After arguing the opposite in the Christmas bubble thread yesterday, Mrs K has countered my argument firmly in that we are having the in-laws and 89yo great Nan around for Christmas. My Mil uses London public transport for essential work as a social worker to other people houses, Mr K has immunity complications and both the kids are swanning about in separate schools. It follows the rules but I’m not comfortable, I’ll have to medicate my nerves with booze all day to get through it :/

Sounds like a done deal, and quite likely you’ll get away with it. But the statistics suggest that quite a few families will be burying relatives in January because of infections they passed on along with the cranberry sauce over the Christmas dinner table.

My mum died a couple of weeks ago. We’re going to the funeral next week in a socially-distanced way, have ruled out the grandkids mixing for ‘refreshments’ afterwards. And my stepdad has decided it’s not sensible to travel down to us during the festive period despite the comfort that would bring him.

The government has thrown in the towel on Christmas because any regulations will just be ignored anyway. Doesn’t mean their guidance is right, though.

Sorry for your loss, Martin.

Sorry to hear that Martin.

I agree re the throwing in the towel, and I think they’re using the impending vaccinations as a crutch too.

I think it’s clearly been rising since September, and the changes then.
Education mixing is driving it.
And being managed terribly, without any significant test,trace,isolate that is working.
It’s based on a lie that schools are covid secure.
I think they’ll use the Christmas deregulation and any rises, to distract from and ignore the main problem – schools.

What do we make of the story in the FT today about questions over AZ’s vaccine data – calling out the small (?) sample of the 90% and the sub 55 age group in that data set.

I figured the p value was the p value… so it was fine?

https://www.ft.com/content/4583fbf8-b47c-4e78-8253-22efcfa4903a

Might be behind a paywall:

Disquiet is growing over the way that Oxford university and AstraZeneca have handled the early readout from trials of their coronavirus vaccine, which much of the developing world may rely on to emerge from the pandemic.

The results were hailed a success for showing an average efficacy of 70 per cent — a figure reached by pooling the results from cohorts on two different dosing regimens.

One set of participants received two identical doses a month apart, while the other group received a half-dose, and then a full dose. The efficacy for the first, larger group was 62 per cent. In the second subgroup, it was 90 per cent.

It has emerged that administration of the half-dose started with a mistake. It was then given to a smaller number of participants than those who received two full doses, making the discovery of its greater effectiveness look like a lucky break.

Yet on Tuesday, Moncef Slaoui, the head of Operation Warp Speed, the US government’s funding programme for vaccine development, disclosed that second subgroup was also limited to people aged 55 or below, a demographic with lower risk of developing severe Covid-19.

Oxford and AstraZeneca did not disclose the age breakdown on Monday, when results were released.

“There are a number of variables that we need to understand,” Mr Slaoui said. It is still possible the difference in efficacy was “random”, he added.

Markets have taken notice. London-listed shares in AstraZeneca have lost more than 6 per cent since the announcement. By comparison, since trial results from their vaccine were released earlier this month, showing an effectiveness of 90 per cent, shares in Pfizer and BioNTech have gained 6 per cent and 14 per cent respectively; Moderna is up 11 per cent since its vaccine trial data came out, on top of big gains in the run-up to publication.

One early critic this week, Geoffrey Porges, an analyst at SVB Leerink, said he thought it was unlikely the AstraZeneca jab would get approval in the US after the company “tried to embellish their results” by highlighting higher efficacy in a “relatively small subset of subjects in the study”.

John LaMattina, a former president of Pfizer’s global research and development unit, said in a tweet it was “hard to believe” US regulators would issue an emergency-use authorisation for a “vaccine whose optimal dose has only been given to 2,300 people”.

Much of the confusion stems from Oxford and AstraZeneca not being fully forthcoming on the reason for the two different dosing regimens — which changed unexpectedly as trials progressed.

In a statement late on Wednesday, Oxford acknowledged a difference in manufacturing and measurement processes meant later phases of its clinical studies resulted in half a dose being mistakenly administered instead of a full one.

The Wednesday statement said this was discussed with regulators at the time, who agreed to use two testing regimens. “The methods for measuring the concentration are now established and we can ensure that all batches of vaccine are now equivalent,” it said.

Richard Lawson, a UK trial participant who still does not know whether he was given the vaccine or a placebo because the trial has not yet been unblinded, told the Financial Times he was informed of the mix-up in July, before getting a booster shot.

As a general rule, vaccinologists usually aim for the lowest dose that is still effective, but the efficacy of the lower dose is still not explained. Oxford professor Sarah Gilbert has said it is possible that a smaller initial dose primes the immune system in a way that better mimics natural infection. But there is no precedent for other vaccines to be administered in this way.

“We just don’t have all the information we need to tell whether these results are reliable,” said Natalie Dean, an assistant professor of biostatistics at the University of Florida. “We certainly don’t have enough information in the public domain to decide whether this half dose is really working.”

Prof Dean contrasted the AstraZeneca disclosures with those from other trials. “We had this precedent set by the other vaccines with Moderna and Pfizer/BioNTech and these were single trials, with a protocol released in advance,” she said. “We had a chance to look through it . . . It was fairly straightforward.”

There are also concerns at variations in the trial of the Oxford vaccine in different countries. As well as different dosing regimens, there were also differences between the control groups in different countries: in the UK, participants who did not get the Covid-19 vaccine were administered a meningococcal vaccine; in Brazil they got a saline placebo.

These discrepancies have led to the suggestion that the data is too patchy to combine into a single convincing efficacy result.

An AstraZeneca spokesman defended the trial, saying they were “conducted to the highest standards” and met their primary efficacy endpoint. The company has said more data will continue to accumulate and additional analysis will be conducted, refining the efficacy reading and establishing how long the vaccine protects against the virus.

The results will appear in a peer-reviewed journal, and regulators have set an efficacy threshold of 50 per cent, meaning a jab with a 70 per cent efficacy would still get approved.

Despite the questions over efficacy, the Oxford/AstraZeneca vaccine does offer some undisputed advantages. It is cheaper than the mRNA vaccines from Moderna and Pfizer/BioNTech and can be stored in a refrigerator rather than a freezer.

Oxford university said it “completely” understood the interest in the discovery of the dosing mistake and the switch in dosing tactics, which was approved by UK regulators.

“As this is a complicated scientific area, our scientists would like to wait until the peer-reviewed publication of the interim phase 3 results in The Lancet [medical journal] before discussing this further, which we anticipate will be in the next few weeks,” it said.

So according to the ONS 1 in 85 people in the uk has Covid at the moment 😮

cobblers tier 2, not exactly “post” lockdown :/

Tier 3 here in Manchester as feared. Utterly fed up with it now. Like, it can go **** itself.

So far we have:

Tier 2

Liverpool & London

Tier 3

Manchester, Hull, Newcastle, Birmingham, Wolverhampton and Kent.

My mum died a couple of weeks ago. We’re going to the funeral next week in a socially-distanced way, have ruled out the grandkids mixing for ‘refreshments’ afterwards. And my stepdad has decided it’s not sensible to travel down to us during the festive period despite the comfort that would bring him.

I’m sorry to hear that.   I’m struggling to balance that I don’t want any negative outcome and the kids then find somehow they might have been to blame in the future – possible overthinking but who knows.

Full list of areas by tier here

You can only ever make decisions for what you think is the best with the information in front of you.

With regards to the Ox/AZ vaccine results. Any randomised clinical trial is first analysed using an “Intent to treat” analysis. This is the primary analysis. You conduct the analysis based on what subjects were randomised to – NOT what they actually received. In this case that is vaccine or placebo. The efficacy is 70%. It doesn’t matter if you received a half-dose first, no dose second, the wrong treatment (placebo not active or vice versa – it happens). The ITT analysis is the truth, everything else is post-hoc.

What the misdosing calls into question is the veracity of the trial. It appears that the contract manufacturer had a suspect assay and hence the doses added to the vials was incorrect. That would be a serious finding in any audit. In any other clinical setting it would probably sink the trial results! If it failed manufacture, what else might have failed?

Clearly the 70% is sufficient for approval, but the subgroup is what we would normally call “hypothesis generating”. We would then conduct a confirmatory trial at the lower dose. Also the trial is powered to detect a difference of active from placebo – say 50%. Any smaller differences are less likely to be significant and could be a chance finding.

[t:dr] A chance finding in a poorly executed trial calls into question the veracity of the data as a whole and makes regulatory approval more challenging.

Tier 3.
Which immediately makes me question why we locked down and the effectiveness of the tiers given we’ve gone up 2 levels.
Surely we should be down a level given the government said the tiers and lockdown were to reduce infections.
Anyone would thinking keeping schools open was a bad idea…

Another planned weeks holiday bites the dust. I’m looking back on my 3 nights in Keswick in October like some kind of round the world trip now.

South Cambs has a lower rate than the Isle of Wight.

But they’re in tier 1, and we’re in tier 2. What’s that all about?

not just rate

maybe your areas growth is high enough
maybe your areas ITU capacity isn’t looking good
etc.

Lockdown has worked well for Kent gone from Tier 1 to 3.

Lockdown has worked well for Kent gone from Tier 1 to 3.

Dudley too.
Good job we’re not putting all the rules on hold over Christmas too…

maybe your areas ITU capacity isn’t looking good

Good point. ITC occupation is still rising nationwide IIRC, and some regions have very little spare capacity already… never mind if demand keeps rising.

EDIT: third graph here… https://coronavirus.data.gov.uk/details/healthcare

And the annual “winter NHS crisis” (always unforeseeable, despite always happening) is coming…. we need this epidemic to be much better under control by then… not just not worse.

One of Swale Boroughs councillors (I think) has stated that their exponential rise is based on the fact that pretty much no one could be arsed to observe the lockdown.  Maidstone and Medway border Swale, so…

@kentishman @Kryton57 exactly, Kent is not too bad overall (numbers falling) but the bad districts are REALLY bad (amongst the worst in the country I believe) Dover, Swale, Thanet, Gravesend etc. It’s disappointing as I’m in an area of fairly low incidence where people generally ARE observing the lockdown restrictions, but totally expected!

Dover, Swale, Thanet, Gravesend etc

Has Farage been on tour, telling people that (now, he’s said the opposite before) lockdown is misguided, and should be resisted?

@Kelvin if I were to suggest that the sterotypically “pleb” areas were trending towards non-compliance and rampant coronavirus infection, whereas the traditionally more affluent areas were behaving themselves and are doing OK I would be jumped on by the STW-woke-massif, so of course I will not be suggesting that 😉 I will just note that absolutely no-one in Kent is surprised in the slightest by this micro-regional variation in infection rates!

What you’re seeing in Kent is what’s been going on in W Yorks and NW England since the end of July. If you live outside the hotspots/inner city areas, it’s irrelevant as you’re all lumped in together at a council or county level.

There isn’t an easy way to do it though.

[t:dr] A chance finding in a poorly executed trial calls into question the veracity of the data as a whole and makes regulatory approval more challenging.

thanks @TiRed. I saw that for some of the placebos it was actually the meningitis vaccine rather than just (i assume) distilled water). Assume that doesn’t matter…

As of 2 weeks ago, East Sussex had the lowest rates in England. Its been sky rocketing since. My local experience shows a lot of uni children coming home from bad areas before lockdown to live with family.

I kinda feel that the above several posts answer the questions as to why the new Tiers/allocation are as they are.   They are they to stop current increases, and with an anticipated bump over Christmas protect ITU in Jan/Feb.

I kinda feel that the above several posts answer the questions as to why the new Tiers/allocation are as they are. They are they to stop current increases, and with an anticipated bump over Christmas protect ITU in Jan/Feb.

So shut the schools and non-essential shops as these are a bigger causes of infection than any of the places that have been closed.
It’s the lack of logic that annoys people.

With Swale in Kent much of the infections were in the prisons on the island with east Sheppey have a rate of over 1200 per 100K last week.

So shut the schools and non-essential shops as these are a bigger causes of infection than any of the places that have been closed.
It’s the lack of logic that annoys people.

I’m not defending the point despite having two kids of my own in school, but Hancock said earlier and specifically in parliament, that the strategy was a balance of economy, education and to protect the NHS.  Of course what he didn’t add to that – not my insensitive words btw – was acceptable loss which is surely in their consideration

Slight detour but @zilog6128 are you based in Kent? I am from Kent original and family all live there still so regularly visit (not this year though).

My sister is in the NHS in Kent and has seen the impact of the increase in hospitalisations and infections directly. My niece is currently self isolating due to a positive case in her school bubble.

I’m not sure where @pondlife has gone to

But re his discussion about Ofcom censoring ‘the science’

Here is a good example of how IPSOS is plainly not up to the job of shutting down fake news, I this case Facebook actually stepped in

Facebook have rated Heneghan’s face masks article in @spectator
as fake news… which is a pretty astonishing position for an Oxford professor of evidence-based medicine to get themselves into. pic.twitter.com/Hju3XDDgif

— Martin F. Robbins (@mjrobbins) November 20, 2020

The Spectator should not be able to get away with publishing this kind of rubbish, the headline & the article both misleading & neither reflect what the study said, nor the reality.

saw that for some of the placebos it was actually the meningitis vaccine

That doesn’t help with interpretation. In the most cautious view, they go with the 60%.

There is some jest in what I say, I have a niece who is back at school and is like a different child now she’s interacting with kids of her own age again so I know how important keeping schools open is. I also know there is a balance to be struck.

But it doesn’t change the fact that the places that the virus spreads the most are being left open when places that the spread is much much lower and being forced to close.

I’ve got no kids but I do remember being one.
Destroying their education and future is not a viable option (even for a government who in theory care only about the short term and pensioners).

I also know there is a balance to be struck.

There is. Which is why a two week half term, and national “lock down” timed to coincide, was the right policy… but we missed that opportunity… and it’s not hindsight, it was clear at the time. From where we are now (we shouldn’t be here, but there you go) closing schools early is required if families are going to be encouraged (you can say allow, but in reality, that’s not how this works) to mix the generations together at Christmas.

As an aside, schools around here are in a mess right now… a week longer half term would have hurt the education of kids around here far less… as long as people were told to stay at home for that half term, rather than mingle and go for trips.

I said it a few pages back, but will say it again, there is very little evidence that Tier 1 was sufficient to control spread. Places like the SW showed impressive increases in hospitalised patients, which have now tailed off since lockdown after reaching the spring peak.

Lockdown shrinks the epidemic.
Tier 3 controls spread and may shrink the epidemic.
Tier 2+ may control spread.
Tier 1 does not control spread.

All of those are with schools open. With that in mind, today’s announcements look sensible. Effects take up to two weeks to manifest in admissions and a further week for deaths.

My daughter is dropping out of her 2nd year of a-levels to do an apprenticeship in January – her teachers have given up, her school has given up, she’s getting sod-all help. The education of millions is already ruined.

@the-muffin-man – It’s not the end. I dropped out of A-levels twice then went to uni at 22 as a mature student after a few years of dead-end jobs. It made me more determined to succeed whilst there. It must be hard for her but life continues and it could be the making of her.