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Comment by sh1mmer | Hacker News Reader

> 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.

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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?

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?

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

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.

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.

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.

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?

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..

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.

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.

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.)

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 ?

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-...

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.

> 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?

Isn’t 3 weeks about 21k deaths?

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.

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.

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...

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

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...

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.

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