March 24, 2021 - 3:10pm
I wanted to say a few things about the Oxford-AstraZeneca vaccine. The US National Institutes of Health have released a statement saying that AZ’s press release claiming 79% effectiveness in its US trial was based on “outdated information”; AZ have responded. It’s caused a big furore.
Here’s what I have to say. About 28 million people have been given the first dose of a vaccine in the UK so far. How many of them have had the Ox/AZ jab isn’t completely clear to me, but let’s say half. (It started later than the Pfizer jab, but we have much more of it, so that’s probably a reasonable guess.) So about 14 million people.
That is an extraordinary dataset. The Phase III trials of the vaccines had a few tens of thousands of people. The rollout is three orders of magnitude larger than that.
It’s worth noting that true clinical trials have other advantages — subjects are randomly allocated into having either the vaccine or the control, which means that the two groups should be similar. In the real rollout, it’s slightly harder to compare the two groups: they’re non-random and might differ in some clinically important way.
That being said, there is plenty of evidence showing that the Oxford/AstraZeneca vaccine is effective. A study looking at 7.5 million (!) over-70-year-olds in England found that 35 days after their first dose, patients were 73% less likely to develop symptomatic disease, and those that did were a further 37% less likely to be hospitalised. (Which makes it about 80% effective against hospitalisation.)
There was quite a lot of uncertainty around those exact numbers, but they match other estimates. A study of five million Scottish people found that recipients of the AstraZeneca vaccine were 94% less likely to be hospitalised with Covid than unvaccinated people. A Public Health England analysis from February suggests a single dose of the Oxford vaccine led to a 60 to 70% decrease in symptomatic disease, and a greater than 80% decrease in severe disease. The Pfizer/BioNTech vaccine had broadly similar outcomes.
Also, there don’t seem to have been any serious side-effects. There are reports of some sore arms and short-lived flu-like symptoms in a reasonably large minority of people, but the “yellow card” system for reporting adverse reactions has found that, apart from a very small number of allergic reactions immediately after vaccination, there is no evidence of danger, including blood clots.
So let’s go back to the Oxford/AstraZeneca issue. It seems to arise because the trial released data taken up to a prearranged cutoff date. The trial’s Data Safety and Monitoring Board (an independent body) thinks the investigators should have included another month’s worth of data which includes more cases and brings the efficacy down a bit, to between 69% and 75%.
I’m completely happy to believe that AZ have buggered up here. They have done repeatedly, with confusing press releases, weird accidental dosing regimes and so on. If they’ve released data early to make themselves look good, that is amazingly stupid and harmful. If they’ve done it through incompetence, then that’s still not great. Even if it was a prearranged cutoff, it would have been good to be ostentatiously careful about not overstating the effectiveness, and to release the most inconvenient data they have.
But I do not understand why the DSMB and the NIH would want to then publicise a minor disagreement — is it 79% effective or 69% to 75% effective? — when the outcome of this trial is already kind of unimportant? We have evidence from tens of millions of real-world patients; a 30,000-subject clinical trial can’t tell us much that’s new. Besides, it finds roughly the same as everyone else anyway, whoever’s version of events you believe.
From a utilitarian point of view, it seems amazingly likely to me that this announcement, by decreasing public confidence in an obviously pretty good and very safe vaccine, will do a lot more harm than it does good. Maybe the NIH and DSMB have some ironclad regulatory requirements that mean they have to behave like this, but my guess is that some non-trivial number of people will die as a result.
Join the discussion
Join like minded readers that support our journalism by becoming a paid subscriber
To join the discussion in the comments, become a paid subscriber.
Join like minded readers that support our journalism, read unlimited articles and enjoy other subscriber-only benefits.
SubscribeThe point is always the same: politics. The fallacy is the assumption of good faith when entire political classes are put under pressure because of bad decisions, and will scramble like rats to save their skins. That is not aimed specifically at the EU, it applies to any grouping at all.
“One of the worst things about life is not how nasty the nasty people are. You know that already. It is how nasty the nice people can be.” ― Anthony Powell, The Kindly Ones
But what political motivation can there be here for the US in publicising this minor disagreement? As far as I know they haven’t messed up their own procurement procedure like the EU…
So there are clearly lobbying pressures over there from various groupings who are supporting different pharma companies making vaccines. There is no doubt a war underway about whose vaccine is favoured for the remaining people to be injected. AZ making their vaccine available at cost may be viewed as undercutting by the other pharma companies, and they are responding by ‘soft lobbying’ (low intensity undermining) in exactly the same way corporates lobby bodies within the EU against each other for various reasons. This feeds into the politicians, where if once political side is supporting one corporate stance, the other side are lobbied (bribed is too strong a word) by the other companies and therefore take a counter position. No one is necessarily making the best decisions, but those on behalf of whose lobbying wins out.
Yes: Pfizer and Moderna have reason to discredit a cheaper, easier to distribute rival product. There are also other US vaccines in the pipeline; next up Johnson & Johnson.
Pfizer and Moderna already have their contracts with the federal government, the vaccines were paid for under Operation Warp Speed. Would you like the federal government to break them?
J & J is not next up. It’s in use now. There were 10,000 J & J shots given in my city in a football stadium last Saturday.
Absolutely follow the money is usually a good maxim and it is pretty clear who benefits if the one at cost vaccine loses out to it’s more high priced competitors. Just who would put it past those competitors to be using their vast lobbying resources to to
The vaccine is free in the US. It’s all paid for by the federal government.
Yes, the federal govt is paying on behalf of the individuals for their personal jabs.However, the federal govt is paying the pharma companies their prices to obtain the vaccines at their demanded prices.
So the comments about lobbying are valid.
No. Actually, the federal government basically went into business with them to get the vaccines developed. So, it’s not that they are paying them, they have already done so. Who do you think gave the pharma companies the money to develop the vaccines under operation warp speed? The tooth fairy? Why would the US shun 800 million doses it has already paid for?
The U.S. government’s Operation Warp Speed program has invested about 10 billion in six potential coronavirus vaccine candidates. The Trump administration has locked in a minimum of 800 million doses as soon as the vaccines are approved.
Uh, please correct – payed for by the US taxpayers to benefit their fellow citizens.
No paid for by the federal government.
I see. Well that is fairly obvious now you’ve pointed it out. I guess I still would like to believe that in a situation like this, the public’s health would come first.
You will never get Macron to admit it, but I bet he was lobbied by Sanofi, which contributed (in combination with other such events) to a chain reaction, the consequences of which we see now.
And this is the irony, it could so easily have gone the other way – all it would have needed is for one or two smart scientists at Sanofi to crack through a sequence of essentially engineering problems – in which case he would have emerged smelling of roses.
Luck, see.
Yes, right at the start of this there were reports that France lobbied so that no more biontech vaccine would be procured than the Sanofi one…which then failed anyway.
Oh well, there goes my last bit of youthful idealism….I got to 38, that’s good going.
Ha ha. Good one.
Oh, you weren’t joking? My bad.
It does. The vaccine is free to anyone who wants one.
Yes. “When the search for truth is confused with political advocacy, the pursuit of knowledge is reduced to the quest for power.”
If this is the case, it is sick. Money has taken priority over lives. I wish a journalist would investigate possible lobbying against AZ. It would be the biggest scandal in my lifetime.
How has money taken priority over lives? No one is paying for the vaccine in the US, it’s free to everyone. Plus we already have three vaccines in use with large supplies of all of them.
No it isn’t free to everyone. The tax payer is paying via federal govt., whatever the pharma companies demand.
Yes, it is free. To everyone. No one has been charged for the vaccine. The pharmacy companies were GIVEN the funds to develop the vaccines by the federal government. Under operation warp speed. Honestly, how can you not know this? It isn’t pay as you go, 800 million doses were paid for BEFORE the vaccines had even been developed.
The U.S. government’s Operation Warp Speed program has invested about 10 billion in six potential coronavirus vaccine candidates. The Trump administration has locked in a minimum of 800 million doses as soon as the vaccines are approved.
A European Official Reveals a Secret: The U.S. Is Paying More for Coronavirus Vaccines – The New York Times (nytimes.com)
1) AZ is not approved for use in the US
2) should the federal government dump its existing contracts with other pharma companies for an unapproved vaccine?
3) the vaccine is free in the US to anyone who wants one.
Perhaps you establish the heart of the matter. The FDA was upset over the first trial data and required remediation. That was done but apparently not well enough. Meanwhile the US procured enough vaccine from others to match their needs. Good that they will ‘donate’ their stock of AZ. To all intents and purposes the AZ seems a better vaccine. Good for the world.
Your timeline is off. It was not “in the meantime”. The US government paid for its vaccines way back in 2020 when Operation Warp Speed secured 800 million doses as part of its funding to pharma companies. To buy AZ doses now, the federal government would have to by pass doses of other vaccines that have long been paid for.
Pfizer and Moderna want to make money. Protecting their vaccine adoption is a boon for US shareholders and CEOs. Not so good for the people who are ill or die while waiting for a vaccine because someone has rejected an AZ vaccine on their behalf.
The vaccine is free in the US. Not to mention, the federal government basically went into business with several pharma companies. So are you saying that the federal government is trying to charge itself as much as possible? Does that make sense to you?
Follow the money.
Not only has the US not screwed it up we already have three vaccines in use and shots are going in arms rapidly. There’s not even a waiting list anymore where I live.
Thank Trump!
Pfizer stands to lose significant revenue/profit as AZ is not-for-profit and far, far cheaper. Ergo, US wants Pfizer to rake in profits in order that the US can tax those profits. Is my cynical take on it.
The federal government is paying for the vaccines. They are free to anyone who wants one. So you are claiming that the US federal government wants to pay as much as possible so it can then turn around and tax companies on the profits made off the federal government? Really? Pfizer was paid for its doses way back in 2020 as part of Operation Warp Speed. In fact, it contracted and paid for 800 million doses.
I suppose it has nothing to do with the fact that AZ is the only vaccine manufacturer to make and supply their doses at no profit? When considered in global terms, if the AZ vaccine is favoured by most countries this will have a significant impact on potential profits to be made by the rest of big Pharma.
My guess is that AZ will be the last vaccine standing once this is over. While perhaps slightly less effective, fewer side effects are a benefit. So logistics alone suggest AZ will stick around.
Not for the US it doesn’t have anything to do with that. To buy now from AZ, the federal government would have to not use 800 million doses of other vaccines already paid for by Operation Warp Speed. How would that make sense?
Are you on commission?
Unfortunately, AZ are doing this at cost. Pfizer are not. Pfizer have hundreds of lobbyists and a budget for them of tens of millions of $.
There’s a similar affect with things like opensource software – it does what 95% of people want, but no one is pushing it because there’s no money in it.
There’s a massive flaw in free market thinking there. Other examples are companies like Nike where 50% of the cost of the item is celebrity endorsement.
Rory Sutherland (albeit a marketer) has an interesting theory about this. If you have two products one is branded the consumer is paying for confidence in it working and getting it fixed if it breaks. E.g. a Samsung TV for 400 vs an unknown Chinese brand for 300. Might even be made in the same factory but it’s not irrational for the reduction in hassle.
I’m not sure it applies for free products but I could see there being some advantage for example in people who want to avoid malware ridden products. Anyway, just a thought and I suspect you are probably still right about Nike et al.
Pfizer and Moderna also negotiated agreements with the US govt for the purchase of millions of doses. Has AZ done so? I think not. Thus Pfizer and Moderna are protecting their contract. Tough shit AZ, should have made a deal when deals were available.
The federal government is paying Pfizer for the vaccines. They are free to everyone.
So you keep saying, but the federal US government isn’t the only potential purchaser in the world.
The bizarre irony is that the reason for the vague NIH statement that has further undermined confidence in this vaccine was justified by the need to be transparent about the all trial data such that confidence in the vaccine is maintained. Go figure.
Well, they’ve achieved the opposite for the sake of clarification. I’m not a conspiracy theorist but something doesn’t smell right when Pfizer, Moderna and others have a lot to gain from a loss of confidence in the AZ vaccine.
The real world casualties (people) have a lot to lose by this attack and other US/EU attempts to undermine a cheap, easily stored but effective vaccine.
If I was offered the AZ vaccine, I would take it in an instant. I don’t want Covid-19 and I know this offers me real world protection with very little personal risk. This is a pandemic, this is an emergency – we do not need more death and illness. The NIH has blood on its hands.
“The bizarre irony is that the reason for the vague NIH statement that has further undermined confidence in this vaccine was justified by the need to be transparent about the all trial data such that confidence in the vaccine is maintained. Go figure.”
I strongly suspect that, as another commenter has suggested, competing pharma companies are trying to undermine the AZ shot, but I think the main reason for the NIH announcement is as stated above. All the regulatory agencies are trying to be scrupulously transparent in their handling of covid vaccines and now the law of unintended consequences is at work. It certainly doesn’t help that AstraZeneca keeps making mistakes in the way it reports data and results. Nonetheless, I, too, would happily get the AZ vaccine today if I could.
There is an interview in Forbes today by the Moderna CEO. It’s reported he became a billionaire (through stock in his company) last April and now has a net worth over four billion dollars (yes, there’s real money involved in the vaccine wars). He laid out plans for his company in the next couple of years, including annual improvements to the covid vaccine to deal with mutations (he foresees annual covid shots as for flu), and a new flu vaccine based on mRNA technology that is over 90% effective. I’m not so sure about the flu vaccine if it is a two-shot regimen like the covid vaccine. People will tolerate a two-shot jab for the sake of covid, but I think it will be too much hassle for flu.
Sadly, people really are dying while regulatory agencies and pharma companies fight and dither over vaccine approval and distribution.
I read the NIH statement when it was released on Tuesday:
https://www.nih.gov/news-events/news-releases/niaid-statement-astrazeneca-vaccine
It’s vague enough to spread alarm and implies that AstraZeneca withheld data that would have changed the reported figures. As far I know, AstraZeneca were reporting data obtained prior to 17th February. This was prespecified and disclosed.
This comment in the statement is particularly unfair as it implies there is a significant problem without any explanation or context:
Moderna and Pfizer have seemingly created excellent vaccines. In terms of protecting human health and the costs associated, even their vaccines are not expensive. But they don’t appear to have anything like the scrutiny and suspicion levelled at AZ/Ox and I find that troubling.
All of these vaccines are approved under EUA – Emergency Use Authorization – in the US. Comparably elsewhere. On the inserts, they all say – unapproved vaccine – meaning they have not passed FDA approval. They are listed as investigatory. Translated into more common language, these vaccines are experimental.
If you want to take an experimental vaccine, then it’s your choice, but they have not been proven safe. AZ may be safer long-term than the mRNA vaxes, because of the ADE problem (see Dengvax in the Philipines for criminal prosecution of bad vaccines by Pfizer).
They may be safe, but Chivers is lying when he claims they are safe, because he cannot know that. They have not existed long enough for that statement to be made. Long-term testing cannot have occurred by definition on a vaccine created only recently.
AZ is not approved, even for emergency use in the US.
Tom, can you tell us why even after so long we have no internationally agreed firm data on the effectiveness of things like masks, distancing, open-air engagement, etc? Has it been withheld so that Governments can dictate terms rather than allowing us to make our own rational decisions on risk? I don’t know where to look for answers to these questions.
Isn’t it obvious what this is about. AZ is a British company. Moderna, Pfizer and J&J are US companies. They want to shut the competition out of the market. There are billions of dollars at stake and the US has already plenty of vaccine from the 3 US companies to vaccinate everybody in the US who wants it.
On another note, I do wish that Chivers would be accurate about blood clots and the AZ vaccine (which incidentally probably applies to all the current vaccines given that they are all producing spike protein): it is perfectly true that the incidence of run-of-the-mill blood clots responsible for deep vein thrombosis has not increased. However, the incidence of rare blood clots associated with low platelet counts, including disseminated intravascular coagulation ( condition with around 50% mortality if not more) occurring almost exclusively in young, fit women under the age of 50 following the AZ vaccine has increased 10-fold according to the Robert Koch Institute in Germany responsible for looking into such things in Germany.
Yes, one can always say move on, nothing to see, but all medicines, including vaccines, have potential side effects, and anybody listening to any advert on TV for some medicine or other in the US is always provided a huge list of rare but potential and often deadly side effects at the end of the ad. It is far better to be upfront and honest. Otherwise confidence in the vaccines will decrease. Associated with this is the fact that COVID-19 is generally a mild disease for anybody under 60 in good health without a slew of co-morbidities. Thus the risk/benefit ratio is going to vary depending upon age, general health, gender, etc…. As I have noted previously, if you happen to be a young, heathy 40 yr old woman, at virtual zero risk of death or hospitalization from COVID, and then you develop disseminated intravascular coagulation post-vaccine, that individual is going to be none to happy, especially since they then have a 50% chance of a very nasty death.
Please send all of your unused OxAsZe vaccine to the UK where we will gladly use it up as quickly as we can.
“I’m completely happy to believe that AZ have buggered up here. They have done repeatedly, with confusing press releases, weird accidental dosing regimes and so on. If they’ve released data early to make themselves look good, that is amazingly stupid and harmful. If they’ve done it through incompetence, then that’s still not great. Even if it was a prearranged cutoff, it would have been good to be ostentatiously careful about not overstating the effectiveness, and to release the most inconvenient data they have.”
This alone makes the vaccine questionable. But the larger point is that the vaccines already in use, Pfizer, Moderna and J & J are already doing the job. Where I live, they are seeking people to take the vaccine and offering it to out of area folks just to use supplies. There’s no more waiting lists. I’d be in favor of sending the AZ to Europe or other areas that need supplies.
‘That alone makes the vaccine questionable’. Really? I’m glad that you are happy to line corporate pockets at your taxpayers’ expense. I’m sure that if you look carefully, you will find similarly questionable announcements from the other companies. Just remember that AZ are doing this at cost ($3-4 per dose: around 1/10th of other vaccines), with no profits to be taken until the pandemic is officially over. The development costs are around $1billon.
I’m willing to forgive a few PR errors in these circumstances.
I agree totally.
I had my first dose of the Oxford/AZ vaccine at the end of January – and I am a Cambridge man! I am 78, with a significant heart condition, and I experienced no ill effects whatsoever. I expect to get a second dose in late April or May, and I will take it willingly.
Let’s be realistic. Any intervention carries risks. But all the vaccines seem to be roughly equally effective and risk-free. There is a tiny risk of a blood clot, but that seems to be at least three orders of magnitude less than the risk of not being vaccinated. So better to roll out all the different vaccines we can as soon as possible, and get economies moving again.
There are no “safe” or “risk-free” vaccines or medicines, as you mentioned. There are tens of thousands of patients in the US alone that have gotten lupus or vasculitis (both conditions without cures), from what the author of this article would claim, is a “perfectly safe vaccine” – the flu vaccine. These are people genetically predisposed to these auto-immune issues, but without any knowledge of this predisposition at the time they take the vaccine. Unfortunately for them, most of these conditions go both undiagnosed, and often unacknowledged by MDs and RNs actively immunizing people. It’s a sad state of affairs all around. People giving you the flu shot, are looking you in the eye, and telling you that its perfectly safe, and there’s “nothing to worry about”. When you go back a couple weeks later with all sorts of auto-immune symptoms, they say “its perfectly expected and normal”. You keep going back, and eventually they call you an anti-vaxx nutjob. Years go by with you suffering, going to various doctors and specialists, and find nobody willing to listen or help you. Then eventually you get lucky, and get seen by a virologist at the Cleveland clinic, or the Mayo Clinic or one of these places that is considered an upper-echelon research hospital. The virologist looks you straight in the eyes and says “you got vasculitis, likely as a result of the flu vaccine. I see this all the time. You should tell all of your family members to never take any vaccine again. You as well.”. <— this is the reality for some of these people. You start wondering about all of the other people (how many more thousands?) impacted without ever knowing their underlying predisposition or post-vaccine, lifelong disease. Completely untracked. Meanwhile, the last 50 years has brought on the largest increase in auto-immune related diseases in the history of man. Everybody’s stumped. Hmmmmm.
What could you possibly be on about? Operation Warp Speed provided $10 billion to six pharma companies to develop the vaccines and buy 800 million doses. The US paid for its vaccines BEFORE they were even developed. Where do you think the funds came from to develop them? The vaccine fund fairies? Should the US shun vaccines it has already paid for and switch over to other vaccines? The US is providing everyone in the US vaccines free of charge.
This is not about PR. This is about vaccines already paid for. I realize that the media did a really bad job covering Operation Warp Speed because they didn’t like Trump but the information is all available.
Part of the AZ press issues relates to the rather unique partnership in the development. The established companies have entire PR departments and much experience.
Not a thing to do with press issues.
Not such a nice company https://www.independent.co.uk/news/world/africa/pfizer-pay-163-50m-after-deaths-nigerian-children-drug-trial-experiment-1663402.html
My view is that there is some heavy lobbying going on in the USA and EU to besmirch AZ’s reputation. This view is based upon the EU’s relentless attacks on AZ with none on Pfizer. Further, as the AZ is being done on a ‘not-for-proft’ basis – and as it is far cheaper than anything else – other vaccine producers will lose revenue/profit to AZ. Why would the USA and EU act in this way? Profit equals taxation. I truly hope that this is not the case but the attacks on AZ have become so relentless (and, now that the USA has joined in), it cannot solely be a Brexit-related hissy fit.
The US paid for 800 doses of vaccine before they were even developed.
Apparently there is some misunderstanding about how the vaccines are funded in the US, leading to all kinds of lobbyist conspiracy theories. So let’s start with Operation Warp Speed, in which the US basically went into business with pharma companies for the development AND purchase of vaccine doses. It bet on six different candidates. Here is the basic info. I’d post the link but unherd doesn’t seem to like links.
The U.S. government’s Operation Warp Speed program has invested about 10 billion in six potential coronavirus vaccine candidates. The Trump administration has locked in a minimum of 800 million doses as soon as the vaccines are approved.
So, the vaccines for the US have already been paid for since Moderna and Pfizer (and their partners) and J & J were among the companies who received funding for the development of the vaccines as well as their purchase. IOW they were purchased BEFORE they were developed, enough for everyone in the US several times over. The vaccines are free to any American who wants one. In fact, they are free to anyone in the US, American or not. So it isn’t about AZ undercutting anyone it’s about vaccine doses that have already been paid for. So let’s stop with the conspiracy nonsense.
I think your point ha been made. The article is more concerned with the world situation. AZ is not a real player in the US market right now because all needed supplies are on contract, probably more than enough but there are billions of doses required elsewhere. That’s the AZ conspiracy regarding world supply.
Yes you have said this repeatedly. It just has nothing to do with my comment.
More for us!!
Let’s get on with 🙂
The thing everyone is ignoring is their are rules. Whether we like a set of rules or not is not really the issue. AZ knows the rules at FDA and did not play by them. It did not have to go to FDA, it wnated to do so market reasons. We cannot retrosepctivley trhrow out the rules when we wnat to, we can prospectively change the rules but not ignore them. You are saying it is okay this time to ignorte the rules, who gets to make toise decisions and when will require more rules.
It does turn out that finally AZ has gotten past the gates. The exacting rules were passed. Were the rules as necessary for AZ given outside field data can be debated. The thalidimide experience gives the FDA great caution. But the AZ risks are not like thalidimide and seem not so different than the J&J and much less risky than the mRNA vaccines given the immature technology.
Why are the US worrying about formal testing of a few tens of thousands when their is a mass of real-world data covering tens of millions?
The vaccine is being delayed until Big Pharma has made billions in profits. It is a deliberate protectionist campaign against a low-cost competitor. Big Pharma has the US Government in its pocket, bought and paid for.
Should the US shun 800 million doses it has already paid for to buy from AZ?
“I’m completely happy to believe that AZ have buggered up here. They have done repeatedly, with confusing press releases, weird accidental dosing regimes and so on. If they’ve released data early to make themselves look good, that is amazingly stupid and harmful. If they’ve done it through incompetence, then that’s still not great. “
“But you’re irrational if you’re wary of their vaccine.”
“Studies show…”
Look, the death stats are corrupt as everyone knows. The government, the government scientists, big pharma and assorted convergent opportunists have every motive to big up the vaccines. Maybe they’re right, but I sure don’t trust them to tell me if they’re wrong.
Vaccine for what?
Political motive and an effort to promote national pharmaceutical companies.
Another pro-vax article, based on information on a pharmaceutical product still in trials! No long term studies, just conjecture on figures collected for the study that still has a year to complete! About half the people I personally know who have had these injections have had slight to moderate adverse reactions, and have not reported them, even after being specifically told to do so if they occurred. So how can situations like I have explained above, not produce skewed data. I would also like to point out, that none of the people described above were told when having the injection, that they were now part of the phase 3 trials.