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How Pfizer delivered a Covid vaccine in record time (wsj.com)
162 points by wallflower on Dec 13, 2020 | hide | past | favorite | 218 comments


> To assemble its mRNA production network, Pfizer used its own money and didn’t take any from the federal government. Executives said they didn’t want to give agencies outside the FDA more leverage over the design of the trials.

> Rival Moderna, which took funding from a division of the U.S. Department of Health and Human Services, suffered a three-week delay in completing its own mRNA trial after federal officials there asked the company to slow down enrollment to boost the racial and ethnic diversity of study subjects.


Sounds like the 3 week delay was merited if Moderna originally had a mostly white study group and thus wasn't properly testing the effects on the entire population. This is very important to do in medicine. And I wonder if that means that Pfizer did not use a broad sample set of the population and DHS was not there to keep them in line? Or maybe they did this correctly from the get-go and it was sheer luck that Moderna had the additional needed oversight?


Pfizer trial demographics are on page 31 of this PDF: https://www.fda.gov/media/144246/download

You can compare that with the demographic table of the US. Looks like they don't quite align, but are presumably within the guidelines. FWIW, all the comments I saw from people more familiar with medical data were pretty positive about the demographic spread.

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


Notably, specifically look at the phase 1 demographics. It was 100% white.

I’m not saying anything for or against this, but I bet it was in the first phase where the concerns for equity were brought up.

Edit: the difficulty becomes the argument between recruiting equitably vs recruiting quickly, both are going to have downsides. Ideally you would do both at once, the question becomes why is this so hard in the US, and there are lots of reasons.


Is that why African Americans don't trust the US medical establishment? Phase 1 is meant to select the safest dose. If Black people did not take part in Phase 1 and were only added in Phase 2, that means that folks in Phase 2 were exposed to unnecessary risk.


It's still very difficult to convince black people to partake in medical trials, largely because their trust in the system was so thoroughly violated in the not-so-distant past: https://en.wikipedia.org/wiki/Tuskegee_Syphilis_Study

It's not hard to imagine a patient noping out of an experiment if he's the token black guy in a room full of white doctors poking and prodding at him.

I work for a company that makes medical devices for people with diabetes, (a disease which disproportionately affects people of color), and we go out of our way to ensure that we have a diverse cast of people who interact with the patients in our studies.


I see the Tuskegee example trotted out pretty often and frankly I was ignorant of it. Is this a well known and discussed thing among black people or might it be more about a general distrust of the government, etc. and as you pointed out, being historically under represented in medicine.

I am just guessing a fairly small people asked about Tuskegee would know what it is but maybe it's just me. I am just suggesting maybe asking black people why they don't want a covid vaccine for example and address those issues.


Yes, the Tuskegee study is well known among black Americans, and it's been written about extensively. They've even shown that the study might be responsible for as much as half of the life expectancy gap between white and black American men today, because it directly led to mistrust of the medical establishment and caused black men to avoid going to the doctor.

That said, I recently read that most black people (falsely) believe that the Tuskegee subjects were deliberately infected with syphilis, but I can't find the source right now, and it's kind of splitting hairs anyway.


That's not what phase 1 is for.

Phase 1 is essentially to test "will this drug cause terrible harm to people who receive it in a reasonably short time frame?" In terms of dosage guidelines, phase 1 studies often don't have variable dosing, or if they do, not an awful lot - because the question around optimal dosing is the target of phase 2.

(Sometimes you can roll 2 and 3 up together, for instance, if the difference in dosing is in duration of therapy rather than an actual difference in drug administered per unit time.)

Phase 1 usually has terribly small samples, because it's only looking for terribly large effects. Seeing homogeneity there, of any stripe, is neither unexpected nor problematic.

(A lot of the vaccine studies rolled up phase 1/2 together because we already have a pretty good understanding of what these delivery mechanisms do to people, and so while you'd be cautious in administering to the initial study participants, it really didn't merit a "test it on five people and hold your breath" approach.)


I have no insight into how volunteers were recruited in the study but I would imagine that it is partially a cycle of African Americans being less likely to volunteer due to a history of mistreatment by medical community.

A lot of studies also recruit people who have a connection to the study (maybe friends/family members, students at the local university, etc...). If there is less diversity in the company and people running the study, I think this would also lead to less diversity in the participants. Again, I have no knowledge of how this one was done.


This is something that Pfizer got asked about during the hearings on Friday -- their execs stated that they tried to recruit minorities heavily in the beginning of the study and continued doing so in later recruiting rounds (I don't recall if they mentioned actual number though).


There's a lot of history there, unfortunately. The US medical establishment has a long track record of experimenting on Black people -- from performing experimental surgery (without anesthetic) on slaves to infecting Black US soldiers with syphilis to study how the disease progressed that continued until the 70s.

All this to say nothing of how the medical establishment generally under serves minorities. There's quite a bit of writing on why it might be so hard for these major pharma corps to find volunteers from these communities.


If I were a black man in America, and they wanted me as a volunteer in Phase 1, I have to say that the history there would be a pretty big negative factor in my mind. Volunteering for Phase 1 is an act of trust, because by definition there's not much data yet. If I were an African-American, I don't know that I would have that kind of trust in big corporations.


Why would you trust big corporations as an American, period? History shows us that they will take every opportunity they are given to make or save a buck, from virtually enslaving people via company towns and company scrip, to killing people for unionizing, to polluting the places we live, to covering up evidence that their products do harm, and to suppressing evidence of the severity climate change for literal decades.

These things are all so well known, it isn't even worth the effort to track down citations for them, and you still trust them?


The monolith? Or the few who had people with lapses in judgement?

Are you saying corporate structure in the law causes these actions?


For purposes of the current discussion, it doesn't much matter. We see corporate abuse happening all the time, every day. If I had to speculate it's that corporate executives have very strong incentives to do everything to make or save a buck, up to and including the things I've mentioned and more.

The things I mentioned previously did not involve any lapse of judgement at all. Saying that is just being an apologist. I'm not saying you're suggesting lapses of judgement are responsible for these things, merely that actually suggesting so would make one an apologist. They are all done with eyes open, focusing on the dollar signs at the end of the road, public interest be damned.


You're taking negative actions by some and applying it to a class.

I'm simply stating that they are negative actions by some. If that didn't come across, here it is.


Maybe the corporations do sometimes positive stuff too. You know, like vaccines.


Of course they do. If I were an African-American, I would be suspicious that they might be doing that in a way that puts more risk on me, and more benefit on people that look like the ones in the boardroom. Not saying that's true, but I could totally understand how any African-American who knows their history, would be more suspicious than the average white American.


I hate to Godwin this thread already, but, you know, Hitler did positive things, too. For neither corporations nor Hitler do these things make up for literal crimes against humanity they have committed.

https://www.quora.com/We-all-know-the-evil-that-Hitler-did-W...

Edit: Well, since people are obviously not even reading the link, I'm going to quote the bullet points from the first answer in nearly their entirety:

> Nazi regime was the first to introduce animal rights and limited hunting seasons. Hitler had outlawed animal testing (who needs animals when you got thousands of Untermenschen).

> Nazis had the first public anti smoking campaign at a time when smoking was not linked to cancer.

> Hitler had authorized extensive research on cancer and various venereal diseases and abundance of medicine for public.

> Nazi labour laws were best in contemporary world. Reduced work hours, periodic breaks, paid holidays and sponsored trips to Italy as perks.

> Promoted sports culture among youth which led to Germany being a sports power house.

> Hosted the 1936 Berlin Olympics.

> Hitler had announced loans of 1000 Reichsmark (10 month salary in 1939) for married couples at minimal interest and waivers for birth of first child.

> Volkswagen - people's car. Personalized Cars for average germans was laid out in 1937. Volkswagen is an extremely popular brand now.

> German Autobahn(super highways) was introduced in Hitler's era.

> Hitler had forbade German army from using mustard gas or any sort of chemical weapons on enemy forces because of the trauma he suffered in WW1 from mustard gas. As a result, deadly gas warfare of WW 1 was never seen in WW 2.

> Nazis were pioneers in rocket science. America's space programs were guided and led by former Nazi scientists like Werner von Braun and Arthur Rudolph.


> Nazi labour laws were best in contemporary world. Reduced work hours, periodic breaks, paid holidays and sponsored trips to Italy as perks.

They got sponsored trips to a lot of places in Europe: Poland, France, Russia...probably best to avoid that last one though.


You know that's precisely my point, right? There's a long list of things they did that were right, good, and/or positive, but that doesn't excuse crimes against humanity.


If I were a black man in America, which I am, and they wanted me as as volunteer in Phase 1, I'd say hell yes.

You say "if I were a black man", as if you have any idea of what it means to be a black man in America


Serious question, can someone who downvoted the parent comment please explain why? This sounds in line with what I've heard about treatment of African Americans by the US medical system, so I would love to hear if there is evidence to say this is wrong.


The paper is available [1]. They did a reasonable job - 9% black/african-american and nearly 30% latino (the trial was run in Argentina and Brazil). Subgroup analysis similar efficacy between groups. Around 25% were more than 65. Maybe not so ideal as that is one of the key groups. Immunocompromised were excluded, which is understandable, but the data would have been interesting.

[1] https://www.nejm.org/doi/full/10.1056/NEJMoa2034577?query=RP


> the trial was run in Argentina and Brazil

why not run the trial in the country where the vaccine is going to be sold?


To keep your market larger?

/s

Most trials were run in countries where a large number of new cases were expected over the trial period. Government measures in almost all first world countries brought the R rate right down, which is disastrous for a trial looking for results.


Brazil just committed to purchasing 70 million doses..


The 3 week delay was most likely because this was Moderna's first Phase 3 ever. They didn't even know what forms to fill out and needed FDA guidance the whole way. Pfizer on the other hand has the former head of FDA on their board and hundreds of other trials conducted successfully.


> Pfizer on the other hand has the former head of FDA on their board

That's a bit sus


Isn’t 3 weeks about 21k deaths?


We're gated on production capacity, not approval speed. A 3 week delay in the Moderna vaccine's approval doesn't remotely cause anything close to 21k deaths. But the risks of incorrectly approving a vaccine that does turn out to be harmful in unexpected ways to certain groups of people are much worse -- that would permanently damage the public trust in coronavirus vaccines and would contribute to more than 21k deaths in the long run.


If we had used a challenge approach we could have saved hundreds of thousands of lives globally. Most of the time it took to develop the vaccines was government red tape (only some of which is reasonable at all). You won't find very many people that want to have that conversation however, they just stick their head in the sand and hide from it. It's morally revolting and evil that the US didn't utilize a challenge trial and move far faster on the vaccines.

They talk about how fast this vaccine was delivered. We could have done it a lot faster. An incredible number of lives and livelihoods could have been saved.

Take 1,000 diverse volunteers from the US military, start an isolated challenge trial (if something very unexpected happens, they're contained). Then expand it after those first thousand show success. Done in half the time that this took. We'll send those soldiers to die in pointless foreign wars, and then we won't do something so obvious as this to actually save American lives. The US would have had as many volunteers as you could handle for a challenge trial, hundreds of thousands of volunteers would have been trivial to get.


Well for example in the UK, we have rolled out the Pfizer vaccine and people started having a reaction to it, so now anyone with an allergy cannot have the vaccine and everyone has to be monitored for 15 minutes after taking it, something that should of been picked up during adequate testing.


Do you have a source for this? Never heard about it


Section 2.4 of NHS standard operating procedure for COVID-19 local vaccination services deployment in community settings:

https://www.england.nhs.uk/coronavirus/wp-content/uploads/si...

See also the press release from the regulatory agency specifically about anaphylaxis: https://www.gov.uk/government/news/confirmation-of-guidance-...


> anyone with an allergy cannot have the vaccine

Or "anyone with a history of anaphylaxis to a medicine or food should not get"? Do you have a source for anyone with any allergy being denied the vaccine?


I don't think this is really a UK-specific issue - it presumably would have come out in this way whoever approved it first (if it was actually a vaccine reaction).

It's also rather surprising to me (as a relative layman) that this wasn't picked up during safety trials. I get anaphylactic reactions to some food and medicines and carry an EpiPen. There are a few vaccines which have been counterindicated for me due to this so I have always thought it's a relatively well-known potential side effect from at least some vaccines (and other medicines of course). As such I would have expected it to be looked/checked for during safety trials.


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> Humans aren’t that different.

This is true, except when it's not. Then it really matters.

I do agree some in this thread are exaggerating a little.


A coronavirus vaccine that has only been demonstrated to work for white people would be great and well worth pumping billions of dollars into. Any drug company executive would agree.

It's still reasonable that the federal government would be reluctant to fund such a vaccine, though.


Your post is technically true and not at all relevant. You've gotta think about the context and not just post technically correct contrarian stuff.

There's no excuse for bad testing demographics. If only whites are tested then we'd only find out in the wild if it works on non-whites or has adverse effects on non-whites, which is obviously hideous.

We'd also flat out reject a vaccine that only works on non-whites because we'd never know it.

It's fine to say that a vaccine that only works on some known part of the population is a good thing. It's better than no vaccine. But we have to know who it works on. That's what testing does, and that's what's being discussed.


> There's no excuse for bad testing demographics

There never is a "bad testing demographic". The testing demographic can only be "good" or "bad" in relation to the population the vaccine is going to be certified for.

> If only whites are tested then we'd only find out in the wild if it works on non-whites or has adverse effects on non-whites, which is obviously hideous.

That's absolutely correct, if a vaccine is tested on a specific demographic, it should only be certified for that demographic, and only be given to other people after additional tests. In this context, if the FDA notices that there are not enough non-white people in the testing group, the FDA should not certify the vaccine for non-white people. White people can already start being vaccinated, and additional tests need to be performed on non-white groups. The role of the FDA is precisely to notice these stuff, react accordingly, and keep phrama companies in check.

It's already what we are doing for people suffering for immunodeficiency. We develop a vaccine explicitly without including them in the trials - because it's harder to make a vaccine considering them. We certify the vaccine for the non immunodeficient people - as fast as possible. Then we will start looking for a vaccine for immunodeficient people at a later stage. First by testing the already developed vaccine - or by looking in another way if that does no work.

What Pfizer exec decided to do, is put speed above all. And they were absolutely right to do so. They published they trial sampling details and it's up to the FDA to certify the vaccine for the part of the population the FDA think the sample was good enough for. And require additional tests for the others.


> In this context, if the FDA notices that there are not enough non-white people in the testing group, the FDA should not certify the vaccine for non-white people.

The FDA does not certify vaccines as being safe for particular races, for one simple fact -- races are a social construct, not a biological reality. What we call "races" are actually mishmashes of a large variety of different ethnic groups, many of which have little to nothing in common with each other genetically.

Vaccines are certified by age and by gender and that's it. There will never be a "whites-only" vaccine and the very idea is morally repugnant and biologically ridiculous.


> races are a social construct, not a biological reality

I do agree with you, but then what should anyone care about the distribution of ethnic groups in a medical trial if those ethnic groups have absolutely no impact on the result of the trial.

Either it makes sense to differentiate the vaccine according to $variable and testing groups as well as certifications need to reflect that. Or it makes no biological sense to care about $variable, then we should have no requirements about making sure that $variable is correctly sampled in the test groups.

In this case, ethnicity probably has 0 impact on the effectiveness of the vaccine, therefore why does anyone care about the distribution of ethnic groups in the sample ?


A three week delay is not "merited". If you want to require resources for people to determine if their subgroup (race, preexisting conditions, weight, gender, etc) then just set up a website for people to understand what the more personalized risk assessments are. Many subgroups will not be well represented even in large trials, but we can use techniques to show people relative risks. Which in vaccines cases, are basically always very low.

The FDA is supposed to issue EUA if the "benefits likely outweigh the risks". That bar was crossed after phase I trials, frankly, definitely after phase II, and is 1000x safer after a phase III trial (even if you don't love everything about it). The FDA is clearly not abiding to this standard, and is instead going with "almost no conceivable downside" standard. That has cost many lives.


Or just release it for the group(s) you have tests as and when they're done?


What makes you think the way people are being grouped together due to being visually different are the same factors that dictate the largest differences in efficacy between people?


It's what the U.S. Department of Health and Human Services thought [1], and it's clear from the thread that the comment to which you responded was predicated on that.

There's no need to imply it's the GP's own opinion, and sotto voce that the GP is a racist.

[1] https://news.ycombinator.com/item?id=25408088


Those two things are not the same. Increasing the diversity of a study is not the same as thinking that the differences are so great between different ethnic groups and not so great between any other distinctions that it would make sense to test and roll out to them in isolation. No one implied anyone was racist, you might want to sotto voce reread the definition of that word.


I actually don't think that, I'm just pointing out there are options for those who do...


They "suffered a three-week delay" because they made the mistake of recruiting an unrepresentative sample.

As others have pointed out, Pfizer got this right entirely on its own.

It's telling that the top-voted comment happens to be one that bends over backward to somehow turn this into an argument on "political correctness".

FWIW, the Moderna vaccine was the first to apply for approval, and is expected to be approved "within a week" (https://www.businessinsider.com/moderna-vaccine-slaoui-likel...). A one-week difference on a 9-months science project doesn't quite sound significant enough for any conclusions as to the effect of taking government funding, let alone individual events connected with that funding.


Pfizer’s phase 1 was a 100% white according to a commentor above.


Representation matters, not for some woke reason, but because 1)you want the vaccine to work for all populations, and 2) different populations react differently to medicines. A prominent case comes from early health research that largely excluded women from research samples, just assuming what was good for men was good for women. For example, it was uncovered after a number of car accidents that due to physiological sex differences in metabolism of zolpidem (Ambien) in women, dosages of Ambien were too high for women, who'd then drive impaired in the morning. In 2014 the NIH introduced a policy requiring the consideration of sex as a biological variable, because “studying both sexes is a guiding principle in biomedical research that will expand knowledge toward turning discovery into health.


Yes! And there is also a significant number of people that do not know what populations they may or may not actually belong to!


This is actually one of the instances where racial and ethnic diversity is really crucial, and not just a totem to allude to in CEO speeches.

Our genetic makeup is very varied and we know that a lot of medical conditions only manifest in people of certain heritage, or disproportionately among them.

It is far from unthinkable that some ethnic group could react to a novel vaccine badly, or at least in an unexpected way.


Rival Oxford, which took funding from the UK [1], produced a vaccine which was first to be published demonstrating successful efficacy results [2].

[1] https://www.ovg.ox.ac.uk/news/funding-and-manufacturing-boos...

[2] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...


Biontech (the company that developed the "Pfizer" vaccine) received 375 million Euros from the German government: [1].

1. https://www.faz.net/aktuell/rhein-main/wirtschaft/coronaviru...


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Still not the same thing as taking R&D money from the government.


How? To use a scenario that HNers are likely more familiar with: this is like when a video game company does preorders for a video game.

Or a concert promoter sells tickets before the event is built, etc.

The purpose is to offset risk. Pfizer didn't have to take a risk on this vaccine, because they had already sold enough of it to cover their development costs. They may have "used their own money", but that ultimately comes down to an accounting technicality for a company that large.


Suppose the vaccines didn't work or had massive side-effects. Then Pfizer wouldn't get any money. Conversely Moderna would still have gotten much of this research money.


IMO a pre-order guarantee is not the same as taking money that is spelled out as a development-funding commitment (https://investors.modernatx.com/news-releases/news-release-d...).

Moderna's initial funding didn't have an order attached to it, not that was disclosed. In August the US Government did go back and actually purchase vaccines under a separate agreement (https://www.hhs.gov/about/news/2020/08/11/trump-administrati...). Also:

> The May 21, April 16, and March 30 HHS agreements with AstraZeneca, Moderna, and Johnson & Johnson respectively include investments in manufacturing capabilities.

(https://www.hhs.gov/coronavirus/explaining-operation-warp-sp...)


Ask Philips and their ventilator division how much these guarantees are worth.

https://www.reuters.com/article/us-philips-us-ventilators-id...


The pre-order guarantees (for all manufacturers) exist to allow them to begin manufacturing of their vaccines before their testing could be completed. If it turned/turns out a company's vaccine fails trials they would be out millions of dollars for vaccine doses that will go in the trash. More importantly they have finite manufacturing limits.

If all told the various companies can manufacture a million doses a day it will take a year to manufacture enough vaccines for everyone in the US. By the government pre-paying for the vaccines the manufacturers could spin up the lines when they were in early trial phases. Six months worth of trials means many tens of millions of doses available as soon as the FDA gives approval of the vaccine.


From the article:

> The arrangement is an advance-purchase agreement, meaning that the company won’t get paid until they deliver the vaccines

They didn't take funding, they signed a contingent contract. Only their own money was at risk.


Also, the $2B order was only a fraction of what was proposed for an initial order, which the Trump Administration for some baffling reason reduced.

https://www.nytimes.com/2020/12/07/us/trump-covid-vaccine-pf...


It's not baffling: the Pfizer vaccine required extremely cold temperatures to distribute and was more expensive than other vaccines under development.


It also was the most promising and those lack of orders from Pfizer did not result in an increase somewhere else.

You are being deceptive in saying so.


Asking for Moderna to delay seems reasonable to me. Different ethnic groups may have different responses to the vaccine. Fortunately Pfizer’s numbers in the article show good efficacy across all groups (except it’s lower for Brazilians?)


What is particularly interesting is the response in the elderly population, as it's this group that seem most at-risk. The earlier studies were done in a younger population without co-morbidities, but later studies included all-comers. The pfizer study included older patients, though not many by the looks of it. They allowed for those with chronic conditions, though not if they were immunocompromised as a result of it. 9% black/african-american and 28% hispanic.



Related to this topic is a conversation Steve Levitt had the other day with Moncef Slaoui, who has been a scientific lead for "Operation Warp Speed": https://podcasts.apple.com/us/podcast/moncef-slaoui-its-unfo...


I like this article too [1] which describes the long prior research that led up to mRNA vaccines at BioNTech and Moderna.

[1]: https://www.statnews.com/2020/11/10/the-story-of-mrna-how-a-...


I think Pfizer also has some proprietary processes that they wouldn't want to share, something about special lipid capsules that protect the mrna while to traverses the intercellular medium.


A German(+Pfizer) vaccine which is still not approved in EU (it is in UK).

Time is a bit pressing here.


It's going to take many months (over a year?) to fully distribute, and the first few months of vaccinations are going to deliver the most important phase IV data points. Waiting just a little bit longer isn't entirely unreasonable. Why take chances if the Brits and the Americans are willing to do the final tests?

The main reason why vaccines are so safe (and why the anti-vax movement is so silly) is that they've been tested on hundreds of millions of people. But until you vaccinate those millions you cannot be absolutely sure about the safety.


This article is very US-centric and self congratulatory.

The vaccine is called BNT162b2, because it was fundamentally developed at Biontech.

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

>Tozinameran[1] (INN), codenamed BNT162b2 and more commonly known as the Pfizer COVID-19 vaccine, is a COVID-19 vaccine developed by BioNTech and manufactured and distributed by Pfizer

https://www.thelocal.de/20201110/biontech-four-things-to-kno...

>While global headlines tend to lead with Pfizer's involvement, Şahin insisted to Spiegel: "It is our technology."

It bothers me how Americanized the Western media has become. If Biontech was a US company and Pfizer was European, exactly 0 US media would call it the „Pfizer vaccine“. Yet most European media outlets have adopted the US-spin and now call it „Pfizer Vaccine“ (or „Pfizer-Biontech“ at most).

> In a series of interviews over more than seven months, senior Pfizer executives and other managers shed new light on how the vaccine project took shape.

Reading the article, it doesn’t look like the spoke to anyone at Biontech.

> BioNTech simply plugged the genetic code for the spike protein into its software. On Jan. 25, BioNTech Chief Executive Ugur Sahin designed 10 candidates himself.

Ah yes, the Germans simply plugged it into their software. Disregard over a decade of fundamental research done by hundreds of scientists with hundreds of millions of Euros in funding. Now let‘s focus on all the hard work American pharmaceutical Managers did.

>To assemble its mRNA production network, Pfizer used its own money and didn’t take any from the federal government. Executives said they didn’t want to give agencies outside the FDA more leverage over the design of the trials.

Yes, but: https://en.wikipedia.org/wiki/Tozinameran

>In September 2020, the German government granted BioNTech 375 million euros ($445 million) for its COVID-19 vaccine development program at a time when Pfizer funded its portion of development costs without government funding.[20] BioNTech had also received 100 million euros ($119 million) in financing from the European Commission and European Investment Bank in mid-2020.[21] Also: https://www.bloomberg.com/news/articles/2020-11-09/pfizer-va...

And speaking of „Operation Warp Speed“: Coincidentally, „Light Speed“, the name Biontech gave its vaccine development effort, started in mid January. A time when almost nobody had even heard of the virus. Operation Warp Speed wasn‘t announced until April 29, three and a half months later.


Thank you for this. Taking or redirecting credit for others’ work and investment, especially on such a massive effort is not right.


I am not sure why this post gets downvoted. I had the same feeling when reading this article. I would expected better from WSJ.


I don’t know for sure, but I think some of this is up to the reader’s interpretation.

> BioNTech simply plugged the genetic code for the spike protein into its software. On Jan. 25, BioNTech Chief Executive Ugur Sahin designed 10 candidates himself.

When I read this, I didn’t take it as dismissive of BioNTech but more (1) a brilliant demonstration of the technology they’ve developed and (2) admirable that the CEO is still in touch with the underlying research.


I completely agree. It's sad and disappointing to see this being labelled as Pfizer vaccine when it's actually the BioNTech vaccine. But I guess that's what you get when one company has a massive marketing department and the other doesn't.

Pfizer isn't even the only company distributing it, Fosun does the distribution is China...


But also, is it really a “record” time?

For example, Russia already has 3 vaccines: two of their own, and one Chinese.


I think it is record time, as I understand it if this vaccine (and many others) had been under the regulatory regimes in those jurisdictions they would have been ahead of that pace as well. As far as I can tell the 1st phase of the Spunik V trial was injecting everyone in the building where they were developing it and fully half the participants got a fever from the vaccine: https://www.thelancet.com/article/S0140-6736(20)31866-3/full...

(The fever thing I don't think is actually a big deal, but is certainly not desirable if you want people to take a vaccine!)

The vaccines in question mostly got out ahead of their production capacity anyway too, so the difference is not consequential.


> fully half the participants got a fever from the vaccine

A mild fever, with one participant getting a moderate fever. Very small sample size, so it's not clear how that compares to the Pfizer vaccine. That appears to cause severe enough fever on occasion (~0.1%) that "who pays for the rare precautionary hospitalizations?" could be a very a real issue in countries like the US without public health care. The % of temporary side effects reported is significantly more than most other vaccines.

As you say, the fevers are probably just temporary side effects of the immune response and the supermajority of people recover very quickly (~24hrs or less). But it is an issue that needs monitoring - the trials really aren't that big, so it'll take quite a bit more data to know if those vaccines are safer than covid itself for the not-at-risk population.


The point is that if many organizations developed vaccines in the same timeframe it’s not really a “record”.


In Soviet Russia, vaccine develops you.


TLDR: They bought it and scaled it.


How to read this without subscribing?


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What's something they would have done in the normal process that they skipped?


Absolutely nothing.

In fact the acceleration in testing was mostly facilitated by the western world's absolute bungling of the COVID-19 response! If the planet were not blanketed in hotspots that match the demographic profiles required we would still be waiting for statistically significant results.


Not fast enough to save 300,000 lives despite the vaccine being made very quickly.


politics and incompetence are responsible for a large chunk of those deaths.


Those lives were not sacrificed on the altar of meticulous vaccine development. They were offered to the "business as usual" gods instead.


Speak in facts, not vague political jargon. The vaccines were developed quickly, then delayed for months for testing purposes, and they have finally been declared effective (all of them, as far as I’ve heard). So it is a fact that if people were given an option not to wait for the authorization, a lot of suffering, disability and death would have been prevented, and the economy would be in a better shape, as well.


Testing isn't a delay, unless you think being reckless is a scientific virtue.


Phase 1 testing had to be done. However, gambling on efficacy would have been a very reasonable approach and could have gotten tens or hundreds of millions of people vaccinated by now.


Even with tens of millions vaccinated COVID is too contagious and deadly to avoid social mitigation like restricting businesses, large gathering, mandating masks, and even lockdowns.

The long incubation period and asymptomatic carriers makes for easy spread of the virus. It's hospitalization rate means a wide spread will literally shut down hospitals in whole regions. At current infection rates we're seeing hospitals being overwhelmed at regional levels.

Even if vaccines had been delivered after a Phase 1 trial of "no one died immediately" in the trial group, we wouldn't have enough vaccinated people to avoid social mitigation. We'd be in a similar situation as we're in right now.

It will take something like 75% of the population to be immune (by vaccine or previous infection) to have effective herd immunity. Even if vaccines had started distributing months ago it would still be a long time before we hit that 75%. Distributing vaccines after the phase 1 trials might ultimately get an immune population to that 75% sooner but it wouldn't stop any of the damage happening until that number is reached.

Even if no one died from COVID the "long hauler" after effects can be crippling. Some 10-20% of COVID patients end up "long haulers". If the virus were to spread to significant portions of the population because no one practiced social spread mitigation because they assumed the vaccine would fix everything you're still in a terrible situation.


> The long incubation period and asymptomatic carriers makes for easy spread of the virus

Long? The median is between 4 and 6 days. The 14 days often quoted is the 99th percentile. Can we stop perpetuating this myth?

> asymptomatic carriers makes for easy spread of the virus

Actually, most of the spread comes from superspreading events. Most people with the virus don't spread the virus at all, or spread it very little. True asymptomatic people are far less contagious than symptomatic people (up to 10 fold or so less). Severity of the symptoms is also associated with higher chance of spread.

> It will take something like 75% of the population to be immune (by vaccine or previous infection) to have effective herd immunity.

This is often calculated considering an equally susceptible population (which is not the case) with uniform mixing (same), so it's a very pessimistic estimate. The actual figure might be lower (though not as low as 20% as some "skeptics" say).


I am looking for 14 days quoted in the parent comment and not finding it.

> Actually, most of the spread comes from superspreading events.

I don't know if we can say this for certain at this point. I was very firmly on the "superspreader" train some time ago but I find it hard to believe given the spread we are seeing in places like Canada where most of what we thought were superspreader circumstances are now illegal. I am sympathetic to the idea but being overconfident about this stuff is also not helpful.


> I am looking for 14 days quoted in the parent comment and not finding it.

2 to 6 days incubation time is not "long".

> I am sympathetic to the idea but being overconfident

It's not being overconfident: it's what the currently available data says. The largest contact tracing study I am aware of, in India, reported that the largest cause of spread were superspreading events.


Saying that you are not being overconfident with that level of confidence seems like a red flag.

If COVID-19 is primarily driven by superspreader events that are largely not happening anymore in the 2nd wave that is causing case increases across nearly every jurisdiction in the world I have doubts.


> Saying that you are not being overconfident with that level of confidence seems like a red flag.

Were it just me, I'd agree with you, however it is the data that we must look at:

https://science.sciencemag.org/content/early/2020/09/29/scie...


In the spirit of open discussion I would like to raise to you some salient facts.

The article in question does not address the fact that I raised, and also you shouldn't make claims the authors are not making:

"Our findings, based on comprehensive surveillance and contact-tracing data from the Indian states of Tamil Nadu and Andhra Pradesh, provide insight into the epidemiology of COVID-19 in resource-limited populations."

Specifically: "Whereas incidence declined steadily at ages older than 30 to 39 years in the two Indian states, incidence increased at ages of ≥65 years in the United States."

So their finding might be applicable if the general trends matched but the study specifically says they don't, in the way that I generally pointed towards.

Also the study in question points to "superspreading individuals" but not "superspreading events" and that difference is significant. A "superspreader" who attends an event that can cause superspreading event, but a superspreader that goes to many places and meets just a few people at those places can super-spread! It's different! The study does NOT support your implied claim that asymptomatic spreaders can't be superspreaders.


A six day incubation period is a long time. Even four days is a long time considering how infectious the virus is. That's a work week being unknowingly infectious.

Considering we're in the middle of a huge spike in cases that started two weeks after Thanksgiving, suggesting superspreader events are the primary source of infections is ludicrous. Canada had the same problem after their Thanksgiving holiday.

You're also seeming to dismiss asymptomatic carriers because individually they are less infectious than symptomatic carriers. This completely ignores the behavioral component of infection. An asymptomatic carrier will have no reason to seek out testing or participate in contact tracing programs. Someone that becomes symptomatic will know to at least inform recent contacts so they can get tested and attempt to isolate themselves to limit the spread.

Not all vaccines are going to be compatible with one another. If millions of people take your early-release vaccine and it's ineffective they may not be able to get a second one or not get it for a while. This apparently is an issue with the Russian vaccine because of the way it's introduced to the immune system.

This is why vaccines are tested in multiple phases. It's not just to make sure people don't have immediate adverse reactions but to find the edge cases and boundary conditions.


True asymptomatics are rare in the infected population. Most of people are presymptomatic (=they will develop symptoms), and their peak infectiousness is one or two days before symptom onset, according to published data.

> If millions of people take your early-release vaccine and it's ineffective

Phase 3 studies on Moderna, Pfizer, and AstraZeneca vaccines have shown that they are effective (and nowhere close to an "early release"). Statistics don't lie in that regard.

> This apparently is an issue with the Russian vaccine because of the way it's introduced to the immune system.

I'm not aware of any of such issues. Do you have a primary source I can look up?


This paper is the specific issue I was talking about [0]. Individuals who were Ad5 seropositive had an immune response to subsequent Ad5-based treatments. They developed an immunity to Ad5 which is just a delivery vector for the viral protein you're trying to introduce.

The CanSino vaccine also uses Ad5 as it's viral vector. An immunity to Ad5 from say Sputnik V would apparently prevent you from being able to get the CanSino one should Sputnik V prove ineffective for you. You'd also not be able to get a booster of Sputnik V later.

There's lots of adenovirus strains and a few other vaccines are using them for their delivery vectors. Ad5 is an edited adenovirus that has it's replication system retarded/removed. There's other articles I've seen but can't find now lamenting the use of Ad5 specifically. There was also the STEP study that showed increased HIV susceptibility in people that had received Ad5 vaccines.

I am not a medical professional but I do understand immunology is extremely complex. Effective vaccines in vitro aren't necessarily effective in vivo. There's also complex issues around dosing which is part of human trials. Even if a vaccine is "effective" it's not necessarily obvious or known what sort of dosing is appropriate for wide deployment in the general population. A completely "effective" vaccine at the wrong dose can end up being ineffective.

[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756115/


Sputnik is two vectors: Ad26 and Ad5. That looks like the reason why they kept having a high efficacy (today's press release from Gamaleya says 92%).

Dosing is done in Phase 1 trials, which also included antibody level testing. This has been already taken into account in the current trials.


Gambling on efficacy would not have been a reasonable approach.

I understand the temptation to think that this would be a good way to proceed but developing a complete supply chain for a dud would have been a total disaster for everyone involved and would have taken resources away from viable vaccines.

All of the big vaccine producers had full faith in these candidates and they poured money into their production in advance of phase 3 trials and we are still supply constrained. Making the same bet a month or so earlier (the largest gain possible) would have had a small incremental gain but an enormous downside.


A vaccine distributed month earlier would have saved ~40,000 lives?


A vaccine scaled up to 1 billion doses 2 or 3 months later would by that logic cost 120k lives.

You are assuming that there are no costs associated with one choice vs the other, but we know that is not the case.


An Australian vaccine candidate was discarded after phase one trials last week, and presumably there are other vaccine candidates that never even got that far.


The reason why is really interesting: it would occasionally cause you to falsely test positive for HIV, because it caused some people to generate HIV-reactive antibodies. Doesn't appear that it directly had any other harmful effects. But obviously false positives for HIV could be a disaster for HIV containment, and lead to many more people killed by actual HIV in the long run.

It'd be really interesting to know how easy that was to catch: was it guaranteed that they'd notice that kind of issue? Or did they get lucky?

https://www.bbc.com/news/world-australia-55269381


https://www.nytimes.com/2020/12/11/world/australia/uq-corona...

> The use of the H.I.V. protein posed no risk of infecting the volunteers with that virus, the researchers said. But the clamp generated the production of antibodies recognized by H.I.V. tests at higher levels than the scientists had expected.

They thought it was a possibility.


Thanks!

I'll stress: that sounds like a perfectly reasonable approach to try, and they figured out the problem very early on, with very little harm actually done.


Yeah I'd also be interested to learn the details.


The "meticulous vaccine development" is a religious belief in the middle of a pandemic. It helps no one but makes the elites feel better I guess?


Just showing that testing on humans (for the level of safety desired) and physical delivery (the way humans like it to be done) are harder problems than developing even a new vaccine. To be honest, if these two were as malleable an objective as the development (usually R&D is easier to speed up) by allowing mass inoculation (rather than individually shipped vials) or reduced safety/efficacy then they could be sped up too.

And of course, if the govt (leaders) was competent there wouldn't have been 300k lives lost, and arguably economic damage could have been minimized as well. I'd argue that's a goal post that moves independent of delivery time.


That's grading on a curve. Ten years to one year is pointless if it doesn't save enough lives.

> And of course, if the govt (leaders) was competent there wouldn't have been 300k lives lost, and arguably economic damage could have been minimized as well. I'd argue that's a goal post that moves independent of delivery time.

Pure whataboutism. We are stuck with the world we live in now and need to optimize for that.


> That's grading on a curve. Ten years to one year is pointless if it doesn't save enough lives.

But, who says it won't save enough lives? It was estimated to wipe out millions, seems like saving millions is enough to me.


How many lives were lost in New Zealand? Your argument doesn't make sense.


The argument of it saving millions of lives in the future, is not good enough for you?

And there are more people in my city than in New Zealand. You can't compare the world to a tiny island. Your comparision is unfair and unrealistic. Europe for example couldn't just close it's borders, it's logistically impossible.


Approving vaccines faster does save lives going forward. That is the whole point.


Umm your argument is that we needed to speed up the delivery of vaccines to save 300k people who have already died, but also think that what happened in New Zealand is a reasonably likely possibility? So would you have also given an untested vaccine to everyone in New Zealand in March? Your answer seems to be yes... and it probably would have only killed or maimed 100ppm or ~5 thousand people, and it would have saved roughly 0.


Grading on a curve assumes we knew how many people would die when the investment was made then... and the same for the effectiveness of the vaccine? If you claim you knew that the US would be so atrociously bad at dealing with this in March (and I bought N95 masks at the beginning of Feb plus I'll offer free advice on Wuhan hotels for foreigners), or that you knew how effective a vaccine was before it was tested in humans then please share your insight.

If none of the first vaccines were more effective than a placebo, then your $Bs would be wasted until the one 10 years later was developed. Wear a mask, test and contract trace, or find some other solution is a better investment.

We invest in the world before we know the answer to things, so we look for answers as quickly as there's ROI, if that's whataboutism then you have a new definition. Putting together distribution and testing take time no matter how quick the vaccine development is and those are hard parallel problems, whatever the answer to the vaccine effectiveness question is.

There are ways that optimize the time to deliver those as well (mass inoculation, challenge testing), but I don't see you suggesting either of those. Note that we still don't know long term consequences of the vaccines (auto-immune responses were and still are a possibility). I don't expect them to be bad, but then I didn't expect 20% of the US population to deny a viral infection was real and/or the germ theory of disease.


paywalled...


I'm surprised Pfizer or pharmaceutical industry in general, didn't get Time Person of the Year - development of COVID vaccines in record time is BY FAR the most consequential action in this crazy year, perhaps this century.


The BioNTech team who made the vaccine probably should get a lot of public 'credit'.


Who cares? Time is pretty irrelevant as a magazine, not even in the top 10 by distribution in the United States. Gamestop's Game Informer has almost 3x the circulation, and I'm pretty the majority of the people here don't really care about either of them.


Time is owned by Mark Benioff lol.


It doesn't mean much more, but how about a nobel prize?


A Nobel Prize will definitely follow, once the Pandemic dies down. My guess is that the Nobel Commitee would recognize the leading vaccines deployed worldwide, not just Biontech.


the hard, pioneering work was done by the NIH and universities. Pharma refined it, applied it to covid and creating the distribution infrastructure


Yes, I have no doubt that that preliminary research in part or wholly originated from universities. Big Pharma should get this recognition anyway because as you said: "Pharma refined it, applied it to covid and creating the distribution infrastructure"

Don't worry though. Time would never give this award to Big Pharma, as evidenced by the fact they gave it to Biden/Harris, one of the most milquetoast tickets in recent history, in a year where the first big pandemic in a century is ravaging the world. I'm also surprised they didn't go down the feel-good route of giving it to frontline healthcare workers, but Trump is a bigger deal, apparently.


I'm not sure that we should give that kind of credit until we see which (if any) vaccine gets manufactured and distributed and is successful in quantity, before the virus has infected the majority of the population. I sure hope they do, but at the current rate of spread in Europe and the Americas, it is not totally implausible that they won't be able to make it in quantity until it's too late to have an impact on this pandemic.

Which would not be a reason not to have made it (we would want it for the future), but it's still rather early to say how much impact this vaccine will have. There is also the possibility that some other vaccine will be able to roll out doses for 300 million people before this one has successfully made doses for 10 million. I'm not saying that's likely, but it's certainly within the plausible range of possibilities.


Honestly the Russian vaccine and possibly the astrazeneca Vaccine appears to be the safest bet.

No mRNA just the old school modified cold virus delivery mechanism.

Method been done for years .. easier and cheaper to manufacture and distribute.

Call me a cynic but I think the US (and UK) will push through a somewhat experimental version by Pfizer because “money”.

Hope I am wrong. But I would imagine in a year or so we will “discover” that the cheaper vaccine works great (after giving Pfizer plenty of time for $$)


Aren’t there issues with adenovirus vectors?


Yes but these are known variables. Hypothetically the newer mrna vaccines should be safe .... but there honestly is no long term information. A MRna vaccine has never been approved for human use until now.


I believe the same is true for adenovirus vector vaccines: none have previously been approved for human use. [1] That said, both mRNA vaccines and adenovirus vector vaccines have a history of clinical trials stretching back at least a decade. [1] [2] So in addition to there being no major long-term risk in theory, we do have some real world experience with both types of vaccines in tests.

[1]: https://cen.acs.org/pharmaceuticals/vaccines/Adenoviral-vect...

[2]: https://www.nature.com/articles/nrd.2017.243/tables/2


A lot of the articles I’ve read (including this one) say that Pfizer had to invest $2B to develop this vaccine.

However this article says they bought seven $200M machines to manufacture lipid nanoparticles. This implies to me that $1.4B of $2B Pfizer is supposed to have spent on development was actually just updating their supply chain for mRNA based vaccines.

While I’m happy that they made such a dramatic investment in the interests of bringing a product to market as fast as possible I think it’s also fair to imply it’s R&D that can’t be applied to other products later.


The very promising crispr anti-cancer trial recently also used lipid nanoparticles. Seems it's a useful tech for delivering stuff into cells.


> have spent on development was actually just updating their supply chain

Warp Speed funding to AstraZeneca, Moderna, and Johnson & Johnson also included money that was earmarked for manufacturing capability investment.


Are you sure the amounts overlap?


Overlapping doesn't matter - large multinationals' decisions over spending are more likely to look like: "if we receive $X from the government to spend on Y, then we'll have a spare $X to spend on Z"


If the development spending happened prior to negotiating the manufacturing deals it matters (they had been working on mRNA vaccines for other viruses). The decision to spend the money on the development wasn't necessarily made with knowledge of the government purchase guarantee.


I think it is fair to say that they invested $2B, if it were a dead end there was a chance that the machines would not be that useful, or at least they would incur a large loss on paying a premium for them at the time.

Conversely it shouldn't be frowned upon that they invested and believed in BioNTech's methods that made it trivial to almost immediately produce a vaccine candidate on an unproven platform.

Moderna likewise had their vaccine candidate within days of having the sequence, vaccines are mostly pretty easy when your first try works!


Pfizer is BioNTech's manufacturing partner and did logistics for clinical trials, they didn't do the R&D. There are other international licensees of the same vaccine, e.g. Fosun in China.

And I suppose they spent a handy sum on marketing to pull off this being known as the "Pfizer vaccine" in domestic media despite this. Note the article headline is "How Pfizer Delivered ..." not "Developed".


"Pfizer couldn’t meet every target set by its chief executive. Mr. Bourla wanted the vaccine done by October and as many as 100 million doses by year’s close, enough for 50 million people. Instead about half that will be produced."

It'll be very interesting to see just how many people will take the vaccine over the next 6 months or so. I just had two nurses tell me that they will NOT be taking the vaccine, they are too scared of it. Based on what other folks have said, I'm guessing the number is going to be much lower than hoped. I am really hoping I'm wrong. It doesn't worry me at all.


Here in Sweden almost everyone I've talked with said they would consider taking the vaccine, but that they wouldn't be first in line.

It worries me that so many seem so hesitant towards vaccine and I'll gladly stand first in line, but we're rightly prioritizing the elderly and their caretakers.


I'd guess part of the hesitation is due to the Pandemrix-caused narcolepsy cases during the A(H1N1) pandemic in 2009. It was just 11 years ago, still fresh on people's minds.


Is the narcolepsy caused by Pandemrix permanent or just temporary?


Permanent, unless someone innovates medical therapy to fix the damage.


Afaik it seems to be permanent.


It also doesn't help that the H1N1 vaccines came too late to do much good: while Pandermix was just one of many vaccines, and the only one I'm aware of known to cause problems, in most places they hardly made a difference because infections had already peaked by the time they were distributed widely. Eg here in Canada, I've seen estimates that vaccines reduced H1N1 deaths by about 5% at best. H1N1 still infected around 20-30% of the entire world population, and Canada was no different. A significant % of people were already immune, so natural herd immunity is the main thing that stopped it.

Given how fast COVID-19 appears to be spreading even in places with strict lockdown, I won't be surprised if it turns out that vaccines don't actually make much difference with it either.


I think part of the problem is we were told it would take 18 months, then in half that time we have a vaccine with a fast track testing process. And then within 24 hours of the vaccine being used in the UK there were reports of people having bad reactions to it due to that group being excluded from the testing. Vaccines have been getting hit hard by anti-vaxers for so long that this seems to have fallen right into their lap with a bunch of easy to use propaganda.


"I think part of the problem is we were told it would take 18 months"

We were told a lot of things by the media, nearly all of it oriented towards pessimistic outlooks, worst-case scenarios and often just complete misrepresentation of the science. If you asked the people working on these vaccines back in May, they would have told you 18 months was some made up nonsense.


> We were told a lot of things by the media

This actually came from experts. Maybe not the same ones working on the specific vaccines but ones who have decades of experience within the vaccine space. Just because you read it in the media does not mean the media came up with it. They don't actually make things up. And 18 months was not worst-case it was average case with the best case in the media being Autumn. Just because the best case came out, doesn't remove the point that we were repeatedly told by experts (WHO) that 18 months was a good case scenario. While other experts said that was super optimistic.


"And 18 months was not worst-case it was average case "

It was the average case for a once-in-a-generation vaccine development process with unlimited resources, occurring in 2020, with ample research done on similar virus mere years prior?

If not, then it sounds like a useless "average" that was picked to fill air time and not to represent the best data we had at the time. And who had the best data at the time? The vaccine teams that had already developed the vaccines that are now being injected into the arms of Americans today. But they don't trot out on TV, so they had to grab some filler scientists to pretend they knew what they were talking about.


Is it propaganda if it's true events?


Just because the event is true doesn't mean it's presented with the correct statistical context. For example, if, hypothetically, 2 people developed complications from the vaccine out of a treated population of 20 million, a front page headline exclaiming "Covid Vaccine Causing Complications" would be technically true, but also propaganda.


The same goes the other way. We see articles "A young person dies from COVID-19". True, but it aldo true that half of the COVID-19 victims were in the age bracket that is 10 years older than the life expectancy in the country.


The two allergic reactions were from health workers who were allergic to vaccines. They knew it might happen and were ready.

People who are allergic to vaccines are not in trials for obvious reasons...


As someone who would heartily be first in line (and even be part of trials if I were eligible), I understand how people can be hesitant to try such a new and fresh vaccine, iff the reason is "it's too new and has been developed way too fast for comfort".

Beyond that though, to hell with people who still somehow think "only those at risk need to be vaccinated".

I somehow came across an acquaintance who was telling me "I can't wait for people to take the vaccine so everything can reopen, but I would never get it myself". Such absolute trashy selfishness.


I really don't get the rationale behind this argument (if there even is one, at all), by medical professionals no less.

How is getting a properly tested vaccine with a known 1 to 10% probability of side effects such as headaches or fever scarier than the prospect of contracting COVID-19 with roughly a 10% probability of developing severe to life-threatening symptoms?

Yes, there might be as of yet unknown vaccine side effects but the same is true for chronic symptoms that might be caused by COVID-19.


> the prospect of contracting COVID-19 with roughly a 10% probability of developing severe to life-threatening symptoms?

Citation needed. For 45-65 year olds IFR seems to be in the 0.3% rate, for under 45s it's way lower.

Hospitalisations about 2-4 times the number of deaths, so that seems to be in the 1% range for 'severe' symptons if you catch it and are towards the older age of nurses


You're responding with IFR, which deals with infections (including many asymptomatic) and mortality, when your parent comment is discussing cases and severe morbidity.

That is, you're comparing apples and oranges.

IFR is almost always significantly lower than CFR for infectious diseases. That's particularly the case with Covid.


A case is just a detected infection. If you have no tests, then your cases will be low. Your infections will be high.

A "Case Fatality" is a pretty meaningless number. You can't avoid the consequences of covid19 by not being tested.


A lot of people who don’t want to take it cite the lack of testing, actually.


There hasn't been a lack of testing. The vaccine in question went through all the usual required testing phases.


I really feel like it's just sublimated fear of shots and chemical manufacturing processes. If you could offer the vaccine as a herbal remedy, I doubt there'd be any serious opposition to it; people are happy to try random weird herbal teas without expecting a demonstration of their safety.


10% of severe symptoms is a known. Whatever the covid vaccine causes is not known.


Hopefully the highly-vulnerable populations (elderly, obese) are willing to take the small unknown risk enough to drive down death rates. I'm not personally super bothered of a bunch of young and healthy people choose to forgo the vaccine pending more time and studies.


One of the issues is that young people also end up on the IC. If you were to just 'let young people' out and about, hospitals would still be overwhelmed.


>One of the issues is that young people also end up on the IC.

The rate is important. If the rate is miniscule, then it may still be an issue, but not an overly important one.

>If you were to just 'let young people' out and about, hospitals would still be overwhelmed.

Are we sure about that? Any numbers you can share?


It's important to realize, in today's (Western) world, young is not longer synonymous with healthy. Obesity, diabetes, addiction, vaping, etc. are all close to the broader population.

That said, young + healthy generally mitigates the risk of Covid 19.


Not in the numbers that would cause any additional burden for the system.


The problem is that 70% of adults are overweight and obese.


Unfortunately the testing was done on healthy people, not the elderly or those with pre existing conditions.


>I just had two nurses tell me that they will NOT be taking the vaccine, they are too scared of it.

That is their right, but then they should be given a leave of absence or fired.


It's really hard to fire imaginary people, though.


I suspect you're correct. OP could be making this up. Having said that it's a big country and there may be health professionals, including nurses, who may balk at receiving the vaccine.


It's interesting there wasn't direct economic injection from governments.

Both the humanitarian and economic toll of COVID is off the charts. 20% contraction in the economy, is like 4 Trillion in GDP loss for the US alone, maybe 20 Trillion for the world.

And that's just the money, not the human loss.

Given that, I don't get why nations didn't give them basically blank cheques, enabled the socialization/commandeering of factories and equipment, 5-10% of the Armed Forces for whatever needs etc..

Literally every drug company can 'report their assets' to the COVID task force and they will get deployed as needed. The companies will be happy to do that because they'll earn 3-10x return on those assets otherwise anyhow.

That seems a little dramatic but it's basically nothing compared to the damage COVID is causing.

Also: they didn't go into the actual manufacturing details to much, sadly.

Edit: also interesting would be the sunk cost / opportunity cost calculation on ramping up production of untested vaccines.

If opportunity cost didn't factor in i.e. if ramping up one vaccine didn't come at the cost of another, my bet is that it would have been worth any price.

If the US had spent $2B on ramping up every vaccine candidate before they were approved, and only 1 out of 10 came through, costing $20B for the first massive batch and accelerating subsequent batches, instead of merely $2B - would it have been worth it?

$200 a dose instead of $20 dose?

The math would say it's way beyond worth it. There's a case for 'prepping' every single vaccine candidate to the extent it's possible and even starting to manufacture in quantities way ahead of time.

This financial calculus doesn't work in the context of Pfizer - it doesn't make sense for them - however it absolutely does in the bigger picture.

A 'remedy' for this could have been to offer Pfizer massively increased price per dose for earlier delivery, in which case it would have made sense for the to spend $20B instead of $2, or simply some kind of national 'blank cheque' intervention. The former concept is neat but would be hard to nail down, the later is probably more workable.

Given that vaccine manufacture is 1/2 the equation, not just the R&D, I hope the 'after action reports' will put this in context.


The article answers this. Because further government involvement would slow down the process. E.g.

“To as­sem­ble its mRNA pro­duc­tion net­work, Pfizer used its own money and didn’t take any from the fed­eral gov­ern­ment. Ex­ec­u­tives said they didn’t want to give agen­cies out­side the FDA more lever­age over the de­sign of the tri­als.”

“Ri­val Mod­erna, which took fund­ing from a di­vi­sion of the U.S. De­part­ment of Health and Hu­man Ser­vices, suf­fered a three-week de­lay in com­plet­ing its own mRNA trial af­ter fed­eral of­fi­cials there asked the com­pany to slow down en­roll­ment to boost the racial and eth­nic di­ver­sity of study sub­jects.”


So basically the answer is that government is completely incapable to give money with no strings attached. There are always strings and they always slow things down.


Another way to interpret this is that when unrestrained, Pfizer cut some corners and insufficiently represented the test population. Of course, this all depends on the reasoning behind that request.


That's a completely unsubstantiated allegation.


It's not meant to be an allegation; my point is that the government asking to increase test diversity isn't inherently a negative. However, the parent comment interpreted that it was, because it was stated earlier that it "slowed things down", without showing that such a request was frivolous.


"Executives said they didn’t want to give agencies outside the FDA more leverage over the design of the trials" substantiates it, given that this was the leverage sought.


No it does not. Your assuming that was the leverage sought. You're also assuming that's the primary reason for avoiding government interference when there are many reasons for that. The primary possibly being that bringing the government into it would slow things down. Finally you're assuming that they didn't have a diverse trial, and you're wrong about that:

https://news.ycombinator.com/item?id=25408528


The FDA still has to approve and cutting corners will end up being when searching for approval


yeah but it increases government's control. Which, depending on how you see it, may be a good thing.


1) The FDA sets the rules, even in a pandemic, not Pfizer - and this is good. It's pointless to test a vaccine if the result are not valid for Black people. This is not an example of 'slow government bureaucracy' - this is normal regulatory oversight, akin to 'approval' of the drug in the first place.

2) That they didn't take the money is a second order issue in the context of $4 Trillion hit to the economy with 300 000 dead in the US alone. Pfizer will do whatever is best for their economic outcome. Not taking money because they believe it may have slowed them down is one thing, but not taking it because they'd not make as much profit is another.

The profit motivation has obviously distorted early response, to the point that good organized leadership would have required some kind of regulated but open regime for manufacture, with some kind of negotiated price.

Why on earth are we only letting Pfizer manufacture it? The answer is 'free markets' - except they are obviously dysfunctional at the moment.

A better answer would be some kind of 'Open IP' agreement whereby an established royalty would be set for the vaccine, and basically anyone can make it.

We already have government established rates for every single natural resource, and we have controlled rates for energy as well - this is not a new idea.

Also - the government could provide 'infinite credit' for approved pre-production of select vaccines by select manufacturers at a set price, thereby encouraging mass-manufacturing of vaccine candidates even if the candidate failed.

i.e. socialize the risk.

Its counter-intuitive but only in a regular market based context. The math shows how that's upside down though, the ROI is much, much higher with intervention.

Now - if the government has is literally incompetent in every operating capacity, that's another storey, but what I have described here is not 'government manufacture', but rather, a different kind of market-based solution, with a different incentive structure.


If we didn’t waste so much time in dealing with politics and formal gossiping we’d would be living in the future.


> It's interesting there wasn't direct economic injection from governments.

I didn't read the article, but I don't believe this is true. The vaccine is ultimately not Pfizer's but BioNTech's, and the German government gave them $445 million to develop it.


We're talking about trials and manufacturing, not development of the vaccine itself.

The former is R&D intensive, the later is op-ex expensive.

The former relies on talent, the later is mostly just bodies and money. The former can be done much earlier in the process if the risk equations are aligned, which they are not, which is why Pfizer ramped up in October, and not back in April, when the could have, but wherein it wouldn't make sense for them.


The humanitarian and economic toll has nothing to do with virus itself but more of because of the government response to it. Namely the lockdown.


They were pretty smart about it. The guy leading project warp speed knew all the new vaccine platforms and funded 2 companies for each approach. I don’t think you could’ve gotten things much faster than this. Big pharma wants to cover their tail because a serious side effect would tarnish their - and vaccines reputation for decades and cause existential lawsuits.

Moncef Slaoui is the guy in charge. He also mentions how they filter out candidates - for example ones needing an exotic ingredient that would make scaling manufacturing too hard. Check out his interview on Steven Levitts new podcast.

It’s pretty incredible the mRNA vaccine candidate was created only a few days after China released the genetic data of the virus.


"I don’t think you could’ve gotten things much faster than this. "

???

It could have been done 5 months ago, by 5 different manufacturers.

We could have had 50M doses in Oct, the rest by January.

Why didn't Pfizer start ramping up? Because of the risk involved with an unproven candidate. That's literally in the article.

It's 'financially crazy' for them to invest billions ramping up on an unproven vaccine. But only 'crazy' for them, not for us. This speaks to the dysfunction of markets in crisis situations.

And why are we entrusting the manufacture of this essential IP to only one company? Pfizer? Because they paid for it? 'We' can 'pay for it' as well. And we can pay a lot more.

If the government established royalty rates for a vaccine, thereby ensuring Pfizer gets a cut if the vaccine is a winner, and allows any manufacturer meeting regs to manufacture it, you'd 10x production.

If the government basically 'pre-paid' or provided guaranteed credit for any manufacturer (up to standard) for any 'early candidate' vaccine, then not only would 10 manufacturers be involved - not just one - but they would have started 5 months ago.

It would have been 'insanely' more expensive to do it this way, probably costing 10x as much.

... but it's actually not 'insane' is my point, it's extremely rational for us to put $200B on the table to accelerate this by 5 months. It's a bargain. It's a win-win-win - Pfizer frankly makes just as much profit (royalties have no underlying unit cost), manufacturers make some, Americans are safer and the economy starts earlier.

We handled it 'poorly' because we didn't manage the situation, put in the right regs, or create the right incentives.


The current systems support elaborate ways for people to keep other people in check. These systems suck at fighting viruses (or anything else - except other people).


You think minorities are more or less likely to trust a rushed out vaccine?


??? What does this have to do with 'minorities' (If you are referring to the FDA requirement, it's not about public trust so much as literally a medical requirement to include people of different ethnic groups to measure potential differing response, which is normal in such trials)

??? And what are you talking about 'rushed'. I'm not talking about changing the nature or timeline of the trial. I'm talking about ramping up production before the vaccine is proven to be safe and working, because the opportunity cost of 'COVID shutdowns' are 1000x greater than the lost opportunity cost of wasted spending on manufacturing vaccines that work.

Again: we should have been mass producing the potential 'good candidate' vaccines months ago. It doesn't matter if some of the failed to pass muster, it would have been well worth any potential wasted money on making vaccines that we can't use.


We pretty much have DNA/RNA printers that can make anything from data.

And turning RNA into "mRNA vaccine" is just putting in in a little ball of fat (I think) which they know how to do because they worked on this technology for years.


Random question: why are we saying, "the economic toll of covid," rather than, "the economic toll of the response to covid?" If the lockdowns hadn't happened, more would have died, but presumably the economy would be fine.


Why does everyone seem to think the economy would be fine without lockdowns? You think that the entire population would've continued just headed to restaurants while hospitals declared "not accepting patients anymore" and refrigerator trucks stacked up outside nursing homes?

What actually happened in stupid countries is that they reacted too late, too lightly, and everyone's been complaining that "oh the cost was too high". It takes a lockdown of ONE month, enforced strictly, to clear out COVID from the population and resume effectively normal activity (you still need to limit international passenger travel but that's proportionally far simpler).


I think some if it is that it is an appealing contrarian take, and even as stark as things are, it is common to not have suffered much personal impact from infections (either direct consequences or severe illness/death of friends/relatives).

I'm not terribly well connected socially so I don't take it as a universal, but the people I've heard about having it are a single friend of a friend and my doctor's husband (she volunteered the info during a routine appointment).

So the responses are more visible in peoples minds than the pandemic, and they are thinking intuitively about it, not reasoning about the precarious situation that (pretty much continuously) exists with such a fast spreading infection.


I think that's definitely true for a lot of people. But there also seems to be a more active sort of intense denialism, fueled by a need to score political points at all costs, that leads even people who _have_ been directly impacted by COVID to continue insisting it's not a big deal.

It's why Herman Cain's staff kept tweeting even after he died from COVID. And why people in the White House have been making a big show of hosting superspreader events, even as so many of them have to rely on the best medicine other people's money can buy to recover. Ultimately, I don't think there's a way to understand it rationally, because as you say, it's not rational; it's an emotional response.


It's both. Both a dwindling number of folks with no personal connection to the virus, and the political stuff going on.


Doesn’t it tell something that every government on earth “chickened out” and did some kind of lockdowns when the numbers got bad enough? Sounds extremely naïve to think the economy would’ve been fine with unmitigated spread and hospitals becoming unusable. You’d be off by several orders of magnitude on the chaos that would cause in society


And interestingly in many places there were excess deaths in the first wave, but not the second. So it is a big question just how many more would have died.


Even more interestingly, this is bullshit.

(Unless you mean countries like New Zealand where the second wave just isn't happening)

There is a lag between cases and death, and death and the publication of cumulative reports on all-cause mortality.

If you happened to have read anything on the topic during the first wave, you'd know as much. Because it was repeated ad nauseam, until it became too ridiculous for even the most dedicated to keep on insisting that there were no excess deaths.


The case fatality rate was considerably lower in the second wave in almost all cases, and the total number of deaths generally lower as well.

The 'lag' is accounted for in that most 'second wave' places have past the peak over their waves.

Deaths were 'higher' in the second wave in places that had a small first wave, like Austria.

But for places that had a 'real' first wave, the second wave was generally milder in terms of overall deaths, and much milder in terms of CFR.

We can't ignore the real risk of 'waves' but it's also important not to deny the nuanced reality of them. In particular, the 'second wave' had many more younger people, probably accounting for the lower case fatality rate.


We had few COVID deaths in the first wave and no excess deaths. Now we have lots of cases ~3000 daily, some 20-30 daily deaths but excess mortality is waaaay higher than COVID deaths. Most can ve explained by reduced accessibility to the medical services because of COVID precautions and general fear in public. Only now we start to feel pressure on the healthcare system caused directly by COVID cases.


How on earth would the economy be fine when people die left and right?

Do you really think shops were full and everyone was out an about just ignoring their health (and potentially death) just because of some government mandate? Do you think people don't have their own will or brain?


In my home Sweden the government has enforced no limitation in liberty due to this virus - they have recommended social distancing, but no force.

Restaurants, shops, and bars have fewer customers, but they and other business is surviving.

That is just one data point, but it’s something


The drop in economic activity in Sweden is, roughly, just as large as in Norway, Finland, and Denmark. But with 4 to 10 times the number of deaths. So, no, the lack of lockdown (which is a fallacy itself) didn't protect Sweden from economic impact.


Most of the deaths in Sweden happened early in the pandemic and are more result of a bad luck than some policy. Now my country has more daily deaths than Sweden despite having 1/3 of the population and being in the second quarantine since Nov 7th. The restrictions will be way stricter from this Wednesday.


Dateline today, 2020-12-13:

"Sweden's neighbours offer them emergency help as its hospitals fill up with coronavirus patients"

[1] https://www.businessinsider.com/sweden-offered-urgent-corona...


No more deaths in Sweden this year than previous years.

Our hospitals already suffered from lines long enough for people to die before getting care. Waiting in line is always the result of socialist government monopolies, and this was the case before COVID as well.

https://emanuelkarlsten.se/number-of-deaths-in-sweden-during...


Swedish King Carl XVI Gustaf says coronavirus approach 'has failed'

https://www.bbc.com/news/world-europe-55347021


No. The lockdowns didn't cause the economic damage, the people's response to the risk of death and injury caused it.

To recover the economy you have to suppress the virus. Period. There's no magic wand to let people party away.




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