Oxford vaccine shows sustained protection of 76% in 3-month gap til second dose
ox.ac.uk
ox.ac.uk
I wish my country and others would take note and give priority to handing out as many first doses as possible, but my hope for such quick adoption of scientific findings has been rather diminished by the whole event.
The bright side is that, if the rate of vaccination continues to increase, those denied the first dose now should still get the first dose soon after. Let's hope we don't hit some manufacturing bottleneck.
Frustratingly, I'm guessing the timelines for a study on the durability of single dose moderna/pfizer would take about as long as it will take to ramp up production.
Unless this virus is magically different from every other virus we create a vaccine for, waiting longer for the booster will create a better / longer-lasting immunity afterwards.
So it's very important to follow the protocol here as much as possible until we know otherwise.
The question is whether or not they have verified it in this context.
As for 3-4 weeks being too short, I'm not aware of any specific research there. But I'll assume you're right, and also tell you it's irrelevant: If a booster in 3-4 weeks improves efficacy, but doing it later would work even better, that does not mean we should wait longer: We still need the boost now. All your point means is that we should also do a second booster at some optimal time further down the road.
If you try to give the person a second dose, that means you're causing another person to be walking around completely unprotected.
Because if the vaccine wears off quickly. Then, the issue of the second person it moot. Vaccinating them becomes a net 0: Person A that got the first vaccine is losing their immunity while second person is gaining immunity.
However, assuming the pharmaceutical companies can & are massively ramping up production, and given that the logistics network for distributing & administering the shot is improving, We will hopefully get to the point when all of the above is completely irrelevant because there will be ample supply and ample bandwidth to administer the dosesto everyone.
I think in the short term we also get a little bit of a boost from the folks who have already been infected. AFAIK, their resistance may not last long-- as little as 6 months perhaps. But in terms of getting spread rates under control, and assuming twice as many people have been infected as the official record shows (which might be conservative, it's just educated guess) Then that means in addition to those getting vaccinated, We have about 55million formerly infected people that should have some level of resistance.
Anyway, thanks for an interesting conversation.
Late 2020 there was a paper published where they demonstrate this effect for SARS-Cov-2 in human cells, then they look for those variants in humans and find that they were already infecting humans, demonstrating this selection activity happens in the wild [1]. I totally hear you about the 1 does vaccine argument. I think the kicker is two-fold. First, we do not know whether vaccinated individuals can still be infected with and spread COVID. Second is the rollout is currently very slow. You could imagine a scenario where enough folks are vaccinated to add pressure, but not reduce widespread transmission. If the data comes out that you can't transmit covid after the first dose (and I believe that Moderna has this data, but not ready to publish), I think the answer is clear to delay the second dose. But I think it is the absence of the transmission data, not whether evolution will happen to the virus, is part of the reasoning for the current strategy of completing the vaccination course in the ~3 week timeline.
Does 1 dose prevent the spread of COVID19?
If it requires 2-doses to get a true "efficacy" (lower spread), then it might be more worthwhile to push 2-doses, rather than 1-dose (where everyone gets "less sick", but the virus continues to spread exponentially).
Real problem: 1-dose wasn't really tested on a large "phase 3" style 10,000+ person test. Its impossible to answer this question (yet). It will take further testing to know.
----------
I think there's something to be respected about sticking with what was tested, even if the scientific theory argues for a different approach.
Just because the theory says so, doesn't mean that the theory is true (at least, not until the theory is well tested).
Doing something different and hoping for the best just because its kinda correct theoretically is... overly optimistic. I wouldn't necessarily be against it, but it makes sense to stick with what was formally tested.
If 1 dose, followed by a 2nd some time, can cut that number down a lot (some people won't get Covid, and few will get a bad one), hospitals can be freed and start returning to their usual work - cancer treatments etc. That's a big win. I think it's still the case that more people die of cancer than of Covid.
But that said, I also worry whether the vaccines will work with the longer spacing - I hope results like this show us they would.
Preventing the spread of COVID19 has an exponential effect on all stats.
If 1-dose only reduces the symptoms (but continues the exponential spread), then 20% vaccination rate means that you have 20% fewer hospitalizations after a month.
-----------
In contrast, if 2-dose prevents the spread, then 10% vaccination means 10% fewer spread *PER GENERATION* of COVID19.
That's 90% of the hospitalizations in one generation (~1-week period). After 2-weeks, you have ~81% hospitalizations. After 3-weeks, down to 73%. After 4 weeks, only 65%.
Controlling the spread is the #1 health priority that has exponential effects. I'd take 1/2 the vaccination rate if we have a better chance at tackling the exponential-spread issue.
Another study supporting "First doses first".
Check out the data on the UK Gov dashboard if you've not seen it:
https://coronavirus.data.gov.uk/
Also - we are all in lockdown, which helps.
* for major countries (incidentally, the UK territory Gibraltar is 2nd in the world if you include minor countries), and only considering the first dosage, which in fairness, appears to be the correct for this specific vaccine.
The UK (in particular, England) is currently reporting the second highest new death rate per capita in the world, still higher than it was at any point in 2020. It continues to report 1000+ unnecessary deaths per day.
And, is it still the case that the UK has 50% more excess deaths than it is reporting in the daily coronavirus figures? A mystery...
Deaths will start to stop soon, COVID infections are already dropping in many countries, with vaccines being part of the reason (but only part - again we cannot know how much)
I believe it's (now) listing UK up to 2020 Week 51, and Bulgaria to 2021 Week 3.
That's a 5 week difference in which Bulgaria was hit pretty hard. We don't see the effect in this data set of the British variant yet.
Having messed this up so very badly doing idiotically risky things from the start the latest big risk taken by the UK government didn't actually backfire as badly as the previous ones. Others have pointed at the current per-capita deaths. This completely ignores the long-term effects to survivors accross the population.
It can be a challenge to see how the UK government could have dealt with this worse. It's a highly educated population that has put the brakes on the most destructive policies from the very start.
I really hope the wider population comes to an appreciation of "asymmetric risk" from this the way "metal fatigue" entered popular usage with the aeroplane disasters of I think the DC-10.
...taking a flyer on an utterly unproven vaccination strategy was a huge, huge risk and had it not come off there would be no vaccination strategy. Relying on being lucky doesn't seem like a "spot on" strategy to me.
"We gambled everything on red it and came up so we deserve credit for the strategy."
edit: This is in relation to the additional time between first and second jabs that was untested in the strategy - for which this result suggests we no longer need to be concerned that the vaccination might be reduced in protection as we were before this data came in.
When they do well you still say it's because of their incompetence.
At every turn they’ve had credible expert advice telling them to do contradictory things. They’ve had to use judgement.
If only they had the sense to use hindsight, like you.
There were rather a lot of people suggesting that doing an unproven vaccine strategy of getting the maximum number of people their first vaccine and a longer period between first and second that had not yet been trialed, at all as a thing that was risky. People said it in advance. Who were the credible experts who recommended it? What support did they give that it wasn't a pretty big risk? If there was some and I missed it I'll put my hand up and say I was wrong. As I recall there was some serious doubt about whether anyone would get benfit from vaccination at all. Again if it was /known/ that it was likely to work that's not a bad decision - but I haven't seen that analysis. Have you? Please do link it if you have. I'm also not clear about what the upside for running that risk was. Are there better results for people contracting covid after only one jab? Do we have data? Or was that a flyer that it might turn out to be? Any links you have with an analysis of that is welcome.
The "herd immunity" strategy was also described as risky by most experts that I saw. I think the word I used when looking at it, in advance of the numbers coming in was "insane," while being well aware there was at least a nonzero chance it could work better than the conservative approach. To say it has not come off is an understatement. If it did come off somehow due to dumb luck it would have been equally terrible decision making. It's too big a risk to take, the downside is immense.
It is reasonable to criticise a risk-loving gambling strategy for a nation's health whether it comes off or not. I criticisised it before and after and I criticisise it when it comes off and when it doesn't. By contrast a considered and careful strategy is to be commended even if it turned out to be incorrect based on subsequently available facts.
This is literally gambling on uncertain outcomes with people's lives and health. You want to do that as sensibly as you can. You want the analysis. You want it public. You're paying the downside. Getting lucky to get results out of bad decisions does NOT make a decision a good one.
But hey, take the thing as a whole. Has it been good, covid management in the UK or not? It's worthwhile analysing what when wrong and why and how that compared with other, differing strategies. Taiwan's looked pretty good initially and continues to. South Korea and Japan looked to have pretty good strategies and continue to. New Zealand and Australia had very different strategies to the UK.
It's entirely reasonable to criticise a gambling addict's decision making when they bet the rent check and the bet wins.
I hope that makes the point clearer for you, please disagree if you like but it should be clear that hindsight has nothing whatever to do with the criticisim.
But the EU also gambled - they gambled that more time thinking would pay off, and it didn't. I think this is where you're going wrong with your argument: spending more time for care and consideration is also a gamble.
How do you know how much care and consideration is the right amount? Is more care and consideration always better? Would it be better to still be considering whether to buy any vaccine at this stage? Would you commend that? No, obviously not. So at some point more care and consideration is bad, and you can't just say 'more care and consideration please' forever. At some point you need to apply judgement to stop considering and act. That's a judgement. That's a gamble. It's a gamble to stop considering your situation and it's a gamble to keep considering your situation.
Both the UK and the EU took a gamble. The EU gambled that more consideration was better and they were wrong.
So everyone's a gambler, if you want to look at it like that. But one gambler had better judgement than the other.
If my impression of risk-loving decision making is wrong and there really was careful analysis of risks I'd love to hear it. It would restore a /lot/ of faith.
What was the assessed risk that that an increased period between first and second jabs would greatly reduce the coverage?
What was the advantage of the increased period? (ie is it likely that one jab will keep more people alive and/or do less damage to more covid survivors).
Is the risk of going with a longer period between first and second worth it? With the benefit of hindsight there appears not to be a downside. To be totally clear: this is very, very, very welcome news. Now it's a proper asymmetry and it seems like this strategy is all upside from here.
The alternative was to give people the two vaccine jabs the exact amount of time apart as had been tested and was known until this data came in. Then switch to this strategy. That is the conservative decision as you pretty much know what you're going to get. Is the longer period between first and second to get more people a first jab faster going to pay off? Again to be 100% clear let's hope so. Really let's hope it's a huge, huge win.
This analysis of UK vaccination policy and the maximum coverage of first jabs that the new 3-month data helps to further (but not completely) inform has nothing to do with the EU or New Zealand or Taiwan or Brazil.
Assessing the UK's gamblers' strategy of taking flyers is a reasonable thing to do in comparison to other EU nations, or NZ or Brazil...
There are other aspects to the UK's various strategies that don't have much to do with the Oxford vaccine showing sustained protection of 76% ...
If the UK has made some good calls in there based on risk asymmetry and balances of probabilities to go with the plethora of terrible ones they probably should trumpet them very loudly just restore people's faith that it's possible and that we can do better than 'gut-feel' or taking a flyer or "if she comes home we'll be loaded!" Which is how it's looking.
The Joint Committee on Vaccination and Immunisation. Membership listed here: https://www.gov.uk/government/groups/joint-committee-on-vacc...
> What support did they give that it wasn't a pretty big risk?
Analysis available here: https://app.box.com/s/iddfb4ppwkmtjusir2tc/file/759357623956 (via the minutes hyperlink on the JCVI page above)
Relevant conclusion:
"The Committee advises initially prioritising delivery of the first vaccine dose as this is highly likely to have a greater public health impact in the short term and reduce the number of preventable deaths from COVID-19."
>The "herd immunity" strategy was also described as risky by most experts that I saw
Herd immunity was not government policy: https://www.bbc.co.uk/news/uk-politics-54252272
>Others, however, have suggested, despite the denials, that "herd immunity" was indeed the strategy for a period of time.
So I'm one of those. I'll accept that it wasn't announced as government policy by name, but what of that?
https://www.standard.co.uk/news/health/uk-herd-immunity-coro...
https://www.bbc.com/news/science-environment-51892402
Obviously denying the bet was made is the best course of political action to do otherwise would be a resignation letter.
Accepting responsibility for the very large losses would take some kind of integrity, bravery and honnesty that is more than a little unusual accross the entire spectrum of professional politicians.
I think you're admitting here that you're determined from the start to assume the worst under all circumstances, success and failure, that you will never believe anything they say either way, and that no amount of reason will persuade you to give them an inch of credit or even just tolerance for them trying to do their best and it sometimes not being perfect.
I hope you aren't subject to this kind of cynical, relentless, and impossible to satisfy abuse in your job as you're dishing out to them.
The policies have had a massive cost countable in deaths and misery. Those who advanced those policies have to deny that consequence or resign. They deny like weak politicians. I don't believe them. I'm not alone among people who would much rather be noting their successes.
If the long wait between really was a good bet with limited downside and not yet another big risk I would be so relieved. That wasn't the way it was reported at the time.
If you take one thing to understand about this point of view I am expressing make it this:
Being conservative about risk with decisions where countless lives are at stake is a good thing. Gambling and winning does not retropsectively make it a good decision.
It's not necessarily! Being too conservative can be as bad as being not conservative enough! If you wanted maximum caution you'd never take a decision and never do anything. If governments did nothing yet about COVID and were still carefully considering a course of action at this stage we'd be fucked. No thanks.
"But I made it home without killing anyone." Is not a defence for downing 3 family sized vodkas and driving. "You'd condemn me weather i killed people or not!" Quite. Being too conservative we'd never have put the wheel on a vehicle. SFW.
Sensible conservative approaches to public health policy with tens of thousands of lives at stake is a reasonable thing to insist on. Herd immunity policies were NOT that. The additional, un-tested time between jabs was widely reported as being risky. If it wasn't actually terribly risky, then the prior risk assessment was spectacularly badly communicated.
"I made it home alive." Which this report, mercifully, confirms to my relief and joy, forms stuff all part of analysing the risk that was taken and the sense behind it.
Noting also you can take every reasonable precaution and still get a bad result without that result being sufficient to condemn the decision making. So absolutely the result is not the most important thing when there's a risky decision made. But it's really, incredibly bloody hard to ignore when 3 family-sized vodkas in, having been told not to drive you do anyway, straight into some children. Or 110,000 covid deaths. Those kind of losses are rather hard to ignore when they're the consequence of risk-taking. Even if at first blush you didn't think it was pretty reckless even though it was described frequently as such, in advance.
As has already been pointed out to you, there was no herd immunity policy.
https://www.bbc.co.uk/news/uk-politics-54252272
You need to be able to tell the difference between someone using the words 'herd immunity' in a sentence, and it being official policy.
Your response to this is just 'nah... I'll ignore that and just assume they're lying'. That's where your prejudice is coming into it.
>At the start of the pandemic, the government's chief scientific adviser, Sir Patrick Vallance, spoke about "herd immunity" - the idea that once enough of a population had been exposed to the virus, they would build up natural immunity to it.
This was when the virus spread really kicked off. There was a press conference I saw with disbelief where people were encouraged to attend football games because on average a positive case will infect 5 others so attending football games is fine.
>"Our aim," he told BBC Radio 4's Today programme that morning, is to "try and reduce the peak - not suppress it completely, also because most people get a mild illness, to build up some degree of herd immunity whilst protecting the most vulnerable".
"to build up some degree of herd immunity" is not a herd immunity policy.
See you could call that policy "isolate, trace and contain" and that name does not make any difference to what the policy actually was.
That particular knight of the realm was clearly speaking so badly out of term about the UK following a policy that was not being followed that he was of course immediately fired. I just can't find the link. Maybe it didn't happen and I just assumed you'd have to be fired if you literally lied about government policy in a pandemic and that has been confusing.
>in a BBC interview on 11 March with Dr David Halpern, chief executive of the government-owned Behavioural Insights Team, known as the "nudge unit", and a member of the Scientific Advisory Group for Emergencies (Sage).
He told the BBC: "You'll want to protect those at-risk groups so that they basically don't catch the disease and by the time they come out of their cocooning, herd immunity's been achieved in the rest of the population."
Let's call the policy "Geoffrey" and between us declare that name official to this discussion. That doesn't change anything either.
As long as we can treat this:
>"In a statement, a government spokesman said the emails "make clear… herd immunity has never been a policy aim".
With at least some of the utter contempt mustered by the bbc journalist in that piece.
I hope my another repitition of my rejection of what has "been pointed out" is now sufficiently clear to you. The policy was followed the aim of spreading the virus achieved the hoped for payoff for that strategy has been elusive. Or perhaps they just stumbled into following a herd immunity policy by accident while talking about it. The distinction is not important to me.
It certainly wasn't known. And scientists used to working with statistically significant proof rightly called that out. That said, my understanding is that it works this way for most (but not all) vaccines. So unlike some of the other UK government decisions, it was a somewhat reasonable gamble with quite a high likelihood of working out.
The upside is being vaccinate twice as quickly (esp. valuable early on when supply is constrained).
Is one jab much use to prevent bad results it was that unknown and we're still hopeful that it will turn out that it is?
The issues European production partners (one in Belgium I think) are suffering with the AstraZeneca vaccine are similar to those already solved at the UK production sites months ago because of the risk taken to start production early.
Each production facility can have unique issues that effect yield that simply need time to resolve.
Maybe AstraZeneca over promised, but it feels like risks to production yield were not properly assessed by those in charge of ensuring vaccine supply in the EU.
The unproven strategy that I meant was the one where a longer period ellapses between first and second jabs than had ever been tested. This new data is the test and shows that we probably don't now need to be concerned about that as we did when the strategy was first decided on and implemented.
The conservative approach would have been to ensure everyone got 2 jabs with the elapsed time between them the amount of time that had been tested until this data came in to show that a longer period would actually still work.
I don't know what the advantage of more people with a single jab is. Does anyone? Are you less likely to die? Or we hope so but don't have the data yet - the other leg of this bet so to speak.
The problem is that AZ had also promised the UK it would have priority over the goods produced on its soil :
https://www.irishtimes.com/business/health-pharma/dragging-a...
instead of AstraZeneca plc (.uk parent company) their contract is with AstraZeneca AB (.se subsidiary)
the UK vaccine operation will be under the control of AB plc
I would bet the commission insisted on having it with an EU entity without having thought the ramifications
It's hard to understand how you can mess up worse than that.
For example they could have delayed ordering vaccines, like the Europeans have.
And it took all the way to December to implement testing at the borders for the UK government while they were obviously allowing their citizens to take advantage of those travel policies.
If saving lives is the end goal then countries that took it seriously from the start and had a competent strategy for social distancing and containment are still better off.
Barely a month ago Boris was promising a normal Christmas.
Half the time we look at a country as being a good example of this, things fall apart within a few weeks... When a single person can infect hunreds of others, or none, there's a lot of randomness that models cannot easily account for. There are still a large number of infections where we don't know how the person was infected.
:)
I’m very glad NZ is COVID free but they got lucky by not having much community spread before the first lockdown and closing the border, and they are lucky by geography in this case.
What the UK has gone through is unique to the UK and it is hard to easily compare it to other countries. It's bad, don't get wrong, and I wish that travel lockdowns would have happened sooner, but let's not ignore a huge amount of relevant data so you can have a dig.
Anecdote : I live near a busy high street in London and went out for my daily lockdown exercise at around 6pm today.
About 10% of the "highly educated population", as you say, was wearing a mask. Even more worrying, if you looked through the windows of estate agencies and other such ""essential"" shops, it was exactly 0% indoors.
To people outside the UK reading this : supermarkets here have only made face coverings mandatory a couple of weeks ago ("unless you tell us you're exempt", of course) because the government finally asked them nicely to.
All these months, their CEOs have been emailing us bullshit newsletters about how "your safety is important to us in these unprecedented times", and to that effect they were politely asking customers to "keep your distance" and "wash your hands" and "follow local guidance about face coverings" (i.e. "none"). Meanwhile their employees were free to spend their whole shift unmasked and potentially filling the air with virus, getting their colleagues and customers sick : that was totally cool. And no mention of any effort regarding store ventilation or aerosol risk either.
There is no enforcement of lockdown whatsoever, except for the most egregious cases of partying. It all seems to be based on a gentlemen's agreement, except there seems to be very few gentlemen left indeed. It is all so hypocritical.
This situation is in stark contrast with what I hear from friends & family on the continent. Last time I was in Paris for instance, mask adherence was probably 80% in the street and 99% inside shops. And the French are not exactly known to be fond of rules.
So yeah, B.1.1.7 probably didn't help, the government has probably f**d up on everything except the vaccination programme, but the behaviour of the population alone is in my view, more than enough to explain the terrible UK death/cases figures.
In my area (near Oxford) I haven't seen a maskless person in a supermarket since masks became compulsory.
The UK started out very briefly with a Sweden-like strategy. We now know the Sweden strategy was correct: their results are in line with the EU average[1] despite a drastically smaller decline in GDP, a much smaller backlog of non-COVID health care problems and of course, a critically higher freedom and quality of life. The UK was 'bounced' into this reversal by its most highly educated people: literally university professors.
Later it turned out that those professors had forced the reversal using a computational model that was filled with mission-critical bugs[2][3]. It was so buggy that it produced totally different predictions every time it was run depending on what CPU architecture executed it and how many threads it used. There were typos in the constants of the hand-rolled PRNG, memory corruption errors in hand-rolled sorting functions and of course the whole thing was impossible to understand, being a single 15,000+ line C file in which basically every variable had a single letter name. The guys behind it were not merely incompetent but knew they were incompetent: the lead author (the notorious Ferguson) told a national newspaper, "For me the code is not a mess, but it's all in my head, completely undocumented. Nobody would be able to use it" [4] as if these statements weren't a contradiction. They brought in developers from GitHub to try and patch the code into an acceptable state before it was released, and then did a git squash to try and hide all the bug fixes.
People who pointed these problems out were told that it didn't matter because none of the models actually mattered - all that mattered was that "Epidemiology is not a branch of computer science and the conclusions around lockdown rely not on any mathematical model but on the scientific consensus" [5]. That is obviously 100% pure pseudo-science.
Some UK ministers and MPs have repeatedly expressed frustration that whenever they try and introduce some perspective, quietly ignore obviously dodgy numbers or reduce the damage of the proposed policies, the "scientists" immediately run to the press and whip up a mob that forces them to obey. Yet these people - the most highly educated of them all - have shown consistently very low standards about everything they are expected to know about.
Vaccines are the first chance we get to see what can happen when the British government is able to tackle something without dodgy epidemiologists constantly fucking everything up. Actual scientists, working in the world of real experiments and trials instead of student-quality C programs pretending to be theories, were paired with the private sector and a government that worked hard to clear obstacles from their path. The results have been extraordinary.
[1] https://ourworldindata.org/coronavirus-data-explorer?zoomToS...
[2] https://lockdownsceptics.org/code-review-of-fergusons-model/
[3] https://lockdownsceptics.org/second-analysis-of-fergusons-mo...
[4] https://www.thetimes.co.uk/article/neil-ferguson-interview-n...
[5] https://www.telegraph.co.uk/technology/2020/05/16/coding-led...
It feels like the number doesn't mean much without having a similar number for the null cases.
But more importantly, there were no hospitalizations or deaths in the vaccinated people. This is a point the media often overlooks.
Look at the two charts[2] in this paper from the UK's JCVI. They show the number of severe incidents (severe COVID or death). The linear or exponential growth curves are for people on the placebos. The almost flat lines are for people on the Pfizer-BioNTech and the Oxford-AstraZeneca vaccines, respectively.
Oh, after just the initial dose, not the booster!
[1] https://www.nytimes.com/2021/01/18/briefing/donald-trump-par...
[2] https://www.cas.mhra.gov.uk/ViewandAcknowledgment/ViewAttach...
I wonder why the evidence of lack of it isn't being publicised.
Asbestos was considered a great building material.
While science had improved in absolute terms, there is a chance to screw up in new ways.
Vaccines have been around for a very long time and have proven to be incredibly effective and safe. Nobody is embarrassed about how the vaccines for smallpox, polio and measles have worked out (apart from some misinformation in recent years -- you’ll have to do your own research on that one. If you come to it with an open mind I think you’ll come to agree those vaccines are safe.)
The stated efficacy/protection percentages that have been presented so far have been for the reduction of _symptoms_.
There haven't been any studies on vaccines preventing infections, probably due to lack of resources for testing everyone in a trial multiple times.
If that's the reduction of symptoms here, ok.
I spent last night puzzling over what "efficacy" means vis a vis this video: https://www.technologynetworks.com/immunology/videos/covid-1...
The author explains that the efficacy number is derived from the the number of the number of people in the control/placebo group infected divided by the total number of infections in the study.
76% efficacy means that, for a given population of people who contracted a disease (ignoring all uninfected), 24% were vaccinated (vaccine failures), 76% were not vaccinated. It has nothing to do with reduction of symptoms.
I think this is unintuitive because the "real" solution that laypersons want is, what percentage of vaccinated people exposed to a disease get infected? We can't measure that directly because we can't just expose a bunch of folks to Covid and hope for the best. But if the sample of placebo and vaccinated people is truly random, this would appear to arrive at the same ratio. (re: when I said "ignoring all uninfected"? in a good sample, the ratio of unexposed vaccinated and control units should be about the same)
We can, but medical ethics hasn't caught up yet. I would participate in a challenge trial, for instance.
Me too. And nearly everyone I know in my risk tier.
We had an entire globe of low-risk people willing to be part of the most acute spread, whether for research, for personal immunity, or to be able to isolate for a defined time to protect loved ones, and we squandered it in favor of pseudoscientific horizontal interdictions like lockdowns. It's really an incredible abandonment of basic principles of public health.
But there's a lot of information we left on the table. We had an opportunity to systematically formulate a controlled acute spread, studying the virology in a longitudinal way, studying the immune response in a more intimate and controlled way (from antibodies to the immune response after antibodies fade), and to examine the prevalence and role of innate immunity.
Beyond research, we had a chance to have tens of millions of people with verifiable immunity in Spring or Summer. People who then were in a great position to render aid to the marginalized communities who are instead bearing the brunt of lockdowns.
Instead, we traded all that for zero upside. And we have to deal with the enormous side effects of the horizontal interdiction as well.
It would mean handling live virus, which requires a Biosafety Level 3 facilities.
And, it's not going to get your vaccine approved any quicker.
Quite the example of the asymmetry. If you engage with the problem you have to operate absolutely perfectly. Way better not to engage with it and kill a few hundred thousand people. After all, no one can blame you for that part.
And of course it's not going to get the vaccine 'approved' quicker because yeah, 'approval' is also subject to the same people. But it will let us know if it works and whether it hurts.
Those things are not true alternatives.
I said "it's not going to get your vaccine approved any quicker" in the hope that you would understand: vaccines have reached the point of global distribution without doing the additional deliberate harm of intentionally infecting people.
Of course I am healthy, my family has had the vaccine or the disease and punched through, so I don't really care all that much.
The bottleneck has generally been manufacturing rather than approval so far. It may shift to distribution.
There is so much confusion and missinformation flying around, when even here on HN there is discussion about the meaning of basic numbers.
(but please carry on discussing it)
It's very difficult to get even a basic grasp of the details because you need to grok some complex statistics, biology, and public health to really dig in. Journalists sure aren't going to get the nuances so of course you have to read the academic literature.
Wouldn't that make a vaccine that does nothing 50% effective, instead of 0% effective (which is what one would expect)?
Furthermore, let's say you had 200 infections, split equally between the junk and the placebo.
So yeah, 100 / 200 = 50% effective. A coin toss, which is to say, no better or worse than not getting the vaccine.
Again, this isn't measuring "what one would expect" (how many vaccinated people, exposed to the virus, get the disease), it's "what proportion of vaccinated people get sick relative to unvaccinated people." (again IANAD)
If you measured efficacy as "1 - (vaccinated infections / unvaccinated infections)", it would be much more intuitive, and you could even get a bit of negative efficacy in the case where your vaccine did nothing.
This study has looked at that. From the press release: "Analyses of PCR positive swabs in UK population suggests vaccine may have substantial effect on transmission of the virus with 67% reduction in positive swabs among those vaccinated"
This was posited (but has not been confirmed) as one of the reasons it was posting lower numbers - it was catching some asymptomatic cases
You won't have neutralizing antibodies in the mucosal surfaces in the upper respiratory tract which would be required to completely prevent infection.
You will have NAbs in the bloodstream which should very effectively isolate the infection to the upper respiratory tract. Immune responses will also be primed so that the infection in the upper respiratory tract will be dramatically reduced. In many cases though the infection will be detectable via rtPCR but that won't be significant since the person won't be symptomatic, won't "feel sick" (or very sick) and will be very unlikely to transmit the virus. It should also entirely cut out the multi-organ involvement of covid since the neutralizing antibodies in the blood will prevent spread to the lungs/kidney/heart/brain/etc.
Testing via rtPCR for "infection" would be an expensive waste of time in a vaccine which isn't expected to confer that level of protection. And when it failed to confer that level of protection you're left trying to explain why that low number doesn't matter to a population expecting some kind of medical miracle.
Instead they watch for symptoms and then they confirm that is a SARS-CoV-2 infection via rtPCR, and this is the typical "efficacy number" which is reported (I think the initial Oxford trial results did report the results of randomized rtPCR testing so their numbers were dramatically lower, which has caused all kinds of confusion since its not apples-to-apples with the mRNA vaccine results).
Reduction in transmissibility is more difficult to determine which is why those numbers aren't reported, it is assumed that reduction in symptoms correlates with reduction in transmissibility. So none of the vaccine trials can conclusively rule out asymptomatic spread in vaccinated individuals. However since the people are being followed over time what is caught is any infection which subsequently produces symptoms. So the vaccinated asymptomatic individuals would be truly asymptomatic and not just presymptomatic. Dramatically cutting down symptoms is expected to be a pretty good proxy to dramatically cutting transmission.
Relevant quote from a recent BMJ article on truly asymptomatic transmission:
> The transmission rates to contacts within a specific group (secondary attack rate) may be 3-25 times lower for people who are asymptomatic than for those with symptoms.1121415 A city-wide prevalence study of almost 10 million people in Wuhan found no evidence of asymptomatic transmission.16 Coughing, which is a prominent symptom of covid-19, may result in far more viral particles being shed than talking and breathing, so people with symptomatic infections are more contagious, irrespective of close contact.17 On the other hand, asymptomatic and presymptomatic people may have more contacts than symptomatic people (who are isolating), underlining the importance of hand washing and social distancing measures for everyone.
https://www.bmj.com/content/371/bmj.m4851
The title study here on HN on the Oxford vaccine is pretty clear that they're looking for "primary symptomatic COVID-19" which means they're not screening for asymptomatic infection, they're waiting for symptoms, then confirming.
They found that one shot conferred good protection (76%) for at least 90 days post vaccination (after the first 2 weeks) with little waning and some evidence that it gets better. They also found that the BEST boosting interval was 12+ weeks or more, reaching 82% efficacy. This matches what I've heard some virologists yap about informally online that longer boosting intervals are generally what is recommended (more or less letting the learning immune response bake longer while letting the immediate response to the vaccine vector wane) but the early studies used short intervals due to pandemic driven concerns around giving health providers and the elderly the best immunity in the shortest period possible. Now that we're transitioning to needing to vaccinate literally everyone the message may unfortuntely shift in ways that make people suspicious.
https://www.medrxiv.org/content/10.1101/2021.01.15.21249731v...
The FDAs failure to approve Astrazeneca is the most horrifying government agency failure I have ever seen.
Fingers crossed.
Correlation is enough.
(or rather don't)
It doesn't matter who reports the data. FDA, CDC, some other TLA. Some mommy blog will claim that autism rates are up 25% since we started distributing the COVID vaccines and the anti-vaxxers will eat it right up.
Reason is that early on they were rushing data and approvals on grounds of national pride, in a very similar way to the Chinese and Russian authorities.
Pfizer and Moderna seem to have been more thorough.
I don't disagree about the process, though.
We knew back in December how effective just one dose[1] of the Oxford-AstraZeneca vaccine is, at stopping death. See figure 2 on page 28.
I have no qualms with the Moderna vaccine, I consider it and the Pfizer to be the most effective and least questionable.
What an absolutely ridiculous statement to make. I can only believe you are trolling in some way, or have you own nationalist pride over Pfizer/Moderna.
Initially they pretended this was done on purpose, and claimed 90% efficacy:
https://www.bbc.com/news/health-55040635
Later it came out this was an accident and cover-up, spun as a lucky discovery:
https://www.wired.com/story/the-astrazeneca-covid-vaccine-da...
https://www.reuters.com/article/us-health-coronavirus-astraz...
Even now, the lower bound of 95% C.I. around efficacy with two doses is 63% which is quite low, relative to the headlines:
https://www.ox.ac.uk/news/2021-02-02-oxford-coronavirus-vacc...
I'm not a troll, just a critic of a lab and a U.K. government that fudged some data because they needed a PR win.
https://www.bloomberg.com/news/features/2020-07-15/oxford-s-...
"I hope we can improve on those timelines and come to your rescue.” - Sarah Gilbert
That kind of hubris made it hard to admit process errors and low efficacy rates.
[1] https://www.npr.org/2021/02/01/962705729/eu-to-get-9-million...
https://www.nytimes.com/2020/12/08/business/covid-vaccine-ox...
It's great the vaccine is as effective and safe as predicted, but fumbling the most important clinical trial in the companies history reflected very poorly on their competence.
That's not a "full trial which proved safety and efficacy".
In the EU AZ is under delivering doses at present[0], also they had that whole trial dosing mishap.
In the US AZ wasn’t as fast at delivering a vaccine as Pfizer & Moderna & AZ isn’t a US company, but Moderna & Pfizer are. So not really a shock that they get most of the buzz in the US.
Interestingly the US has ordered more AZ doses than any other vaccine & AZ is the most ordered/purchased vaccine worldwide[1].
It’s no surprise to me that countries are hyping up their own products and/or getting them approved first. As for the EU, they are certain to be sore given the lack of doses they’ve been able to acquire & their vaccination strategy in general.
[0] https://news.ycombinator.com/item?id=25964197
[1] https://www.bloomberg.com/graphics/covid-vaccine-tracker-glo...
Personally I think the UK approach is the way to go and that the EU being cautious might backfire. We know the Oxford/AstraZeneca vaccine is pretty safe and the UK has been giving it to over-65s quite happily. If it does turn out that it’s less effective, then we’ll still have gotten some efficacy across the vast majority of our population much quicker, and probably not added to the deaths. If it turns out that it’s just as effective as on everyone else, then the EU will have lost time yet again and have left their older population at risk for longer.
In a month or two there will be more data, but in Q2 there will also be more supply of Pfizer and Moderna in the EU.
The EU can be cautious with AZ to elderly now because it can afford to due to large quantities of rna vaccine.
A few thousand elderly will die waiting for the slow buildup of rna delivieries while AZ could be made available. That’s the obvious drawback of this caution.
With Pfizers (and Moderna) ~95% efficacy and AZ at 60% I would give AZ to only those that want to jump the line or as the last resort.
You don't want doctors to spread COVID (40% vs 5% that can spread is huge).
Poland wants to give AZ to teachers, a group that has contact with many children (which have contact with their families) - this is poor thinking. AZ should go to people that don't have much contact with others, e.g. unemployed or volunteers.
I'm very excited that RNA vaccines are now a reality.
But the logistics for these RNA vaccines is much more difficult. Specialist freezers are required. Meaning it takes longer to vaccinate folk.
That's because the FDA is waiting for the completion of AZ's trial in the US. This should be definitely better run than the meta-trials done elsewhere and give clearer numbers.
A likely readout would be in March, or April.
The Oxford vaccine simply isn't that important to the US accordingly. We have Pfizer/BioNTech, Moderna, Johnson & Johnson, Novavax, along with Oxford. The US will end up with far more vaccine options than it needs. The EU is desperate for any vaccine supply because of how they massively screwed everything up. The US by contrast is going to be flooded with vaccine supply and is barely breaking a sweat. Given the US didn't even put forth its best effort and it's showing up the EU so dramatically, you know the EU really botched things.
Beg to differ there. We need to vaccinate the world. This is in the interests of the US. (Consider mutation etc). The analysis of the Oxford vaccine is that it is much easier to perform the logistics because of the significantly more modest refrigerations requirements. The US needs 7 billion to be vaccinated as much as anyone is my understanding.
$140 billion to vaccinate the world is not a large cost, and many nations will choose (have chosen) their own solutions, for the remaining, perhaps $60bn, that's not a large amount for developed nations to pay compared to the costs of reduced trade and potential further mutations, that's $60-$100 per person in developed countries in cash, or more likely however countries want to amortise that.
I can't speak for India but I imagine that they are happy to have access to this vaccine as well, as they are similarly going to manufacture it, and to a scale that will dwarf everyone else. And it not needing a special cold chain is even more of a plus in India of course.
AZ had production problems in the EU -- perfectly understandable as it’s a complex operation and they started somewhat later than in the UK. The EU Commission responded by threatening legal action (??) and almost bypassing the hard-won Northern Ireland border agreement (!!??!!) before backtracking. Ridiculously petty, dangerous, and does nothing to solve the problem and save lives.
You may want to read this for a more balanced view :
https://www.irishtimes.com/business/health-pharma/dragging-a...
It was really AZ's screw up. The fact is that the EU had a contract with AZ that explicitly required the use of UK plants for fulfilling the EU's orders if need be. But the problem is that AZ had also promised the UK it would have priority over the goods produced on its soil...
The threat to invoke the border protocol was absolutely shocking to me, so I’m very interested to learn more of the background.
Edit to add: for others reading this thread, here’s an article from the same site about that border protocol dispute: https://www.irishtimes.com/news/politics/shellshock-in-bruss...
The UK has many issues, and it's gone through a horrible few years but, in the case of the Oxford/Astra Zeneca vaccine specifically, I am incredible proud of what they have done.
What you're saying is that we must assume the worst case, that the FDA-approved vaccines are like 2-pack epoxies: that first doses give 0% immunity, and all the efficacy comes from applying the second. That seems completely absurd.
Observational reports so far on the tens of millions additional doses given (compared to a mere ~15-20K in phase 3 trials) is also suggestive of 1-dose efficiency. (Most recently, a retrospective study in Israel – the nation with the highest proportion of its population immunized – found 51% efficacy against "confirmed COVID" looking at just days 13-24 after a single dose – and that's in a world with far more variants than the original mRNA studies. It's reasonable to conjecture from other results that the efficacy would be even better later, and better against "severe disease".)
Plus, there's everything we can reason about from similar diseases & vaccines.
The reason to wait for 2nd-dose-plus-7d in study "primary endpoints" is to have a singular, legible, stark readout for rather-simpleminded regulatory processes. But smart people who live in the real world know the actual mechanisms are far more fluid/incremental, with immune processes starting immediately from one dose, then accelerating over weeks (even without a booster).
You can read the FDA briefings for Moderna & Pfizer which review the 1 dose data, its very readable.
The empirical data is overwhelming from many sources and the data matches our current disease models. All signs suggest overwhelmingly that: (1) 1 dose appears to be 100% effective at preventing death in all candidates >14 days after the 1st dose. (2) The marginal benefit of the second dose is real but comparatively much smaller. (3) The delaying the second dose appears to confer additional immunity.
Focusing on 1st doses is by far the best decision.
The Pfizer/Moderna mRNA vaccines might be just as effective, 30d-onward after one dose, as the "1-dose" J&J.
The tested 21d/28d spacing for the mRNA vaccines might be far shorter than optimal, so the ad-hoc "emergency" delays of booster shots by many jurisdictions might actually be benefitting long-term immunity.
The "1-dose" J&J might benefit greatly from a booster 30d, 90d, 180d later.
Even the dosings could be far from optimal, with some hints that half or less of the mRNA vaccines may be just as effective, especially in younger patients. And of course there was the AZ/Oxford glitch that mistakenly gave half the intended dose in the 1st shot - & that subgroup seemed to have even less disease after the 2nd full-dose shot. (While this could be a statistical fluke, maybe also a "booster" that's stronger is read by the immune system to mean that the disease is continuing to become even more of a threat, so it reacts even more strongly than to a "same as we beat before" dose. Until lots more study is done – who knows?)
So: people who treat the officially/rigorously evaluated doses/schedules as "optimal" or "the only safe course" are way overclaiming what the data shows. They data we have are a series of singular draws from the possibility-space, showing some points of reasonably-safe and -effective approach.
With plenty of other data constantly arriving, hinting at other equally- or more-effective approaches, regions & practitioners should be free to use their best-judgement to navigate risk/reward tradeoffs.
Is it a different dose or different timeline?
https://www.bloomberg.com/news/articles/2020-12-08/astra-vac...
Turks also find that the Sinovac vaccine is %91 effective when others reported less.
I guess it depends on the variant, on what do you understand by “protected” or on how much you want it to work.
Second, it went under the radar because it's probably not attributable to the vaccine. The people who died were over 80 and already extremely frail with pre-existing conditions. They either died from those conditions or from their inability to cope with the mild side-effects of the vaccine, which everyone already knows about. Death rates in Norway are well within the historical range, so it's fairly likely that there were no excess deaths caused by the vaccine at all.
Their dying after having the vaccine does not mean they died because of the vaccine.
The entire series is well worth a listen, data driven and statistics heavy.
[0] https://www.bbc.co.uk/sounds/play/m000qblw
Edit - because the beeb want registration, alternate link: https://podcasts.apple.com/gb/podcast/vaccine-hesitancy/id15...
Never heard this term. From context I'm assuming it's slang for the BBC?
> It is also known colloquially as "The Beeb", "Auntie", or a combination of both (as "Auntie Beeb") [0]
But anyway, “frail elderly patients” have a tendency to have a short life expectancy whether there is a pandemic on or not. The thing they will have to sort out is whether those 23 are coincidental or not. Ie what number would we have expected to die, had we not vaccinated them. This is pretty elementary statistics and I expect that they’ll sort it out shortly.