The vaccines | vaxxed boosted unvaxxed? New poll

[Pogue Mahone]

I'm not obsessed, it is just the logical aim if we are to get out of this shitshow ASAP. I doubt places like the US and UK will get there sadly but it should be the aim.

Politicians should be selling it as your civic duty to get vaccinated to save the economy and to save those who can't be vaccinated. Of course BoJo and his Evil Clown Posse will be selling themselves as the Elf on the Shelf who "Saved Christmas".

Those are a strange couple of countries to choose. I can think of a hell of a lot of other countries who would be considerably less likely to successfully vaccinate a high % of their population. Not to mention that the relatively high case numbers in the UK/US will help inflate the numbers of immune citizens. I think the UK/US will get to a higher % of immunity than the vast majority of countries in the world. And they’ll get there quicker. Despite this, I don’t think they’ll reach herd immunity any time soon, if ever.

 

[evil_geko]

Men of science have often committed the cardinal scientific sin of forgetting they don't know what they don't know, and when worried citizens suggested maybe we don't know about all the risk factors of this rapid development, they often resorted to pointing out the ignorance of these non-scientific folks and ridiculing their beliefs. Sometimes it was their own ignorance they couldn't see, and sometimes the actions they took to invalidate the concerns of others backfired in their ultimate goal to make this new technology as widely adopted as possible. The way you want the world to work isn't how it works, and ridiculing people into submission won't achieve what you want. If you don't recognise any validity in people's concerns about vaccination then they won't listen to you, nor will the people on the fence, because there is some validity. You and they might disagree on how much there is, and you might make progress in closing that gap, but dismissing them is entirely counterproductive because, among other things, it is not entirely factual.

Great post this.

 

[Wibble]

Those are a strange couple of countries to choose. I can think of a hell of a lot of other countries who would be considerably less likely to successfully vaccinate a high % of their population. Not to mention that the relatively high case numbers in the UK/US will help inflate the numbers of immune citizens. I think the UK/US will get to a higher % of immunity than the vast majority of countries in the world. And they’ll get there quicker. Despite this, I don’t think they’ll reach herd immunity any time soon, if ever.

I'm sure there are worse, Poland and Serbia sound much worse for example, but the UK and US stand out partly because that is the focus on here and partly because they should be the nations who most want to mass immunise due to the sheer incompetence of their response to the pandemic so far, yet seem to have very high levels of vaccine resistance.

 

[Traub]

Is it true that you'd rather your population not vaccinate if less than the majority (i.e. 50%) refuse vaccination, as the virus will be rife for mutation?

 

[africanspur]

I'm sure there are worse, Poland and Serbia sound much worse for example, but the UK and US stand out partly because that is the focus on here and partly because they should be the nations who most want to mass immunise due to the sheer incompetence of their response to the pandemic so far, yet seem to have very high levels of vaccine resistance.

People keep on saying stuff like this, what exactly is the evidence? The evidence seems to point to the UK's population being one of the most trusting of vaccines in general, as well as one of the ones most keen on getting the covid vaccine once its rolled out.

https://www.ft.com/content/fd3264ea-dc97-489e-969f-a933288babbe

https://www.politico.eu/article/coronavirus-vaccine-skepticism-by-the-numbers/

 

[Pogue Mahone]

Heh.

 

[Wibble]

People keep on saying stuff like this, what exactly is the evidence? The evidence seems to point to the UK's population being one of the most trusting of vaccines in general, as well as one of the ones most keen on getting the covid vaccine once its rolled out.

https://www.ft.com/content/fd3264ea-dc97-489e-969f-a933288babbe

https://www.politico.eu/article/coronavirus-vaccine-skepticism-by-the-numbers/

I hope that it is true - the sentiment from the UK on here seems far more reticent.

 

[slyadams]

So why not release the vaccines with zero testing?

Presumably because a full testing roadmap is required to prove safety.

So if that full testing roadmap has had some corners cut for covid-19, it's a perfectly valid reason to be wary of the result. Those original roadmap corners were designed with a purpose in mind, and the economic motivations of rushing a vaccine ASAP (for both governments and pharmaceutical companies) mean that safety can't be taken for granted in the same way it would be for any previous vaccine that followed the full roadmap.

The Tory government that's loosened regulations for vaccine development is the same Tory government that fecked the pandemic response in a multitude of other ways this year. Blind trust shouldn't be the default response.

I get it if you're a vulnerable, or have family that are, or are in regular contact with the elderly. But for those of us who are happy to continue to self isolate and indefinitely wear masks in public, the cost-benefit of taking a rushed vaccine may not be enough to persuade us to join the queue.

I'll happily take it in a year or so, though, after a bunch of other people have safely had a go.

Obviously, if the pandemic is significantly ruining somebody's life, the cost-benefit analysis will be different for them than it is for me. I'm certainly not going to try and dissuade anyone from taking the vaccine. I probably would do too if I were an old codger.

Could you outline the corners that have been cut?

 

[Ayush_reddevil]

 

[Ayush_reddevil]

A lot of questions being raised by scientists about the Oxford vaccine and the way they have presented the data

 

[Pogue Mahone]

That’s a very good/fair critique. I’ve been confused by the way they’re combining results from a phase II and phase III trial to give a single % for efficacy but hadn’t appreciated the stuff about the varying ages of the different treatment arms and the way a lot of these analyses don’t seem pre-planned. The regulators will go to town on this. It’s so important they maintain public trust, I can see AZ being told to go away and run more trials (or at least generate a hell of a lot more data from these ones)

On the plus side, what she says about the mRNA vaccines is encouraging. Proper, rigorous science. Should be a good chance of getting approved quickly.

 

[Pogue Mahone]

This timeline is interesting, for anyone who wants to get nerdy on where it all went wrong.

 

[Pogue Mahone]

And it goes without saying, it’s fecking madness that their headline efficacy figure comes from accidentally giving trial subjects the wrong dose. Not exactly giving confidence in their scientific rigour, are they?!

 

[Wibble]

That’s a very good/fair critique. I’ve been confused by the way they’re combining results from a phase II and phase III trial to give a single % for efficacy but hadn’t appreciated the stuff about the varying ages of the different treatment arms and the way a lot of these analyses don’t seem pre-planned. The regulators will go to town on this. It’s so important they mawill get intained public trust, I can see AZ being told to go away and run more trials (or at least generate a hell of a lot more data from these ones)
Craig
Craig

I'd like to know the p value of the 90% effective regime.

 

[spontaneus1]

Heh.

Well it stands to reason that if you believe the virus is a conspiracy you think the vaccine would be harmful.

 

[Pogue Mahone]

I'd like to know the p value of the 90% effective regime.

They claim it’s <0.001 in their press release but when you run a whole bunch of different comparison (which they seem to have done) you trust the p value less and less because of multiplicity.

You can avoid this by having a pre-stated hypothesis with a single primary end-point, defined in advance. AZ seem to have repeatedly sliced and diced their data in the hope of turning up something positive. That’s bad science.

 

[Pogue Mahone]

Well it stands to reason that if you believe the virus is a conspiracy you think the vaccine would be harmful.

Thinking the virus is a conspiracy would be a different venn diagram, featuring a much smaller collection of loons (thankfully). He’s talking about the “open up, it’s just a bad flu” crew.

 

[Wibble]

They claim it’s <0.001 in their press release but when you run a whole bunch of different comparison (which they seem to have done) you trust the p value less and less because of multiplicity.

You can avoid this by having a pre-stated hypothesis with a single primary end-point, defined in advance. AZ seem to have repeatedly sliced and diced their data in the hope of turning up something positive. That’s bad science.

You can also adjust for multiplicity. I wonder if they have and/or have done so adequately? Press releases ahead of finalised study and peer review have a huge potential for this sort of thing.

 

[Brwned]

They claim it’s <0.001 in their press release but when you run a whole bunch of different comparison (which they seem to have done) you trust the p value less and less because of multiplicity.

You can avoid this by having a pre-stated hypothesis with a single primary end-point, defined in advance. AZ seem to have repeatedly sliced and diced their data in the hope of turning up something positive. That’s bad science.

Given it's widely acknowledged that that's bad science, and this is such a public event with intense scrutiny from the global medical community and serious pressure on the regulators, it's a bit difficult to understand why they would take that approach. Obviously it wasn't their intention going into it but why would they think it's a good plan B?

Is there a good explanation for why 1 1/2 doses would work better than 2 doses, if the test populations were equal? EDIT: might be limiting the effect of the neutralising antibodies on the adenovirus itself, but the fact it was a mistaken dose in the first place makes that seem borderline implausible

 

[Pogue Mahone]

Given it's widely acknowledged that that's bad science, and this is such a public event with intense scrutiny from the global medical community and serious pressure on the regulators, it's a bit difficult to understand why they would take that approach. Obviously it wasn't their intention going into it but why would they think it's a good plan B?

I have no idea. Well, other than that they’re looking for any reason at all to be positive. Which is understandable.

 

[Pogue Mahone]

Should also be clear, I’m accusing them of bad science without having all the pieces of the puzzle. Which is harsh.

 

[Wibble]

Should also be clear, I’m accusing them of bad science without having all the pieces of the puzzle. Which is harsh.

You often have suboptimal data and design but I hope they have adjusted appropriately. I guess time will tell.

I'd also like to know if we have any suggested mechanism as to why a half dose then a full
dose worked better (assuming the data backs this up sufficiently) and if it has implications for giving a booster to people who have been infected but were asympyomatic?

 

[Ayush_reddevil]

Given it's widely acknowledged that that's bad science, and this is such a public event with intense scrutiny from the global medical community and serious pressure on the regulators, it's a bit difficult to understand why they would take that approach. Obviously it wasn't their intention going into it but why would they think it's a good plan B?

Is there a good explanation for why 1 1/2 doses would work better than 2 doses, if the test populations were equal? EDIT: might be limiting the effect of the neutralising antibodies on the adenovirus itself, but the fact it was a mistaken dose in the first place makes that seem borderline implausible

My feeling is that the desperation for a vaccine & the press releases by the other vaccine kind of put pressure on this group. That's why I didn't like how this became a sort of a competition

 

[Revan]

Reading a few things, seems that the Oxford/AZ might have fecked up their trials and many people are saying that they should do another trial.

 

[Brwned]

This is what they said about the dosage back in July:

During the Phase I/II trial the vaccine has been evaluated in more than 1,000 healthy adult volunteers aged between 18 and 55 years in a randomised controlled trial. A subset of these volunteers (10 people) received two doses of the vaccine. Between April 23, 2020 and May 21, 2020, 1077 volunteers, received the vaccine ChAdOx1 nCoV-19 or a placebo MenACWY vaccine. There were no serious adverse health events related to ChAdOx1 nCoV-19.

“We saw the strongest immune response in the 10 participants who received two doses of the vaccine, indicating that this might be a good strategy for vaccination,” Professor Pollard continues.

The fact they only gave 2 doses to 1% of the trialists in phase I / II implies their initial instinct was that it wasn't the right approach, but then based on undefined positive results from a tiny sample size they thought it was worth switching to 2 doses. In the process of trying to implement that new preferred regimen, they somehow managed to give people the wrong dosage when rolling out phase 3. And the two doses supposedly don't work all that well after expanding the sample size, perhaps due to their original concerns that a first full dose allows the body to develop the adenovirus antibodies, which limits their effectiveness in spreading the useful part of the second dose. Or because the study populations are substantially different and not reasonably comparable.

It's possible they stumbled upon the right formula with that odd mistake but it's not unfair to say they seemed a bit haphazard on it. But then you probably would expect things to be a bit more variable in a rushed timeline. Which is what a lot of people intuitively have unverified concerns about.

My feeling is that the desperation for a vaccine & the press releases by the other vaccine kind of put pressure on this group. That's why I didn't like how this became a sort of a competition

Yeah seems it. I wonder about UK government adding pressure here. There did seem to be some nationalism involved in the US vs. UK vaccines. If there was government involvement (not necessarily interference) it would add credence to a lot of loose concerns. Even more so if they have to take a step back from original claims after regulators review.

 

[Tony Babangida]

Should also be clear, I’m accusing them of bad science without having all the pieces of the puzzle. Which is harsh.

I’m not sure it’s that harsh. It doesn’t make sense to get to 70% efficacy by averaging two dosing regimens. They needed more numbers in the low/high arm before releasing any information in my opinion. It might turn out that 90% efficacy figure doesn’t hold up and then they look clueless.

 

[Pogue Mahone]

I’m not sure it’s that harsh. It doesn’t make sense to get to 70% efficacy by averaging two dosing regimens. They needed more numbers in the low/high arm before releasing any information in my opinion. It might turn out that 90% efficacy figure doesn’t hold up and then they look clueless.

It is possible there’s more logic to their approach than we can see right now. At the end of the day there are some very smart people analysing these data and we’re speculating based on not much information.It does seem to be a bit of a mess though.

 

[jojojo]

It is possible there’s more logic to their approach than we can see right now. At the end of the day there are some very smart people analysing these data and we’re speculating based on not much information.It does seem to be a bit of a mess though.

Yes, I'm trying not to be impatient or too critical about the missing information because all we really have is a press release. I do hope they're going to give us something more solid though.

There's too much missing from their press release. Including other factors (participant bias and timing) that might impact the half/full results. It feels like they might be onto something with the half/full trial and if they'd called it an expanded phase 2 everyone would be impressed. Plus they just jump past the potential adverse events that put the trial on hold.

Right now you're left with the feeling that a month ago, the 60% would have been the Phase 3 interim report and everyone would have been impressed, and they'd be mentioning the half/full experiment as an area where they would continue trialling. The Pfizer/Moderna results have upped the stakes and instead of announcing a Phase 3 v2 trial (like Jansenn have) we've got a kind of hybrid report.

 

[Tony Babangida]

It is possible there’s more logic to their approach than we can see right now. At the end of the day there are some very smart people analysing these data and we’re speculating based on not much information.It does seem to be a bit of a mess though.

It’s possible that the very smart people aren’t that happy with the press release. In academia scientists results are often distorted by the uni press department; the needs of the PR team are different to those of the scientists. But as you say, they know the full story and we don’t, so all we can do is speculate at this point.

 

[Pogue Mahone]

Yes, I'm trying not to be impatient or too critical about the missing information because all we really have is a press release. I do hope they're going to give us something more solid though.

There's too much missing from their press release. Including other factors (participant bias and timing) that might impact the half/full results. It feels like they might be onto something with the half/full trial and if they'd called it an expanded phase 2 everyone would be impressed. Plus they just jump past the potential adverse events that put the trial on hold.

Right now you're left with the feeling that a month ago, the 60% would have been the Phase 3 interim report and everyone would have been impressed, and they'd be mentioning the half/full experiment as an area where they would continue trialling. The Pfizer/Moderna results have upped the stakes and instead of announcing a Phase 3 v2 trial (like Jansenn have) we've got a kind of hybrid report.

Yes. I think that’s a good/fair summary of the most likely scenario.

 

[Tony Babangida]

https://www.wired.com/story/the-astrazeneca-covid-vaccine-data-isnt-up-to-snuff/

Apparently the low/high dose arm didn't include anyone over the age of 55. There needs to be published data on these trials alongside any EUA approval, full transparency so people can be confident in the vaccines without any suggestion of the regulatory bodies being too lenient.

 

[hobbers]

Would not expect AZ and Oxford to drop the ball quite so publicly.

 

[Wibble]

It’s possible that the very smart people aren’t that happy with the press release. In academia scientists results are often distorted by the uni press department; the needs of the PR team are different to those of the scientists. But as you say, they know the full story and we don’t, so all we can do is speculate at this point.

This is what I'm hoping. Emergency approval at the better tested but less effective regime and continued phase 3 testing for the more effective regime maybe? Get that going now (assuming it isn't already) and you could have results in time for a public roll out in March/April more or less on schedule (assuming success)?

 

[Wibble]

I’m not sure it’s that harsh. It doesn’t make sense to get to 70% efficacy by averaging two dosing regimens. They needed more numbers in the low/high arm before releasing any information in my opinion. It might turn out that 90% efficacy figure doesn’t hold up and then they look clueless.

The large gap between the effectiveness of the 2 treatment regimes does stand out like dog balls.

 

[berbatrick]

On the plus side, what she says about the mRNA vaccines is encouraging. Proper, rigorous science. Should be a good chance of getting approved quickly.

Good article.

About Moderna/Pfizer - they didn't do PCR tests of their subjects, confining analysis to people who developed and reported symptoms. You can imagine, as things reopen, the virus spreading through vaccinated asymptomatic carriers in a mostly-not-vaccinated population.

 

[Pogue Mahone]

Good article.

About Moderna/Pfizer - they didn't do PCR tests of their subjects, confining analysis to people who developed and reported symptoms. You can imagine, as things reopen, the virus spreading through vaccinated asymptomatic carriers in a mostly-not-vaccinated population.

Yup. Although hopefully not too much of a problem if elderly population vaccinated before things reopen.

 

[Zlatan 7]

Reading a few things, seems that the Oxford/AZ might have fecked up their trials and many people are saying that they should do another trial.

My feeling is that the desperation for a vaccine & the press releases by the other vaccine kind of put pressure on this group. That's why I didn't like how this became a sort of a competition

It’s quite bizarre to see things like the scientists fecked up the trials and there’s a clear race to be the first or best vaccine but if you show the slightest bit of concern to this and wary of the results you get shouted down and called ignorant and selfish because you must believe the science!!!

 

[Pogue Mahone]

It’s quite bizarre to see things like the scientists fecked up the trials and there’s a clear race to be the first or best vaccine but if you show the slightest bit of concern to this and wary of the results you get shouted down and called ignorant and selfish because you must believe the science!!!

The problem here is people judging these vaccines based on press releases.

Proper scientists won’t form an opinion until they’ve read all the details. Which is what happens when a new medicine gets a license. Trained scientists working for the regulatory authorities - who are independent from the pharma companies - do a forensic review of all the available data. From the first mouse it was tested on, all the way through to every last detail of the phase III trial. This is all digital now but in the days of hard copy the data provided used to fill a whole wall full of lever arch folders. And they have to read every page. Then hold multiple meetings with the developers to challenge and understand anything they are unsure about. This usually takes months and months but has been sped up by them starting this analysis on animal data before the human trials are complete (which is unprecedented, as it would be a collosal waste of their time if the human trials failed)

Only after they all agree that the medicine is effective and safe will they give it a license to be used. Then it’s over to physicians to review the peer reviewed publications of the phase II and III trials (again, with a load more details than we have now) and decide which safe, effective drug is best for the patient they are writing the prescription for.

If, at that point, the patient decides they know more than the regulators and the doctor in front of them then they really are ignoring the science. But we’re a long way off that right now.

 

[Withnail]

It’s quite bizarre to see things like the scientists fecked up the trials and there’s a clear race to be the first or best vaccine but if you show the slightest bit of concern to this and wary of the results you get shouted down and called ignorant and selfish because you must believe the science!!!

Isn't this a bit of a false equivalence?

One trial seems to be flawed, with calls to re-reun the trial, when the results have been put under scrutiny.

Shouldn't that give you confidence in the others if their results hold up under the same level of scrutiny?

 

[Zlatan 7]

The problem here is people judging these vaccines based on press releases.

Proper scientists won’t form an opinion until they’ve read all the details. Which is what happens when a new medicine gets a license. Trained scientists working for the regulatory authorities - who are independent from the pharma companies - do a forensic review of all the available data. From the first mouse it was tested on, all the way through to every last detail of the phase III trial. This is all digital now but in the days of hard copy the data provided used to fill a whole wall full of lever arch folders. And they have to read every page. Then hold multiple meetings with the developers to challenge and understand anything they are unsure about. This usually takes months and months but has been sped up by them starting this analysis on animal data before the human trials are complete (which is unprecedented, as it would be a collosal waste of their time if the human trials failed)

Only after they all agree that the medicine is effective and safe will they give it a license to be used. Then it’s over to physicians to review the peer reviewed publications of the phase II and III trials (again, with a load more details than we have now) and decide which safe, effective drug is best for the patient they are writing the prescription for.

If, at that point, the patient decides they know more than the regulators and the doctor in front of them then they really are ignoring the science. But we’re a long way off that right now.

Thanks for all that info, I’ve read most of your posts in this thread so do read them when I see your name.

I agree at that point people would be silly to doubt it but at the moment people screaming science science and that one is dull and ignorant for not running out begging for the vaccine for the greater good are way off the mark imo and got lost in their own hole of wishful thinking, There’s simply not enough known, because as you say, it’s just a press release.

a few days ago people buzzing about the Oxford vaccine and you have to take it for the greater good, take it next week or you’re selfish, but then a few days later there’s confusion over the results and even how they got them by mistake. So to me that shows the initial hesitance was more than justified.