When will this shit end?

[shoptildrop]

1 minute ago, jparx said:

Takes some serious balls to go forward with any type of Christmas market after Nottingham binned theirs within a day.

It's ridiculous IMO 

[stuartbert two hats]

12 minutes ago, shoptildrop said:

So Manchester rates been coming down and they are doing this!! Whats the bloody point now?? 🤤

 

I'm not going anywhere fucking near those markets.

[stuartbert two hats]

And Manchester's numbers are still high and flattening FFS.

[Ozanne]

It's madness, it's like they learn nothing from past events.

[stuartbert two hats]

Tier 2 a good idea in Manchester? Not during Christmas shopping season.

Edit: Stockport is on the way up now. Not a blip, a trend.

Edited December 8, 2020 by stuartbert two hats

[Crazyfool01]

7 minutes ago, stuartbert two hats said:

I'm not going anywhere fucking near those markets.

isnt a market where it all started ?!!  

[shoptildrop]

6 minutes ago, stuartbert two hats said:

And Manchester's numbers are still high and flattening FFS.

Exactly so let's put some bloody markets selling crap on for 10 days!!!

[shoptildrop]

Just now, stuartbert two hats said:

Tier 2 a good idea in Manchester? Not during Christmas shopping season.

 

Mmmh not great Bury rising again as their drops not been as rapid

[stuie]

6 minutes ago, stuartbert two hats said:

I'm not going anywhere fucking near those markets.

Yeah, fuck that.  They are horrible wallet raiders at the best of times.  I've got enough tat from previous Christmases and I will survive without a £10 bratwurst for one year. 

[Ozanne]

1 minute ago, stuartbert two hats said:

Tier 2 a good idea in Manchester? Not during Christmas shopping season.

 

We are seeing the first in the region going up in cases now too...

[Toilet Duck]

So...had a read of the Lancet paper. There’s an awful lot of info in there!

if you don’t want to read the rest of this, bottom line, they’ve cleared the bar for emergency use and the MHRA and EMA are likely to approve based on this data (FDA seem to be playing hardball and want the US trial completed first)...

Anyway, first off, important to note that this is the first peer reviewed publication of phase 3 data for a COVID vaccine, therefore it’s subject to the kind of public scrutiny that the other candidates aren’t currently. 

So, what did they find...basically, they found that the vaccine administered as planned provided 62% protection from symptomatic disease. Just as importantly, administered as planned, it prevented 100% of hospitalisations (and severe disease) 21 days after the first shot. They also found that a low dose/high dose regimen provided 90% protection from symptomatic disease (this finding is one of the controversial elements). Intriguingly, given that they were swabbing participants weekly, they also found this low dose/high dose regimen provided 58% protection from infection at all (the standard dose regimen only provided 3.8% protection from infection). They also found that variance in the gap between shots had no appreciable impact, so there’s some flexibility on administrating the two doses which should ease the logistics of the roll out. There were slightly fewer serious adverse events in the vaccine arm compared to the control arm (so not related to the vaccine) and there were 3 cases of transverse myelitis (one in the vaccine arm, one in the control arm and one as yet not unblinded). These were the cases that caused the pause and the independent evaluators decided that they were undiagnosed pre-existing conditions (the last case is not fully resolved yet).

In terms of the participant characteristics, the trials were conducted in the UK and Brazil and were heavily skewed towards including healthcare workers. This means that different ethnicities were included, though in the UK, there were more younger female participants. However, given that a lot of healthcare workers were enrolled, they were likely exposed to viral loads that would be in excess of most other exposures. Older participants were enrolled and immune responses did not differ from younger participants, though there haven’t been enough cases in older participants to fully say that there’s any difference in the performance of the vaccine in those subgroups. 

So, all of the above is pretty promising! It works and it’s safe.
 

Where are the problems and why are some crying foul? Well, instead of being one big trial like Pfizer and Moderna, Oxford/AZ have run a series of separate trials. Along with the dosing snafu, they also have different controls (meningitis vaccine in the UK, saline in Brazil). Oxford claim running different trials is good, they show how the vaccine works in diverse populations (though you can do this by opening the same trial in different places). The control difference doesn’t make much difference to efficacy, and given the serious adverse event profile is lower in the vaccinated group, it’s not so important for the safety profile either. The statistics are robust and the analysis plan (including leaving in the high dose/low dose regimen) was agreed before they froze the data and unblinded, so it wasn’t engineered to find significant results (which is what most criticisms of subgroup analyses fear), rather, it was agreed before they started their analysis. 

There are a few things that still need to be ironed out though. First, the dosing. The inadvertent low dose prime shot has caused them a serious headache given that efficacy in terms of preventing disease and of protecting from infection is so much better than the planned regimen. They are right on the border of having sufficient events to prove this, but it is robust (in terms of protection from disease). They safely clear the lower threshold for confidence in their result, so it’s possible this regimen gets approved for the age groups it was tested in (18-55). The other thing they need to firm up is whether the vaccine does indeed provide a degree of sterilising immunity. The confidence intervals for the protection from infection are huge and I don’t think that’s fully proven yet (though it’s encouraging, and the fact the more efficacious dosing regimen in terms of disease protection is also the one with the best infection protection is also a good sign). 

So, what does this all mean? Well, it means that the vaccine is likely to be approved for emergency use (at least in the UK and EU initially). What the regulators need to decide is how it can be used. Based on the data, I’d seriously consider approving the full dose regimen for over 55s and the low dose regimen for under 55s. There’s 3 benefits to that. More vaccine to go around, potential better efficacy (but risked in a lower risk group) and potential better herd immunity to protect the higher risk groups that have a lower efficacy dose since there’s a signal for sterilising immunity in the low dose regimen (and the younger age groups that would get this dose would probably have more contacts). Further trials with the low dose regimen (and indeed combinations with the other vaccines crossing the line) will likely alter how these are used in future, but suffice to say that based on the data published, it looks like another vaccine approval should be on the horizon. 

 

 

[stuartbert two hats]

3 minutes ago, shoptildrop said:

Mmmh not great Bury rising again as their drops not been as rapid

Salford, Tameside and Stockport all up on yesterday and they dropped off pretty quickly. I'm going to blame Christmas shopping. Tier 3 was enough to keep R under 1 before lockdown, but not now.

Tier 2 and markets could well fill the hospitals again. We're so close, so frustrating.

[stuie]

[shoptildrop]

7 minutes ago, stuartbert two hats said:

Salford, Tameside and Stockport all up on yesterday and they dropped off pretty quickly. I'm going to blame Christmas shopping. Tier 3 was enough to keep R under 1 before lockdown, but not now.

Tier 2 and markets could well fill the hospitals again. We're so close, so frustrating.

Tameside going up?? Nooooooo

[shoptildrop]

3 minutes ago, stuie said:

I saw a brilliant picture deplicting this on Twitter earlier but didn't save it

[Leyrulion]

13 minutes ago, Toilet Duck said:

so it’s possible this regimen gets approved for the age groups it was tested in (18-55

That's what the person I know working on it was speculating. 

Really changes the dynamics of the u.k. vaccine roll out if so. Do you start giving teachers and other key workers the Oxford vaccine?

[stuie]

3 minutes ago, shoptildrop said:

I saw a brilliant picture deplicting this on Twitter earlier but didn't save it

Was it this one? My mate just sent both and said he’s collecting them for the next time anyone mentions bill gates 😂

[Punksnotdead]

11 minutes ago, stuartbert two hats said:

Salford, Tameside and Stockport all up on yesterday and they dropped off pretty quickly. I'm going to blame Christmas shopping. Tier 3 was enough to keep R under 1 before lockdown, but not now.

Tier 2 and markets could well fill the hospitals again. We're so close, so frustrating.

Given the shops have been open less than a week though, is this likely? I thought it normally took a couple of weeks for this to affect the figures?

 

[Ryan1984]

Thanks as ever to @Toilet Duck for breaking the clever stuff down for us. Do we stick with cautiously optimistic or upgrade to optimistic for ‘normal’ life around Easter?

[Toilet Duck]

3 minutes ago, Leyrulion said:

That's what the person I know working on it was speculating. 

Really changes the dynamics of the u.k. vaccine roll out if so. Do you start giving teachers and other key workers the Oxford vaccine?

Adrian Hill was even suggesting that the low dose regimen could be physician/patient choice given that there’s no safety implications. Will be interesting to see how this pans out!

[stuartbert two hats]

3 minutes ago, Punksnotdead said:

Given the shops have been open less than a week though, is this likely? I thought it normally took a couple of weeks for this to affect the figures?

 

I keep forgetting it's been that recent. Because I'm still living the lockdown lifestyle, in my head we've been in tier 3 since the local tiers were announced a few days earlier. 

It is a bit soon for tier 3 to kick in. Fucked if I know - lockdown fatigue along with the usual* seasonal related related reasons for respiratory diseases increases.

Either way, going into tier 2 and cramming people into markets seems stupid.

* I don't actually know how this works. Something to do with humidity and being indoors or something.

 

[Toilet Duck]

2 minutes ago, Ryan1984 said:

Thanks as ever to @Toilet Duck for breaking the clever stuff down for us. Do we stick with cautiously optimistic or upgrade to optimistic for ‘normal’ life around Easter?

I’d say optimistic of a lot more normal by Easter and more or less normal by summer (I know that sounds a bit vague!). 

[stuartbert two hats]

5 minutes ago, Toilet Duck said:

Adrian Hill was even suggesting that the low dose regimen could be physician/patient choice given that there’s no safety implications. Will be interesting to see how this pans out!

I think I heard on the radio that the UK regulatory framework did allow discretion in the dosage.

It really puts whoever makes the decision in a tough spot over the old people. There's not enough supply of the Pfizer vaccine to cover all the older population in a timely fashion and the efficacy of the full dose AZ vaccine, although sufficient for approval, it really is woeful compared to half/full or Pfizer. There must be a big temptation to half/full dose some older people. The improved sterilising effect alone is massive.

Presumably all the younger healthcare workers will be getting the AZ vaccine in half/full dosage - and sooner rather than later?

The big question is - how soon can they determine whether it's safe+effective in the older population with the half/full dosage? Have they already started trialling it?

[stuartbert two hats]

I'm getting sick of typing half/full. Need something snappier 😄

[steviewevie]