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(Guardian)   Turns out the higher efficacy of the Oxford vaccine when initially given as a half dose was less 'carefully-thought out plan' and more 'oops, we screwed up. How do we salvage this?'   (theguardian.com) divider line
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3605 clicks; posted to Main » on 24 Nov 2020 at 9:29 AM (9 weeks ago)   |   Favorite    |   share:  Share on Twitter share via Email Share on Facebook



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2020-11-24 5:08:38 AM  
So? Many important scientific discoveries have been made by accident.
schlockmercenary.comView Full Size
 
Xai [TotalFark]
2020-11-24 6:25:08 AM  
Remember, the difference between a cock up and science, is that one hides the mistake and the other publishes the results in full - good or bad.
 
2020-11-24 8:52:39 AM  
It got more effective the less you gave? Oh no, have I been making fun of homeopathy unfairly all these years?

/Just kidding, homeopaths still deserve to be punched in the face until there's bits of bone in their stool.
 
2020-11-24 9:33:46 AM  
Everyone makes mistakes, even scientists. Dumb people try to cover up their mistakes while smart people learn from them. In this case they learned a better way to administer a very important vaccine.
 
2020-11-24 9:34:40 AM  

Prank Call of Cthulhu: It got more effective the less you gave? Oh no, have I been making fun of homeopathy unfairly all these years?

/Just kidding, homeopaths still deserve to be punched in the face until there's bits of bone in their stool.


Women have known things get more effective the less they gave for many years
 
2020-11-24 9:35:21 AM  
This is so very interesting, it seems that the half dose primes the immune system to allow for a greater response on the full dose. I wonder if they gave a 1/4 dose before the 1/2 if that would prime the immune system to allow for a 99% coverage.
 
2020-11-24 9:39:40 AM  

Thisbymaster: This is so very interesting, it seems that the half dose primes the immune system to allow for a greater response on the full dose. I wonder if they gave a 1/4 dose before the 1/2 if that would prime the immune system to allow for a 99% coverage.


You know, medicine is not an exact science, but we are learning all the time. Why, just fifty years ago, they thought a disease like your daughter's was caused by demonic possession or witchcraft. But nowadays we know that Isabelle is suffering from an imbalance of bodily humors, perhaps caused by a toad or a small dwarf living in her stomach.
 
2020-11-24 9:40:25 AM  
I'm a bit suspicious of the Oxford vaccine

I thought it'd be the opposite, I thought I'd trust the vaccines out of Europe more

I'm ready to take either of the American vacine's though
 
2020-11-24 9:43:35 AM  

I Ate Shergar: So? Many important scientific discoveries have been made by accident.
[schlockmercenary.com image 780x343]


Also relevant: SMBC "How Discovery Happens"
 
2020-11-24 9:45:33 AM  

Prank Call of Cthulhu: It got more effective the less you gave? Oh no, have I been making fun of homeopathy unfairly all these years?

/Just kidding, homeopaths still deserve to be punched in the face until there's bits of bone in their stool.


It wasn't just a smaller dose, it was a half dose followed by a full dose later. Nothing is said about a half-dose alone.... Which leaves me wondering what is the effectiveness of the half dose would be? Did they miss a point? What about two full doses? Is it the month between that does it?

/inquiring minds
// without coffee
/// GAH!!
 
2020-11-24 9:45:41 AM  

Prank Call of Cthulhu: It got more effective the less you gave? Oh no, have I been making fun of homeopathy unfairly all these years?

/Just kidding, homeopaths still deserve to be punched in the face until there's bits of bone in their stool.


As a homeopathic chiropractor, I take exception!

Also cash, checks, and major credit cards.
 
2020-11-24 9:47:36 AM  
Viagra, penicillin, pacemakers and x-rays were all discovered by accident
 
2020-11-24 9:49:38 AM  
I once meant to order a burger from Fuddruckers, but I was drunk, and ordered from Fatburger instead.  It may not have been what I intended, but the burger was delicious.
 
2020-11-24 9:50:18 AM  

Xai: Remember, the difference between a cock up and science, is that one hides the mistake and the other publishes the results in full - good or bad.


Eh, not 100% true, as frustrating as it is. It is VERY hard to get a negative result published, a "I meticulously did this to try to achieve this. It did not work, and Y is what happened instead", unless Y is really, REALLY interesting. Most journals just won't publish a manuscript on failed results unless you can spin it *really* well.

It's frustrating because those can still be really useful, whether to keep other people from wasting their time on the same thing, or because years down the line someone may WANT result Y. There really needs to be a "Journal of Failed Experiments" or something.
 
2020-11-24 9:52:03 AM  
Welcome to SCIENCE
 
2020-11-24 9:52:08 AM  
Hmmm, the additional good news is this will in effect increase the number of people they can dose with the volume of vaccine they're able to produce. I wonder if any other vaccine makers will give this dosing regime a try with their products?
 
2020-11-24 9:52:10 AM  
Isn't this Oxford telling a funny anecdote just trying to get more press for a vaccine to help them save a little face when up again 2 other company's vaccines that are more effective?
 
2020-11-24 9:52:31 AM  

I Ate Shergar: So? Many important scientific discoveries have been made by accident.
[schlockmercenary.com image 780x343]


Underpowered post-hoc analysis on a dosing error treatment arm does not fill me with confidence. I have no idea why people are giving them so much leeway on this - data for both mRNA vaccines are superior and everyone is like "yeah but it's expensive."
 
2020-11-24 9:52:42 AM  
I can't wait for the long term side effects to come to light.   Years down the road, opps!  our vaccine causes cancer in 26% of the people we gave it to.  "It's not our fault -- the government rushed us!" will be a nice defense and blanket immunity will be given.

/something like this will happen
//you just wait
 
2020-11-24 9:54:36 AM  
Kind of like how you learn to masturbate.
 
2020-11-24 9:57:03 AM  

huntercr: Isn't this Oxford telling a funny anecdote just trying to get more press for a vaccine to help them save a little face when up again 2 other company's vaccines that are more effective?


It might be common behavior across all manufacturers. Be interesting if the others tried this. If not, I assume they would have to go back to trial.
 
2020-11-24 9:57:40 AM  

CarnySaur: Kind of like how you learn to masturbate.


Get out of my head.
 
2020-11-24 9:58:34 AM  

ltdanman44: I can't wait for the long term side effects to come to light.   Years down the road, opps!  our vaccine causes cancer in 26% of the people we gave it to.  "It's not our fault -- the government rushed us!" will be a nice defense and blanket immunity will be given.

/something like this will happen
//you just wait


It already did. In 1976.
There seemed to be linkage between the federally "rushed" swine flu rollout and subsequent cases of Guillain-Barre syndrome.  Lawsuits followed.
 
2020-11-24 9:59:46 AM  

Mikeyworld: Prank Call of Cthulhu: It got more effective the less you gave? Oh no, have I been making fun of homeopathy unfairly all these years?

/Just kidding, homeopaths still deserve to be punched in the face until there's bits of bone in their stool.

It wasn't just a smaller dose, it was a half dose followed by a full dose later. Nothing is said about a half-dose alone.... Which leaves me wondering what is the effectiveness of the half dose would be? Did they miss a point? What about two full doses? Is it the month between that does it?

/inquiring minds
// without coffee
/// GAH!!


This one puts the coronavirus spike protein into an adenovirus vector. The immune system will react to whatever viral proteins it sees. If the first dose triggers a strong enough immunity to that carrier virus, the second dose might be neutralized before it can do anything. A single half dose would probably produce weak protection against both viruses.

It might also be random variation due to a small sample size. Let's see if they can reproduce the effect, e.g. by measuring antibody levels in a fresh group of test subjects who are given various dose combinations.
 
2020-11-24 10:01:25 AM  

Prank Call of Cthulhu: It got more effective the less you gave? Oh no, have I been making fun of homeopathy unfairly all these years?

/Just kidding, homeopaths still deserve to be punched in the face until there's bits of bone in their stool.


You larf, but I ran the numbers and if I dilute the vaccine by a factor of a million, my homeopathic cure will give everyone 999 billion percent immunity.
 
2020-11-24 10:05:06 AM  

zepillin: I'm a bit suspicious of the Oxford vaccine

I thought it'd be the opposite, I thought I'd trust the vaccines out of Europe more

I'm ready to take either of the American vacine's though


Like Moderna, the Oxford vaccine might does need to be kept at -70 degrees.  So it has that going for it.
 
2020-11-24 10:09:55 AM  
I hereby declare the name of the pause between the half dose and the full dose to be the "Oxford comma".
 
2020-11-24 10:16:13 AM  

mrshowrules: zepillin: I'm a bit suspicious of the Oxford vaccine

I thought it'd be the opposite, I thought I'd trust the vaccines out of Europe more

I'm ready to take either of the American vacine's though

Like Moderna, the Oxford vaccine might does need to be kept at -70 degrees.  So it has that going for it.


I really don't have any reason to feel that way other than something struck me intuitively when I was watching the first news video's about the announcement of its success.

I'm really old and intuition has served me well in the later half my life as I have worked on tuning it. Sometimes when I ignore it for cognitive reasons I end up having regrets so I pretty much just go with it now.
 
2020-11-24 10:18:06 AM  
It's probably basically fine but there is something off about it
 
2020-11-24 10:22:06 AM  
I hope it serves the third world well
 
2020-11-24 10:28:03 AM  

Ivo Shandor: This one puts the coronavirus spike protein into an adenovirus vector. The immune system will react to whatever viral proteins it sees. If the first dose triggers a strong enough immunity to that carrier virus, the second dose might be neutralized before it can do anything. A single half dose would probably produce weak protection against both viruses.

It might also be random variation due to a small sample size. Let's see if they can reproduce the effect, e.g. by measuring antibody levels in a fresh group of test subjects who are given various dose combinations.


This.

The large first dose caused a strong enough immune response.  The half-dose primed the immune system, but didn't overwhelm the 2nd dose (which would prevent the desired, tuned response).

It is possible that it was a mistake.  But it's also possible that someone had a procedure that flew in the face of what the manager wanted, and they have to say it was a 'mistake,' to get the correct process through.
 
2020-11-24 10:28:08 AM  

Felgraf: Xai: Remember, the difference between a cock up and science, is that one hides the mistake and the other publishes the results in full - good or bad.

Eh, not 100% true, as frustrating as it is. It is VERY hard to get a negative result published, a "I meticulously did this to try to achieve this. It did not work, and Y is what happened instead", unless Y is really, REALLY interesting. Most journals just won't publish a manuscript on failed results unless you can spin it *really* well.



The lesson starts early.  It is very hard to get a good grade in high school science lab if you get the "wrong" answer.
 
2020-11-24 10:28:38 AM  

Felgraf: Xai: Remember, the difference between a cock up and science, is that one hides the mistake and the other publishes the results in full - good or bad.

Eh, not 100% true, as frustrating as it is. It is VERY hard to get a negative result published, a "I meticulously did this to try to achieve this. It did not work, and Y is what happened instead", unless Y is really, REALLY interesting. Most journals just won't publish a manuscript on failed results unless you can spin it *really* well.

It's frustrating because those can still be really useful, whether to keep other people from wasting their time on the same thing, or because years down the line someone may WANT result Y. There really needs to be a "Journal of Failed Experiments" or something.


With peer review. Wouldn't be awesome to see a paper in JFE retracted because peer review showed a way to make the experiment work?
 
2020-11-24 10:32:41 AM  
For those questioning the half dose thing:

The Oxford vaccine uses a 'traditional' technique of using a real but genetically neutered virus as the carrier for the new instructions to make coronavirus spikes.

Our immune system can still respond to this carrier virus like any other.

It seems likely that a full dose for the first jab creates enough of an immune response that the second booster jab is destroyed by the immune system before it's fully triggered production of coronavirus spikes - it's notable that the error was discovered *because* some people were having less of a reaction to the first injection (flu/cold like reactions typical of fighting off a virus).

So it's quite reasonable that a lower first dose gets the carrier in under the radar, but still enables triggering of the corona spike response, and then the second booster dose is able to actually do its job without being killed off.

The Pfizer and Mediva vaccines use a different carrier (a lipid, a sphere of fatty molecules) as the carrier, so don't have this problem (but need freezing to stay intact, instead).
 
2020-11-24 10:35:23 AM  

GardenWeasel: huntercr: Isn't this Oxford telling a funny anecdote just trying to get more press for a vaccine to help them save a little face when up again 2 other company's vaccines that are more effective?

It might be common behavior across all manufacturers. Be interesting if the others tried this. If not, I assume they would have to go back to trial.


It's a protocol violation and often you have to discontinue patients when this sort of thing happens. The study doctors can write up justifications or modify the trial to permit it, and I'm guessing that's what they did here. The thing is, if this happened in phase 3, I am shocked they didn't have to expand their participant pool because anyone who received the half dose would need to be pulled out separate form those with the full dose and you don't necessarily have enough participants remaining to keep the same efficacy model.
I'm sure they lobbied hard to keep these people in the trial since it upped the overall odds and trial criteria and urgency of the drug probably makes expansion difficult.

I am speaking only from what I learned over the years listening to my ex wife talk about work, so I could be way off base here.
/ex wife was a clinical trials manager
 
2020-11-24 10:35:23 AM  

Prank Call of Cthulhu: It got more effective the less you gave? Oh no, have I been making fun of homeopathy unfairly all these years?

/Just kidding, homeopaths still deserve to be punched in the face until there's bits of bone in their stool.


I homeopathicly assault homopaths. I spent all day punching water, then I throw that water at their face.
 
2020-11-24 10:36:26 AM  

Thisbymaster: This is so very interesting, it seems that the half dose primes the immune system to allow for a greater response on the full dose. I wonder if they gave a 1/4 dose before the 1/2 if that would prime the immune system to allow for a 99% coverage.


Even better, give a half dose at the end instead of the full dose, to take it to 110%.
It would be odd to end up with a vaccine sequence which was composed of fractional doses.
 
2020-11-24 10:37:24 AM  

Felgraf: Xai: Remember, the difference between a cock up and science, is that one hides the mistake and the other publishes the results in full - good or bad.

Eh, not 100% true, as frustrating as it is. It is VERY hard to get a negative result published, a "I meticulously did this to try to achieve this. It did not work, and Y is what happened instead", unless Y is really, REALLY interesting. Most journals just won't publish a manuscript on failed results unless you can spin it *really* well.

It's frustrating because those can still be really useful, whether to keep other people from wasting their time on the same thing, or because years down the line someone may WANT result Y. There really needs to be a "Journal of Failed Experiments" or something.


At the high end, it is absolutely true.  If you are working on CERN level science, the difference between cock-up and science is whether you publish the good and the bad, or not.

I've personally witnessed this many times.  When the scientist didn't get what they wanted, they still published.  And you need details on the results, because there may be clues for the next attempt in there.

A great example of this is ICECUBE.  The AMANDA array and ICECUBE have not found the large emitting neutrino sources they had hoped for, but it led to system upgrades and new investigations into the nature of neutrinos and particle physics in general.

Trying to force a pet project so you can get an article in Scientific American is ... unfortunately, a thing.  But the good science doesn't have that as a driving goal.  Narcissists do.  And people attempting to develop a cult of personality.  Avoid those people when you invest in a science project.
 
2020-11-24 10:47:42 AM  

Thisbymaster: This is so very interesting, it seems that the half dose primes the immune system to allow for a greater response on the full dose. I wonder if they gave a 1/4 dose before the 1/2 if that would prime the immune system to allow for a 99% coverage.


My fist thought as well - can they tweak the first or second dose to boost the coverage. There's a few two stage vaccinations so it'll be interesting to see what they find and whether it can be applied elsewhere in immunology.
 
2020-11-24 10:49:05 AM  

Felgraf: Eh, not 100% true, as frustrating as it is. It is VERY hard to get a negative result published, a "I meticulously did this to try to achieve this. It did not work, and Y is what happened instead", unless Y is really, REALLY interesting. Most journals just won't publish a manuscript on failed results unless you can spin it *really* well.It's frustrating because those can still be really useful, whether to keep other people from wasting their time on the same thing, or because years down the line someone may WANT result Y. There really needs to be a "Journal of Failed Experiments" or something.


Word to that. That is one of the biggest shortcoming in science publication is that no one does the due diligence of replicating results so the original study is taken as gospel even if it's total crap.
 
2020-11-24 10:51:16 AM  

Snarfangel: Prank Call of Cthulhu: It got more effective the less you gave? Oh no, have I been making fun of homeopathy unfairly all these years?

/Just kidding, homeopaths still deserve to be punched in the face until there's bits of bone in their stool.

As a homeopathic chiropractor, I take exception!

Also cash, checks, and major credit cards.


My chiropractor practices ART, do you do anything similar?
 
2020-11-24 12:27:33 PM  
My favorite line from TFA

"Scientists said they still could not fully explain..."
 
2020-11-24 12:43:13 PM  

zepillin: mrshowrules: zepillin: I'm a bit suspicious of the Oxford vaccine

I thought it'd be the opposite, I thought I'd trust the vaccines out of Europe more

I'm ready to take either of the American vacine's though

Like Moderna, the Oxford vaccine might does need to be kept at -70 degrees.  So it has that going for it.

I really don't have any reason to feel that way other than something struck me intuitively when I was watching the first news video's about the announcement of its success.

I'm really old and intuition has served me well in the later half my life as I have worked on tuning it. Sometimes when I ignore it for cognitive reasons I end up having regrets so I pretty much just go with it now.


Not like you are going to get to choose which vaccine you want when they all come out.  You will get access to the first one you get access to and then you have to decide how long you are willing to wait for the one you prefer to get.   How long would you be willing to wait for your preferred vaccine?

As a Canadian, the Oxford vaccine might be the first one I have access to and I would likely take it, if it was.
 
2020-11-24 12:47:26 PM  

mrshowrules: zepillin: mrshowrules: zepillin: I'm a bit suspicious of the Oxford vaccine

I thought it'd be the opposite, I thought I'd trust the vaccines out of Europe more

I'm ready to take either of the American vacine's though

Like Moderna, the Oxford vaccine might does need to be kept at -70 degrees.  So it has that going for it.

I really don't have any reason to feel that way other than something struck me intuitively when I was watching the first news video's about the announcement of its success.

I'm really old and intuition has served me well in the later half my life as I have worked on tuning it. Sometimes when I ignore it for cognitive reasons I end up having regrets so I pretty much just go with it now.

Not like you are going to get to choose which vaccine you want when they all come out.  You will get access to the first one you get access to and then you have to decide how long you are willing to wait for the one you prefer to get.   How long would you be willing to wait for your preferred vaccine?

As a Canadian, the Oxford vaccine might be the first one I have access to and I would likely take it, if it was.


I'm 67 And a smoker Who is just beginning to pay the price  so I'd definitely take it

If I was 27 I might hesitate
 
2020-11-24 12:49:28 PM  
Course if I was 27 I'd likely already have had it having to work at all

In which case I'll probably wait six months from when I suspect I was infected
 
2020-11-24 12:50:09 PM  
Or maybe not
 
2020-11-24 12:51:38 PM  
 I don't know about the Oxford vaccine
 
2020-11-24 12:52:04 PM  
I'm definitely open to changing my mind on that one though
 
2020-11-24 12:57:04 PM  

zepillin: mrshowrules: zepillin: mrshowrules: zepillin: I'm a bit suspicious of the Oxford vaccine

I thought it'd be the opposite, I thought I'd trust the vaccines out of Europe more

I'm ready to take either of the American vacine's though

Like Moderna, the Oxford vaccine might does need to be kept at -70 degrees.  So it has that going for it.

I really don't have any reason to feel that way other than something struck me intuitively when I was watching the first news video's about the announcement of its success.

I'm really old and intuition has served me well in the later half my life as I have worked on tuning it. Sometimes when I ignore it for cognitive reasons I end up having regrets so I pretty much just go with it now.

Not like you are going to get to choose which vaccine you want when they all come out.  You will get access to the first one you get access to and then you have to decide how long you are willing to wait for the one you prefer to get.   How long would you be willing to wait for your preferred vaccine?

As a Canadian, the Oxford vaccine might be the first one I have access to and I would likely take it, if it was.

I'm 67 And a smoker Who is just beginning to pay the price  so I'd definitely take it

If I was 27 I might hesitate


That's a fair point.  I'm also at risk and my mother who I look after is 89 - and I'd advise her to take it.  I have two kids also so I might want them to wait if a more trusted/better vaccine will take a few more months.
 
2020-11-24 1:16:01 PM  

Nocrash: My favorite line from TFA

"Scientists said they still could not fully explain..."


I suspected that would be their answer when I first read about this one. It has been a long time since I took immunology, and even then it was because it was required not because I was interested in it. I thought about it trying to come up with a rational explanation and decided on 'that's just how it is'
 
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