How a British Covid-19 vaccine went from pole position to troubled start

It has been! But if my lab experience was any guide, it's not necessarily a good light sensor. Spectrophotometry is great for getting coarse accuracy results out of. True precision... that is, and will remain, difficult.

You not only describe how you measured your drug concentration, but you also test the limits. And those limits should go beyond anything you might encounter in actual manufacturing.

If your aim is to confirm a concentration of 5mg/mL, then you test all the way down to 0mg/mL and then 50mg and 500mg/mL. Then if you have a saline mixture, you test different concentrations of NaCl.

You’re basically trying to break the analysis to show where it doesn’t work.

The fact they did a UV vis and didn’t account for a different emulsifier is a big miss.

"Some experts say the dosing discrepancy raises doubts about the robustness of the study’s findings. And they worry about another acknowledged peculiarity of the study: The half-dose regimen wasn’t tested on anyone over 55 - the group considered at high risk from COVID-19."

Maybe another problem is that it won't provide absurd profits to big pharma companies.

Now that the UK have already over 500k doses of the other vaccine administered we will see new data on the effectiveness and safety of the vaccine (in comparison to CoVid-19, don't forget that!).

Blinding and placebo control helps prevent behavior modification from the intervention itself, but it's possible that people who receive the saline placebos behave differently, since they don't get any side effects. I believe AstraZeneca's trial in the US uses a saline placebo, presumably because an active placebo might accidentally also work against the virus.

I think the ChAdOx study wasn't quite as large. Someone know ?

I’m struggling to understand that. It can’t be random, with so many people in each treatment. So why are their treatment arms unbalanced? And how do they control for that in the analysis?

Would you rather have something that works at best at 75% or something that works at 67%?

Are there any risks in giving a smaller dose to the older cohorts (besides maybe smaller efficiency?)

In what setting have you _ever_ encountered a rational person?

I've met people who were capable of calmly evaluating a situation rationally -- sometimes even under a decent amount of pressure. But in my undergrad at MIT or in my career as a software engineer, I have never met a rational person.

Once the outcome disparity was noted, it's unimaginable that BOTH blunders would not be revealed: 1) low concentration in the first dose, and 2) exclusion of age 55+ patients.

More troubling is error #2. That degree of mistake is unforgivable. Heads should roll, and that should include the subsequent apologists who blithely dismissed the gravity of their team's carelessness.

You must really feel for AZ at this point, and wonder how much they want to partner with academic scientists at such a critical stage.

You wouldn't believe how many software engineers with years and years of experience make amateur mistakes during interviews.

Pressure does weird things to people's performance.

One group mixed the vaccine, and the other tested. The first group added a filler that throws off the UV measurement. They didn’t tell the second group about the additive because they didn’t realize the second group would use UV to measure the concentration.

Neither group could have avoided the problem without access to information they did not have. Both groups under-communicated. This sort of screwup is by far the leading cause of software bugs (most bugs occur at the interfaces between teams).

It's still possible that regulators will decide that 1) a sufficient number and range of ages and co-morbidies have in fact been assessed and that 2) the differential outcomes of the two groups is big enough to show the necessary level of efficacy and safety. But the 90% efficacy group clearly does NOT yet satisfy constraint #1, so until more 55+ year old subjects are added to the 90% efficacy part of the study, I suspect authorization will have to be based only on the 62% efficacy portion of the study.

The naming change is likely due to who is leading the charge. The vaccine was developed at Oxford, so at the first news, there was no AZ involvement. As we move towards approval and production, the vast majority of work is being done by the team at AZ. The resources and experiences for manufacturing and distribution are the reason Oxford partnered with a pharma company.

Leaked prices from the EU:

-Oxford/AstraZeneca: €1.78

-Johnson & Johnson: $8.50

-Sanofi/GSK: €7.56

-BioNTech/Pfizer: €12

-CureVac: €10

-Moderna: $18

You wouldn’t. Poorer people in poorer countries will get the less effective vaccines. Richer people in richer countries will get the better ones. There is a difference therein. But nothing compared to the vaccinated-unvaccinated gulf.

As I understand the state of things I'd be more comfortable getting the AZ/oxford vaccine than the Pfizer/BioNTech vaccine because the underlying technology is less novel, and therefore there is less potential for unknown long term side effects (of the unknown unknowns variety).

As of currently there is a huge production backlog for Moderna and Pfizer, but not the simpler AZ and Sputnik vector vaccines. Mass vaccinations need to happen last month, not in May to be effective. In May/June when our batches will be ready, the wave would already be over and you would be protected for the next 6 months with almost no risk. The next useful vaccination period would be fall 2021.

With the two simpler vector vaccines you could start now for everybody, as did Russia, Hungary and Argentina weeks ago. Well, with Sputnik not the elderly.

This is completely mysterious, in the opposite direction of every other vaccine candidate, and should we be following normal safeguards, there is zero chance this vaccine would be approved.

It also raises concerns of rushedness/negligence. When you get two conflicting measurements of the dosages, the correct response is to test it a third time, not assume the second is correct. This failure mechanism was the same in Boeing.

Not that we need to be: we already have Pfizer and Moderna, that did their trials properly and showed proper results.

It's a remarkable f*ck up for a clinical trial. These decisions should have been made with data from gold standard analytical methods.

I'm also pretty convinced if a "mishap" like that came to light about the Russian Sputnik, or one of the Chinese vaccines, then the combative and critical tone would go straight to "How Putin/Xi personally wanted to kill millions of people!" with news outlets all over the planet constantly regurgitating headlines along that line and Hanlon's Razor given zero consideration.

While this article ends on the notion of how this is just some kind of "oddity" and yet somehow at the same time allegedly a universal problem of "reporting having slightly nationalistic tone".

The article is so muddled up, and long-winded, the result of which is that it barely gains any traction in the online sphere, can't a find a single submission about this on Reddit with more than a dozen upvotes. The few there are the top-comments are very ad-hominemy "Good thing journalists never make mistakes!", which is a reminder that stuff like this [0] is a very real thing.

[0] https://theintercept.com/2014/02/24/jtrig-manipulation/

And of course the method itself is suspect, as the main benefit is that it is cheap and quick, not accurate. And then taking the wrongly performed measurement with the worse method over the qPCR by the manufacturer (who likely has much more robust QC than someone in academia) is just insane.

There is an increasing likelihood several vaccines will be used by every country, almost continuously for the next decade.

Also a few weeks shouldn’t change anything. We are talking about a 6-12 months vaccination campaign.

I suspect the 80% number you mention is to eradicate the virus. I think at this stage it is a bit unrealistic. Between poorer countries that will not be able to vaccinate everyone and animals which can carry this disease, I would imagine the virus is here to stay. I think the primary objective is for it to cease to be a major public health issue. That it keeps contaminating people at low intensity in the background shouldn’t be a major concern.

Even 60% is better than nothing. Add the percentage that already passed the virus and you get a decent % that no longer get sick or transmit. Not a bad thing, for now.