SARS CoV-2 coronavirus / Covid-19 (No tin foil hat silliness please)

[Pogue Mahone]

AZ vaccine only 8% effective in over 65s?
Corona-News am Montag: AstraZeneca-Impfstoff laut Bericht bei Risikogruppe kaum wirksam - DER SPIEGEL

Dunno what their sources are but they’re predicting that the EMA won’t give a license for use in >65yo because they were so poorly represented in the trials (and evidently didn’t get a great response)

It does fit with how they supposedly got their best efficacy in the half dose/full dose cohort. That cohort were all under 55 (can’t remember exactly, if not all then most?) so it was always a possibility that dose was a red herring and being young the main driver for good efficacy.

Such a fecking mess though. Really poor effort at running a phase III program.

 

[redshaw]

Well at least the production delays don’t matter that much anymore!

Yes possibly.

They'll want it for under 65s though and seems they're furious about delays and want to know where it's been produced and delivered to for potential exporting banning to third countries.

Press statement by Commissioner Kyriakides (europa.eu)
"You know that AstraZeneca's vaccine is currently in the final stages of the approval process with the European Medicines Agency.

If all requirements are met, the European Medicines Agency could recommend market authorisation by the end of this week.

But there is a problem on the supply side.

Last Friday, the company AstraZeneca surprisingly informed the Commission and the European Union Member States that it intends to supply considerably fewer doses in the coming weeks than agreed and announced.

This new schedule is not acceptable to the European Union.

That is why I wrote a letter to the company at the weekend in which I asked important and serious questions.

The European Union has pre-financed the development of the vaccine and the production and wants to see the return.

The European Union wants to know exactly which doses have been produced by AstraZeneca and where exactly so far and if or to whom they have been delivered.

These questions were also discussed today in the joint Steering Board of the Commission and the 27 Member States with AstraZeneca.

The answers of the company have not been satisfactory so far. That's why a second meeting is scheduled for tonight.

The European Union wants the ordered and pre-financed doses to be delivered as soon as possible. And we want our contract to be fully fulfilled.

In addition, the Commission has today proposed to the 27 Member States in the Steering Board that an export transparency mechanism will be put in place as soon as possible.

The European Union has supported the rapid development and production of several vaccines against COVID-19 with a total of €2.7 billion.

We want clarity on transactions and full transparency concerning the export of vaccines from the EU.

In the future, all companies producing vaccines against COVID-19 in the EU will have to provide early notification whenever they want to export vaccines to third countries.
"

 

[massi83]

Yes possibly.

They'll want it for under 65s though and seems they're furious about delays and want to know where it's been produced and delivered to for potential exporting banning to third countries.

Press statement by Commissioner Kyriakides (europa.eu)
"You know that AstraZeneca's vaccine is currently in the final stages of the approval process with the European Medicines Agency.

If all requirements are met, the European Medicines Agency could recommend market authorisation by the end of this week.

But there is a problem on the supply side.

Last Friday, the company AstraZeneca surprisingly informed the Commission and the European Union Member States that it intends to supply considerably fewer doses in the coming weeks than agreed and announced.

This new schedule is not acceptable to the European Union.

That is why I wrote a letter to the company at the weekend in which I asked important and serious questions.

The European Union has pre-financed the development of the vaccine and the production and wants to see the return.

The European Union wants to know exactly which doses have been produced by AstraZeneca and where exactly so far and if or to whom they have been delivered.

These questions were also discussed today in the joint Steering Board of the Commission and the 27 Member States with AstraZeneca.

The answers of the company have not been satisfactory so far. That's why a second meeting is scheduled for tonight.

The European Union wants the ordered and pre-financed doses to be delivered as soon as possible. And we want our contract to be fully fulfilled.

In addition, the Commission has today proposed to the 27 Member States in the Steering Board that an export transparency mechanism will be put in place as soon as possible.

The European Union has supported the rapid development and production of several vaccines against COVID-19 with a total of €2.7 billion.

We want clarity on transactions and full transparency concerning the export of vaccines from the EU.

In the future, all companies producing vaccines against COVID-19 in the EU will have to provide early notification whenever they want to export vaccines to third countries.
"

Yeah obviously. Just a joke. Such shit news that what else is there to say. I am hopeful still that the numbers are not that bad, if they are, how could UK approve it.

 

[Pogue Mahone]

Yeah obviously. Just a joke. Such shit news that what else is there to say. I am hopeful still that the numbers are not that bad, if they are, how could UK approve it.

I know, right? In my experience the MHRA are super detail focused and competent. They have to be. That’s their main job description. Seems impossible they could have missed such a gross deficiency in the data.

 

[worldgonemad]

AZ vaccine only 8% effective in over 65s?
Corona-News am Montag: AstraZeneca-Impfstoff laut Bericht bei Risikogruppe kaum wirksam - DER SPIEGEL

@redshaw, I don't suppose you have a link to an English source do you?

 

[carpy]

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[jojojo]

AZ vaccine only 8% effective in over 65s?
Corona-News am Montag: AstraZeneca-Impfstoff laut Bericht bei Risikogruppe kaum wirksam - DER SPIEGEL

I'd be interested in reading how the number was derived. The AZ Phase3 trial had a lot of flaws and the research report was a confusing read but 8%? Presumably there's been a new dataset released? If so, has anyone got a link?

Back in December when they did their first published results they only had a tiny number of cases in the over 55s trial - just 5 cases included in the original review. The criticism at the time was that they had too few over 55 test subjects/cases to say anything useful on efficacy, and nothing to report in the over 70s other than minimal side-effects and decent immune response measurements.

 

[redshaw]

@redshaw, I don't suppose you have a link to an English source do you?

No sorry, you'll have to use a translate tool or perhaps a German member can give more details. @do.ob

 

[worldgonemad]

No sorry, you'll have to use a translate tool or perhaps a German member can give more details. @do.ob

Thanks for that. I can only imagine numbers of over 65s in the trial were VERY low as a percentage of the total. Otherwise the UKs vaccine program will surely be in complete disarray.
On a personal note, my mam got her 1st jab yesterday ( 71 yrs old with copd)
Hopefully these reports turn out to be exaggerated or inaccurate.

 

[Mickeza]

To call that Bild story irresponsible would be putting it mildly. No named sources. IF true it would bring the Government down. However, considering they only have access to the same trial data we have then I don’t see how they can possibly know. Plus they called it a highly effective vaccine a week ago before 60% of their supply got cut.

 

[Rooney1987]

AZ vaccine only 8% effective in over 65s?
Corona-News am Montag: AstraZeneca-Impfstoff laut Bericht bei Risikogruppe kaum wirksam - DER SPIEGEL

I might be cynical here but it does seem oddly timed that a story about the Oxford vaccine coincided with the fact there is EU supply issues for the Oxford vaccine.

 

[redshaw]

Thanks for that. I can only imagine numbers of over 65s in the trial were VERY low as a percentage of the total. Otherwise the UKs vaccine program will surely be in complete disarray.
On a personal note, my mam got her 1st jab yesterday ( 71 yrs old with copd)
Hopefully these reports turn out to be exaggerated or inaccurate.

I hope so too. Seems at best more data is required and will be surely above that but this report may trying to spin a story on low data.

Still, I remember seeing the data quickly and thinking it's flawed and how would one determine.

 

[Pogue Mahone]

Thanks for that. I can only imagine numbers of over 65s in the trial were VERY low as a percentage of the total. Otherwise the UKs vaccine program will surely be in complete disarray.
On a personal note, my mam got her 1st jab yesterday ( 71 yrs old with copd)
Hopefully these reports turn out to be exaggerated or inaccurate.

To call that Bild story irresponsible would be putting it mildly. No named sources. IF true it would bring the Government down. However, considering they only have access to the same trial data we have then I don’t see how they can possibly know. Plus they called it a highly effective vaccine a week ago before 60% of their supply got cut.

Just looking back at the Lancet publication (that’s how exciting my life is these days) Only 418 out of the 11600 subjects in the primary analysis were aged 70+. So was always going to be a stretch to be confident it works in elderly.

Likely that EMA got data cuts that weren’t available at time of MHRA submission. Assuming still very small numbers of >70yo would only take a few cases of covid in the vaccine arm to completely undermine efficacy data submitted in UK. If that’s the case then the MHRA will have to amend Uk license.

Interesting few days ahead!

Should also say, re-reading the Lancet paper reminded me what an absolute fecking shambles it was. I still think/hope it’s a decent vaccine but they made an awful bollix of proving it. On the plus side, there’s more data being generated all the time. So at some point there will be really solid evidence to work through.

 

[Camy89]

I received my first dose last Monday, only had a sore arm for a few days. Irritatingly I was given a hand out explaining my second dose due in 21-28 days. My appointment for dose 2 is the 30th March...

It's likely been done to death in here, but i find it insane the UK can just prolong the interim period on a whim. Pretty sure Pfizer themselves questioned this move. UK government knobs.

 

[Pogue Mahone]

To be fair to everyone involved this is all completely unprecedented in terms of the speed involved. This whole “rolling review” they’re doing means the goalposts move from one analysis to the next. Submission to approval usually 6 months, with all studies closed out beforehand. These approvals have been done with studies still recruiting. Crazy stuff really. But all for the greater good, so (arguably) worth the risk.

 

[worldgonemad]

Just looking back at the Lancet publication (that’s how exciting my life is these days) Only 418 out of the 11600 subjects in the primary analysis were aged 70+. So was always going to be a stretch to be confident it works in elderly.

Likely that EMA got data cuts that weren’t available at time of MHRA submission. Assuming still very small numbers of >70yo would only take a few cases of covid in the vaccine arm to completely undermine efficacy data submitted in UK. If that’s the case then the MHRA will have to amend Uk license.

Interesting few days ahead!

Should also say, re-reading the Lancet paper reminded me what an absolute fecking shambles it was. I still think/hope it’s a decent vaccine but they made an awful bollix of proving it. On the plus side, there’s more data being generated all the time. So at some point there will be really solid evidence to work through.

What happens if it turns out it really does have low effectiveness in over 65s though pogue? Would they then be able to re vaccinate those age groups with the other vaccines?

 

[Dumbstar]

What happens if it turns out it really does have low effectiveness in over 65s though pogue? Would they then be able to re vaccinate those age groups with the other vaccines?

Also what is the proven efficacy for under 60s? If it's 80%+ the AZ vaccine can be started on the younger community earlier? Police, teachers, etc.

 

[Camy89]

What happens if it turns out it really does have low effectiveness in over 65s though pogue? Would they then be able to re vaccinate those age groups with the other vaccines?

I know you didn't ask me, but personally I think this would be unlikely - both for it having a low efficacy in over 65's and using the other vaccines. I have read that they would wish to avoid concomitant vaccines (within a certain time period anyway).

It doesn't make sense in my head that just due to your age, the vaccine should be so significantly less effective. My haematology and oncology patients likely wont be able to mount such a robust response obviously due to being immunosuppressed, but a majority of over 65's don't have a significantly impaired immune system so should be able to respond appropriately.

Like Pogue mentioned, I reckon this has been extrapolated dubiously from the study and made into a headline.

 

[Tibs]

Interesting development re Oxford vaccine. Hopefully bullshit

 

[arnie_ni]

Interesting development re Oxford vaccine. Hopefully bullshit

?

 

[worldgonemad]

I know you didn't ask me, but personally I think this would be unlikely - both for it having a low efficacy in over 65's and using the other vaccines. I have read that they would wish to avoid concomitant vaccines (within a certain time period anyway).

It doesn't make sense in my head that just due to your age, the vaccine should be so significantly less effective. My haematology and oncology patients likely wont be able to mount such a robust response obviously due to being immunosuppressed, but a majority of over 65's don't have a significantly impaired immune system so should be able to respond appropriately.

Like Pogue mentioned, I reckon this has been extrapolated dubiously from the study and made into a headline.

Thanks for this Camy. I do hope you are right. I find it astounding though that the Germans, for whatever reason, think its acceptable to play such high stake feckwittery. You just know the anti vaxxers out there will be frothy over this and if doubt in this vaccine takes hold, it could easily pass to the others

 

[Wolverine]

Nothing wrong with being pedantic!

In addition if you look at the twitter thread it seems like they haven't even tested all of the 128.000, only people with known exposures or symptoms. So the 99.99% is even more inaccurate.

Of course there would have been plenty of asymptomatic and potentially infectious patients. So you are right. But if your clinical end point with regards to efficacy is preventing severe manifestation of the disease (and in real terms thats the most significant for preventing health systems becoming overwhelmed) then its good news that no body in the vaccine side/arm got really unwell.

 

[Pogue Mahone]

I know you didn't ask me, but personally I think this would be unlikely - both for it having a low efficacy in over 65's and using the other vaccines. I have read that they would wish to avoid concomitant vaccines (within a certain time period anyway).

It doesn't make sense in my head that just due to your age, the vaccine should be so significantly less effective. My haematology and oncology patients likely wont be able to mount such a robust response obviously due to being immunosuppressed, but a majority of over 65's don't have a significantly impaired immune system so should be able to respond appropriately.

Like Pogue mentioned, I reckon this has been extrapolated dubiously from the study and made into a headline.

Also. Absence of evidence isn’t evidence of absence. I’m sure that was rammed into you in med school! Just because they haven’t adequately proved it works in elderly people doesn’t mean it won’t work in elderly people. If there are doubts about efficacy in the elderly it doesn’t help that the number of elderly people in the study is so low. 97%+ in primary analysis 69 or younger. They only started recruiting 70+ yo’s late in the day. So there’ll be more and data on this age group in the weeks/months ahead.

 

[Camy89]

Also. Absence of evidence isn’t evidence of absence. I’m sure that was rammed into you in med school! Just because they haven’t adequately proved it works in elderly people doesn’t mean it won’t work in elderly people. If there are doubts about efficacy in the elderly it doesn’t help that the number of elderly people in the study is so low. 97%+ in primary analysis 69 or younger. They only started recruiting 70+ yo’s late in the day. So there’ll be more and data on this age group in the weeks/months ahead.

Yep yep, definitely rammed into my head! I was just using my own thoughts physiologically.

I remain confident there'll be good data/more reliable coming out for them. What worries me is that articles like this can erode public trust very quickly. Until statistically significant evidence is available, these stories don't help with the relief effort!

 

[groovyalbert]

Had a work meeting with someone based in Israel. 40 years old, fit as a fiddle, first dose received and second scheduled for 2 weeks time.

I know their population is way smaller, and they've only got 3 health bodies which means coordination is way easier, but they've done so well to avoid all the BS bureaucracy which is just infuriating here. I mean, you currently have King's College in London throwing away doses on a daily basis because they're only permitted to give it to people affiliated to the university in some way. It's actually grotesque.

 

[Mickeza]

https://www.theguardian.com/world/2...-astrazeneca-shortfall?CMP=Share_iOSApp_Other

 

[jojojo]

AZ didn't have sufficient case numbers amongst the over 55s to quote efficacy, and even less for the over 70s. They did however do tests for antibodies produced, which they used to suggest that they were expecting similar results across agegroups.

From the December AZ report:
We have reported immunogenicity data showing similar immune responses following vaccination with two
doses of ChAdOx1 nCov-19 in older adults, including those older than 70 years of age, when compared with those
younger than 55 years.6 As older age groups were recruited later than younger age groups, there has been less time for cases to accrue and as a result, efficacy data in these cohorts are currently limited by the small number of cases, but additional data will be available in future analyses.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext

If there's new data with EMA, then that will be quite a revelation. Hopefully the story in Bild is a misrepresentation.

 

[Pogue Mahone]

They didn't have sufficient case numbers amongst the over 55s to quote efficacy, and even less for the over 70s. They did however do tests for antibodies produced, which they used to suggest that they were expecting similar results.

From the December AZ report:
We have reported immunogenicity data showing similar immune responses following vaccination with two
doses of ChAdOx1 nCov-19 in older adults, including those older than 70 years of age, when compared with those
younger than 55 years.6 As older age groups were recruited later than younger age groups, there has been less time for cases to accrue and as a result, efficacy data in these cohorts are currently limited by the small number of cases, but additional data will be available in future analyses.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext

If there's new data with EMA, then that will be quite a revelation.

If the rumour in Bild is true then either the EMA is insisting on hard clinical endpoints to demonstrate efficacy in the elderly or they’ve seen a more recent dataset.

When you take a step back, it is quite a big ask to license this for use in the elderly based on such scanty data.

 

[jojojo]

If the rumour in Bild is true then either the EMA is insisting on hard clinical endpoints to demonstrate efficacy in the elderly or they’ve seen a more recent dataset.

When you take a step back, it is quite a big ask to license this for use in the elderly based on such scanty data.

The small number of test subjects in the over 70s group is worrying in itself. When you combine it with the relatively small number of test subjects in the over 55 group it seems even worse. Especially as almost all those over 55s come into the trial quite late (and the over 70s later). Only 5 cases included in that report from the over 55 cohort.

I can believe that the trial ran for long enough to pick up safety data from the over 55s, but there's no actual efficacy data in the December paper. It all seems to rely on the antibody data.

 

[Pogue Mahone]

The small number of test subjects in the over 70s group is worrying in itself. When you combine it with the relatively small number of test subjects in the over 55 group it seems even worse. Especially as almost all those over 55s come into the trial quite late (and the over 70s later). Only 5 cases included in that report from the over 55 cohort.

I can believe that the trial ran for long enough to pick up safety data from the over 55s, but there's no actual efficacy data in the December paper. It all seems to rely on the antibody data.

The data in the December publication will have come from an analysis done several weeks before that. So it’s likely that the EMA submission included a more recent analysis, which none of us have seen yet. I agree it’s probably too soon to have generated any solid evidence of efficacy in the elderly. Which may be the sticking point.

 

[T00lsh3d]

Day 4-6(?) today. No noticeable effects at all so far, slight headache and tiredness maybe but that’s a bit of a reach as I’m prone to both. Hoping I’m one of those that’s naturally handled it well but not getting complacent yet

 

[Wibble]

Dunno what their sources are but they’re predicting that the EMA won’t give a license for use in >65yo because they were so poorly represented in the trials (and evidently didn’t get a great response)

It does fit with how they supposedly got their best efficacy in the half dose/full dose cohort. That cohort were all under 55 (can’t remember exactly, if not all then most?) so it was always a possibility that dose was a red herring and being young the main driver for good efficacy.

Such a fecking mess though. Really poor effort at running a phase III program.

That seems like a far bigger drop off than you would normally expect.

 

[Chipper]

Day 4-6(?) today. No noticeable effects at all so far, slight headache and tiredness maybe but that’s a bit of a reach as I’m prone to both. Hoping I’m one of those that’s naturally handled it well but not getting complacent yet

Best of luck with it.

I'm around a week in, not been too bad either. Had light coughing that mostly stopped after 2 or 3 days. Mild headache the whole time, still there now. Eyelids are sensitive to touch. Stiff muscles over the weekend, still slightly there now but easing. Developed a bit of a runny nose the past day or two, can sort of feel it on my chest but not much.

Last Friday was the worst day so far, shivers and feeling dizzy on top of some of the above.

 

[11101]

AZ didn't have sufficient case numbers amongst the over 55s to quote efficacy, and even less for the over 70s. They did however do tests for antibodies produced, which they used to suggest that they were expecting similar results across agegroups.

From the December AZ report:
We have reported immunogenicity data showing similar immune responses following vaccination with two
doses of ChAdOx1 nCov-19 in older adults, including those older than 70 years of age, when compared with those
younger than 55 years.6 As older age groups were recruited later than younger age groups, there has been less time for cases to accrue and as a result, efficacy data in these cohorts are currently limited by the small number of cases, but additional data will be available in future analyses.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext

If there's new data with EMA, then that will be quite a revelation. Hopefully the story in Bild is a misrepresentation.

AZ were told in no uncertain terms that the December data was not enough for EMA approval. There is new data but what it contains is as yet not public.

 

[Pogue Mahone]

AZ were told in no uncertain terms that the December data was not enough for EMA approval. There is new data but what it contains is as yet not public.

I’ll admit that I only just realised the Lancet publication had basically zero efficacy data in the elderly. It looks as though they’re trying to justify use in this cohort based on phase II studies showing an increase in antibodies but with no clinical endpoints. That’s a very big ask. Would be unprecedented.

There surely must be some proper phase III results in >70s by now. It’s just that nobody has seen it apart from AZ and the EMA.

 

[T00lsh3d]

Best of luck with it.

I'm around a week in, not been too bad either. Had light coughing that mostly stopped after 2 or 3 days. Mild headache the whole time, still there now. Eyelids are sensitive to touch. Stiff muscles over the weekend, still slightly there now but easing. Developed a bit of a runny nose the past day or two, can sort of feel it on my chest but not much.

Last Friday was the worst day so far, shivers and feeling dizzy on top of some of the above.

Good luck to you also pal. Hopefully we’re both over the worst

 

[do.ob]

No sorry, you'll have to use a translate tool or perhaps a German member can give more details. @do.ob

-The article credits Handelsblatt as the first to report this. The supposed source are "goverment circles".
-Unlike Bild, Handelsblatt ("trade paper") is not a tabloid
-They ("goverment circles") supposedly calculate with an efficacy of 8% in over 65 year olds, Bild reported that it looks like EMA will only license the vaccine for under 65 year olds
-German goverment is supposedly re-evaluating their age centered vaccine rollout strategy.
-A final result regarding efficacy of the A/Z vaccine is not possible at this point, because studies barely featured older people. MHRA themselves objected that reliable results couldn't be derived from those studies.

 

[golden_blunder]

so who is liable IF it’s proven that AZ has not been tested enough on the older population and if it goes pear shaped?

 

[giggs-beckham]

You are exactly right

Then why didn't you say as such

You are exactly right

I was thinking why you didn't say something similar whilst reading your bicker as it looked like you were prioritising the lives of nhs over other sectors and that's what he was getting at.

 

[jojojo]

There surely must be some proper phase III results in >70s by now. It’s just that nobody has seen it apart from AZ and the EMA.

I'd expect them to give any data like that to the MHRA - and I'd expect the MHRA to insist on it. Of course that might just be an ethical not a legal requirement.

My guess is that the numbers in the over 70 are still too low to narrow the efficacy error margin, and someone is waiting the worst case (and AZ will quote the best)

Anyway, AZ have got some explaining to do today.