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Oxford-AstraZeneca coronavirus vaccine approved for use in UK (bbc.co.uk)
376 points by agd on Dec 30, 2020 | hide | past | favorite | 417 comments



Interesting shift in strategy. Instead of giving the second dose within a few weeks of the first they’re going to allow up to 12 weeks between doses. Allows them to get more widespread level of some protection with dose 1 before later boosting protection.


They are considering the same strategy in Belgium, but with even bigger gap. It seems that it’s the only way to achieve at least some herd immunity before summer.


(I am a Belgium resident)

I think the only reason they're considering this in Belgium right now is because they are unprepared in the extreme. They have frankly pissed away their time instead of actually preparing for the vaccine, the past nine months.

The current vaccination rollout plan leaves healthcare workers unvaccinated until march. HEALTHCARE WORKERS.

https://www.brusselstimes.com/news/belgium-all-news/147133/c...

There's been some pretty severe backlash to that, and rightfully so (I don't know of any other country that isn't vaccinating its health workers in the very first phase alongside senior citizens). I ran some numbers the other day and if you're distributing the vaccines exclusively via the 40-ish Belgian hospitals that can store the Pfizer one (and only 6 in Brussels), then there is no way to achieve herd immunity before end of 2020. The only real solution to that is to allow for more widespread distribution via pharmacies. (Yes, medium-term storage is an issue, but AIUI the Pfizer vaccines can still move around after thawing for some time so short term redistribution is possible if you've prepared for it).

So they're trying whatever they can to compress the timeline. It's not necessarily a bad decision, but it's a workaround to a worse one.


This is happening in the US as well, and now they're acting shell shocked at receiving 2-3 million doses because that is actually indeed a lot of doses which means you need lots of trained people on how to handle them and inject them. This is gonna take a long time. Hopefully Biden will scramble more people and resources. Depending on corporations as the sole distributors is a bad, bad idea.


Yes, and all the parties from the beginning of summer till days before new lockdown. I don’t know how it goes in other countries, unfortunately common sense is anything but common.

Also I’ve read that “Belgium accounts for 25% of Europe’s biotech”. I wonder why there’s no domestic vaccine yet given such R&D capacity.


Belgium is going to investigate smaller doses to go faster too.

It looks really promising, but investigation is required.


We tried the same thing, in Canada, with the yellow fever vaccine. There were shortages about 6? 7? years ago, and 1/5th dosage was consider a stop-gap, by conveying some immunity.

(And, better outcomes overall, too)

Not sure how all of that wound up, but:

https://www.who.int/emergencies/yellow-fever/mediacentre/qa-...

edit: For clarity, there wasn't an outbreak in Canada, but just shortages if you wanted to travel, and needed the vaccine.


> just shortages

I had the yellow fever vaccine last year in America. I received an, otherwise identical, Europe-manufactured vaccine instead of an American one because the shortage is on-going.


Supposedly identical, yet the European one (French?) wasn't approved for use in Canada yet.

Your response made me think back to my research a few years back. Mostly, because I am surprised that there are STILL shortages! For more than half a decade?!

Found this:

https://www.ashp.org/Drug-Shortages/Current-Shortages/Drug-S...

Quote:

Sanofi Pasteur has YF-Vax multi-dose vials and single dose vials on back order and the company estimates product will be available in 2021.[1]

Sanofi Pasteur has worked with FDA to make another vaccine, Stamaril, available in the US under an investigational new drug program. Stamaril is yellow fever vaccine manufactured by Sanofi Pasteur in France. It is not licensed in the US.

This, I recall. I also recall some more research, which I cannot find now, in that there were different production methods between the two vaccines. Hence, the lack of quick approval. Yet Yellow Fever is crazy spreadable! And still the vaccine is not fully approved in the US/Canada?!

I recall reading a report, where one person with yellow fever was briefly in an airport lounge. 20 minutes later, a few people passed through, and most caught it! Just... it makes COVID look like a joke, yet here governments are dragging their heels over approvals due to production methods over the same strains?

And those production methods / that company has been making and administering that version for decades? To hundreds of millions?

It really makes you think a bit about COVID approvals. Talk about a change of heart.


Recent reports mention 95% effectiveness for the Oxford-AstraZeneca vaccine if the doses are taken 3 months apart, which would be great if confirmed.

https://www.businesstoday.in/current/economy-politics/oxford...

https://www.thetimes.co.uk/article/covid-vaccine-boost-for-m...


they always seem to find additional data supporting this or that. Idk, to me it seems like their reporting is literally all over the place, how did they confirm 95% effectiveness? what's the trial-size, is it also 30k participants like the others? What's the age-distribution of those that took part in this 3-months trial, there are a ton of unknowns with that vaccine, and neither Oxford nor AZ are particularly helpful with clearing those doubts atm.


They gave more data to MHRA. Let's not forget that the data used for the Lancet publication was from November 4th.

And the Jenner Institute in Oxford doesn't do preprints or press releases for data, they go for publications (so that takes more time).

That said, I expect the missing information to appear in MHRA's guidance notes.


They have in many ways been more rigorous and transparent than other vaccine trials (weekly swab testing of all subjects, publishing the paper first rather than in the media first, being honest about mistakes made). They don’t control the media reporting.

That said it seems the group who received smaller doses by mistake was only 1300, not sure where they got the data on 12 weeks but presumably it’s also a small number or they’d be going with that for everyone.

Things should become clearer over time and I hope they can shift to the smaller doses first as it’d give us double the number of initial vaccinations when supplies are limited.


the just tried to fit in numerous trials into a single trial, whereas Biontech/Pfizer and Moderna were super clear about their trial-architecture and data (same 2-dose regime, given 3 weeks apart), we seem to have a ton of small trials with different data for that Oxford/AZ vaccine. Those 1300 participants who got the half dose full dose vaccine also turned out to be significantly younger than the other group who got the two full-dose regime, making those two groups really difficult to compare (apart from the fact that they were also differing in size)

Now we have a new number out there, 90% if the two doses are given 3 months apart, does anyone here now what the trial-size was? the age distribution? The statistical significance for that finding?


Don't forget that the BioNTech/moderna trials weren't really comparable - they relied on self-reported symptoms to trigger checks for infection. That is likely to lead to a higher apparent efficacy at the same underlyng efficacy.

By now it's clear that for all three vaccines regardless of the exact efficacy of the vaccine, the chances of getting a severe case is greatly diminished. It's at least plausible that getting a vaccine reducings the severity of an infection in general; specifically that it might push what would otherwise have been a mild case into the asymptomatic (but infected) category. I don't know how large that group is, but given how many mild cases there are, it could be quite sizable. And those cases would not have been included in moderna and biontech/pfizer's efficacy numbers, but would have been included in the oxford/AZ trial's numbers.

So while I'm no expert in any of this, I think it's at least fair to say that it's not trivial to compare the efficacies reported from the two mRNA vaccines to that of the oxford/AZ vaccine, because of this difference in methodology. Including vs. mostly excluding asymptomatic cases will affect the numbers.

The point being? All of these trials have their limitations; the oxford/AZ trials may have had bumps (but nothing all that serious sounding), but they also have extra data in the form of asymptomatic cases. The comparison isn't straightforward.


that 62% number is for symptomatic cases, I think it was around 50% for asymptomatic cases - the different efficacy-rates are fairly comparable



From the news report it's 95%, not 90%. Presumably the data about sample size etc. will be available when they publish. You can't reasonably expect that level of detail from a news article reporting prior to publication.


What would be interesting about that is what happens when people are not going to get the booster for various reasons.


All that happens is that they have somewhat smaller protection for a shorter time.

Unless the vaccine or virus is very different from normal ones.


I think early data showed that you still get ~60% protection with the first shot (or was that for the Moderna vaccine?) Still, you get some level of immunity, booster only makes it higher.


The two dose studies provide incomplete information about the single dose efficacy — administration of the second dose ends the data collection for the first dose alone.

The data collection also includes the period of time that the body spends responding to the vaccine (so if you get the shot and get infected that day, the shot gets counted as not being effective).

And then on the other side of it, they don't have data on how long immunity from a single dose would last.

But it's likely that the Moderna and Pfizer vaccines have quite high effectiveness after the initial immune response.


Sure, while it's not perfect, the data for those 3 weeks between the first and second shot still can provide a lower bound approximation for immunity, which I assume is where the 60% comes from.

The point about how long single dose immunity lasts is fair though.


Why would they not get the booster?


Why do people miss their flight?

So much so that airlines can oversell a substantial number of tickets on any given flight and usually the plane departs with empty seats?

Why do people get divorced?

Why do...


Some will forget, some won’t realise they need it, some will get symptoms the first time and not want it. I don’t expect it will be widespread but humans will be human


You must not be a software developer


Mutation?


Mutations happen all the time regardless of vaccines. The vaccine adds evolutionary pressure and will likely give an advantage to the bearers of particular mutations.


If the virus has a smaller base of infected people who grow it, there will be less mutations. From that point of view, the sooner all the world is vaccinated, the better. The risk of a new, more dangerous mutation decreases.


Good idea indeed!


Is this driven by the desire to vaccinate more people, or more to do with the logistics of vaccinating this many people?


I believe it's because preliminary experimental results suggest that the efficacy is greatly increased.


I can no longer edit this comment, but I was wrong. The reasoning behind the longer gap between doses is logistical, and attempt to get as many first doses in as short a time as possible. It is scientifically unfounded.


This is the way


The whole thing is ludicrous. This strategy also applies to the Pfizer vaccine. By having the booster further apart, it lowers its efficacy from over 90% to around 80%. Given the mistakes the UK government has made along the way, this just fills me with further dread for the situation (I have family there).


80% protection for 2 people is better that 90% for 1.


I would agree if this was for the general population but consider the most vulnerable are being vaccinated first. They should be treated with great care and priority and I think it’s unethical for the UK to lower their chances, especially considering the huge numbers of vaccines they are going to have over the coming weeks.


Prolonging the 2nd dose interval increases the level of antibodies elicited after the 2nd dose.

Dose Interval --> 28 days after dose 1 --> 28 days after dose 2

<6 weeks --> 8,734.08 --> 22,222.73

6-8 weeks --> 7,295.54 --> 24,363.10

9-11 weeks --> 7,492.98 --> 34,754.10

≥12 weeks --> 8,618.17 --> 63,181.59

from https://www.gov.uk/government/publications/regulatory-approv...


This is in the case of the Oxford/AstraZeneca vaccine. Not the Pfizer.


Looks like they approved the two-dose 62% ~effective~ efficacy regiment.

There was a lot of hope for the one-dose given the supply constraints or a retrial for the more promising half+full dose for greater efficacy.

I wonder if people will ask which vaccine they're receiving. 62% is kinda underwhelming when there's two 95% ones (Pfizer/Moderna), a 92% one (Gamaleya), and a 79-86% one (Sinopharm). With the latter two also not needing subzero temps.


I believe there's a journal article being published shortly. In the meantime this article:

https://www.bbc.co.uk/news/health-55308216

"""Unlike other vaccines being trialled, the Oxford team had been taking weekly swabs from all volunteers to check whether they were infected but showing no symptoms. If the vaccine could prevent silent transmission it could stop them from unwittingly passing on the virus. "That's a big deal. Because that means the virus could be stopped in its tracks," says Pollard.

Intriguingly, when the trial results came out, there were indications it may partly suppress transmission of the virus. But more evidence is needed."""

and

"""Crucially, no-one who got the vaccine was hospitalised or got seriously ill due to Covid. Whereas in the control group there were 10 serious cases and one death."""

Perhaps, regardless of immunity, it reduces symptoms to "not serious", and may reduce transmission, which the other vaccines do not? Which seems like a fair trade for high immunity percentages, and possibly better for the wider community.


Pfizer has the highest efficacy endpoint (95% at preventing symptomatic infection, which would theoretically also prevent spread and symptoms at higher percentages) with equal efficacy across age groups.

Moderna is 95% at preventing symptoms (100% for serious symptoms in their trial but insufficient sample size). They also reported slightly lower efficacy for the elderly.

AstraZeneca is 62% for preventing symptoms (unknown for infection and spread).

So it's not quite a trade-off of spread prevention vs symptom prevention, because Pfizer claims to do both significantly better.

edit: reading the data in more detail, all 3 don't have sufficiently significant data to claim anything other than symptoms. So preventing spread is just PR-hype.


> Pfizer has the highest efficacy endpoint (95% at preventing infection

Cite, please. Pfizer's primary outcome measure was symptomatic infection. Only Oxford/AZ in the UK carried out weekly PCR tests to check for asymptomatic infections.


Reading the journal paper from AstraZeneca[1]. I don't think AZ can claim anything about preventing asymptomatic infections. You're right in that they're the only ones with that data, but that data is practically identical between control (37/2760) and vaccinated (34/2751) groups.

Side note, the more I read about the AZ trials in detail, the more it becomes obvious how messy their trial was compared to the Pfizer/Moderna ones. They have so many more methodologies and outcomes and much smaller samples.

[1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...


They did find fewer asymptomatic infections in the half+full dose arm but the N is not large enough.


Looks like it was edited? Yea, only symptomatic infections were tested by Pfizer iirc


The other trials simply didn't collect data about impact on transmission. So there isn't data to support a statement in either direction.

Typically, high levels of antibodies will suppress infection and thus transmission. But there isn't data to make a conclusive statement about it.


> Unlike other vaccines being trialled, the Oxford team had been taking weekly swabs from all volunteers to check whether they were infected but showing no symptoms.

FTR, this only happened for one of the trials (the AZ results are actually from several trials combined) in England and Wales. In Brazil, for example, this was not done.


Presumably they also counted the numbers of cases with symptoms in control and experiment? I assume the ratio there was also not as favourable as in the mRNA vaccines?


> no-one who got the vaccine was hospitalised or got seriously ill due to Covid. Whereas in the control group there were 10 serious cases and one death.

I can only imagine what it must be like for these researchers. You give some people a dummy and let them get seriously ill and one even dies.

No idea what else we could possibly do, this is probably just how this must be for the greater good, but wow must that feel horrible for everyone involved. You have to tell the family "Sorry, she was in the control group!" Peak 2020 moment for everyone involved right there.


Double blind trials are the standard for establishing efficacy. Unfortunately, there is no ethical way of getting around the problem you mentioned.


We should have been doing challenge trials from the start. Hundreds of thousands of lives if not more could have been saved, and people of sound mind could have decided for themselves if they want to participate and accept the risk. I know I would have.


I wonder if more authoritarian governments like China or Russia would be willing to do challenge trials.

Outside of ethical concerns, it comes with other complications, like how to design infecting the challengers so that it would be representative of real world infection/viral load.


Seems at least 60% is good enough:

> Simulation experiments revealed that to prevent an epidemic (reduce the peak by >99%), the vaccine efficacy has to be at least 60% when vaccination coverage is 100% (reproduction number=2.5–3.5). This vaccine efficacy threshold rises to 70% when coverage drops to 75% and up to 80% when coverage drops to 60% when reproduction number is 2.5, rising to 80% when coverage drops to 75% when the reproduction number is 3.5.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361120/

Also, it prevents hospitalisations completely which is crucial.

I asked elsewhere but seems this thread is the busiest:

Also, does anyone know - supposedly the Oxford vaccine had swab tests for the virus every week to catch cases even if trial participants weren’t showing symptoms, whereas for the Pfizer/BioNTech vaccine they were only swabbing if someone showed symptoms. Would that not have a large effect on efficacy numbers?


From the linked paper:

> Using Microsoft Excel, version 16, with the Crystal Ball add-in, the team developed a computational transmission, clinical, and economics outcomes model

I did not expect the simulation model to be written in Excel. Never heard of "Crystal Ball" before. From Oracle's website:

> Use Monte Carlo simulation to automatically calculate and record the results of thousands of different what–if cases


It is well known in the Excel modelling world and a lot of people use Excel for modelling.

I’m not sure coding these things up is always a great idea. I’ve done various types of programming over the years but in Excel you get things like dependency tracing, error checking, UIs for every components, Excel does have advantages for a lot of work. The equivalent code these domain experts produce is usually pretty awful.


And that’s part of the reproducibility crisis. R/Python code published on GitHub is a much better way.


There‘s whole books on numerical simulation with Excel. Which is absolutely incomprehensible - if you are math-wise enough to do simulations, you should be computer-wise enough to use a real programming language.


I’ve done this type of numerical work in code and it’s much more difficult than it first appears. It’s not like web development this stuff is much more like real computer science.

Tools like Excel and Matlab exist for a reason.


Matlab, yes. Matlab code can be versioned, and opened in VIM for independent review. It can have unit and integration tests. It can also often be run in alternative implementations with few changes, such as Octave.

Excel? You'd be lucky if Excel N-2 can properly handle the file, much less an "alternative implementation" such as LibreOffice Calc.


You can have manual tests (automated through VBA if you wanted) and reviews. The review tools are lesser known features built into Excel. I know from my experience accounting firms will take your spreadsheets and code too and audit it. I’ve worked with bankers who would effectively run a suite of tests before using their updated spreadsheets. These concepts aren’t unique to programming.


Curious as to how your claim follows?


I upvoted this. It's quite a lot more important than your elegant one-liner reveals. I think there's a gaping hole in many people's skills that need to be addressed. We're educating people in how certain models work, with lots of equations and diagrams, but we don't give most people access to the power of computation that would greatly help their studies.


> some participants routinely swabbed themselves for SARS-CoV-2 testing, even if they weren’t showing symptoms. Differences in infection rates between people who received the placebo and those who got the Oxford vaccine suggest the vaccine blocks transmission, says Ewer. (The Pfizer and Moderna trials tested only people who showed symptoms.)

https://www.nature.com/articles/d41586-020-03326-w


the 62% efficacy rate was for symptomatic cases, which makes those numbers comparable to the Biontech/Pfizer one. I think it was around 50% effective in stopping asymptomatic cases, which is also pretty good. But that main number comes from symptomatic cases


Yes Pfizer/Moderna didn't do weekly swab tests and only tested the ones with symptoms unlike Astrazeneca.

The other big difference is the sample size is much bigger with Astrazeneca one and is across continents as well.


One thing I have been wondering: Given that R has been near to 1 in many countries, wouldn't we need much lower immunity rates and/or vaccine efficiencies if we maintain the minimal impact measures such as public masks?

My understanding would be that 10% immunity for instance would push R down by 10%. Once we get it below 1.0, we effectively won.


Is this for a vaccine that confers sterilizing immunity (ie, prevents infection and therefore onward transmission, as well as preventing severe disease)?

I don't believe we yet have evidence that any covid vaccine provides this. I've only read that any vaccine prevents disease or hospitalization.


There are some indications in animal studies for Moderna and Pfizer, and some preliminary data given by Moderna at the FDA meeting about reduction of transmission, but it's nothing definitive.


60% is not good enough to be worth taking it for me, personally. I am sure it is good enough for society, but I want a vaccine that allows me to go back to normal life, and if I take the 60% it becomes a coin-flip, plus I will be at the end of the line for the effective vaccines.


The fun thing is to read the paper and see Bruce Lee in the author list.


In Germany only 2/3rds of the population want to get vaccinated. So they'd better be vaccinated with a vaccine with very high efficiency.


70% efficacy in that case wouldn’t prevent an epidemic, but since it prevents hospitalisations and severe effects of the disease it’s still worth it.


It’s interesting how the vaccination speed affects epidemic. What’s the effect of vaccinating everyone within a month vs within half a year.


I wouldn't call 2/3rds as "only", this is quite high. In Poland we have only ~40% that want to be vaccinated (but maybe this a result of Germany having much older population).

I'm a bit reluctant to vaccinating until I see some more tests on wider population and we could test for long term complications (e.g. reduced fertility which couldn't be tested earlier) and I'm a person that vaccinated my children (and myself) for all kinds of diseases.

So I assume there are more people like me (aside from the usual "anti-vaccination" crowd).


The 2/3rds already include people who in principle want to get vaccinated but would like to wait a bit more, like you. Only 1/3rd wants to get vaccinated as quickly as possible.


^ This. Although it is better than nothing. However, whatever I am offered, I am taking.


I feel like we’re watching a medical ethics textbook unfold in real time. When the cold judgement of impartial history books come out, it will be interesting to read about. I also am wondering about the mindset of people getting a 60% vaccine. Maybe they will expand access to it to younger front line workers, who know they would have to wait really long for the mRNA version


I expect if you are offered the Oxford/AZ vaccine and refuse it, you would not later be offered one of the mRNA vaccines.


But aren't 50% vaccines usually deemed effective enough?


50% is effective enough for a society to squash corona, but a purely self motivated person will surely prefer the 90% version.


Yes. The wacky back-seat epidemiology is new with the many vaccine candidates. Most people won't get an actual choice, they'll be offered what their healthcare provider offers and they can take it or leave it.


Well typically there isn't such a large gap in vaccine performance.

62% is about as bad as vaccines get, and in any other circumstance the manufacturer would retrial instead of seek approval. Even the WHO recommends a 70% minimum during pandemic times (with 50%+ being a measure of last resort, which I guess we're at now).

On the other hand, 95% is better than the best of the best.


Most important thing - no-one who was given the vaccine in the trial got seriously ill.

Even if that’s all the vaccine can do for me, here’s my arm.

Remember the biggest threat is health care systems being overwhelmed. That’s when people will die at much much higher rates because they don’t get respirators/oxygen.


A bit off topic, but as far as I understand (not a medicla expert), respirators are not as important as they were though to be back in the spring when countries were fighting for equipment deliveries

Extra oxygen is critical.


Yeah it seems so - but they are still needed and in much more limited supply than oxygen.

I listened to an ICU doctor on the radio this morning saying the problem is that ANY kind of illness with covid is problematic because even fairly mild cases often require some medical attention, even if it’s just a doctor to reassure you you’re OK, that’s fine a doctor could be spending doing something more life-saving.

Here in the UK with this nee strain, the NHS is running out of resources in hotspot areas so any kind of vaccine will help.


The announcement [0] says they are going to prioritize everyone in risk groups getting their first shot over some people getting two, and as a result might have up to 12 weeks between the two shots. That seems like a reasonable way of dealing with the supply constraints, without entirely throwing out the protocol established via testing.

[0] https://www.gov.uk/government/news/oxford-universityastrazen...


If you're in a high risk group surely you want the more effective vaccine?

I doubt you can have both (even if safe, it's not tested at all).


Given the choice, yes but anything now is better than something in a few months, time, especially looking at current UK mortality rates. These are now rivalling the first wave, even with treatments learning in the last nine months and NHS fully geared up.


UK cases have surpassed the first wave (with obvious caveats about far more testing now).

The hospitalised patients per day is probably a more reliable measure - that has not surpassed the first wave yet on either patients per day or patients in hospital, but it does look like it might surpass it in January.

UK deaths are nowhere near the first wave yet, though it may approach it in the coming weeks, however at present deaths are trending down as stricter measures were finally put in place again in December and we may be starting to see the impact of that. We will then of course in a few weeks see the impact of the government attempt to 'Save Christmas' so things will probably get worse again in January.

https://coronavirus.data.gov.uk

https://coronavirus.data.gov.uk/details/deaths


> that has not surpassed the first wave yet on either patients per day or patients in hospital

In England (and probably the rest of the UK) more patients are in hospital compared to the first peak.

https://www.independent.co.uk/news/health/england-hospitals-...


Perhaps the stats on this website are a little behind, but I trust them more than a newspaper. See the second chart down.

https://coronavirus.data.gov.uk/details/healthcare

The UK totals for patients in hospital on the 25th December hadn't passed the peak yet, though they are very close. Doesn't matter too much though, they will no doubt pass that total of 21.6k at some point in January if they haven't already, especially as fewer patients are dying this time round.


I've been quite unimpressed by the official stats on that page throughout the pandemic.

If you click on the "Data" tab, it says for 28th Dec the total of 23,771.

I've no idea why the graph doesn't show that.


> looking at current UK mortality rates. These are now rivalling the first wave

Are you sure? This is the data I'm looking at:

https://ourworldindata.org/coronavirus-data-explorer?zoomToS...

This link goes to "confirmed deaths" per million people, see also the "case fatality rate" setting. The former is about 6.8 now versus 13.8 at the peak in April; the latter is 3% versus 15% at the peak in April. There are half as many deaths and a fifth of the deaths per case. That's not even close to "rivaling it despite being geared up", at least from this data. Is this data wrong?


Here’s the official UK data:

https://coronavirus.data.gov.uk/details/cases

https://coronavirus.data.gov.uk/details/deaths

Deaths are a bit lower. Cases are higher. Hospitalisations are about the same as the previous peek, but heading further up.


Cases can't really be compared with the first wave because of significantly higher testing (450k per day now vs 60k per day in May, or 20k per day in April at the peak of hospitalisations).


Note that the official data on deaths only includes those confirmed (through a positive test) to have COVID-19; this almost certainly understates the total number of deaths in the first wave due to lack of testing capacity.


There's no almost about it, if you look at the percentage of positive tests.


Yes, that’s true, but neither can deaths as more is known about how to treat severe cases.


Deaths are also a lagging indicator. This happened in the first wave too.


If you look at the charts you’ll see a marked difference in outcomes after hospitalisation. Deaths are significantly lower this time, probably a combination of the most vulnerable dying in the first wave and better treatments.


Both vaccines seem to stop hospitalisations completely, which seems to be the most important part.

> No hospitalisations or severe disease observed in the vaccinated groups from three weeks after first dose

https://www.ox.ac.uk/news/2020-12-08-first-peer-reviewed-res...


I'm thinking more the other way around. All the vaccines practically prevent hospitalization/death. But the AZ one is coin flip odds for symptoms, however minor. But even minor symptoms from COVID can have medium term damage (loss of smell/taste/lung capacity) that may not be recoverable.

If you're part of the elderly high risk group, long term isn't that much longer anyway. It's the people with most of their life ahead of them that has to pick between the long term damage of COVID vs the unknown potential of long term effects from mRNA/adenovirus.


Mixing vaccine types is under consideration. An experiment is proposed combining AZ and Sputnik.


If it was like my experience, you're told which one it is before you get the vaccine. I was given a 2-page write up on the Pfizer vaccine as I waited to receive the shot.


Amazing news, and so happy to see a lot of good sense here from the UK.

They have distanced themselves from the US with the fastest approvals of Pfizer and Astrazeneca, the smartest targeting of the population (a focus on saving lives by targeting most vulnerable groups first), and the enormously helpful focus on getting some immunity first before worrying about second doses.

The UK is no longer constrained by manufactured doses or anything else. The faster they put that existing supply into people, the faster they are done. They could be done with the pandemic by the end of January.


> They could be done with the pandemic by the end of January.

There are only 500,000 doses available for the first week of Jan according to Hancock's statement in the commons a few minutes ago, so it will be a while before everyone gets their first dose.


My understanding was always that AZ had capacity to produce many billions of doses by year (2021) end, and already had a large supply ready to go: is it possible that “first week of January” is referring specifically to the number of doses that can be administered by then which is limited by more than supply? Distribution, appointments etc. And if so, could we see the second week of January jump substantially? Access to just 500k doses would be a significant shift from the expectations that have been shared so far.


In Johnson's press conference just now they said the number of vaccinations was entirely limited by the available supply, not the ability to administer it, nor the distribution of it. They were explicit about this.


That’s a shame, back in November AZ said:

“Where we stand today is we have four million doses available right now and we've got enough active that we think we will be able to make a further 15 million available to the UK by the end of this year. Subject to regulatory approval, it could actually be 19 million doses by the end of this year (to the UK)."

That seems like something has clearly gone wrong, if more than a month ago they were in that position and now we are so limited by available dosage.


Is it possible that some of what was said was aimed at getting approval? Could another country have swooped in and reserved some of the supply?


There's more info at https://www.bbc.co.uk/news/health-55500238

> There are thought to be more than five million doses of the Oxford vaccine in the UK, but only just over 500,000 are ready for use.

> That is because vaccines have to be put into vials and batched and certified.

> Sources at the NHS expressed frustration at the situation. "The NHS is ready to go, but we can only go as quickly as supply allows," one said.


That would be suprising, given the quantity already produced by their partners worldwide. Because of the more standard supply chain they have many manufacturing partners. But I'll look for sources. Astrazeneca was always supposed to be a high volume player vs the others.


I've just read we are expecing about 2M doses a week of the AZ vaccine, so I guess we won't be done by end of Jan but I would expect the numbers to be coming down swiftly by then.


> the smartest targeting of the population (a focus on saving lives by targeting most vulnerable groups first)

Can you elaborate on this?

IIRC the US recommendations take into account the population's chance of infecting others, rather than just solely the risk of death.


The parent's info is out of date. There was a big fuss a week or so ago about how the CDC's draft recommendations for how states should distribute vaccines prioritized "essential workers" instead of the elderly, which would've increased the total number of deaths, but these ended up not being the final recommendation. A large number of uninformed people are still raging about it though.


The present guidelines are still substantially worse than the UK’s though. Door dashers are still put ahead of the elderly outside of nursing homes.


An issue that I basically never see come up is - why not administer the vaccine earlier on (pre-approval) to the most vulnerable? if P(death|vaccine) < P(death|covid) then it seems really barbaric not to give it. Many dead people now could be alive had that been done (and mRNA candidates were apparently available extremely early on).

The Oxford vaccine is a more classical one so wasn't available quite as early, but apparently the mRNA ones were developed in a very short space of time (weeks - months) and future development could cut that even further (and preemptive vaccines for potential pandemic-causing viruses could be kept in stock) - perhaps introducing a Bayesian triage pre-approval could be an important strategy in fighting viruses in the future?

In any case this and the mRNA vaccines are really tremendous achievements and somewhat restores my faith in humanity after a terrible year...


[...] why not administer the vaccine earlier on (pre-approval) to the most vulnerable? if P(death|vaccine) < P(death|covid) then it seems really barbaric not to give it.

The full equation is: P(death+injury|vaccine) < P(death|covid)

Before widespread testing, you don't know the severity of a treatment's side effects, especially in vulnerable subpopulations like children and elderly. The risk of severe complications for a novel drug are especially of concern when the immune system is involved, since it's often unstable or senescent in early and late age groups, and overreaction (e.g. cytokine storms) may prove toxic.

You don't want the cure to be worse than the disease unless the untreated mortality rate is sky high and no other therapy is viable, as it is for many cancers. In the case of Covid, with a 2-10% death rate (depending on age and region), such desperate measures are hard to justify, especially in low risk groups, until risk of injury is better known.


In the case of highly vulnerable patients the death rate is vastly higher, easily into the double-digits, e.g. https://www.manchester.ac.uk/discover/news/frailty-old-age-a... - with extreme risk factors and old age the death rate is staggering.

If you had e.g. a 75% chance of death but the vaccine had a 0.01% chance of killing or seriously impairing you, even taking into account all the issues and the risk of actually catching it the risk seems worthwhile.

However this discussion does make me think that the candidate range is going to be pretty narrow, and of course all concerned would have to be able and willing to give informed consent many of whom presumably would not.


Isn't safety the result of phase II tests? Weren't those complete in June for those vaccines that are getting deployed now?

And, anyway, I'm sure getting safety data from a large scale trial, where every vaccinated person is a data point is much faster than getting effectivity data, where only the people exposed to the virus count.

Shouldn't vaccines made with proven technology carry a somewhat high prior of efficacy?

(And, anyway, with all those problems people are finding on the trials, we are still green lighting them. What's only fair, because it's very likely that the problems aren't important. But why can we make that calculation now, but couldn't in June?)


Safety is the primary purpose of P2, but the size of those trials is often still too small (often 100 to 500) to detect rarer toxicity events, especially in secondary groups often excluded (e.g. juveniles) in trials that initially target a different primary group (e.g. old folks) for approval.

Many drugs fail due to toxicity only during/after P3 when the number of subjects (often 1000 to 30,000) is sufficient to engage sufficient contraindication factors and power needed statistics to reveal detail in the edge cases.


What is a reasonable prior for the toxicity of an old tech vaccine (like viral vector, that is reasonably common for COVID) that passed P2? We have been making vaccines for a while, we should be able to answer that.

Also, how long do we need to wait on P3 before we get the toxicity result?

A really rigorous answer is that we need several years because some problems appear very slowly. Yet, we are not waiting those years. We are declaring definitive success with incomplete information. What is very reasonable, because it is very unlikely that those vaccines will have long term toxicity... but then, why are we using that prior, but refuse to use the P2 or early P3 results to make a temporary decision?

Why we decided that it was ok to try the vaccine on 10s of thousands in June, but couldn't expand that number to 100's of thousands on July, or millions by August? The decisions were taken by calgo culting regulations, and caused a lot unnecessary harm.


> why not administer the vaccine earlier on (pre-approval) to the most vulnerable?

The issue is less tangible and less quantative that that. It's about trust and public buy-in. If vaccine is rolled out despite not fully understanding its efficacy and safety and there are even minor side-effects, there will be fewer people who take the vaccine when they are asked to do so.


At the cost of how many lives? And if the vaccine is successful how would that harm buy-in? If not then it's a failed experiment (though obviously the PR impact could be rather negative!)

I think it's pretty clear from the past year that we need different tools and approaches to dealing with pandemics. One part is clearly faster vaccine development (mRNA seems very promising for this) and pre-emptive vaccine development, another might be permitting very much informed consent take up early on.


The cost of a dangerous vaccine could be one hundred years of lower uptake of ALL vaccines decimating the populations of nearly every country in the world. Not worth the risk if you ask me.


I'm not sure a small subset having a bad reaction to a known-untested vaccine they volunteered to have would have quite as bad an impact as you say, certainly not 100 years of lower uptake! It would likely have some kind of an impact though, and give fuel to anti-vaxxer types (yuk) but I am not sure the impact would be quite so severe.


>if P(death|vaccine) < P(death|covid) then it seems really barbaric not to give it.

No, it would have to be P(death|vaccine) < P(death|covid) * P(covid) because not everyone would get covid during the pre-approval period. That's a far higher bar.

Also, let's not forget P(covid|vaccine). People would behave very differently once they had the vaccine and feel safe. So if the vaccine isn't effective, that could be catastrophic.


That's a very good point, latter should be P(death ^ covid) I suppose!

I still think the numbers would arguably work out well given the general safety especially of the mRNA vaccines (as I understand it).

It wouldn't be a simple or easy decision but it's one that should be considered (very carefully!)


> An issue that I basically never see come up is - why not administer the vaccine earlier on (pre-approval) to the most vulnerable? if P(death|vaccine) < P(death|covid) then it seems really barbaric not to give it.

Not sure, but I would think it comes down to hospitals not being overrun in the case of a widescale negative response to the vaccine. But since the whole thing is a game of probabilities, I do share your view.


You could distribute it in limited batches to only the most vulnerable which should reduce any risk of that. I think the most vulnerable are in any case most likely to already be heavily using the health services anyway (and would be the ones engaging them the most if they caught the virus).


Because of ethics in drug development. And these rules are there for a reason. Not sure what could have been done better with Covid vaccines, we have three now roughly a year after the first cases. All of them work and are either certified or on the track to soon be. We even have four if you include the Russian one.

Summing up the ethics part: Studies include volunteers in a controlled environment. Just administering un approved stuff to people means using people as guinea pigs. I don't want that, and it is doubtful we would have gained anything. Because now it is "simple" distribution and production problem.


'Because of ethics' and 'these rules are there for a reason' are not arguments, they're 'shut up' encoded. Present arguments please.

The progress of the vaccine has been incredible compared to usual, but that doesn't mean more could have been done. Every death is a tragedy.

People are constantly used as guinea pigs... as long as there is informed consent as per the Nuremberg code it's fine. Not suggesting anybody would be forced or ill-informed.

So back to my argument - you can make a reasonable guess at estimating P(death|vaccine) vs. P(death|covid) and set a big margin, then offer people to VOLUNTARILY agree to take it who are most at risk of dying.

The average age of death in the UK is 82 mostly with co-morbidities. I am sure many of these dead would have been happy to take the chance.

And in the case of the mRNA vaccines this not some trivial difference - some were developed within weeks/months, but took nearly a year longer to pass all testing.

It's really obvious that pandemics need different handling than the 'lock down and loads of people die anyway, both from the virus and the consequences of lockdown while ruining the economy + wait 2yrs for a vaccine to be fully distributed' approach we've got.

I hope lessons are learned from covid (I'm actually optimistic they will be, in countries other than the one where the virus emerged anyway).


> I am sure ... many would have taken the chances

So you never asked anyone. The problem is, if you ignore ethics, which of course says a lot about your priorities, still two fold.

First, you have development. That was arguably the fastest vaccine development in history. Not sure what could have been done faster here.

Second, you have production and distribution. Ramping up these two doesn't make much sense before you know whether or not the vaccines work. Now they are ramped up really fast. Going "fast and breaking" things may have resulted in more people being vaccinated early on. But this small benefit would have caused tremendous issues in a couple of weeks / months. The goal is to get millions vaccinated, not just a few elderly so that some people can go out partying again without feeling bad.


>So you never asked anyone. The problem is, if you ignore ethics, which of course says a lot about your priorities, still two fold.

This is offensive and I suggest you re-read my post (as well as the HN comment guidelines). I am not ignoring ethics, I specifically mention informed consent. I also have no idea what you mean by 'so you never asked anyone' - this is a hypothetical??

>The goal is to get millions vaccinated, not just a few elderly so that some people can go out partying again without feeling bad.

You're also strawmanning me pretty hard here.

> But this small benefit would have caused tremendous issues in a couple of weeks / months.

Not even sure how you come to this conclusion (you seem 100% certain that distributing the now-proven safe mRNA vaccine early would have caused tremendous issues, somehow).

You seem to want to be aggressive to me and strawman me as somebody who doesn't care about covid victims (my grandmother is 85 and has serious comorbidity risks thank you very much) so I am not going to respond further but I suggest you focus on arguments, not insults and dismissive comments. You can go to reddit and much of the rest of the internet for that.


So we agree to disagree. No problem for me. Regarding distribution, I saw way to many rushed logistics and supply chain initiatives in my life to know how things turn out when people cut corners for some limited early successes. I am happy authorities seem not to do that right now.


60% effective but 100% effective at preventing severe illness. That's really what matters. It's not about making sure nobody gets the virus (none of the vaccines can offer that) it's about making sure we can live with this thing until it goes away.

I live in the UK and if they offer this, I'm taking it.


On a different note, some research must be done to investigate such low prevalence and fatality ratio in countries like India and Pakistan.


Super easy, they just have very, very few old people. Different population pyramids. Hence low fatality ratio. And low prevalence is just because vast majority of people are young and have it asymptomatically.

It may also play a role that asymptomatic carriers have lower chance of transmitting infection, so R0 in those countries is lower.


Thoughts on countries like Japan with a super-aged population but with low fatality ratio?


Culture of discipline. If government says you to wear masks, you don't run a rally because not wearing a mask is your "human right". You wear a mask.


The key take-home about this vaccine is it is a more traditional approach using an adenovirus vector, which doesn't have the cold chain logistical constraints of the pfizer vaccine. This means it will be possible to vaccinate in the community away from the cold storage found in large teaching hospitals, and also means that this vaccine can be supplied to parts of the world where it wouldn't otherwise be possible. Apart from a non-selfish point of view that the world should be protected from this virus, I also wonder how important it will be to control the virus in a global scale to reduce the chance of further mutations that may cause another pandemic in the near future.


The other key take-home is that nobody got a serious case so that's 100% effective at preventing the collapse of the healthcare systems of the world.

It's really good news all round.


Does anyone have a good link for the current status of the Gamaleya (Sputnik V) vaccine? I’ve been hearing and reading a lot of FUD about it, but if you were to take the (self reported) stats in this BBC article at face value it looks like one of the best options.

I found eg this Wired article that talks a lot about the geopolitical maneuvering of Russia/China/India in Africa and South America: https://www.wired.co.uk/article/russia-covid-vaccine-sputnik...

But really, despite a lot of pejorative language in there -- “Once they have this relationship, they can extort whatever they want” -- it just sounds like the same strategy the UK has been attempting (both politically, and in terms of vaccine development and approval), except the Russian version sounds more successful so far.

Edit to add: apologies in advance for dragging politics into this! But it seems like politics and vaccines are unfortunately intertwined.


their website has a good explainer of the differences (uses 2 different adenoviruses, which are also different from the ones the AZ vaccine uses): https://sputnikvaccine.com/about-vaccine/

Their Phase 1/2 results were published in Lancet[1], which also printed an opinion about the politics of the vaccine[2]

They have reported their final data for their phase 3 study in a press releace which states they will be published in a journal soon [3].

1. https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

2. https://www.thelancet.com/journals/laninf/article/PIIS1473-3...

3. https://sputnikvaccine.com/newsroom/pressreleases/the-sputni...


Thanks for that second link especially, this is exactly what I was looking for!

It sounds like much of the communication and release of scientific data has been bad, but in general the approach is sound and it’s likely to work well.

The same criticism about miscommunication could be (and has been) levelled at AZ, over the full-dose/half-dose mix-up.


> it just sounds like the same strategy the UK has been attempting

You mean selling the COVID vaccine to 3rd world countries at cost/zero-profit, or others prior to this?

https://www.theguardian.com/global-development/2020/nov/23/o...


Well, yes! Substitute “zero profit” with “low cost” and it sounds like the same idea.

The key question would seem to be, who can produce and distribute those billions of doses first? Is the AstraZeneca vaccine being produced at a large enough scale already, and/or has the current capacity already been bought up by the EU and other rich countries?


"Big Pharma" needs to make a profit from somewhere to finance r&d. 9 in 10 drugs (warning, made up statistic alert) don't reach the market, or something like that. And then they need to spend money on manufacturing. Then of course you have 'generics' when the drug is out of patent and other companies can produce it without royalties.

From the BBC article(s) I believe the UK has ordered 100m doses. I have no idea who is producing those though, and how long it takes.


Multiple factories, though one is the Serum Institute of India, said to be the largest in the world.

https://in.reuters.com/article/us-health-coronavirus-india-c...


https://www.nytimes.com/interactive/2020/science/coronavirus...

As far as I can tell the data on the Chinese Sinovac and Russian Sputnik (which are of the same type) are consistent with the data for Oxford/AstraZeneca.

So politics aside, this is hopeful.


Excellent link. A lot of detailed information.


Not sure if you've heard this as well, but Astra and Gamelaya are actually trialing a combination vaccine (1 AZ dose, 1 Sputnik-V dose).


Astra has some new unpublished data showing similar efficacy to the mRNA vaccines, and 100% severe COVID prevention.

https://archive.is/pMhDo

The UK really needs to roll this out fast because the current sudden growth in hospitalisation rates is a disaster, NHS is near full capacity again. I suspect there will be a full lockdown in January too.


It's so odd that he would make these statements in an interview without the data or a press release published. I mean this should be information subject to mandatory publication with regards to their shareholders. Astra has been by far the least trustworthy of the major companies so far. I just hope their jab works anyway.


From how I see it T4 is already a full lockdown and iirc over half the country is in T4 already so I don't see how things can be much different in January.


There's the 'school closures' lever still to pull.

Then there's things like only being allowed out of your house once a day for exercise.

And maybe if your work can't be done from home you're paid to stay home and not do it unless it's an essential service?

Key things are

1. This is only for a short and bounded time while we roll out vaccine 2. We need to get numbers down so that vaccine rollout isn't impinged


Yes the UK is about to hit a healthcare meltdown at this point.


It's not clear if this is on an emergency basis or not. Also interestingly, the UK has not approved the Moderna shot yet


I believe the UK has relatively few orders of the Moderna vaccine whereas they are highly reliant on the Oxford one. Makes sense for the regulatory to put all resources on Oxford once Biontech had been approved and then (I presume) look at Moderna next.


UK deliveries of the Moderna vaccine aren't until April or later (and only 5m doses total) AFAIK so the Government / MHRA have probably placed it on the backburner.


I do not understand why there is a strong sentiment in the comments here about how a 63% efficacy rate is dissapointing. First of all, this is for the 2 doses 4 weeks apart regime, there is already some evidence to suggest that a 1.5 dosing regime results in a higher efficacy, along with other evidence about a theoretical 3 month wait time between the two doses for a higher efficacy rate.

Secondly, this vaccine already prevents hospitalisation and severe illness! That's already a game-changer in and of itself. If you vaccinate the 20m or so who are the most vulnerable to COVID-19 and the most likely to require hospitalisation, then you immediately solve the hospitals-may-be-overflowing problem out of the pandemic (which is the only reason we go into lockdown in the first place). This will allow life to return to normal!


How long does it take to vaccinate the whole population?

I did not look for better sources, but I read in this [1] CNN post that in 2021: AZ is producing 3 billion doses, Pfizer 1.3B and Moderna less than 1B.

So in total we are going to have 5 billion doses in 2021. Each person requires two doses. So we end up vaccinating around one third of the world's population. It seems to me even at the end of 2021 our lives will be still far from "normal".

Are there other promising vaccines on the way?

[1] https://us.cnn.com/2020/12/30/investing/premarket-stocks-tra...


This is the type of vaccine that can end the pandemic. Cheap to produce, cheap to distribute, old well-understood technology.

Also many countries have the capacity to produce a similar vaccine. For example here is a feel good story from RT about Venezuela buying Russia's similar Sputnik vaccine:

https://www.rt.com/news/511063-sputnik-vaccine-venezuela-dea...

10 m. doses to be delivered within 3 months. How long time would it have taken Venezuela to procure a similar amount of mRNA vaccines from Pzifer or Moderna?


> old well-understood technology.

While they have been tested in trials for long, all of the adenovirus-based vaccines are new. There is only 1 commercially approved adenovirus vaccine, for rabies in wild animals.


I believe I've read somewhere that US military had been using it for some time. Not sure what for.


That's one more than mRNA vaccines had been approved before the Covid one.


Also J&J's Ebola vaccine, which is IIRC approved in Europe.


It is not old understood technology. This approach is nearly as new and novel as the RNA vaccines.


So because only the 2-full-dose trial had large enough N, that's the one that's approved, so people will be given what is most likely 60% protection even though it's possible, likely even, that if the person administering the vaccine simply doesn't inject the whole first dose - the protection will be higher? What will happen when the 0.5+1 dose trials are finished? Will the dosage recommendation simply be changed then?


Seemed to take a surprisingly long time. Let's hope the time had been well spent planning the roll out.


The reverse actually.

Whilst Oxford had the (generic) basis of the vaccine ready to go, prior to the COVID outbreak, it was the removal of all bureaucracy in this, and other, vaccine trials, that has allowed them to go from r&d to approved in 10 months or so.

Which is apparently what researchers will tell you is the 'real' time it takes to develop a vaccine. No time writing proposals and rewriting them when they get rejected, no awaiting someone to approve the proposal, no applications and waiting for grant money, no time spent waiting for volunteers for clinical trial groups, and so on.

Regarding the dosage, more information here: https://www.bbc.co.uk/news/health-55308216

(edit) and the time to develop here: https://www.bbc.co.uk/news/health-55041371


The biggest speedup factor was how easy it was to get people sick. A certain number of people had to get sick within the trial groups before results could be conclusive. With how widespread COVID is and how many people caught it, they hit that requirement significantly faster than they normally would.


Yes. Listened to one of the researchers talking about this. They said just that, this time difference here is almost all down to not waiting for funding or going through the usual grant process.


What was long about it? It only months instead of years, and for mRNA vaccines this whole time was spent on the validation and approval process while the vaccine design itself took only about ~2 days right after SARS-CoV-2 was sequenced.

From https://nymag.com/intelligencer/2020/12/moderna-covid-19-vac...:

> "Moderna’s mRNA-1273, which reported a 94.5 percent efficacy rate on November 16, had been designed by January 13. This was just two days after the genetic sequence had been made public"


I assume you are referring to the approval process. I've been thinking that too.

I don't want to be that person who thinks a really complicated thing should be trivial, so: Can anyone suggest why it would take weeks to approve these vaccines? What might the regulator actually be doing in this time?

They're clearly going to know that the request is urgent, and know when it's going to be arriving in their inbox; they could ask for anything apart from final data ahead of time to check everything is as they want it. I don't see why they can't have made sure they were happy with everything else ahead of receiving the final data.


Both Pfizer and Moderna were approved within a week of request. So it's not expected for the approval process to be slow.

If you compare the data between Pfizer[1] and AstraZeneca[2]. The AZ trials were significantly more complicated, with variations in methodology between phases and locale and much smaller sample sizes. It looks like they had to massage data and combine phases and explain differences, why they were doing it, and why it should still be considered safe.

Pfizer just submitted a giant sample size homogeneous trial result.

I would imagine it's way easier explaining and approving the one methodology/result with a giant sample size from Pfizer than the four methodologies/trials with small sample sizes and different doses within those trials given by mistake from AZ.

[1] https://www.nejm.org/doi/10.1056/NEJMoa2034577 [2] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...


in the findings for AZ, there is 1 reported death. So this means particapnt got the virus outside and vaccine didn't work right?


> From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death.

Means they didn't get the vaccine at all.


ahh ok all in the control arm


Given the pace, and the lack of years-long trials, they perhaps brought in a lot of additional people to help analyse the methodology and data.


By what standard? The article says specifically:

    It has been developed at a pace that would have been unthinkable before the pandemic.

    The new vaccine approval comes after Public Health England said the country was facing "unprecedented" levels of infections



This is a approval for all of the people who said to just allow Hydrochloriquine for everyone, because after all, its a pandemic, and how bad can it be? (turns out, it gave people heart attacks).

Not only have AZ lied about their test plans (claiming that the two differing dose was deliberate in the first press releases), lied about who was at fault with dosing errors (they insisted that the Italians where at fault), "pooled" results with different populations to try and make a argument they were not testing for (which critically didn't include people over 55) - they just managed to get the UK to approve a dosing strategy that they never even tested.

It's a pandemic - and the UK has invested a lot in both loves and national prestige in this vaccine. But the shortcuts here may come back to haunt. Or it may be what stops this disease in it's tracks.

it's a hell of a gamble either way..


Counterpoint, it's been proven safe based on all available data (which is more than for any other vaccine) and it reliably prevents serious illness even if it doesn't prevent all infections as reliably as the mRNA vaccines.

If we want the best possible vaccine, wait 6 months. If we want a safe vaccine that can end the pandemic as quickly as possible, this is the vaccine for the job.


Except none of that data is actually public yet - and a ton of work is going to have to go into bias-work because of the half-assed pooling work that AZ did.


<70% effectiveness is...not so great to say the least when you have vaccines from BioNTech and Moderna at 95% effectiveness already.


The half + full dose regime appears to have greater efficacy but wasn't approved because of insufficient data. I hope more data comes in and permits this. Also:

"However, unpublished data suggests that leaving a longer gap between the first and second doses increases the overall effectiveness of the jab."

That may well help too. But at the end of the day, the world needs a lot of vaccine. It's better to have Pfizer/Moderna and the Oxford vaccine at our disposal, particularly when the latter is also much cheaper and easier to store (this will be crucial in developing countries and/or rural populations). What matters is having fewer people get sick or die, not ensuring everyone is given the vaccine with the greatest efficacy.


The world would have 2x the vaccine available if they can fast track approval of the lower first dose. Hopefully given the prevalence in the UK they can now quickly do that work.


4/3x?


2x the initial rate, assuming we are constrained by supply right now but not so later on. In a few months supplies in developed countries will probably be sufficient for other things like logistics to be a bigger constraint.


That assumes the bottleneck is in the actual vaccine constituents, and not in manufacturing or sourcing the billions of delivery mechanisms.


Freezers, vials, and syringes are all easily mass produceable and already available in large quantities.


Yes, but this isn't software. Out in the physical world supply chains take time to ramp up.


And they are ramping pretty fast right now. We are not talking about books shipped by Amazon here. I for my part am really satisfied with vaccine distribution right now, quite the opposite to mask distribution and sourcing.


There are many factors at play:

* Cost of vaccine

* Ease of manufacturing

* Ease of distribution

* Prevention of severe cases and hospitalisations

It seems all vaccines currently approved so far prevent hospitalisations completely. It won’t stop the epidemic completely depending on coverage but it’s enough to stop killing people.


Exactly. I expect and assume everything with the highest standards and outstanding research and development with anything having the 'Oxford' name.

But when I see '<70%' effectiveness compared to 95% effectiveness with the Pfizer-BioNTech and Moderna vaccines, the Oxford-AstraZeneca vaccine looks very disappointing and far from the top standard I have expected.

That is not good enough.


That's such a naive way to look at it. It's not like we could've known beforehand which type of vaccine would be more effective. Some tried mRNA, other tried other techniques, and they all have to go through a lengthy phase 3 trial. This is a novel virus, and if everyone just did one kind of vaccine, and that kind failed, they we would've been fucked.

Hell, it's even more complex than that, because even given a type of vaccine, even subtle stuff such as dose size and time between the two doses seem to play a huge role, and this is again something that needs to be tweaked over time, using long phase 3 trials. I would attribute it much more to luck than actual skills here.


BioNTech and Moderna didn't do weekly swab tests and they only tested the symptomatic ones.

The sample size of Astrazeneca is much bigger as well.

With Moderna one, some people are loosing antibodies with in weeks.


Where are you getting your source for Astrazeneca's sample size being larger? Everything I've read so far says this result was based off a sample size of ~11k people. Which would be significantly smaller than the ~40k of Pfizer and ~30k of Moderna.


> With Moderna one, some people are loosing antibodies with in weeks.

That's... how vaccines work? Your anti-bodies don't stick around forever, and they're not supposed to. The purpose of the vaccine is to prime your memory B/T cells so that when the actual virus is introduced to your body the antibodies are produced much more rapidly, enough to kill the virus before it can take hold.


Yes. Maybe AstraZeneca should up their vaccine price by a few dollars and hire the PR-team from Pfizer.


The Medicines and Healthcare products Regulatory Agency (MHRA) has approved two full doses of the Oxford-AstraZeneca vaccine.

That’s the 60% effective version.

This is disappointing, hopefully they are working on getting approval for the 90% effective regime.

They could vaccinate far more people that way.


I believe the 2 doses will be administered 3 months apart. This should help get people their first dose more quickly and there’s a suggestion that this approach also has higher effectiveness.


That sounds good, the article doesn’t make this clear at all.


Do I understand it right that they approved it before the phase 3 trial has been completed? In Russia this strategy has led the trial to a failure because people who got placebo would just go and get the real vaccine.


That is not right at all.


That's what I read in AstraZeneca press-release.

> The MHRA’s decision was based on ... _interim_ analysis of the Phase III programme

> Additional safety and efficacy data for the vaccine will continue to accumulate from _ongoing_ clinical trials.

https://www.astrazeneca.com/media-centre/press-releases/2020...


If we put aside the protocol failure (accidentally giving half dose then full dose), and ignore the fact that they tried to not discuss this for some time until called out on it, of course, you can't stress-test (injection of virus to actually test for immunity) as it's not ethical.

So the summary metric is the Vaccine Efficacy, calculated as 1-relative risk, where relative risk is the incidence of infection in the vaccine group relative to the incidence of infection in the control group.

So with N = 75 the targeted number of post-dose infections, and V = # vaccinated out of the N, P = # placebo out of the N, are they saying that 100*(1-V/N) is the efficacy ? Then if it's 50%, it actually means you have no benefit over the placebo.


This is good news for the UK. However I lack any confidence that the british government will be able to roll this out at any sort of speed.

The government has had almost a year to plan for the rollout. Obviously there are some different logisitics for storing the various vaccines, however the last mile infra is exactly the same.

There is a plan to train 30k st johns ambulance volunteers, however if they want a smooth rollout, they should have been trained already. This hasn't happened yet.

Getting the jabs in the people is only part of the problem, the jab needs to be prescribed, but doctor time is rare (as they are all being hoovered up to provide 45% extra intensive care beds)

Not only that, after the jab, you need to watch the patient for anaphylactic shock. This requires nurses, again very much lacking in numbers.


Good point on the monitoring requirement but not sure why you think this would need a prescription?

Normal vaccinations you just go through some questions on risk factors before the nurse gives you the shot, usually on egg allergy, any past reactions and the like. No reason this would be any different.


In the UK, All vaccinations are prescribed. Any medicine that is not over the counter needs to be explicitly prescribed before it can be dispensed. (this is what my doctor friends tell me anyway)

> Normal vaccinations you just go through some questions on risk factors before the nurse gives you the shot

there are nurse prescribers, that have the power to prescribe a limited number of things. That aside, the prescription doesn't need to be done with the patient present. it can be pre-filled with the nurse/other arranging the dispensing.

this doesn't mean that the rules can't be changed. I suspect that in time there will be special dispensation given to allow non medical staff to prescribe, dispense and administer jabs. However until the first million or so have been done, they'll want to keep an eye on things and monitor the number of "yellow card" incidents that occur.


The whole article skips the question of the differences between the 60% and 90%. We still don't know the effectiveness on old people, but that seems to be the main differentiator. Not writing that in the article is dishonest.


AstraZeneca, Russia's Sputnik V developer to sign cooperation memorandum -Kremlin

https://www.reuters.com/article/us-health-coronavirus-astraz...

So, there is no reason to force down our throats the dubious vaccine from Pfiser which requires -70 C storage facilities. Not to mention of course the its creator has not been vaccinated yet. He said he did not want to take someelse's place.. What a horseshit.


You mean the CEO of Pfizer? He’s faaaar from being the creator of this vaccine, that was created by scientists in Germany, who were unrelated to Pfizer at the time.


Brexit might have some benefits after all. Let the competition begin!


The vaccine was developed prior to the end of the transition agreement, and the UK already had protocols for approving vaccines before rest of the EU (see Pfizer).

What's this got to do with Brexit?


The Oxford-AstraZeneca vaccine has unfortunately been heavily politicized in the UK. The reporting around it has always sounded a bit nationalistic.

For the past few months, the government has been using every opportunity to justify Brexit. The vaccine approval process being one of those.


I disagree. I don't think it's been "heavily" politicized, or even moderately, though I'm happy for you to point me to a clip or link of the Government taking claim for it?

> The reporting around it has always sounded a bit nationalistic.

The press have certainly reported that it's British developed, and why not? I'd say they equally reported that the Moderna vaccine was developed by Turkish Germans/German Turks.


Just jumping in here to share one example: one unit inside No.10 tried to get the union jack printed on this vaccine (but appears to have been unsuccessful): https://www.huffingtonpost.co.uk/entry/oxford-university-ast...


I was not aware of this. I've tended to avoid the press other than the BBC due to the overwhelming and relentless negativity of the last 9 months.


https://www.channel4.com/news/factcheck/factcheck-brexit-did...

Matt Hancock, secretary of state for department of health and social care: "It is absolutely clear that because we’ve left the EU I was able to change the law so that the UK alone could make this authorisation decision. So because we’ve left the EU, we’ve been able to move faster."

See also Jacob monumental fucking bellend Rees-Mogg and Nadine Dorries who made similar claims.


That you don't like someone's politics does not make what they say inherently false.

If Rees-Mogg, Dorries, and Hancock are wrong, then demonstrate it.


> And its chief executive, Dr June Raine, said on Wednesday that "we have been able to authorise the supply of this vaccine using provisions under European law, which exist until 1 January".

The full summary is below. But the short answer is the regulators who did the work are saying it makes no difference

https://www.bbc.co.uk/news/55163730


Any EU member can always approve any vaccine independently.


It's almost like EU countries tend to trust the joint efforts and don't generally go at it alone.

Well, with the obvious exception that happened this year (Brexit).




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