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Post by dan1 on Nov 24, 2020 22:01:38 GMT
Interesting article from Sky News last night.
AZ were monitoring people on the vaccine trial for possible side effects when they noticed that a significant group appeared to be reporting less issues than the rest. On further investigation it was found that about 3000 people had accidentally been given only 50% of the planned dose. Rather than abandon these trials they carried on and gave them the full second dose to see what happened.
As was noted at the time, this could be on a par with Fleming accidentally inventing penicillin.
Putting aside the accidental nature of this half-dose for one minute, will it delay approval from the regulators (MHRA, FDA)? From what I can gather the 90% efficacy is from 2,741 participants whereas the full dose 62% efficiacy is from 8,895 participants. Will they need to enrol more participants in the half dose variant to satisfy the regulators? Can the full dose variant be used as read across to support the safety data of the half dose? I guess the 62% efficiacy with no serious cases is more than good enough yet in the context of Pfizer-BioNTech, Moderna, and the half dose perhaps no longer acceptable? I wonder what the probability that the efficacies of the two cohorts are one and the same given the confidence intervals must overlap? At least we got a fairly candid disclosure, probably as a result of AZN's listing and rules on price sensitive info.
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michaelc
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Post by michaelc on Nov 24, 2020 23:01:42 GMT
Interesting article from Sky News last night.
AZ were monitoring people on the vaccine trial for possible side effects when they noticed that a significant group appeared to be reporting less issues than the rest. On further investigation it was found that about 3000 people had accidentally been given only 50% of the planned dose. Rather than abandon these trials they carried on and gave them the full second dose to see what happened.
As was noted at the time, this could be on a par with Fleming accidentally inventing penicillin.
Putting aside the accidental nature of this half-dose for one minute, will it delay approval from the regulators (MHRA, FDA)? From what I can gather the 90% efficacy is from 2,741 participants whereas the full dose 62% efficiacy is from 8,895 participants. Will they need to enrol more participants in the half dose variant to satisfy the regulators? Can the full dose variant be used as read across to support the safety data of the half dose? I guess the 62% efficiacy with no serious cases is more than good enough yet in the context of Pfizer-BioNTech, Moderna, and the half dose perhaps no longer acceptable? I wonder what the probability that the efficacies of the two cohorts are one and the same given the confidence intervals must overlap? At least we got a fairly candid disclosure, probably as a result of AZN's listing and rules on price sensitive info. Two points to make on this highly topical post: 1/ Why would anyone be "happy" to take a vaccine which in due course _might_ be considered inferior to other vaccines? I wouldn't. 2/ When you say 62% is more than good enough it made me think that I'm sure I read somewhere that if a vaccine was just 50% or above it would be approved (assuming safe etc etc). But that would mean in a large trial where you end up with say 100 participants contracting covid19, 50 would be from the placebo group and 50 from the vaccine. Isn't that actually zero efficacy ?
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Post by dan1 on Nov 24, 2020 23:39:08 GMT
Putting aside the accidental nature of this half-dose for one minute, will it delay approval from the regulators (MHRA, FDA)? From what I can gather the 90% efficacy is from 2,741 participants whereas the full dose 62% efficiacy is from 8,895 participants. Will they need to enrol more participants in the half dose variant to satisfy the regulators? Can the full dose variant be used as read across to support the safety data of the half dose? I guess the 62% efficiacy with no serious cases is more than good enough yet in the context of Pfizer-BioNTech, Moderna, and the half dose perhaps no longer acceptable? I wonder what the probability that the efficacies of the two cohorts are one and the same given the confidence intervals must overlap? At least we got a fairly candid disclosure, probably as a result of AZN's listing and rules on price sensitive info. Two points to make on this highly topical post: 1/ Why would anyone be "happy" to take a vaccine which in due course _might_ be considered inferior to other vaccines? I wouldn't. 2/ When you say 62% is more than good enough it made me think that I'm sure I read somewhere that if a vaccine was just 50% or above it would be approved (assuming safe etc etc). But that would mean in a large trial where you end up with say 100 participants contracting covid19, 50 would be from the placebo group and 50 from the vaccine. Isn't that actually zero efficacy ? 1. Needs must, availability, accessibility, cost? Efficacy isn't everything remember. Lessening severity must be pretty important too. 2. To make the maths easier, say 150 contracted it, then 50 in vaccine group and 100 in control group equates to 50% efficacy assuming equal numbers of participants in each group.
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Post by moonraker on Nov 25, 2020 8:11:54 GMT
1/ Why would anyone be "happy" to take a vaccine which in due course _might_ be considered inferior to other vaccines? I wouldn't. I don't suppose individuals will be offered a choice of which vaccine to take, especially with different storage requirements (some quite demanding) for those already announced. To me, as a complete layman, it seems that the Astrazeneca one isn't as effective as others.
Not that at this stage I can be bothered to make detailed comparisons. If I believe the optimism, I can expect to be offered a jab in the New Year, by which time countless analyses will have been published, some doubtless contradicting others.
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IFISAcava
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Post by IFISAcava on Nov 25, 2020 9:03:21 GMT
1/ Why would anyone be "happy" to take a vaccine which in due course _might_ be considered inferior to other vaccines? I wouldn't. I don't suppose individuals will be offered a choice of which vaccine to take, especially with different storage requirements (some quite demanding) for those already announced. To me, as a complete layman, it seems that the Astrazeneca one isn't as effective as others.
Not that at this stage I can be bothered to make detailed comparisons. If I believe the optimism, I can expect to be offered a jab in the New Year, by which time countless analyses will have been published, some doubtless contradicting others.
The AZ vaccine may not be as efficacious (ie how it works in ideal controlled circumstances) although 1. the jury is still out pending final peer reviewed results and long term follow up and 2. it depends on the outcome chosen - so far all the stats we are seeing mention total number of cases, whereas what really matters is number of severe cases and number of onward transmissions. But it may be more effective (ie how it works in real world use) insofar as you can get it more quickly (70% now as opposed to 90% in 6 months time, and reducing transmission rates for the non-vaccinated as herd immunity builds) and you can get it at all (the logistics of -80C distribution is not straightforward). And it may be more cost-effective in that it is 5-10 times cheaper. The speed at which all of these effective vaccines have been developed is amazing. Bodes well for the future.
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IFISAcava
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Post by IFISAcava on Nov 25, 2020 9:10:13 GMT
Perhaps we should talk more about Greece. They spent very little yet have one of the lowest death rates in Europe. (And so much for those suggesting that Spain and Italy are worst affected because of their Mediterranean culture.) I've spent four months in Spain and three in Greece this year. Not that this makes me particularly eligible to answer the question, just thought I'd get that in there Anyway, I would guess the reasons for this are: 1) Same story as PL/Romania in Spring, they locked down hard & fast. 2) Greece is also locked down quite hard now. I 'participated' in that, and had to fill in an A4 paper form every time I left the house to be able to show to the police. 3) Spain and Greece in my view are more different culturally than you might imagine. Greeks are far less touchy/feely than Spaniards on the whole, and the sort of parties that Spain loves to have are far less frequent there. 4) Finally, Greece has a much lower population and population density. Lots of islands and a population of just 10m. What it certainly isn't is any particular clever systems or anything like that, they had no cash for that. The Greeks also certainly are not 'good' with masks (spanish much better) either. They just locked down properly, closing bars/restaurants and keeping people indoors before cases started spiralling upwards. It's a blunt instrument, it works, and every day you delay doing it causes an exponential rise in cases. You must know a different type of Greek to me. Very touchy and kissy culture, both male and female. Although admittedly I don't know Spain that well so perhaps even more so there. Also current Greek death rate is not good - worse then the UK and still rapidly rising. Health service about to be overwhelmed. Not good at all there.
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agent69
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Post by agent69 on Nov 25, 2020 9:17:13 GMT
Interesting article from Sky News last night.
AZ were monitoring people on the vaccine trial for possible side effects when they noticed that a significant group appeared to be reporting less issues than the rest. On further investigation it was found that about 3000 people had accidentally been given only 50% of the planned dose. Rather than abandon these trials they carried on and gave them the full second dose to see what happened.
As was noted at the time, this could be on a par with Fleming accidentally inventing penicillin.
Putting aside the accidental nature of this half-dose for one minute, will it delay approval from the regulators (MHRA, FDA)? From what I can gather the 90% efficacy is from 2,741 participants whereas the full dose 62% efficiacy is from 8,895 participants. Will they need to enrol more participants in the half dose variant to satisfy the regulators? Can the full dose variant be used as read across to support the safety data of the half dose? I guess the 62% efficiacy with no serious cases is more than good enough yet in the context of Pfizer-BioNTech, Moderna, and the half dose perhaps no longer acceptable? I wonder what the probability that the efficacies of the two cohorts are one and the same given the confidence intervals must overlap? At least we got a fairly candid disclosure, probably as a result of AZN's listing and rules on price sensitive info. If they are getting less of the vaccine than the main group you wouldn't have thought that medically it would be an issue.
Subject to availability I wonder if we might have a 2 tier system:
- people in the higher risk group get the higher cost 95% effective vaccine
- people in low risk group get the cheaper, more easily available, less effective vacine.
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Post by dan1 on Nov 25, 2020 9:27:35 GMT
Putting aside the accidental nature of this half-dose for one minute, will it delay approval from the regulators (MHRA, FDA)? From what I can gather the 90% efficacy is from 2,741 participants whereas the full dose 62% efficiacy is from 8,895 participants. Will they need to enrol more participants in the half dose variant to satisfy the regulators? Can the full dose variant be used as read across to support the safety data of the half dose? I guess the 62% efficiacy with no serious cases is more than good enough yet in the context of Pfizer-BioNTech, Moderna, and the half dose perhaps no longer acceptable? I wonder what the probability that the efficacies of the two cohorts are one and the same given the confidence intervals must overlap? At least we got a fairly candid disclosure, probably as a result of AZN's listing and rules on price sensitive info. If they are getting less of the vaccine than the main group you wouldn't have thought that medically it would be an issue.
Subject to availability I wonder if we might have a 2 tier system:
- people in the higher risk group get the higher cost 95% effective vaccine
- people in low risk group get the cheaper, more easily available, less effective vacine.
To be honest, given a choice*, I'd rather not take Ox/AZN vaccine until I learn more about the cluster**** that is injecting folk with the wrong dose of a experimental treatment. This is way more serious an error than leaving some mold to grow in a petri dish. How the **** can they make that mistake? Jesus *yes, I realise I will have no choice unless I splash out mega bucks - I'll be lucky to be offered any vaccine!
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IFISAcava
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Post by IFISAcava on Nov 25, 2020 9:31:18 GMT
If they are getting less of the vaccine than the main group you wouldn't have thought that medically it would be an issue.
Subject to availability I wonder if we might have a 2 tier system:
- people in the higher risk group get the higher cost 95% effective vaccine
- people in low risk group get the cheaper, more easily available, less effective vacine.
To be honest, given a choice*, I'd rather not take Ox/AZN vaccine until I learn more about the cluster**** that is injecting folk with the wrong dose of a experimental treatment. This is way more serious an error than leaving some mold to grow in a petri dish. How the **** can they make that mistake? Jesus *yes, I realise I will have no choice unless I splash out mega bucks - I'll be lucky to be offered any vaccine! 2000+ given the wrong dose. That's a pretty serious error. Not clear where the error crept in.
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Greenwood2
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Post by Greenwood2 on Nov 25, 2020 10:04:45 GMT
To be honest, given a choice*, I'd rather not take Ox/AZN vaccine until I learn more about the cluster**** that is injecting folk with the wrong dose of a experimental treatment. This is way more serious an error than leaving some mold to grow in a petri dish. How the **** can they make that mistake? Jesus *yes, I realise I will have no choice unless I splash out mega bucks - I'll be lucky to be offered any vaccine! 2000+ given the wrong dose. That's a pretty serious error. Not clear where the error crept in. At least it was half the dose not twice the dose, so an error in the safe direction. Surely it must mean the phials distributed to those doctors involved were a half dose, I wouldn't have thought you would give half a phial, or that two phials would be needed for a full dose. Edit: Or would the trial vaccine be in a larger bottle and drawn up, in which case just the wrong measure used.
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r00lish67
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Post by r00lish67 on Nov 25, 2020 10:56:05 GMT
You must know a different type of Greek to me. Very touchy and kissy culture, both male and female. Although admittedly I don't know Spain that well so perhaps even more so there. Also current Greek death rate is not good - worse then the UK and still rapidly rising. Health service about to be overwhelmed. Not good at all there. Yes, good point. Thessaloniki and Athens hospitals weren't the best to begin with and are struggling. edit: Re: touchy feeliness, it probably varies a lot even within both countries I'd imagine. Islands more than mainland (Greece), South more than North (Spain) ...<he says, speculating wildly>
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michaelc
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Post by michaelc on Nov 25, 2020 14:45:23 GMT
2/ When you say 62% is more than good enough it made me think that I'm sure I read somewhere that if a vaccine was just 50% or above it would be approved (assuming safe etc etc). But that would mean in a large trial where you end up with say 100 participants contracting covid19, 50 would be from the placebo group and 50 from the vaccine. Isn't that actually zero efficacy ? 2. To make the maths easier, say 150 contracted it, then 50 in vaccine group and 100 in control group equates to 50% efficacy assuming equal numbers of participants in each group. Somethings not right. The real numbers for Pfizer are 170 with Covid, 162 from placebo and 8 from vaccine group. That gave them the figure of 95%. 162/170 is 95%. So doing the same thing, in your example we'd have 100/150 which is 67%. That is where my confusion lies. And to think I used to be a mathematician haha....
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mrk
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Post by mrk on Nov 25, 2020 14:57:27 GMT
2. To make the maths easier, say 150 contracted it, then 50 in vaccine group and 100 in control group equates to 50% efficacy assuming equal numbers of participants in each group. Somethings not right. The real numbers for Pfizer are 170 with Covid, 162 from placebo and 8 from vaccine group. That gave them the figure of 95%. 162/170 is 95%. So doing the same thing, in your example we'd have 100/150 which is 67%. That is where my confusion lies. dan1 is right. 0% efficacy means the vaccine is exactly as effective as the placebo, i.e. not effective at all. So if you have 100 cases in the placebo group, you have 100 cases in the vaccine group as well. 50% efficacy means the vaccine prevents 50% of cases compared to the placebo. So if 100 are in the placebo, 50 are in the vaccine group. Pfizer had 162 in placebo and 8 in vaccine. That means the vaccine avoided 162 - 8 = 154 cases. That's 154 / 162 = 95% of cases avoided. It's just a coincidence that in this case you get roughly the same number by using the "wrong" 162/170 formula.
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Post by bracknellboy on Nov 25, 2020 15:50:38 GMT
Somethings not right. The real numbers for Pfizer are 170 with Covid, 162 from placebo and 8 from vaccine group. That gave them the figure of 95%. 162/170 is 95%. So doing the same thing, in your example we'd have 100/150 which is 67%. That is where my confusion lies. dan1 is right. 0% efficacy means the vaccine is exactly as effective as the placebo, i.e. not effective at all. So if you have 100 cases in the placebo group, you have 100 cases in the vaccine group as well. 50% efficacy means the vaccine prevents 50% of cases compared to the placebo. So if 100 are in the placebo, 50 are in the vaccine group. Pfizer had 162 in placebo and 8 in vaccine. That means the vaccine avoided 162 - 8 = 154 cases. That's 154 / 162 = 95% of cases avoided. It's just a coincidence that in this case you get roughly the same number by using the "wrong" 162/170 formula.Not quite a co-incidence though . Its more a mathematical certainty in that the higher the actual efficacy, in both calculations (right and wrong) the value of the numerator trends towards the value of the denominator, and hence comes out with very similar high %age numbers. At lower success rates, they trend apart with at the extreme end (=completely useless), the wrong calculation giving an effective rate of 50% with the right calculation giving an effective rate of 0%.
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Post by dan1 on Nov 25, 2020 15:52:27 GMT
2. To make the maths easier, say 150 contracted it, then 50 in vaccine group and 100 in control group equates to 50% efficacy assuming equal numbers of participants in each group. Somethings not right. The real numbers for Pfizer are 170 with Covid, 162 from placebo and 8 from vaccine group. That gave them the figure of 95%. 162/170 is 95%. So doing the same thing, in your example we'd have 100/150 which is 67%. That is where my confusion lies. And to think I used to be a mathematician haha.... Here's a good read on the maths behind vaccine efficacy... medium.com/swlh/the-fascinating-math-powering-the-covid-19-vaccine-trials-930a5e97c9c9e.g. for my example above assume there are 10k participants for the control and 9999 for the vaccine (someone didn't turn up for their second dose).... VE = 1 - (50/9999)/(100/10000) = 50% (almost!)
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