144 Comments

You are mistakenly mixing the approval of factories with the approval of the vaccine. While related, they are two different things. Also, you must consider the kind of approval. I haven't brought a vaccine to market but I have been involved in getting factories approved.

Factory approval is about process control, temperatures, chemical content, cleanliness, measurement tracking, batch tracking, etc. It's not about efficacy of the drug, other than efficacy approval establishes the quality parameters that must be met.

1. Factory approval requires a level of documented paperwork and demonstrated compliance with procedures that can be staggering. You must track every item, every machine, every process, every worker, every procedure. These must be documented, logged, etc. Every potential problem, actual problem, modification, etc. must be documented, reviewed, and approved. All of this documentation must be available on demand to an FDA inspector, and the inspector must have instant access to the relevant parts of the factory with no warning, no appointment, and no warrant. The initial approval determines what are the relevant parts of the factory and it's agreed by the FDA. If you relocate any people or machines this can change the access.

This level of inspection access is problematic to many people. I've watched multi-year battles between the FDA and some European companies over this level of access. This kind of access is anathema to a closed controlled country like China.

2. The US vaccines are being made in factories that were already approved for manufacture of other similar drugs using the same equipment. Adding one more drug to the process is trivial in comparison to approving a new factory. That's been one of the limits to increasing production. Once the factories already approved and capable of making the vaccine are at 100% capacity it's very slow to get new factories approved. The FDA has not weakened the manufacturing safety rules.

3. The efficacy rules for the vaccine approval were weakened. If you want to read the endless details they are available. The FDA published the Emergency Use requirements about a year ago. They are the basis for all the current vaccine distribution. They are less stringent than regular requirements. The first vaccine to meet the regular requirements was only approved by FDA about a month ago. The manufacturing rules were not weakened.

I agree that the FDA process is excessively risk averse and excessively bureaucratic. It's prioritization is often terrible. This certainly needs work. The careful improvements needed are not the kind of chanage that you are suggesting.

I've also seen and inspected factories that failed the FDA inspections. I was shocked and appalled. The level of filth and contamination of products was staggering. For example, you should expect a factory floor that you are comfortable eating off. (Of course food won't be allowed into the facility, so you won't actually eat off that floor.) I saw factories with muddy dirty floors, bird droppings, etc. These places wouldn't pass routine kitchen inspection at a restaurant.

Many people don't realize what is needed.

The non-FDA factories that I've seen which would pass FDA cleanliness and process control inspection were semiconductor fabs, precision electronics manufacturing, etc. I helped bring one precision electronics manufacturer up to FDA standards and it was pretty easy. We mostly documented and explained how their existing extremely demanding process control met all the goals set by the FDA. It took about 5% the time and cost of bringing a new production facility up to FDA standards, with very little process change needed.

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This post was awesome. The only thing I'll quibble with is this: "This kind of access is anathema to a closed controlled country like China."

Chinese regulators have exactly this sort of access. It will be a cold day in hell when they afford it to the FDA or EMA.

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Ah, correct. I should have said the giving this kind of access to non-Chinese is anathema.

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Ok. The language you used sounded way too close to the standard US-right blithe assumptions about what China is and how it works for me to be sure that's what you meant.

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This post shows the value of Slow Boring, above and beyond the firehose of MY's writing.

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Damn, RJH. Blow me away

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Now I'm wondering what happens when the jet fuel of CDC skepticism meets the steel beams of "Trust The Science".

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I think public health officials cajole rich countries into foregoing booster shots and child vaccination at the peril of global public health. Far better to work on supply. At the end of the day people don't want themselves or their loved ones to get sick or die. Confident, less-stressed rich country residents (who have no reason to complain about people in poor countries) are more apt to support the kinds of global vaccine aid the world needs right now. Reminds me a bit of the climate change sub-debate regarding conservation vs. abundant (green) energy. The latter would be vastly preferable, if it could be pulled off.

In short, rich countries should do more if at all possible, but not at the cost of denying their own citizens medically recommended, optimal vaccine regimens. At least that's my take.

I'm fully vaccinated with Sinovac, for what it's worth.

(Also, Chinese pharma firm Shanghai Fosun is working on a deal with BioNtech, it appears. In the Chinese press, at least, I haven't seen the name "Pfizer" mentioned).

https://www.japantimes.co.jp/news/2021/08/30/asia-pacific/china-pfizer-approval-pending/

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They had the license deal with BioNtech from almost day one, if I recall right. It's just that the Chinese government spent a year badmouthing the foreign, "untested" mRNA vaccines while talking up Sinovac, and then the latter turned out to be near-useless.

Now they're frantically backtracking and touting the "Fosun vaccine" as the fruit of domestic research.

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The CCP is breathtakingly-think skinned in its obsessive nationalism, of that there is no doubt.

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It's basically "foreign policy as conducted by Weibo trolls" at this point.

Every time I thought "they can't get dumber and might finally outflank the US under Trump," they managed to get even stupider still and continued to be a less appealing alternative for all but the most kleptocratic autocrats.

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It seems to me like the underlying utilitarian logic behind denying vaccines to American children so they are available to foreigners is a bit questionable. The moral reasoning might be sound, but we don't follow it in any other context. If every American who vaccinated their kid also gave $100 to a Give Well recommended charity that wouldn't that save more lives than reserving the vaccine supply for foreigners? Wouldn't you gladly spend $100 to vaccinate your kid? In the real world Americans aren't going to actually give an extra $100 to charity, but that's because we don't care much about foreigners!

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"The moral reasoning might be sound, but we don't follow it in any other context."

Interesting point.

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The world is complicated. If every family that got a kid vaccinated gave $100 to a GiveWell charity, the marginal value of those donations would quickly become zero and then negative because the charities would be swamped (part of GiveWell's criteria is choosing charities that actually have productive uses for donations and the capacity to act on them, which is certainly not the case for every charity). And in fact, families-with-vaccinated-kids already do give huge amounts of money to poor countries, through the government's development budget. But again, a feature of huge budgets is that inevitably with them comes waste, bureaurcracy and so on.

None of this is to deny that western countries are selfish, or that we couldn't always be doing more and doing it better to provide a more equal world. But what we have *here*, in this particular case, is a situation where the actions of rich countries have a direct and measurable impact of the same form on developing ones; the correlations are much clearer here.

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First, let me say that I love that you threw shade your panicky neighbors/friends.

I already got my booster shot. I had the Pfizer back in March and April. So I had to come to Argentina to work last week, and I really didn’t feel like ending up in an Argentinian hospital. So I made an operational risk management decision, to get a Moderna booster.

The problem is in Idaho there’s a State Vaccine database, and I already used my insurance on my Pfizer.

The solution was for me to drive across the border to Oregon, and pretend that I was unvaccinated, and that I wanted the Moderna. I just told him that I was self-employed without insurance, and got the shot.

I will say that the Moderna Booster fucked me up for about a day and a half.

I am not advocating everyone do this. But my job involves a lot of international travel working side-by-side with South American technicians. I would say that I am high risk. Add to that that I really don’t want to end up in the south American hospital where I don’t speak the language well. I decided that a little rule breaking was worth it.

As far as the moral argument that I took someone else’s shot. The fact is that these days there’s a lot of vaccine that’s going to waste.

My ex-wife works at a pediatric clinic. And they have given out “boosters” at the end of the day when they have extra vaccine left that will expire.

We half considered vaccinating our 10 and 11 year old, but decided not to. Just on the small chance something happened, we didn’t want to put anyone at risk.

Anyway, even with the vaccine and a booster, I am on day six of my quarantine here in Argentina. I just got my third PCR test. When it comes back negative tomorrow morning, I get to check out of this hotel and go to another hotel to finally start my job.

And while I feel sorry for foreigners, I want my kids to get vaccinated, and I want them to approve vaccines for them.

Yesterday, my 10-year-old got told that she has to sit at home for the next 11 days because she was exposed to someone who had Covid in her class on Friday. My daughter wears a mask, but they aren’t required.

So because of whatever rules, she hast to sit out. My 11-year-old just finished up a 14 day quarantine for the same reason.

At this point, I almost just want every kid in the school to get Covid to just get that shit over with. This in and out of school stuff sucks.

Once vaccines are approved, then we should just treat it like the flu. If your kid is not vaccinated and gets it, send them home, my kids is staying.

I know there’s all sorts of moral and ethical arguments about whether you should help your kids a little bit or foreigners a lot. But, I have no doubt that the Chinese will take care of their own first if they were in the position we were.

On a sidenote, I was speaking with my Trumpy friend who lives in the villages in Florida. Complete anti-VAX dude. He confessed that he got Covid about three weeks ago, but recovered in three days and said it was just like getting the flu. Anyway, he wants me to go to pharmacies here in Argentina and see if I could pick up ivermectin.

Anyway, I feel like this is one of those comment threads/conversations where all of you guys are just a lot smarter than I am. I’m just a blue-collar dude with an average IQ that likes to dictate on his iPhone.

But the good thing is if any of you guys argue with me, I’ve got all day to argue back with you. Bring it on.

As always, I was too lazy to get out my computer, so this whole comment was dictated on my iPhone. So forgive the grammatical errors.

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I think that the interplay of global vaccine availability and individual decisions on getting booster shots or getting their kids the shot is so convoluted that it's not really open to clear moral reasoning by individuals. My take is that if you can get the shot and providers are willing to offer it, go ahead and do so, and leave it to national decision makers to figure out how to balance equities that should determine how supplies will be allocated.

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Yeah - that makes perfect sense for individuals.

A lot of what we're reading, by its nature, comes from pundits, editorialists and journalists who want to move public opinion or influence whole groups of people. So the nature of the argument is a little different. It's a little like how no one individual's vote really matters, because even the closest elections are rarely decided by even as few as a dozen votes. But you wouldn't use that logic to rebut a pundit who was writing about how important voting is.

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Any vaccine that is already available to the consumer is not going to be shipped elsewhere - taking one isn't going to take it away from others because it was never going to be shipped there anyway.

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I don't want to make my local CVS open another vial of 6 doses half an hour before closing time, so that they throw out the other 5 doses when they close. But if my local CVS already opened a vial for someone else, and is about to throw it out, then jab me with it for sure.

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Thank you for all your insights into a different life than my own! I'm glad that this is how you choose to spend your time while stuck in quarantine hotels around Latin America!

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I've been having a debate with friends on why the first dose and second dose vaccine numbers never seem to converge. I wonder how common this kind of thing is and how much it contributes to inaccuracies in the vaccination numbers.

Another anecdote on international numbers is a friend of mine from Mexico told me his mother back home got forged vaccination papers because she believes all kinds of crazy stuff about the vaccine. Which makes me think "how good are the international comparison numbers?" FWIW, he's a highly educated person with a PhD and works in the states for big tech as a software engineer. I'm not as aware of his parents' background but he, at least, fits the profile of someone who would get vaccinated (and he did).

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I wonder how many people are recorded as having had two first doses.

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My husband and I got our Pfizer boosters at Walgreen's a couple of weeks ago. Just got notification we are due for our second shot! I have a feeling the record keeping is a bit awry on all of this.

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I know multiple people with fake vaccine cards in the United States.

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The GIGO problems must be vast, but aside from a few jurisdictions (Florida with vaccine tourism from abroad for example) they should roughly cancel out...

My guess is that the US/Western European/Japanese data is good, Chinese data is good because they're mandating everything, and LatAm and Indian data are bad and will get worse as uptake slows and people start fudging numbers.

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I don't see how we can assume that GIGO (garbage-in, garbage-out data problems, I presume) will cancel out?

Several people in this forum have mentioned doing what Rory did, as in getting a "booster" that was officially recorded as a first dose in a part of the country he doesn't live in. Maybe that happens often enough to overestimate first doses by 5 or 10%, or maybe it only throws it off by 0.1-0.5% ...who knows?

I hadn't even considered vaccine tourism, but it might be a factor of another few percent in another dozen states - I know my Canadian in-laws were very impatiently waiting for does to become available long after we were already begging people to vaccinate, so it's not hard to imagine a few million tourist vaccines spread out around a half dozen states. Who knows?

Add to that our census is much less accurate than I would have guessed before I looked into that matter. As one example of that distorting impact, Hispanic life expectancy is measured at 3 years longer than whites, despite being a lower SES demographic. There's been debate for years over whether that is "real" or a distorting caused by miscounts in the population, but the terrible covid death numbers both in US Hispanics and the origin countries of Hispanics makes me think it's just a counting distortion.

All that is to say if I found out the true Florida to Colorado vaccination gap was 10 points off from the official numbers I wouldn't be shocked at all.

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My thinking is that there are plenty of confounding factors in the other direction as well; people getting vaccinated and refusing to give their information, inadequate "on-the-fly" record-keeping especially in the early "mass vaccination clinic" days, wholesale loss of data before it's reported, last-second "about to expire" dosing of friends and family.

Whereas the main error sources pushing in the "overcount" direction are, as noted, vaccine tourism and DIY boosters. The former is likely to be a decently large confounding factor in some areas, but it's not really possible for it to be a systemic error at any scale given the difficulty involved in travel right now. The latter is a very recent phenomenon and I simply can't envision it being, again, a large error source against a pool of 380 million vaccines dispensed.

I'd guess that even in Florida, we're within a few percent of being accurate, on the high side, and that the general background noise pushes us towards an undercount.

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“I will say that the Moderna Booster fucked me up for about a day and a half.”

How did it compare to the day after your second Pfizer dose?

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I think my arm was a little sore on the second shot. But I never felt sick.

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I've heard in many places that Moderna trialed the largest dose they thought was plausible, while Pfizer trialed the smallest dose they thought would work, and that this might be why more people report each side effect on both first and second dose for Moderna, and might also be related to why Pfizer protection is measurably less during the delta wave.

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I like this, and as an Oregonian, glad you came. Though my doc says that the actual boosters are worth waiting for, as they are better-designed and will be more effective with the variants. I am just "neurotic" enough to worry a LOT about post-vacc covid, not bc of the experience of covid (see below, its "just like a damn cold") but bc of long-haul issues, which this body cannot afford. Some perhaps can.

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I will certainly get any variant specific vaccinations, but I was confident enough in the research to justify the mix and match moderna booster.

And with my travel... I evaluated the risk.

I am not as worried about long covid. I have a suspicion that true long covid with permanent effects will be extremely rare, but if you have worries... most certainly take precautions.

Have a great day neighbor.

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I'm mostly more nervous about my kids getting quarantined than of them getting Covid.

I mean, I don't want _either_.

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I'm not sure if your anecdote about the FDA slow-playing boosters and child vaccination is true, but if the Biden Administration is actually trying to prioritize global vaccination then maybe they shouldn't actively humor these paranoid people.

Right now (fully vaccinated) Joe Biden is wearing a mask around his (fully vaccinated) cabinet and the admin has supported school mask mandates. Maybe the low hanging fruit to encourage Americans to prioritize global vaccination would be to act as though (a) the vaccines work and (b) children are at low risk without vaccination. Otherwise people will reasonably believe that the administration is not confidence in the efficacy of the current approach. Trying to backdoor policy through the FDA seems like a plan B.

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> (a) the vaccines work and (b) children are at low risk without vaccination

I was talking to my parents the other day, about why my brother had canceled on a trip that they were still planning on going on, and they were saying that at least they have been vaccinated, while my brother has to worry about unvaccinated kids at home. In the circles I hang out in, it's been common knowledge that vaccinated people my parents age are at the same risk level as unvaccinated people my age, and that vaccinated people my age are still at higher risk than unvaccinated children, but a lot of people (including people with graduate degrees in mathematics, like my parents) haven't actually spent the time looking at the numbers to realize that age is a bigger factor than vaccination status for safety.

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On the one hand, if the FDA thing is true then it makes me feel better about my children not having access to the vaccine yet - at least it's for a cause I support vs. "my children can't get it and we also wasted 12 million doses in June/July/August - can't we get some of those"?

But I also don't like being lied to about this - this smacks of the CDC mask requirement, which although I personally happened to have read the right things to understand it was about preserving supply rather than saying they were ineffective - came across (understandably) as(or was) a lie to many people which undermined trust.

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My understanding is that we didn't waste 12 million doses. All vaccination drives have some number of doses that don't make it in arms due to equipment failures, human error, accidents, logistical issues, etc... Off the top of my head, I think it's usually in the 5-10% range and for COVID vaccines, it's around 3%. The only way to not "waste" these 12 million doses was to not vaccinate people.

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Great piece. I certainly agree that the most cautious have become a drag on everyone else. My mom, who has not eaten in a restaurant in 19 months, carries hand sanitizer everywhere and won’t take her grandson to gatherings, comes to mind.

There are two basic ways of dealing with this group: (1) slather the cautious and their young children in vaccines to assuage their fears when these vaccines would do much more good in developing countries or (2) tell them they are being silly and need to chill out.

Too little counter scolding has occurred. The covid cautious imposed coercive distancing on people who were aware of covid risks and willing to take them. They frightened healthy young people with exaggerated claims of lethality, failing to note that covid is a pretty minor risk the young and fit. The cautious prostrated our economy out of fear. Now we are supposed to sacrifice middle aged folks in poor countries so that our kids can play with theirs? Rubbish! Better I say that Charlie only plays with children whose parents are not neurotic than that a 50 year old bread winner in India or Iran be denied an mRNA vaccine.

By all means expand supply. That should be uncontroversial. For the moment, there is a tension between children here and 50 year olds in India, and I side with those at hundreds of times greater risk.

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My sister-in-law and mother-in-law barely leave their houses. The ironic thing is, is they are also scared of the vaccine. But to be fair they were pretty much shut ends before that anyway. People just have no sense of risk management.

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I'm forced, near-daily, to point out that with a full course of vaccination what Trump said last year is now true. It's like the damned common cold.

So stop being an idiot, get vaccinated, and get a life back.

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I am convinced there is another motivation for rules that cater to the "most cautious": the desire to quickly determine who is "good" and who is "bad". Vaccine status alone doesn't have any visual cues that allow the scolds to know who has and has not been admitted into the "good" group. Masks -- even the mostly worthless cloth masks worn loosely near one's face -- are sufficient to direct anger at the Bad People.

Biden's recent speech - "WE'VE been patient. But OUR patience is wearing thin. And YOUR refusal has cost all of US." -- clearly defines the bad people. Masks allow us to identify them quickly.

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Ehh, perhaps.

But I have little sympathy for the unvaccinated on either side of the political spectrum, and no qualms at all about using long-established norms to ram a vaccine down their throats and end this fucking nightmare.

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I, too, have little sympathy for the unvaxxed.

I also am sick and tired of wearing a mask and seeing ridiculous and damaging rules imposed on children who should be in school full-time. The long-lasting effects from having a segregated workforce (white collar at home, blue collar delivering all the goods and services needed) and interrupted schooling are corrosive to our society. And with vaccines widely available, we have tilted too far in favor of the overly cautious.

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I think it's a combination of the overly cautious influencing the debate and, well, reality. By June/July, as hot vax summer commenced, people were joyfully dumping their masks and recreating normal life. Then we got the surge and the sense that the threat hadn't gone away, conflicting guidance from health experts, and the nattering of the overly cautious.

I think it's that sense of uncertainty, frustration, and fear of a return to the past that led many people to jump on the masking/semi-lockdown mentality.

And now that reaction is morphing into anger at those who refuse to get the shot, and blaming them -- rightly or wrongly -- for causing the surge and its attendant fear to return.

I have no doubt that if we get this under control, and more people get vaccinated -- whether because of mandates or whatever -- people will again joyfully return to normal life, no matter the squawking of the overly cautious. Girls and boys just wanna have fun.

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No disagreement, in general.

The quarantine rules surrounding in-person schooling are nightmarish. Now that Pfizer has been fully approved, mandate it for schoolchildren over 12, stop pretending that masking kids is anything but theater, and get the fuck on with it.

My unvaccinated child is almost certainly an order of magnitude safer than my vaccinated parents.

As for the broader economy, we need some semblance of normality to get production and supply chains restored; if that isn't achieved by year-end, next year is going to be even more of a mess than this year was.

That will create pressure for the Fed to "do something" about inflation even though it's being driven entirely by sector-specific supply-side problems. Their response will get us yet another strangled-in-the-cradle recovery a la 2011-16, and another lost decade that condemns yet another 5-year cohort of kids to economic doom.

One way or another, whether Delta gets us there or a vaccine mandate, this needs to be over by January.

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Dude. I am the exact same way. I had a discussion with a friend of mine who is anti-vaccine, and was talking about whether mandates were moral. Intellectually get where he’s coming from, but quite simply I just want normal fucking life back.

I hate masks. I like hugging people.

I want to see my Starbucks barista smile.

And if it takes vaccine mandates, I’m good with them.

No one has a right to an easy life.

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As a general rule, if you want to see a barista smile, go to some local place that has full-time employees that are paid well.

It's hard to find a happy Starbucks employee in my experience.

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The evidence for Pfizer boosters, at least for folks over 60, is incontrovertible. Current data shows a 10x reduction in risk of death from booster. Boosters for older Americans should have started at least 2 weeks ago.

https://mobile.twitter.com/EricTopol/status/1437596362153988096

CDC and FDA are not fit for purpose. Their inability to perform basic risk mitigation under conditions of uncertainty will likely kill thousands of Americans just on the booster decision alone. That's on top of the deaths due to ongoing mask guidance and rapid testing failures.

Biden's top priority right now should be to do whatever is necessary to stand up a competent public health agency that can oversee our pandemic response. What we have right now is worse than nothing.

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If any of the relevant folks at the fda are actually taking vaccine exports into consideration that’s really bad. I’ve been told so many times these last 18 months that they couldn’t bend on this or that bc their credibility as a regulator of safety and efficacy was paramount. Well … is it?

Seems to me like the boosters and shots for most kids are ready for EUA. But maybe they have some expertise that says otherwise. Either way, the rest of the world really has nothing to do with the calculation.

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The FDA and CDC are 100% into the "trust but verify" camp for me. It's amazing how much credibility they've pissed away, and I'd struggle to tell you that they (or we) got much out of any of their Faustian bargains.

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This was a bad take on Tweet form and is a bad take in full form.

Like it or not, the Chinese regulatory and political authorities are NOT going to allow production resources to be significant reallocated from domestically-developed vaccines to foreign ones, regardless of global need or efficacy.

They’ve been *frantically* native-washing the Fosun-licensed version of Biontech as it’s become apparent that they need it for use as a post-Sinovac booster shot due to the latter’s poor efficacy. It’s already referred to as 自主研发, “independently developed” all over native media, and the initial wall-to-wall skeptical coverage of mRNA vaccines has dissipated.

Meanwhile, the production capacity simply isn’t there. It’s not clear to me that China could turn out a viral vector vaccine (like Sputnik or AZ) in massive, game-changing numbers, but it’s likely they could make a meaningful contribution to global production at least.

Their mRNA production capabilities are in their infancy by comparison. They’ll have significant trouble scaling production at Fosun even with state resources and strong motivation; there’s just no world in which China is able to hugely contribute to a worldwide rollout of Moderna or Pfizer this year.

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author

This post is not about China producing mRNA vaccines. It's about increasing the output of the existing Chinese vaccines.

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Gah, I deleted several paragraphs on my phone before posting in my pre-coffee addled state. After the opening sentence should have been something along the lines of:

“The problem with the existing Chinese vaccines that’s leading to poor uptake and levels of trust isn’t poor safety, QA/QC, or production consistency, all things to which the FDA or EMA could waltz in and give their stamp of approval.

It’s that their posted efficacy rates, especially that of frequently-exported Sinovac, aren’t great. And, additionally, that China’s reputation regionally is such that virtually no one trusts even those mediocre figures.

Worse, the nationalist sentiment wrapped up in vaccines for China ensures there’s very little flexibility here. There’s no chance China will permit it’s pharmaceutical firms to invite FDA or EMA oversight, and even less that they’d openly retool for production of something that works better.”

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I think one owes it to Matt to read the entire article before commenting. A comment might be on a side point and might not engage everything he said, but you should at least read the whole thing.

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See the above, sorry.

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Seems like this one could have used more time in the oven. Based a suspicion that FDA is dragging is feet on pediatric approval for RNA vaccines to free up capacity for adults in other countries, we should divert FDA resources towards review of other, less-good Chinese vaccines? Because the FDA stamp of approval would persuade other countries to start using the Chinese vaccines, even tho there's nothing stopping them from doing so now?

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author

Perhaps I wrote the post unclear, but this has nothing to do with persuading other countries to use the Chinese vaccines. The Chinese vaccines are being used in countries all around the world.

And contrary to your view that "there's nothing stopping them" from taking Chinese vaccines now there *is* something stopping them — supply constraints. But if we inspect more Chinese factories, we can increase the supply of the Chinese vaccines.

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The article seemed clear but MYs reply muddles things. My read of the article was “stringent regulators, especially the fda and eu equivalent, should inspect chinese vaccine factories and approve worthy vaccines to increase uptake in the developing world”

If the inspections/approvals would not increase uptake in the developing world, what’s the point?

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Now I’m very confused. The NMPA is more than capable of the oversight and inspection regime needed to stand up new vaccine production.

The notion that they need “loaner capacity” From the FDA or EMA to do the job simply isn’t born out by the evidence.

China is not standing up additional capacity because it does not see the need, and if it does not see the need you can be 100% certain that it is not going to permit a foreign government to become involved and stand up capacity “behind its back”.

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Sorry, I still don't get it. Why does China need a US agency to inspect its own factories to manufacture its own vaccines? I mean, if the Chinese vaccines were going to be used in the US or Western countries, sure- but if they're being used in Africa, how does the FDA come in here....? Maybe I'm slow

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Countries which don't have capable local regulators effectively outsource their drug and vaccine approvals to the FDA, EMA, and about half a dozen other rich countries' regulators (aka "Stringent Regulatory Authorities", https://en.wikipedia.org/wiki/List_of_stringent_regulatory_authorities) through a WHO process. As a result, if the FDA/EMA/other SRA approves Sinovac, it effectively gets approved in many other countries automatically, which presumably would allow it to be used more broadly than it already is.

(Whether that would be the actual effect, mmm, who knows. But that's the theory Matt's putting forth.)

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I'm not sure if I followed today's post either. Something was missing in either the background material or the chain of logic, I'm still unsure which.

I think the idea was that the FDA (or similar) agency's approval would lead to other countries, outside of Europe and North America, deciding to approve the usage of China's vaccine. Many countries already are but I suppose more might if the FDA approved Sinovac.

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It's essentially automatic; many countries simply rely on an SRA approval instead of running their own approval process. Notably, China does not have an SRA, so its approval is insufficient.

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That's a lot of speculation on the FDA's motives. Children have very different biology than adults and it's never been as simple as saying, "Just give a 5-year-old a half dose." Without actually seeing the study protocols, we have no idea what these outcomes are or what safety flags have been raised.

As for boosters, we've discussed this here on previous posts, but the statistics suggest that they're unnecessary in most cases *right now* (subject to change in the future). There's very little stopping people who want a booster from getting one, but you're probably changing the efficacy from ~80% to maybe 90% (I'm guessing; I haven't actually seen the Pfizer data on this). That's not nothing, but the utilitarian argument of prioritizing first doses makes sense in that case, not to mention the vast majority of COVID cases amongst the fully vaccinated have not led to hospitalization.

Finally, I agree with the sentiment about Sinovac, but I'm not sure I follow the argument about inspections. Do developing countries need the FDA to inspect the facilities in order to accept the doses? I'm the last guy to say "trust China" on nearly any issue, but if the Chinese government wants to use Sinopharm/Sinovac as part of their vaccine diplomacy efforts, let them do the inspections and show the world that the facilities are up to snuff!

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founding

I think if you read between the lines, Matt is not just speculating about the FDA foot-dragging.

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some shoe leather journalism would be helpful here. someone needs to buy mid level fda scientists drinks and get them talking off the record

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As a mid level fda scientist always happy to accept a drink

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founding

But the FDA/CDC isn't judging whether or not boosters are "necessary", are they? I thought they are just judging whether they are "safe" and "effective". Surely what's good for the aducanumab is good for the comirnaty, right?

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This is where substack needs the LOL button. :D

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>> "but the statistics suggest that they're unnecessary in most cases *right now*

The data from Israel and the latest CDC reports say otherwise.

Here's Eric Topal on this: https://mobile.twitter.com/EricTopol/status/1437596362153988096

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I should've been more clear about "most cases." For the immunocompromised and elderly, boosters should be given. For the rest of the population, they're unnecessary.

This is the Israeli data parsed by age: https://www.covid-datascience.com/post/israeli-data-how-can-efficacy-vs-severe-disease-be-strong-when-60-of-hospitalized-are-vaccinated

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Point taken, although it's becoming clear that rather than just elderly, the cost/benefit cutoff is at least 50 and older based on what we know today.

For example, see details on recent UK booster announcement here:

https://www.reuters.com/world/uk/uk-pm-johnson-set-out-covid-19-booster-strategy-under-winter-plan-2021-09-13

Apparently, they're using either Pfizer or a half dose of Moderna for the booster, even for people immunized originally with AZ.

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I'm happy to be shown I'm wrong on this, but it sure seems like that's a political decision rather than a scientific one. Based on the link I sent earlier, there's a big difference in risk factors at age 50 vs. 70 vs. 90.

Now, whether to provide mRNA boosters to those who received the J&J or AZ vaccines is a different question. The data certainly suggests that J&J's efficacy wanes more quickly than Pfizer/Moderna (not sure about AZ, I haven't seen those studies).

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I don't agree that it's political rather than science. It's certainly out in front of peer reviewed science, but I believe it's still science based and is actually a good use of the precautionary principle.

To me, one of the biggest failings in our pandemic response is the idea that making decisions with incomplete data goes against science. The opposite is in fact true and sound risk management/harm minimization usually requires this. FDA and CDC seem particularly bad at including the cost of delaying a decision while waiting for more data in their cost/benefit math.

Israel provides live raw covid data by vaccine status and the impact of their booster campaign seems relatively clear even in this raw data:

https://datadashboard.health.gov.il/COVID-19/general

- use translate to view page in english

- click morbidity and vaccine research tab on top

- look for bar chart w/ active cases by age by vaccine status unvaxed/vaxed/thrust (thrust is boosted)

- use dropdown to change from active cases to severe cases

This raw graph clearly shows significant improvement in protection against severe disease for everyone over 50. Perhaps there are confounds that are confusing things, but I doubt they'd erase the apparent benefit for > 50. The resolution on the graph makes it tough to see if there are clear benefits for < 50 because the severe rate is so low in this group to begin with.

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It looks compelling, but as the link I posted above shows, you need to look at the rates of vaccination (and rates of boosters given) in each of these subgroups to properly analyze the data, otherwise you end up in a potential Simpson's Paradox area.

Again though, I'm happy to be shown I'm wrong if somebody lays this data out properly.

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I got a Moderna booster after having the Pfizer initially. My justification was that I work internationally in South America, so the risk of getting it, compounded with the risk of going into a foreign hospital system justified it for me.

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Do you have any evidence WHATSOEVER to justify your "strong suspicion" that the FDA is deliberately slow rolling regulatory approval for political ends, or are you just making things up?

Citing Tyler Cowen's increasingly deranged FDA conspiracy theories does not count as evidence.

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I am curious about whether having the FDA inspect the factories in China would help because I'm genuinely not sure. I have a relative in a country that used a lot of Sinovac vaccines and have acquaintances with friend and family members in countries that depended on the Sinovac/Sinopharm vaccines. There isn't a lot of confidence in those vaccines. It's a combination of knowing that they aren't very effective compared to the mRNA , J&J and AZ vaccines, China having sold substandard PPE and Covid tests to many low income countries, and the way China has seemed to strong arm countries into buying their vaccines. On the other hand, even some protection is better than nothing.

Authorizing the NovaVax vaccine would also help. They should have data for the EU in October. It's about as effective as the mRNA vaccines and was specifically designed for use in low-income countries that don't have a lot of freezers. It's also a protein subunit vaccine, so some of the people who don't trust the mRNA vaccines or J&J might be willing to take it. And it seems to have fewer side effects. They're also working on formulating it along with a flu shot.

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This seems like overly conspiratorial thinking. It seems much more plausible to me that the FDA's stated concerns around safety and efficacy of boosters and child vaccines are the real cause of slowness. Two high level people at the FDA recently published an opinion piece describing exactly why they're uncertain that boosters are needed (https://www.statnews.com/2021/09/13/international-review-argues-against-covid-19-vaccine-boosters/), and their paper only mentions equity concerns in passing at the end. For child vaccines, the risk of death from COVID is objectively low, and there is suggestive evidence that myocarditis side effects of the vaccines tend to inversely correlate with age. That was their stated reason for increasing the followup period and increasing the size of the trials. Maybe it's motivated reasoning, and really they're searching for excuses to delay to encourage global distribution of doses, but this is how the FDA has acted for decades: strictly following bureaucratic formulas around what kinds of evidence is necessary and how rigorously it was collected. I mean of course you can disagree about how reasonable this is under the circumstances (I disagree, for the very little that is worth), but there's no reason to think the FDA is not acting on the level.

But also the equity argument for child vaccines is just objectively much weaker than for adult boosters. The doses Pfizer is testing are 1/3rd of an adult dose for 5-12 years and 1/10th of an adult dose for 0.5-4 years. So if the Pfizer vaccine is approved for children at its current dosage, you could vaccinate 10 young children for the cost of vaccinating one adult (or five for the cost of boosting one adult). Children are less likely to spread the disease than adults, and they are more than 10x less likely to experience severe disease than adults. But still, it's not completely obvious that vaccinating 10 young children slows disease spread less than vaccinating one adult. It is fairly obvious that all else equal, a dose is more useful in an unvaccinated adult than boosting a vaccinated non-elderly/immunocompromised adult.

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"But still, it's not completely obvious that vaccinating 10 young children slows disease spread less than vaccinating one adult."

The data suggests that unvaccinated children under 12 are a full order of magnitude or more less likely to contract COVID than even vaccinated adults, so I'm inclined to say that from a purely utilitarian point of view we should definitely be shipping vaccines abroad.

But I'm also a parent, so if you start doing that I'm sticking up a pharmacy to get a tenth dose of Pfizer in my toddler's arm anyway. :p

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What's your source for the "full order of magnitude" number? The numbers I'd seen were more like ~2x less likely to contract COVID and also had an R<1. (e.g. https://www.healthline.com/health-news/kids-are-half-as-likely-get-covid-19-as-adults-heres-what-we-know)

I haven't seen any post-delta numbers for how susceptible children are to delta, but it's reasonable to assume that it's much more than alpha or the ancestral strain, as with adults. Much higher pediatric ICU utilization than at previous points in the pandemic tends to support that.

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Sorry, stupid day for me today. Order of magnitude less likely to die or suffer serious illness, should have said.

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Yup, I said that in my comment: "[children] are more than 10x less likely to experience severe disease than adults". Compared to elderly people it's several orders of magnitude.

My point is that vaccinating 10 children may reduce transmission enough to be better on strictly consequentialist grounds than vaccinating one adult. It's not *obvious* which wins, whereas it is obvious which wins for 3rd shots for vaccinated adults. Some epidemiological modeling would be able to answer which is better, but I haven't seen any analysis along those lines.

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How quickly should we reasonably hope to get the world vaccinated? By tomorrow would be great, but may not be possible. MY's post hints at "next spring" (in terms of when supply will be a lot greater), but we can make a better estimate of that.

About a third of the globe is fully vaccinated now. Currently, global vaccinations are averaging ~35M/day. At just that rate of administration, we would hit 75% vaccinated in five months. But, as MY notes, global supply is increasing. That is, four months is a more reasonable estimate for hitting 75%, probably five months for 80-85% and so on.

See: https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/?sref=SvwPxqpB

Even faster would be better, but what are the chances that new interventions would speed the process up all that much, if not actually slow it down?

The real problem is hitting the laggards, and understanding why that is the case. As MY notes, Africa is way behind. That's especially the case for the biggest countries: Nigeria, Egypt, South Africa, not to mention DR Congo. Is it simply a matter of funding (something the advanced world can and should fix)? Or poor healthcare systems that simply can't administer the shots no matter the supply?

I think these are the more critical questions than figuring out how to give supplies a jolt.

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founding

It really sounds like the bottleneck is getting doses on-site and then into arms, more than getting doses to countries at this point.

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Okay, my big question: When did we all decide that, through this whole pandemic, we were going to use the term “normalcy” instead of “normality”? As someone who prefers the latter term, it’s been wild seeing it just completely discarded.

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Warren Harding.

https://en.wikipedia.org/wiki/Return_to_normalcy

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Yeah, but is everyone really going for the Harding reference? It feels like, after 9/11, more people used “return to normality” or referred to “normality” in general. Google Trends only shows back to 2004, but back then “normality” was definitely on top.

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Ah, thanks for this. I'm very interested in what it will show once it has data from 2020/2021 in it.

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founding

I think the Harding phrase is so ingrained that even when I was back in high school, I remember being surprised to learn that Harding coined "return to normalcy" (and I don't remember what he was saying it about).

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