Developing the Covid-19 vaccine

[Herainestold]

“... this one could be faster because we know the efficacy is high so we need a smaller number of patients.”

Does it actually work like that?

If you want the trial to go faster and/or need fewer subjects you need to do it in a hotter covid spot.

By the way, the Guardian have mentioned that data will be published in the Lancet over the weekend.

Anywhere in America should do. Once they get the volunteers signed up and jabbed, a couple of days should do it.

It looks like the vaccine works, but really they need to re run the trials.

[Millennie Al]

See this excellent article from the always-fabulous Hilda Bastian.

I'm not so convinced about the "always fabulous" bit. That article leads to Covid-19 Vaccines With ‘Minor Side Effects’ Could Still Be Pretty Bad which, towards the end, says:

A participant who had a severe reaction to a particularly high dose has talked in detail about how bad it was: If reactions even half as bad as this were to be common for some of these vaccines,

If you follow that link and read about this particular participant, you find thet he was in a phase 1 clinical trial which administered a range of doses, of which he likely got the highest dose. Since the whole point of the trial was to find the approriate dose, it is to be expected that it will include testing doses which are found to be covering the whole range from ineffective to excessive. It is scaremongering to point to a small number of advserse reactions in a phase 1 trial as if they were likely to recur in an approved vaccine.


Overall, the whole process is thoroughly unsatisfactory. If there are results they should be published: if they are not ready for publication, then they're not results. While it is understandable that scientific papers might be delayed while analysis is checked and wording is perfected, there is no reason why the underlying figures should not be published immediately. It should not be necessary to reverse engineeer data out of press releases.

[sTeamTraen]

If you follow that link and read about this particular participant, you find thet he was in a phase 1 clinical trial which administered a range of doses, of which he likely got the highest dose. Since the whole point of the trial was to find the approriate dose, it is to be expected that it will include testing doses which are found to be covering the whole range from ineffective to excessive. It is scaremongering to point to a small number of advserse reactions in a phase 1 trial as if they were likely to recur in an approved vaccine.

Hilda used to be an anti-somethinger (can't remember if it was vaccines or GMOs or something else) --- she is a huge asset to the scientific community because she understands how the anti-movements work. I take the piece to be saying that you only need 2 or 3 people getting coverage for their bad reactions for the media/Internet complex to start flinging poo. Which is why we need the full information ASAP.

Overall, the whole process is thoroughly unsatisfactory. If there are results they should be published: if they are not ready for publication, then they're not results. While it is understandable that scientific papers might be delayed while analysis is checked and wording is perfected, there is no reason why the underlying figures should not be published immediately. It should not be necessary to reverse engineeer data out of press releases.

No disagreement there. They have these numbers, they could put up a preprint pretty quickly. AFAIK none of the vaccine developers have done so.

[jdc]

Survey of vaccination intention: https://www.tandfonline.com/doi/full/10 ... 20.1846397

To investigate factors associated with intention to be vaccinated against COVID-19 we conducted a cross-sectional survey of 1,500 UK adults, recruited from an existing online research panel. Data were collected between 14th and 17th July 2020.

64% of participants reported being very likely to be vaccinated against COVID-19, 27% were unsure, and 9% reported being very unlikely to be vaccinated.

[EACLucifer]

Survey of vaccination intention: https://www.tandfonline.com/doi/full/10 ... 20.1846397

To investigate factors associated with intention to be vaccinated against COVID-19 we conducted a cross-sectional survey of 1,500 UK adults, recruited from an existing online research panel. Data were collected between 14th and 17th July 2020.

64% of participants reported being very likely to be vaccinated against COVID-19, 27% were unsure, and 9% reported being very unlikely to be vaccinated.

Harry Enten was noting that - presumably American - polling on likely COVID vaccine uptake was very similar to the polling on the Polio vaccine at the time, which ended up deployed quite successfully.

[Martin Y]

Where are you getting this 2:1 thing from?

Steamy's link to the Wired article mentions it and has a link to the protocol itself:

https://s3.amazonaws.com/ctr-med-7111/D ... CSP-v2.pdf

... Approximately 30 000 participants will be randomized in a 2:1 ratio to receive 2 IM doses of either 5 × 1010 vp (nominal, ± 1.5 × 1010 vp) AZD1222 (n = approximately 20 000) or saline placebo (n = approximately 10 000)...

[shpalman]

No 10 wanted union flag on the 70% 90% 60% effective Oxford coronavirus vaccine kits

[Martin Y]

Tch. A bit showy-off. That's not really the British way.

(The British way is to put your flag on someone else's and say it's yours now.)

[shpalman]

Inside Science had a discussion about vaccine effectiveness, and the interviewee obviously got it wrong, as she was implying that it was worth vaccination with a 40% effectiveness on occasion.

She was saying it was the ratio of control:trial so a 90% effectiveness meant that 90% of the infections were in the control leg.

It was clearly a brain fart on her part.

A similar explanation was given on the news this morning. It's not that far wrong as long as the efficacy is quite high and the numbers in the vax and control group are similar.

[shpalman]

People at very high risk of contracting coronavirus due to health problems, who were made to shield during the pandemic, have been given the same priority as the over-70s to receive a Covid-19 vaccine.

[sTeamTraen]

Where are you getting this 2:1 thing from?

Steamy's link to the Wired article mentions it and has a link to the protocol itself:

https://s3.amazonaws.com/ctr-med-7111/D ... CSP-v2.pdf

... Approximately 30 000 participants will be randomized in a 2:1 ratio to receive 2 IM doses of either 5 × 1010 vp (nominal, ± 1.5 × 1010 vp) AZD1222 (n = approximately 20 000) or saline placebo (n = approximately 10 000)...

I don't know who the author of this comment on Andrew Gelman's blog is, but he seems to have some interesting information (for which I've asked him what his source is):

The results combine two trials. One in the UK, with 12,390 participants, one in Brazil with 10,300 participants, so 22,690 participants all up. In the non-placebo group in Brazil, all participants received two full doses. In the group in the UK, 2,791 participants received a half dose and a full dose, and some number received two full doses. The total number of participants receiving two full doses was 8,895, but it is not stated how many of these were in Brazil and how many in the UK, giving 11,636 receiving the vaccine in total – there is a transposition error in the paper. Of the 11,636, 30 became infected. Of the total placebo group, 101 became infected, giving rise to the 70% overall figure, although I can’t get exactly 70.4%.

The 90% claim is for the 2,791 who received the half dose – a lot of speculation along the lines of the above as to how many of these got sick, but most people seem to think either 2 or 3.

There has been some criticism on combining the results from 2 different studies in different countries, but we’ll just have to wait for the actual data to be published to see what the exact numbers were.

If this is correct, it seems as if the press release may have been a bit murky.

[Millennie Al]

It seems quite difficult to find all the studies being done on the Oxford/Astrazeneca vaccine. A search of clinicaltrials.gov using the term "azd1222" finds three, and a search for "chadox1 ncov-19" finds four (all different). However at https://covid19.trackvaccines.org/vaccines/4/ there are 8. Most of them can be found at https://clinicaltrials.gov/ct2/who_table by searching for "chadox1", but there is one anomaly the Brazil study has a different identifier (but it's the same trial of 10300 participants: http://www.isrctn.com/ISRCTN89951424 - which says randomisation was 1:1).

[shpalman]

Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial says

This study is ongoing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137.

https://clinicaltrials.gov/ct2/show/NCT04400838 only links back to this one article.

http://www.isrctn.com/ISRCTN15281137 seems to be the phase I/II part.

[Woodchopper]

Continuing the spate of stunning news about COVID-19 vaccines, the biotech company Moderna announced the final results of the 30,000-person efficacy trial for its candidate in a press release today: Only 11 people who received two doses of the vaccine developed COVID-19 symptoms after being infected with the pandemic coronavirus, versus 185 symptomatic cases in a placebo group. That is an efficacy of 94.1%, the company says, far above what many vaccine scientists were expecting just a few weeks ago.

More impressive still, Moderna’s candidate had 100% efficacy against severe disease. There were zero such COVID-19 cases among those vaccinated, but 30 in the placebo group. The company today plans to file a request for emergency use authorization (EUA) for its vaccine with the U.S. Food and Drug Administration (FDA), and is also seeking a similar green light from the European Medicines Agency.

https://www.sciencemag.org/news/2020/11 ... e-covid-19

[bob sterman]

More impressive still, Moderna’s candidate had 100% efficacy against severe disease. There were zero such COVID-19 cases among those vaccinated, but 30 in the placebo group.

I've done a quick manual 2 x 2 chi-square test on the vaccine vs control / severe vs non-severe data and the significance lookup table gave me this...

https://www.youtube.com/watch?v=xUNqsfFUwhY

[tom p]

This is what a considered, but express, authorisation looks like
So is this
And this is what indecent haste for pathetic jingoistic purposes looks like
There is no chance that Pfizer provided their data to the MHRA earlier than providing it to the EMA. The MHRA has rushed through approval in 1 day. 1. Day.
I never thought the MHRA would be corrupted by this government. I knew that there would be a race to be the first to approve a vaccine, but I assumed that they would at least make a show of doing even a cursory check of the data, maybe give it a week, but no. Shameful. This is drug approval by press release.
There is no part of the state that won't be abused and broken by this government. If you are living in the UK, you have to assume that the rule of law will no longer apply.

[shpalman]

Thanks, I was going to ask you about that.

I also doubt that it makes much difference in terms of how many people will actually be vaccinated this month.

[discovolante]

Well now I'm stressed.

[lpm]

This is what a considered, but express, authorisation looks like
So is this
And this is what indecent haste for pathetic jingoistic purposes looks like
There is no chance that Pfizer provided their data to the MHRA earlier than providing it to the EMA. The MHRA has rushed through approval in 1 day. 1. Day.
I never thought the MHRA would be corrupted by this government. I knew that there would be a race to be the first to approve a vaccine, but I assumed that they would at least make a show of doing even a cursory check of the data, maybe give it a week, but no. Shameful. This is drug approval by press release.
There is no part of the state that won't be abused and broken by this government. If you are living in the UK, you have to assume that the rule of law will no longer apply.

Sore loser. The UK won. We did it yet again, beating the world, our government getting results. And we control our own fish as well.

[Sciolus]

This is what a considered, but express, authorisation looks like
So is this
And this is what indecent haste for pathetic jingoistic purposes looks like
There is no chance that Pfizer provided their data to the MHRA earlier than providing it to the EMA. The MHRA has rushed through approval in 1 day. 1. Day.
I never thought the MHRA would be corrupted by this government. I knew that there would be a race to be the first to approve a vaccine, but I assumed that they would at least make a show of doing even a cursory check of the data, maybe give it a week, but no. Shameful. This is drug approval by press release.
There is no part of the state that won't be abused and broken by this government. If you are living in the UK, you have to assume that the rule of law will no longer apply.

Does the MHRA have the expertise or resources to properly approve stuff? Has it been able to set itself up as a full replacement for the EMA yet? IIRC, before Brexit MHRA and EMA had different roles, and the former had to take on the latter's duties within the last couple of years. Or am I talking crap?

[shpalman]

Most actual British people will probably have to wait for the Oxford-AstraZeneca one anyway, since not that many doses of the Pfizer one have been ordered and it has that cold-chain issue, so it will be aimed at people in hospital first (both staff and patients) and other highest-risk groups.

https://www.bbc.co.uk/news/health-55145696

The UK has already ordered 40m doses - enough to vaccinate 20m people.

Around 10m doses should be available soon, with the first 800,000 arriving in the UK in the coming days.

That means by the end of January maybe 400,000 people will have received their two doses of the vaccine, because "coming days" probably means "next few weeks" and then it's Christmas while "soon" probably means "within a couple of months".

[Sciolus]

For scale, just over 400,000 people live in care homes.

[lpm]

Presumably we can (or someone can) add up the UK numbers in each category?

Shouldn't be any issues with double counting in the first 5. But category 6 will be hard to quantify?

[shpalman]

There's about 2.5 million over 80.

https://en.wikipedia.org/wiki/Demograph ... _structure

[lpm]

That wiki says 2.9 million.

Category 1: 0.4m

Category 2: 2.5m, plus approx 0.5m frontline health and social carers?

Category 3: 2.0m

Category 4: 2.5m, plus unknown "extremely vulnerable"

Category 5: 3.0m

Total: 10.9 million

Category 6: Unknown "higher risk"

Category 7: 3.8m (less people already in categories 4, 6 or frontline health)

Category 8: 3.6m (less ditto)

Category 9: 4.1m (less ditto)

Something like 25 million before under 50s start to get a look in?