a lot of participants? The adult trial for Pfizer had more than 40,000 people in it. I get that itâs easier to recruit adults to a trial and having more people lets them prove the vaccine works faster, and the adult vaccine was more urgent, but this actually seems like maybe not even enough people to identify rare but significant side effects. If the vaccine caused some weird side effect that kills 1 in 100,000 kids who take it, you wouldnât have a great chance of identifying it, but it would still be hugely significant to a cost-benefit analysis given the mildness of the disease in children.
To be extremely clear, Iâm not saying Iâm worried, at all, that the vaccine isnât safe for kids. I just find it very frustrating that weâve waited an entire year for this. I think itâs better evidence of safety that 3 billion people (including a bunch of adolescents) have gotten the vaccine without major issues than that they did an RCT of 2,000 kids and didnât see anything. Also that weâre waiting another 4-6 weeks for vaguely specified paperwork and double-checking.
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The conclusion of this story is that 5-year-old tested negative on some at-home tests, got a clean PCR Sunday and is back in school. But holy fucking Jesus is remote learning absolute hell with a younger sibling. We had both kids at home for the whole pandemic, which was incredibly grueling, but at least they sometimes entertained each other and you could just go to the playground if you needed a break. With the older kid tied up for 6 hours every day (and needing help with something intermittently), itâs completely impossible. And itâs irresponsible to get grandparents or a babysitter!
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Yes, thereâs some serious power issues going on in that study, multiplied by the low negative-outcome rate in the <12 population. Hereâs one discussion of the results and sample:
Pfizer also argued the vaccine was effective, and here is where the data is interesting but also different from adult trials. In the adult COVID trials, the most important outcomes measured were COVID illness (serious illness, hospitalization, death). This outcome is not considered in the pediatric trials because it is too rare even among the unvaccinated group of children.
To see this in detail, think about the numbers. The trial is 2,268 children, of whom two-thirds got the vaccine (one third got a placebo). Even if every single one of the children in the placebo group got COVID during the trial, we would still expect only about 2.5 children to be hospitalized in that group, and no deaths. The actual infection risk is much lower, making these numbers smaller. If we are looking for significant reductions in risk from vaccination, we will not see them, because the baseline risk is so small.
This is very good news for worried parents! But itâs not good for the statistical analysis of that outcome.
To be what statisticians call âpoweredâ to detect an effect on serious illness or hospitalization, weâd need a vastly larger trial. Which could be infeasible and would at a minimum delay vaccines even more. Instead, Pfizer is resting its efficacy claims on the antibody response to the vaccine. Which makes sense, since the way the vaccines work is they produce antibodies. When the company says the vaccine is effective, it means the antibody levels in children were comparable to 16-to-25-year-olds vaccinated with the adult vaccine (in fact, the kids had slightly higher antibodies, despite the lower dose).
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The point of the study is to justify an EUA, which it clearly does, not for a final FDA approval. Those are two vastly different things.
One of the criteria for issuing an EUA is that the known and potential benefits need to outweigh the known and potential risks. I think @bobman0330âs point is correct here:
And I am not saying this to discount the idea of giving vaccines to kids - I will be F5ing my keyboard to make an appointment for my 11yo as soon as its authorized. I think itâs reasonable to question the combination of:
- itâs really taking a long time to run this study, analyze the data, and ultimately get authorization
- given the small sample and relatively low risk of the disease in children, itâs not clear that this sample actually provides much evidence of the cost/benefit of this drug for children
Part of this is me acknowledging that thereâs a risk that the FDA concludes that thereâs insufficient evidence that the drug passes the potential cost/potential benefit hurdle, and doesnât grant the EUA. Thatâs going to be absolutely crushing to me mentally.
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Yeah, I started having those concerns when the boosters were rejected. The booster discussion basically didnt take into account the potential for long-term effects from a COVID infection and focused on severe outcomes vs. effect on society level transmission rates. If the criteria is the same for vaccinating kids then, I dont know, the case for an EUA is somewhat weak. I think these discussions are half Calvinball and theres going to be a lot of pressure to get to a yes on kids, but definitely dont think the EUA is a lock.
The fact that thereâs uncertainty in the final result doesnât preclude an EUA. Regeneron got an EUA with far less data. HCQ had even less.
The chance of some sort of special side effect specific to this population is quite small. The potential benefits far outweigh risks here.
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This is not a gotcha or JAQing question, and itâs fine if you say you donât know. (I definitely donât know):
Does the FDA evaluate costs/benefits at the macro level or just the individual level?
If they consider the societal-level benefits of the vaccine, then it seems like a no-brainer to approve the EUA for kids. But if they only consider the potential costs and benefits to an individual, I think itâs a much closer call (compared to what I had been assuming) given the low risk among under 12s and the limited data available from the study (largely because the control group already has that low risk).
In other words, I think the benefit of authorizing the EUA for kids is largely protection for everyone else. (Maybe this is a hot take?) And if the FDA doesnât take that spillover into account, it would lower my expectations for it getting approved.
Not sure if they do. Donât think so.
I also think youâre being far too reliant on death instead of chronic consequences of minor infections, prevention of hospitalization and PICU stays.
A few tidbits from the latest Osterholm conversation (about a week dated)
----Minnesota is up to 50 outbreaks contact traced to only outdoor exposure. This is not longer just an indoor air risk virus. Obviously indoor riskier, but outdoor transmission isnt a rarity.
----Schools could open relatively safely with protocols before delta. With delta, in person learning is unsafe. Of all the pediatric deaths in COVID, over a quarter have happened in the last four weeks (unclear if this is more severity). Unvaccinated kids should be distance learning. CDC has been captured by politics on this one, in his view.
----Worldwide what we have seen are âSprintâ surges. COVID burns hot for 4-5 weeks then peters out then surges again. Iran has had five such waves. We dont know why yet.
As a result, does not rule out a winter surge in the places that had big winter surges last year (NE and SW) with peak equal/worse to last year (he bets a major surge is coming in New York sooner rather than later, but not a lock)
----1/3 of cases in Minnesota are now breakthroughs (I know this is now 40% in MA). Severe illness definitely increasing, not to unvaxxed levels but higher than previous months. 65 and over the most prominent group as well as high risk, but also healthcare workers. High risk people need to continue to shield even if vaccinated. Young, healthy vaccinated are dying. Still rare, but its happening more frequently. Vaccines help but we got caught up in the euphoria of the vaccines being a complete solution.
âUltimately he thinks by early '22 we will have better answers on vaccines and we will have concluded fully vaccinated means three doses for everyone.
âMasks work, but have to be at least N95. Cloth masks and surgical masks going to do very little for individual protection with delta, âlike using flannel pajamas as a suit for protection in a forest fireâ. Bulk of data, in his view, actually says cloth masks basically dont work. Youd get infected in 20 minutes of exposure vs 15 if 15 was the baseline (and delta the baseline might be 1, hence cloth really does nothing) while fitted N95 protects for 25 hours.
âAny mask is OK messaging is completely wrong given delta is airborne. Combined with the outdoor transmission, everyone should be N95 masking at all times in public in high transmission areas regardless of vax status.
âVariants are worth watching, but current ones are basically being buried by Delta. We need to stay humble, but right now the transmissibility of delta just trumps everything else out there.
âFuture from here pretty cloudy. Third vaccine dose will help, vaccinating kids will help, and in his view these waves will become more regulated in high income countries. At least as long as millions are unvaccinated we will continue to get these waves of cases.
âDoesnt see any evidence it becomes seasonal as it becomes endemic. Maybe it does, but no evidence we will see changes from these constant waves of COVID.
âBasically though where we go from here 
but we need to get nearly everyone vaccinated for starters. Says we are going to have to become more comfortable with the unknown, we dont really know why COVID comes in these waves, we dont know why RSV is surging in the summer, etc.
âEmphasizes we really need to change masking policies and that schools need to get away from the remote learning is over concept and come up with policies on when to switch to remote learning if they insist on giving in school a go.
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Maybe weâre talking past each other? As I understand it, and unlike the adult trials, Pfizer is not basing its efficacy claims on declines in hospitalizations precisely because thereâs not enough hospitalizations in the control group to obtain measurable differences. I think if Pfizerâs study did show differences in those outcomes for treatment vs. control in the <12 sample, we wouldnât be having this conversation.
I think bobâs point was that the study doesnât provide direct evidence on any of those things you mentioned - just increases in antibodies. So the question is, how much reduction in hospitalization (or other outcome) risk does that antibody increase translate to? Particularly when considering the low baseline risk for the <12 cohort.
This is was a helpful reference for me to better understand how Pfizer is assessing efficacy in this group relative to the original adult studies:
https://www.astrazeneca.com/what-science-can-do/topics/disease-understanding/what-does-immunogenicity-mean-in-the-context-of-covid-19-vaccines.html
(This is probably already known information to many here, but it was useful to me.)
But the standard here is potential benefit, and that is a clear potential benefit. Given our adult data, itâs likely that benefit will remain true, even if itâs harder to prove.
A standard of a decrease in death or hospitalization in an RCT is beyond whatâs used for many fda medication approvals for adults. A standard of a decrease in death or hospitalization in an RCT limited to pediatrics only? Thatâs going to be even more rare. Ideally Iâd like that data, but holding up the EUA is unnecessary imo.
I donât think weâre talking past each other, I like this conversation.