FDA grants authorization to Moderna's Covid-19 vaccine • Hacker News Board

Re: FDA grants authorization to Moderna's Covid-19 vaccine

#71

Post by tyre » Sat, Dec 19, 2020, 5:30 AM UTC

finolex1 wrote: post #59

Anyone knows why they insist on both doses given the limited supply of the vaccine and the marginal increase in effectiveness with the second dose? I would imagine every single day counts. https://www.lesswrong.com/posts/Rvzdi8RS9Bda5aLt2/covid-12-1...

From the linked article[0]:

“Yes, Moderna’s vaccine prevents transmission. One dose is good for reducing infection by 63%, two by over 90%.”

The number of people you need to vaccinate with a 63% effective vaccine versus a 90% effective vaccine is a huge gap.

There are two issues with vaccines that staring at these numbers won’t tell you:

1. Not everyone is going to get vaccinated.

2. The number of people who will get vaccinated is directly correlated with public trust.

If you release a vaccine that is 63% effective, the “this vaccine doesn’t work crowd” and their hugely amplified voices on YouTube and social media will be exponentially worse.

That snowballs into fewer people being vaccinated. Unlikely for us, with a less effective vaccine we need far more people being vaccinated.

So you want a more effective vaccine because fewer people need to get vaccinated, more people will trust the vaccine, and more people will get vaccinated.

(To pre-empt the bad-faith replies, this does _not_ mean we would sacrifice another six months to get a 98% effective vaccine (if it were possible) versus starting now. It’s a balance, of course.)

Also very important is that a second dose isn’t just for effectiveness, it’s to boost the immune system’s response so that the conferred immunity lasts significantly longer.

[0]: I struggled through this article. I find this self-congratulating “I’m smarter than everyone and I told you so in this other blog post” writing insufferable.

Re: FDA grants authorization to Moderna's Covid-19 vaccine

#72

Post by tyre » Sat, Dec 19, 2020, 5:35 AM UTC

djsumdog wrote: post #13

maxerickson wrote: post #10

Earlier quoted context omitted.

It's $40, not super expensive. 600 million doses would cost $25 billion, a trifle compared to how much the pandemic is costing.

Well hundreds of millions have already flowed into every major pharma company for development costs, so the price for tax payers in every contributing country is substantially higher than $40/person. That's just the price an individual may see.

It’s fun to shit on Big Pharma but this isn’t true.

Pfizer specifically rejected government funding. It did so because it didn’t want to be dragged into bureaucracy.

Re: FDA grants authorization to Moderna's Covid-19 vaccine

#73

Post by cwhiz » Sat, Dec 19, 2020, 5:41 AM UTC

CyanLite4 wrote: post #66

cameldrv wrote: post #62

Earlier quoted context omitted.

If every single day counted, they would have done challenge trials. What counts is following the FDA's process, and the FDA's process says that you have to administer it in the same way as the trial. No one at the FDA is going to go out on a limb just to save a few thousand lives.

Challenge trials don’t work when 40% of infected are asymptomatic. And challenge trials especially don’t work when 15% of cases require hospitalization and ICU beds are already maxed out.

Citation needed for that 15% number. Even if it’s true, it absolutely isn’t true for all age groups. Give to 20-29 year volunteers. There were hundreds of thousands who volunteered.

Re: FDA grants authorization to Moderna's Covid-19 vaccine

#74

Post by refurb » Sat, Dec 19, 2020, 5:42 AM UTC

seanwilson wrote: post #40

refurb wrote: post #38

Earlier quoted context omitted.

As someone who has been involved in stability testing before, I doubt this is really the case. In order to justify your stability, you need data to submit to the FDA (they don't take your word for it). When doing your initial stability studies, you try and collect data for the most ideal conditions - no refrigeration needed, stable for X years from room temperature to 30C (to account for conditions during shipment).…

> stable for X years from room temperature to 30C How do you get this data for a large value of X without having to wait X years?

Accelerated studies. Usually you test stability for shorter periods of time under harsher conditions. It’s not perfect, but if your product is fine at 50C for 2 months, it’ll probably be fine refrigerated for 12 months.

Re: FDA grants authorization to Moderna's Covid-19 vaccine

#75

Post by Imnimo » Sat, Dec 19, 2020, 5:43 AM UTC

finolex1 wrote: post #59

Anyone knows why they insist on both doses given the limited supply of the vaccine and the marginal increase in effectiveness with the second dose? I would imagine every single day counts. https://www.lesswrong.com/posts/Rvzdi8RS9Bda5aLt2/covid-12-1...

I'm not an expert, but my understanding is that the error bars on efficacy for the single dose are quite large, just because of how the studies are conducted. Moderna's lower bound was below 70% with a single dose, and Pfizer's is below 30%. That's not to say that a single does is definitely not effective, just that there's a lot more uncertainty, and so the bounds are much looser. We also don't know whether giving a second dose a few months later rather than a few weeks later would work as well.

Depending on supply forecasts, it might be worth running a new trial to get a better handle on the efficacy of a single dose, but going that route now would definitely be a gamble. Especially since we're formulating this single dose hypothesis after having run the experiment and seen the results, which is always a dangerous approach.

Still, the data do seem to suggest that it's very plausible that a single dose would be sufficient. If things get bad enough, or supply is low enough, maybe that's a gamble worth taking.

Re: FDA grants authorization to Moderna's Covid-19 vaccine

#76

Post by refurb » Sat, Dec 19, 2020, 5:44 AM UTC

Retric wrote: post #48

seanwilson wrote: post #40

Earlier quoted context omitted.

> stable for X years from room temperature to 30C How do you get this data for a large value of X without having to wait X years?

The general rule is increasing temperature by 10C roughly doubles the rate of chemical reactions. https://www.ddltesting.com/package-testing/shelf-life-testin... Though in practice it’s more complicated. Basically, make predictions based on accelerated testing and then validate them in real time tests. So, if things hold up at 3 and 6 months real time you can probably trust them over longer timeframes.

Exactly. Plus dating tends to get extended post-approval.

If Pfizer has a short-list of candidates back in May, they could have had 6 months of stability data at approval.

They can keep those studies going and by next May have 12 months of data for the FDA to review and potentially update the transportation and storage requirements.

Re: FDA grants authorization to Moderna's Covid-19 vaccine

#77

Post by apsec112 » Sat, Dec 19, 2020, 5:45 AM UTC

opendomain wrote: post #50

I am concerned that the Pfizer vaccine was put on hold [1]. I am also concerned that Moderna has never produced ANY drug beyond the third stage before. [2] How could we research if the approval was politically motivated? How can I know if this is actually safe? (1) https://www.vanityfair.com/news/2020/12/white-house-delays-p... (2) https://www.wsj.com/articles/modernas-covid-19-vaccine-is-cl...

Shipping and distribution problems have nothing to do with safety. There's a lot of data on what side effects the trial participants got, how the vaccine compared to placebo, etc. which has been published by the FDA. With tens of thousands of trial participants, we can be pretty confident that serious side effects are rare.

Re: FDA grants authorization to Moderna's Covid-19 vaccine

#78

Post by kalnins » Sat, Dec 19, 2020, 5:58 AM UTC

stu2b50 wrote: post #52

opendomain wrote: post #50

I am concerned that the Pfizer vaccine was put on hold [1]. I am also concerned that Moderna has never produced ANY drug beyond the third stage before. [2] How could we research if the approval was politically motivated? How can I know if this is actually safe? (1) https://www.vanityfair.com/news/2020/12/white-house-delays-p... (2) https://www.wsj.com/articles/modernas-covid-19-vaccine-is-cl...

It was not "put on hold", rather as many experts expected, especially with the state of the current administration, mass distribution and coordination is a clusterfuck. Which, to be fair, is a very challenging problem with a lot of minutia and moving parts. But "your amazon product will take another day to ship" is very different from "your amazon product is broken". If you're worried that it was rushed by US politic…

It's also expected to be accepted in EU on 21st december. And, if approved, vacination would be started across the whole EU on 27th december.

Re: FDA grants authorization to Moderna's Covid-19 vaccine

#79

Post by IfOnlyYouKnew » Sat, Dec 19, 2020, 6:27 AM UTC

SAI_Peregrinus wrote: post #61

IfOnlyYouKnew wrote: post #12

Earlier quoted context omitted.

Nothing is "banned". AZ accidentally ran their first trial with only half the intended dose. For some reason, this turned out to work better than the intended regimen (90 % vs 60 % in the other trial). When they noticed the mistake, they pretended it had been their intention all along. That's one troubling error, one surprising result that doesn't fit expectations and could, therefore, indicate other, potentially dan…

> For some reason, this turned out to work better than the intended regimen (90 % vs 60 % in the other trial). The difference isn't actually statistically significant. It's probably 60-70% effective overall.

It is utterly impossible for two trials of that size (thousands) to result in 60% and 90% effectiveness, respectively, by chance. I can't quite do a t-test in my head any more, but I'd guess that difference passes the 5% significance threshold somewhere around n=30.

Re: FDA grants authorization to Moderna's Covid-19 vaccine

#80

Post by IfOnlyYouKnew » Sat, Dec 19, 2020, 6:30 AM UTC

chromatin wrote: post #28

IfOnlyYouKnew wrote: post #12

Earlier quoted context omitted.

Nothing is "banned". AZ accidentally ran their first trial with only half the intended dose. For some reason, this turned out to work better than the intended regimen (90 % vs 60 % in the other trial). When they noticed the mistake, they pretended it had been their intention all along. That's one troubling error, one surprising result that doesn't fit expectations and could, therefore, indicate other, potentially dan…

And it turns out the cohort who received the half dose was on average younger than the total study population, this explaining the apparent improvement in efficacy

As far as I can tell, the virus is more prevalent among younger people. Since infection, not death, was the primary endpoint, and also because medicine hasn't used that sort of wishful reasoning for about a hundred years, the age difference doesn't explain anything.