After Admitting Mistake, AstraZeneca (Oxford) Faces Difficult Questions About Its Vaccine

[Meat Pie 47]

5 hours ago, Traubert said:

Somewhere between the beginning and end.

 

That's enough of your passive/aggressive bullying. Onto ignore with you.

I guess you only read the Global Times

[mommysboy]

1 hour ago, partington said:

Unfortunately I agree with some of this.

 

[I'm not completely convinced that the best results came from a group that was all under 55, as the initial phaseII/III data about immunogenicity of the vaccine published in the Lancet recently listed results for two age groups older than 55.

 

 However it is not easy to check what ages were included in the actual trial whose efficacy was just reported.]

 

EDIT: just read on FT website  that AstraZeneca themselves say the group receiving the mistaken low first dose WERE indeed under 55, so please ignore above paragraph in parentheses[ ]. I'll leave it in to own up to my mistake!

 

I don't believe the group on which the 90% efficacy figure is based group was "chosen", it was simply the randomised group that accidentally received the faulty dosages. The group was in the  UK group not the Brazilian group.

 

Similarly I don't believe side effects were "worse or more common than has been claimed".

 

They were exactly as is being claimed. This how the investigators recognised that the incidence of side effects in the UK group that received the faulty dosage was lower than that they had previously documented and published.

 

However it certainly IS  unusual to be allowed to change the dosage specified in a trial protocol, whether by accident or design, and certainly the US protocol for trials of this vaccine (the only one published so far) specify no dosage changes are allowed. https://s3.amazonaws.com/ctr-med-7111/D8110C00001/52bec400-80f6-4c1b-8791-0483923d0867/c8070a4e-6a9d-46f9-8c32-cece903592b9/D8110C00001_CSP-v2.pdf

 

"6.6 Dose Modification

Study intervention will be administered as described in Section 6.1.2. Dose modification is not permitted."

 

When the error was discovered the investigators evidently immediately and correctly  disclosed it, and applied for permission to continue the trial. Perhaps because of the urgency of the COVID crisis they were allowed to do so. But this now becomes a combination of two trials with different protocols - very far from ideal. The different placebos in each arm are also worrying.

 

In addition, as has been pointed out, the study group that received the accidental low first dose is now way too small to have the statistical power for the results of efficacy to be reliable.  The 90%  efficacy figure must now be treated as extremely provisional indeed.

 

It does look very messy, and increasingly alarm bells are ringing.

 

It's very messy, that's for sure.  It's not acceptable as a phase 3 study imho. 

 

But 'alarm bells ringing'. Come off it this study has been under the control of the MRHA all along.

 

It's the study design and process which is cock-eyed and not the drug.  Principally there are dosage issues.

 

It would be wrong to think this vaccine is either ineffective or unsafe.  Salvage or do the trial again I say, and limit its use to the UK for the initial roll out phase.

[partington]

Fair enough - I don't mean to suggest it's unusable or unsafe in anyway.

 

However I do think it's a problem if the real efficacy is 60%, and I do think the initial announcement of "up to 90% efficacy" was an attempt to embellish the results using data that at present doesn't justify this claim.

 

This vaccine will certainly save lives, and so is absolutely an advance, but (unless I'm completely mistaken and I'm not any kind of epidemiologist or very knowledgeable about infectious disease) it would be impossible to get effective herd immunity using this vaccine alone.

 

If you vaccinated every single citizen in a country with a vaccine with an  efficacy of 60%, 60% would become immune (I am here assuming the immunity prevents transmission -itself not actually proven yet) - however all the estimates I've read suggest you need 70+% immunity to stop transmission effectively.

 

A lot of the celebration over the apparent high efficacy of the Oxford AstraZeneca derived from the fact that there is no cold chain requirement and it's cheap, so developing countries could use it more readily.

This is still true, but to stop the pandemic  other vaccines will have to be used simultaneously.

 

 

 

Edited November 26, 2020 by partington

[cormanr7]

7 hours ago, partington said:

If you vaccinated every single citizen in a country with a vaccine with an  efficacy of 60%, 60% would become immune (I am here assuming the immunity prevents transmission -itself not actually proven yet) - however all the estimates I've read suggest you need 70+% immunity to stop transmission effectively.

In real life this would not happen. A major problem is the 'coverage', i.e. the percent of the population that wants to get vaccinated. Smallpox and polio (which killed millions annually) have been virtually eradicated by mandatory vaccination of infants. As far as I am aware there has been no mandatory vaccination program for adults. In many western countries this would likely lead to a revolt and few governments would be willing to take the risk.

So let's take your figure of 60% efficacy but a coverage of only 50%. The data look very different then.

An interesting article (note that it is a model, take it at face value) attempt to calculate the effect of vaccine efficacy and coverage https://www.ajpmonline.org/action/showPdf?pii=S0749-3797(20)30284-1. It shows, for instance, that with 60% efficacy and 50% coverage, the number of infections at the peak of the epidemy would be reduced by 70% or so. They claim that at 60% efficacy, a 100% coverage would be needed to reduce peak infections by 99%. Now let's assume an efficacy of 90%; in this case a 50% coverage would reduce peak infections by ca 80%. These are best case scenarios where only a small part of the population has been exposed to COVID-19 prior to vaccination (which by now is not the case). Additionally, whether a vaccinated person can still spread the virus is unclear at the moment.

So apart from efficacy, convincing people to take vaccinations is critical. Certainly, even a vaccine with modest efficacy will reduce infections. But even if coverage is high, additional measures such as social distancing, mask use etc. might still be required.

[mommysboy]

9 hours ago, partington said:

Fair enough - I don't mean to suggest it's unusable or unsafe in anyway.

 

However I do think it's a problem if the real efficacy is 60%, and I do think the initial announcement of "up to 90% efficacy" was an attempt to embellish the results using data that at present doesn't justify this claim.

 

This vaccine will certainly save lives, and so is absolutely an advance, but (unless I'm completely mistaken and I'm not any kind of epidemiologist or very knowledgeable about infectious disease) it would be impossible to get effective herd immunity using this vaccine alone.

 

If you vaccinated every single citizen in a country with a vaccine with an  efficacy of 60%, 60% would become immune (I am here assuming the immunity prevents transmission -itself not actually proven yet) - however all the estimates I've read suggest you need 70+% immunity to stop transmission effectively.

 

A lot of the celebration over the apparent high efficacy of the Oxford AstraZeneca derived from the fact that there is no cold chain requirement and it's cheap, so developing countries could use it more readily.

This is still true, but to stop the pandemic  other vaccines will have to be used simultaneously.

 

 

 

 

 

Yes.  It's not as good as Pfizer and Moderna.  In fact it more closely resembles the common flu vaccine.  I suspect that will be the way with the cheaper products.  The Pfizer and Moderna vaccines are exceptional.

 

It's not just about primary efficacy. The stated aim all along of the Oxford vaccine is to prevent serious illness and hospitalization, and death of course. It could do this admirably.  In fact initial figures point to this, whereas the Pfizer vaccine did have one casualty (although to my mind this is not statistically significant).  Even if a person is one of the 40% who does not get full protection, it is likely that the course of their disease will be much milder. I would have thought all the vaccines will reduce onward transmission too. 

 

I think herd immunity occurs at a lower number.  This is because 20-40% tend not to get an infection regardless- innate immunity we might call it.  Then of course at least 10% in the community will have acquired immunity having suffered the disease already.  These figures are illustrators only just to explain the point and of course there is overlap.  But we do know that it is about getting the R number below 1.  

 

We don't know that the 62% efficacy rate won't be improved upon, perhaps to 70% or more, or even the stated hope of up to 90%.  And equally we should not become mono focused on this one figure. But eradication is a bit of a holy grail.  Perhaps as many as 20% will decline to be vaccinated, possibly even more so when the extent of initial side effects becomes truly known. And the 2 dose regime will add to the attrition particularly if someone suffers a nasty reaction to the first dose. 

 

The Oxford jab will at the very least make a big dent in the infection all over the world.  Maybe it's all we have really, until logistics are refined with the other two, but even then they are too expensive, so it would be a pity if a smear campaign brings it down, because it is in fact right now efficacious (>50%) and safe by WHO standards.

 

But eradication is a bit of a holy grail anyway.

 

The main fear is that all the furore over incidentals, makes Joe Public believe the Oxford vaccine isn't safe or effective.  We can see that with one person on this thread already.

 

 

Edited November 27, 2020 by mommysboy

[placeholder]

On 11/26/2020 at 4:12 PM, Traubert said:

Somewhere between the beginning and end.

 

That's enough of your passive/aggressive bullying. Onto ignore with you.

Sure. passive - aggressive means asking to back up your claims? You made a claim and couldn't back it up. You got caught in your own dishonesty and now you've run away.  I don't know if your behavior qualifies as passive-aggressive but If anyone was trolling here it was you.

[GroveHillWanderer]

On 11/27/2020 at 11:47 AM, mommysboy said:

Yes.  It's not as good as Pfizer and Moderna.  In fact it more closely resembles the common flu vaccine.  I suspect that will be the way with the cheaper products.  The Pfizer and Moderna vaccines are exceptional.

 

It's not just about primary efficacy. The stated aim all along of the Oxford vaccine is to prevent serious illness and hospitalization, and death of course. It could do this admirably.  In fact initial figures point to this, whereas the Pfizer vaccine did have one casualty (although to my mind this is not statistically significant).  Even if a person is one of the 40% who does not get full protection, it is likely that the course of their disease will be much milder. I would have thought all the vaccines will reduce onward transmission too. 

 

I think herd immunity occurs at a lower number.  This is because 20-40% tend not to get an infection regardless- innate immunity we might call it.  Then of course at least 10% in the community will have acquired immunity having suffered the disease already.  These figures are illustrators only just to explain the point and of course there is overlap.  But we do know that it is about getting the R number below 1.  

 

We don't know that the 62% efficacy rate won't be improved upon, perhaps to 70% or more, or even the stated hope of up to 90%.  And equally we should not become mono focused on this one figure. But eradication is a bit of a holy grail.  Perhaps as many as 20% will decline to be vaccinated, possibly even more so when the extent of initial side effects becomes truly known. And the 2 dose regime will add to the attrition particularly if someone suffers a nasty reaction to the first dose. 

 

The Oxford jab will at the very least make a big dent in the infection all over the world.  Maybe it's all we have really, until logistics are refined with the other two, but even then they are too expensive, so it would be a pity if a smear campaign brings it down, because it is in fact right now efficacious (>50%) and safe by WHO standards.

 

But eradication is a bit of a holy grail anyway.

 

The main fear is that all the furore over incidentals, makes Joe Public believe the Oxford vaccine isn't safe or effective.  We can see that with one person on this thread already.

Best post on the Oxford vaccine that I've seen yet.

[VocalNeal]

On 11/27/2020 at 11:47 AM, mommysboy said:

Yes.  It's not as good as Pfizer and Moderna.

 

Not as good as the figures released by Pfizer and Moderna.? 

[mommysboy]

Just now, VocalNeal said:

 

Not as good as the figures released by Pfizer and Moderna.? 

 

Yes.  We can't really comment on the veracity of those figures, although it may be Astrazeneca trials have been more scrupulous.