GUWonder

AstraZ executives believe they are going to face a delay in getting US EUA for their vaccine because of this, so I'm not sure on what you are basing the "so untrue" talk. When they think they sort of shot themselves in the toe, who am I to say otherwise.

I would make no assumption that a half-dose+full-dose combination would necessarily lead to lower effectiveness than a full dose+full dose combination for every vaccine out there. There is plenty of evidence out there that suggests that it doesn't always work as the general public may expect it to work in that regard.

radonc1

First off, I think that any study which is looking at medications (which have already gone through phase II studies for maximum effective doses), then mistakenly gives half the effective dose that was already tested, the results will almost never be better. It will almost always be worse since you are giving a less effective dose. So your above bolded statement makes absolutely no sense in the research world.

Perhaps we need to do some research. Lets look at one of the available articles.(my bolding)

Analysis: Questions over AstraZeneca's COVID-19 vaccine data risk delaying approval

"“All we have to go on is a limited data release,” said Peter Openshaw, a professor of experimental medicine at Imperial College London. “We have to wait for the full data and to see how the regulators view the results,” he said, adding that U.S. and European regulators “might possibly take a different view” from each other.British drugmaker AstraZeneca said on Monday that its experimental vaccine, developed with Oxford University, prevented on average 70% of COVID-19 cases in late-stage trials in Britain and Brazil.

While the success rate was 90% in the sub-group of volunteers, the efficacy was 62% if the full dose was given twice, as it was for most participants.

That is well above the 50% efficacy required by U.S. regulators. Europe’s drug regulator has said it will not set a minimum level of efficacy for potential vaccines."'

Reading the rest of the article just goes on to delineate why one has to be cautious when doing subgroup analysis. That is all true, but the bottom line is simple. If the data supports AZs contention that it's vaccine is 62% effective, then it has met the criteria for the phase III trial and will be approved by the US and probably Europe. We need the data to be released.

Science should not be done by press release.

doctoravios

It is difficult to know how the regulators will assess the current data. The way I see it is that the study was adequately powered to demonstrate 62% efficacy for the full-dose/full-dose regimen. Therefore, had there been no "errors" in the dosing it would meet the criteria for approval. However, the fact that the half-dose/full-dose regimen showed greater apparent efficacy (though I do not believe this is a true effect and is a consequence of small sample size of younger patients), this poses a dilemma. Would you approve the vaccine for the full-dose/full-dose regimen knowing that there is a possibility that the lower dosing regimen yields better efficacy or would you rather wait for an adequately powered trial on the half-dose/full-dose regimen in case the improved efficacy holds in which case you would only approve this regimen and not the full-dose/full-dose regimen?

I don't know what the answers are, but whatever they are I suspect in the short-term they will be largely political rather than evidence-based.

radonc1

The fun in research is that it spawns more questions than it answers, which is not a bad thing.

However, for this study, the criteria for success was efficacy >50% and it achieved that. Are there better modalities or dosing options....maybe. But that doesn't negate the present findings, just makes the future more intriguing

For now, we can use the vaccine as intended, with full doses. If we find some other dosing schedule will work better in the future, then the current standard will be modified, as it always is when new superior treatment research results supercede current ones. .

doctoravios

I agree with the pre-defined endpoints/criteria but try selling that to the public now. They have just seen a press release boasting 90% efficacy but if only the full-dose regimen is approved with 62% efficacy then people will question why they are receiving an inferior product. Of course the reality is that the 90% efficacy shown for the half-dose regimen is underpowered and likely false. But that is not necessarily what the general public will infer.

Would you want to receive the full-dose regimen knowing there is a possibility the half-dose regimen may be better?

radonc1

Would you prefer to be vaccinated in 3 months or wait another 6 for a second study to determine possible dosing variations???

I deal with people who may very well be Covid + every day.

If my hospital offers me an AZ vaccination next week versus waiting for Moderna in 6 months, it is a no-brainer for me.

If you want to wait, so be it.

nk15

At this point, you may as well get what is approved, and based on their history, they may be giving you the half dose erroneously anyway (which may or may not be better, or even as good), so you may as well leave it to chance and destiny...

cockpitvisit

I do not understand why anyone is taking these 90% seriously. These 90% were achieved in a group without elderly participants. The group was small (only 2K people), the difference between 90% and 62% would have been only 3-4 infected people in the control group. To me, it seems more like a statistical fluke than a trustworthy result.

TTT

I think a few things are worth keeping in perspective with the full-full dosing regimen.

1. It prevented 100% of severe illness and resulted in no hospitalizations, that's a game changer anyway you look at it.
2. Comparing the AZ study to the Pfizer/BioNTech or Moderna studies has some issues; namely that the AZ study conducted surveillance testing on their participants whereas the other studies only tested those who reported symptoms. AZ may have uncovered more positive cases than Pfizer/BioNTech or Moderna simply by testing their participants more frequently.

I'm more curious about the long-term.

1. How long will vaccine immunity last (unknown, I know)?
2. Will AZ be able to offer boosters with their platform given the possibility of an immune response to the viral vector?
3. What are the possible health complications for the individual of taking either a Pfizer/BioNTech or Moderna vaccine after taking the AZ vaccine? Are there potential issues with doing so? Does the risk of those issues decrease with time?

Update on my experience:
Arm got a little sore but otherwise have felt perfectly normal since my initial round of side effects on Tuesday. I will have a phone call this coming Monday to check in on COVID symptoms and whether there have been any changes to my medications or health. I think it's interesting to note that at no point in this study are they assessing vaccine side effects, but I guess that's more in the Phase II anyway. But I have no method to report the nausea, malaise, and muscle aches I felt on Tuesday.

LondonElite

And it’s worth remembering that 90% efficacy doesn’t mean 90 out of 100 people with the vaccine will be protected.

corporate-wage-slave

Both the MHRA and FDA were made aware of this development some time ago. This may have come as a surprise to the wider community due to the way information is disclosed but it was a known factor for some months now. The Oxford team had the option of removing this cohort from the study, and recruiting more (there was no shortage of volunteers) but came to the view there was a benefit in continuing this cohort, and then giving the second dose at the full amount. The reason only sub 56 year olds were in this group was that it happened right at the early stages of Phase III. At that initial stage, for safety reasons only sub 56 year olds, in generally good health, were vaccinated, to ensure there were no age or other related complications, and after about a month they widened the trial to a more representative sample of the adult population. The reason it was noticed was that this particular cohort had much milder reactions to their vaccine than the full dose group, and at that point the fault in the filling device was identified and corrected. By the looks of it the OP got the full dose impact!

The MHRA were doing a rolling review of AZN (and I think Pfizer, probably not Moderna). There are two ways to get MHRA approval, a Section 174 approval (where HMG specifically requests an investigation). and a Section 345 approval (which is the more route but which takes 7 months or more). The Section 174 letter for AZN was sent in last Monday, and the previous Friday for Pfizer and Moderna. However MHRA has agreed to do some of the review process - the sections based on Phase 1, Phase 2 and laboratory work - ahead of Section 174. I suspect we won't have to wait too long to find out (next 10 days is my guess). The FDA has a more programmed approach, so we won't hear much from them until 8 December but their process is more media friendly than the MHRA.

doctoravios

Personally, I would rather wait because I am not in a high-risk category and if exposure to an adenoviral vector reduced the potential efficacy of future vaccines with the same delivery mechanism due to vector immunity then I would want to know about it rather than take my chances. That said, as others have noted, I do not believe the 90% vs 62% difference is genuine, mainly due to differences in the cohort of each group. But my "beliefs" are worth nothing in comparison to a well-powered RCT to address the question which has arisen due to the half-dose subgroup.

On the other hand, if I were over 70 with a lot of risk factors for serious illness then of course I would not wait. I would have a lot more to lose by developing COVID-19 than from taking even a poorly efficacious vaccine.

fransknorge

Question from the people on this thread who are way more knowledgeable about vaccine than me: does the Astra-Zeneca vaccine fare better for immunocompromised people than the Pfizer-Biontech/Moderna ones ? Immuno-compromised people (specifically those taking anti-TNF MAB or anti IL-17/6/23 MAB) can not take active vaccine, it must be inactive. I have not read anything yet on that subject and people with such MAB therapies represent more than 1% of the population in Western countries.

corporate-wage-slave

I don't know the direct answer to that, other than that if the MHRA gives the green light, it will probably come with a list of exclusions (so I would expect children without extenuating circumstances to be excluded) and I'd be fairly confident they would say something about those with compromised immunity. So from a UK perspective we should find out fairly soon. I guess you already know of the Chinese vaccine BBIBP-CorV, which is in Phase 3, and which has been has had some good outcomes in this area. With so many vaccines in devellopment I would hope that at some point there would be a good solution.

fransknorge

Well for some disease the solution for immunocompromised is herd immunity (measles for example, since MMR is a live vaccine). So I am cautious for the time being and prefer to not hope too much. There is an antibody therapy developed by Pfizer but so far this is in early stage.