AstraZeneca (Latest Trials)

[Bouleversee]

I note that this trial was on the basis of a 4 week interval between doses. I wonder why since we have previously been told that the vaccine is more effective after a 12 week interval, which is what is happening here.

[dealtn]

I note that this trial was on the basis of a 4 week interval between doses. I wonder why since we have previously been told that the vaccine is more effective after a 12 week interval, which is what is happening here.

That was the agreed trial standards proposed by the US Department of Health and Human Services ahead of the Phase III trial start date, which was August 28th 2020. Unsurprisingly a lot has happened, and new information been discovered since then.

So the Phase III trial could have taken place with multiple intervals, to discover the most effective, which would have required many more participants, and taken even longer, or a single interval regime could have been chosen for testing. It isn't hugely controversial for the US Department of Health and Human Services to have favoured the latter approach, especially seeing as this choice needed making in the middle of a pandemic with thousands dying daily.

The phase III trial, as it is, is expected to complete in February 2023. These are long, and exhaustive trials, not something you want to be changing frequently.

https://clinicaltrials.gov/ct2/show/NCT ... w=2&rank=1

[daveh]

I note that this trial was on the basis of a 4 week interval between doses. I wonder why since we have previously been told that the vaccine is more effective after a 12 week interval, which is what is happening here.

Probably because they want to get the results quickly so had chosen a shorter dosing interval, also the trial was probably set up before the data came in about the 12 week interval being better. Is it worth changing your trail at that point if the 4 weeks dosing interval works (which it clearly does)? There is a lot of work involved in issuing a trial amendment, plus the longer interval would push back the results. Better to go with what was initially chosen if it works, get the results earlier and get authorisation in the USA.

[Bouleversee]

Does anyone know how these results compared with the 12 week trials?

[dealtn]

Does anyone know how these results compared with the 12 week trials?

The trials are different (assuming you mean these)

https://www.astrazeneca.com/content/ast ... point.html

https://www.astrazeneca.com/content/ast ... ancet.html

or

https://clinicaltrials.gov/ct2/show/NCT ... w=2&rank=1

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext

So unless you can be specific about what you mean by "compare" the easiest way to your answer your question is for you to read them yourself.

[Bouleversee]

The Today programme reported near the end that there had been another report from the US which was mystifying everyone and they looked forward to hearing more later in the day: https://uk.news.yahoo.com/us-astrazenec ... 31732.html. I daresay it won't amount to anything.

[Nimrod103]

You know what? If I was in charge of Astra I'd tell the world to f-off and take my ball home with me.

Isn't it pretty obvious that this is happening to OxAZ because they are offering the jab to the World at cost price, therefore undermining the vast profits of Pfizer and Moderna, and the kickbacks and payoffs to civil servants and bureaucrats all over the World.

[Lootman]

You know what? If I was in charge of Astra I'd tell the world to f-off and take my ball home with me.

Isn't it pretty obvious that this is happening to OxAZ because they are offering the jab to the World at cost price, therefore undermining the vast profits of Pfizer and Moderna, and the kickbacks and payoffs to civil servants and bureaucrats all over the World.

It just goes to show how gauche AZN is. Its share price is down 3.5% in US trading today, on a day when the good news about that trial should have it going up. It is the classic UK story - smart folks producing a good product, and then screwing up the marketing and the message, and woefully under-pricing it.

And this is the number one UK company by market cap.

[Nimrod103]

You know what? If I was in charge of Astra I'd tell the world to f-off and take my ball home with me.

Isn't it pretty obvious that this is happening to OxAZ because they are offering the jab to the World at cost price, therefore undermining the vast profits of Pfizer and Moderna, and the kickbacks and payoffs to civil servants and bureaucrats all over the World.

It just goes to show how gauche AZN is. Its share price is down 3.5% in US trading today, on a day when the good news about that trial should have it going up. It is the classic UK story - smart folks producing a good product, and then screwing up the marketing and the message, and woefully under-pricing it.

And this is the number one UK company by market cap.

Nah. The regulatory authorities in some parts of the World, politicians and press have been bought by Pfizer and Moderna.

[staffordian]

Given the love of profit and entrepreneurship in th USA, I trust that AZ will abandon their selling at cost strategy for any sales they make there.

All academic IMHO, as the USA seem so parochial that they are unlikely to want anything not made there.

Witness the unprecedented spat over their interpretation and apparent suspicion of initial AZ trial data, when it seems AZ were merely doing as requested in giving preliminary data as soon as available with later detail to follow...

[servodude]

Isn't it pretty obvious that this is happening to OxAZ because they are offering the jab to the World at cost price, therefore undermining the vast profits of Pfizer and Moderna, and the kickbacks and payoffs to civil servants and bureaucrats all over the World.

It just goes to show how gauche AZN is. Its share price is down 3.5% in US trading today, on a day when the good news about that trial should have it going up. It is the classic UK story - smart folks producing a good product, and then screwing up the marketing and the message, and woefully under-pricing it.

And this is the number one UK company by market cap.

Nah. The regulatory authorities in some parts of the World, politicians and press have been bought by Pfizer and Moderna.

That's not fair!
Rishi Sunak might have absolutely no idea what's in his blind trust

- sd

[GeoffF100]

Biden is pushing "buy American, make American". He is strengthening the enforcement of that beyond what Trump did for government contracts. The EU is at root a protectionist organisation. It exists to facilitate trade between members and put up barriers to trade against non-members. Free trade has past its high watermark. We have a Prime Minister who is systematically trashing the country's reputation. We are no longer seen as honest, trustworthy and law abiding. Being a British company is not good for sales.

[Bouleversee]

"Today" has just carried an interview with Phillipe Lambert, a Belgian MEP, who made some damning and possibly slanderous statements about AZN , eg "track record of dishonesty", "test data bungled", "cannot be relied on". It will be interesting to see how AZN responds. Perhaps I shouldn't have topped up at over £8.

[GeoffF100]

"Today" has just carried an interview with Phillipe Lambert, a Belgian MEP, who made some damning and possibly slanderous statements about AZN , eg "track record of dishonesty", "test data bungled", "cannot be relied on". It will be interesting to see how AZN responds. Perhaps I shouldn't have topped up at over £8.

His has Parliamentary Immunity;

https://www.europarl.europa.eu/news/en/ ... y-immunity

AZ did bungle tests. We know that they got the dosing wrong in some of them. They had no previous experience of making vaccines. The FDA has just said that AZ quoted selective data in their latest press release. AZ is not selling soap flakes. They have a duty to tell the truth, the whole truth and nothing but the truth.

[GeoffF100]

Here is a new article from the BBC:

https://www.bbc.co.uk/news/world-europe-56509521

"Coronavirus: EU plan for tougher controls on vaccine exports". The video gives some background on AZ's selective data disclosure. This sentence caught my eye: "Last week, European Commission President Ursula von der Leyen complained that the EU had exported more than 10 million doses to the UK but the UK had so far exported none in return." 10 million doses would not go far when you have 450 million people.

[Arborbridge]

Here is a new article from the BBC:

https://www.bbc.co.uk/news/world-europe-56509521

"Coronavirus: EU plan for tougher controls on vaccine exports". The video gives some background on AZ's selective data disclosure. This sentence caught my eye: "Last week, European Commission President Ursula von der Leyen complained that the EU had exported more than 10 million doses to the UK but the UK had so far exported none in return." 10 million doses would not go far when you have 450 million people.

From a European POV they are reasonable to look at tighter controls and have a protocol for the basis on which they will decide. They have a situation which is becoming very difficult and they need to get a grip on it, both supply side and vaccinating people.

Naturally, there will be many arguments (some of my leavers friends [I have two left ] will be ranting about EU "bullying") but I see this as just defending their own as Johnson does - it's what they should be doing. After all, it was our PM who said that we were in a war, and in war we sometimes have to make heartless decisions for our own general good.

I expect there is more than a little flag waving and playing to their gallery on both sides: the real answer is to increase the supply and application of all vaccines so the problem will evaporate.

With regard to the batch of 30 million doses "found" in Italy, the latest I heard was that these were due to go to Belgium.

Arb.

[xeny]

Witness the unprecedented spat over their interpretation and apparent suspicion of initial AZ trial data, when it seems AZ were merely doing as requested in giving preliminary data as soon as available with later detail to follow...

This story, albeit from an American web site, suggests that as late as Monday they chose to use earlier more favourable data against the advice of the trial data and safety monitoring board:

https://arstechnica.com/science/2021/03 ... s-release/

[staffordian]

Witness the unprecedented spat over their interpretation and apparent suspicion of initial AZ trial data, when it seems AZ were merely doing as requested in giving preliminary data as soon as available with later detail to follow...

This story, albeit from an American web site, suggests that as late as Monday they chose to use earlier more favourable data against the advice of the trial data and safety monitoring board:

https://arstechnica.com/science/2021/03 ... s-release/

But even that article quotes AZ as saying...

"The numbers published yesterday were based on a pre-specified interim analysis with a data cut-off of 17 February.

We have reviewed the preliminary assessment of the primary analysis and the results were consistent with the interim analysis. We are now completing the validation of the statistical analysis.

We will immediately engage with the independent data safety monitoring board (DSMB) to share our primary analysis with the most up to date efficacy data. We intend to issue results of the primary analysis within 48 hours."

Which suggests two sides to the story. I'm not trying to defend AZ, merely trying to suggest it might not be as clear cut as the US are trying to imply.

[Arborbridge]

Witness the unprecedented spat over their interpretation and apparent suspicion of initial AZ trial data, when it seems AZ were merely doing as requested in giving preliminary data as soon as available with later detail to follow...

This story, albeit from an American web site, suggests that as late as Monday they chose to use earlier more favourable data against the advice of the trial data and safety monitoring board:

https://arstechnica.com/science/2021/03 ... s-release/

But even that article quotes AZ as saying...

"The numbers published yesterday were based on a pre-specified interim analysis with a data cut-off of 17 February.

We have reviewed the preliminary assessment of the primary analysis and the results were consistent with the interim analysis. We are now completing the validation of the statistical analysis.

We will immediately engage with the independent data safety monitoring board (DSMB) to share our primary analysis with the most up to date efficacy data. We intend to issue results of the primary analysis within 48 hours."

Which suggests two sides to the story. I'm not trying to defend AZ, merely trying to suggest it might not be as clear cut as the US are trying to imply.

It's the difference between the truth and the whole truth. It seems that AZ laid out fairly clearly what they intended to do and the US authorities did not report the whole truth.


Arb.

[Julian]

This story, albeit from an American web site, suggests that as late as Monday they chose to use earlier more favourable data against the advice of the trial data and safety monitoring board:

https://arstechnica.com/science/2021/03 ... s-release/

But even that article quotes AZ as saying...

"The numbers published yesterday were based on a pre-specified interim analysis with a data cut-off of 17 February.

We have reviewed the preliminary assessment of the primary analysis and the results were consistent with the interim analysis. We are now completing the validation of the statistical analysis.

We will immediately engage with the independent data safety monitoring board (DSMB) to share our primary analysis with the most up to date efficacy data. We intend to issue results of the primary analysis within 48 hours."

Which suggests two sides to the story. I'm not trying to defend AZ, merely trying to suggest it might not be as clear cut as the US are trying to imply.

It's the difference between the truth and the whole truth. It seems that AZ laid out fairly clearly what they intended to do and the US authorities did not report the whole truth.


Arb.

To me it seems to all a bit of a “he says, she says” argument at the moment, and one that most of us are having to view through the potentially distorting lens of media reports, but in light of the data and safety committee’s comments and particularly the numbers reported in that Ars Technical article then, even if the above is true (and that is how I understand AZ’s position as well), it still seems like a spectacular AZ own goal to me. Presumably if the data & safety monitoring board (DSMB) had the time and resources to analyse the full data set and come up with that estimate of “between 69 percent and 74 percent effective at preventing symptomatic disease” today (or more likely when they first voiced their concerns privately to AZ) then AZ with its army of statisticians could have crunched the numbers on the full data set in time and not have to release interim results based on a 17th Feb cutoff?

If AZ really had intended to re-release efficacy data based on the full data set only days after releasing the data based on the 17th Feb cutoff then it really isn’t a good look if that final data does end up something like 7% lower than the interim data released only days before. If the final efficacy against symptomatic disease does end up being assess somewhere in the middle point of that DSMB 69-74% range, maybe 72%, that is still very good especially when coupled with 100% efficacy against hospitalisation and death, yet when contrasted with the 79% announcement only days before it all of a sudden looks dodgy and disappointing.

If it is as AZ says then why on earth didn’t it simply go to the FDA and say that it didn’t want to release interim results because final results were only days away and their initial analysis was telling them that the later data yet to be integrated might make a non-trivial difference to the efficacy numbers? It sounds as if the DSMB would have been fully on board with that approach.

- Julian