What lies behind the Astra Zeneca vaccine findings?

[LaValliere]

My understanding is that the 90 per cent efficacy figure is derived from a testing site which erroneously gave an initial half dose, followed by a full dose. The protocol was meant to be two full doses - when that was followed the efficacy was significantly lower, at 62 per cent.

Two questions - first, how on earth could this sort of error happen?

And second, what might explain the finding? Is there any suggestion that the full dose has some sort of adverse effect on the immune system (in that a half dose is better)? If so what are implications for this given that the second dose is a full dose? Will the reasons behind this finding themselves need to be investigated, in case they imply anything about the way in which the vaccine interacts with our immune system?

There's an article on this here www.nature.com/articles/d41586-020-03326-w

And I''m not sure it was an 'error', they were deliberately testing the outcomes of both doses as I understand it?

Worth a read:

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

Oh, apparently it wasn't intentional. I mean

Is there any suggestion that the full dose has some sort of adverse effect on the immune system (in that a half dose is better)?

No, because if that was the case, you’d presumably have seen more people in the vaccine groups getting covid than in the placebo groups. So it looks from this data that the vaccine works, it’s just that half-dose-then-full-dose seems to work better than two full doses.

As for how the error could happen - 🤷‍♀️

It seems like they’re asking the US regulators to include the half-then-full dosage in the big US trials, so that should give more information with a bigger sample size on how much better it works.

I do not think that it was an error, someone involved in the trials said that they were testing out different doses as some people had side effects and they were trying to reduce them.

Worth bearing in mind that the article in Wired is written from a US perspective - they wouldn't want a British vaccine to be better than theirs, would they?!

Also worth remembering that a lot of scientific breakthroughs or innovations are the result of mistakes - penicillin is one, post-it technology is another.

@BIWI

Worth bearing in mind that the article in Wired is written from a US perspective - they wouldn't want a British vaccine to be better than theirs, would they?!

Also worth remembering that a lot of scientific breakthroughs or innovations are the result of mistakes - penicillin is one, post-it technology is another.

Good point about the US perspective.

But the mistake is not going to help convince the sceptics who are being told there's absolutely no way this vaccine isn't safe because it has gone through rigours safety procedures/testing (by people like me.)

Does anyone have more info on the accidental reduced dose? An Oxford source perhaps? (I will search, just wondered if anyone had seen anything.)

@BIWI

Worth bearing in mind that the article in Wired is written from a US perspective - they wouldn't want a British vaccine to be better than theirs, would they?!

Also worth remembering that a lot of scientific breakthroughs or innovations are the result of mistakes - penicillin is one, post-it technology is another.

The author is Australian, actually, and a respected expert in reviewing such trials. Her analysis is as objective as it gets. You can read her take on the Oxford vaccine including a detailed timeline on her website:

hildabastian.net/index.php/100

A snippet:

“Where does this leave us? I discuss issues and red flags in detail at WIRED, but a few major issues didn’t fit there. The press release doesn’t provide the most basic level of detail to enable us to understand what they did: we don’t know how the percentages were derived, exactly what the comparisons were, or what the level of uncertainty (confidence intervals) is around the numbers they reported. We don’t know if they had enough severe Covid-19 events to draw meaningful conclusions about that critical issue.

Given the enormous difference in when second injections were given – in the Brazilian trial it could be up to 3 months – we really need to see what happened to the people in that interval. The primary analyses for efficacy are done after the second injection – but to get an idea of likely effectiveness, we also need to know what happened in between shots, and how many people didn’t get that second shot at all. That’s important for any two-shot vaccine, but it’s particularly critical for one with a high rate of adverse events.

Bottom line? When you consider the press releases from BNT/Pfizer and Moderna alongside the detail they report in their protocols and for their very large coordinated trials generally, it’s easy to be confident those vaccines work very well – even though there’s still a lot to know.
With the Oxford/AstraZeneca vaccine, though, the combination of what we know about their trials, the twists and turns of their interim analysis process, and the contents of the press release, the case for having serious doubts about those results is strong. We certainly don’t want to throw babies out with the bath water. Just because the trials and data analyses are badly flawed, doesn’t mean that the vaccine is too. It just means that the US trial – including any new dosing regimen they want to test – has to be rigorous, and it’s indispensable. What’s just happened has the hallmarks of being “Plan B” after the big US trial they talked about in July took so long to get off the ground – only to be grounded for weeks because of safety review. But “Plan A” shouldn’t all that far off.”

There are direct quotes from Oxford people that it was a “serendipitous” accident, I don’t know why that’s being contested:

“The reason we had the half dose is serendipity,” said Mene Pangalos, executive vice-president of biopharmaceuticals research and development at AstraZeneca.

When university researchers were distributing the vaccine at the end of April, around the start of Oxford and AstraZeneca’s partnership, they noticed expected side effects such as fatigue, headaches or arm aches were milder than expected.

“So we went back and checked … and we found out that they had underpredicted the dose of the vaccine by half,” said Pangalos.

Instead of restarting the trial, he said researchers decided to continue with the half dose and administer the full dose booster shot at the scheduled time

www.theguardian.com/uk-news/2020/nov/23/oxford-covid-vaccine-hit-90-success-rate-thanks-to-dosing-error

... and more testing is being done in US trials too. (From that article in the Guardian, I think)

@BIWI

... and more testing is being done in US trials too. (From that article in the Guardian, I think)

Yeah, I’d love to know when they changed tack to include that half/full dosing regime in the US. Hopefully a while back so we get the results soonish.

Was it serendipity or was it deliberate - was it part of a dosage experiment to check that they had the dosage right ? who knows - but the outcome is what needs to be focused on. The vaccine is based on a older reliable method & one which is stable easier to store & transport.
It is in the American Pharmaceutical interest (to be blunt) to be critical about the Oxford vaccine. (Big money at risk)
What I can tell you is that some countries do not (thanks Trump) trust anything from America - personal contact.