UKH

...may still leave people quite vulnerable in the meantime, for the Pfizer vaccine at least:

https://news.sky.com/story/covid-19-real-world-analysis-of-vaccine-in-israe...

https://www.theguardian.com/world/2021/jan/19/single-covid-vaccine-dose-in-...

So the stats for the number of people vaccinated in the UK may not be quite as positive as they appear, the number who've received both doses may be more meaningful. Let's hope supply problems don't prevent second doses being available in time.

The good news is that it does still appear to be very effective after the second dose is given - this may still be a good way to administer them as long as people who've only had one dose are considered mostly unprotected (and as long as the second doses really are forthcoming).

There are some concerns as well that having a lot of people with partial vaccine-induced immunity *could* increase the chance of having people with chronic but asymptomatic Covid, which in turn would increase the probability of mutations able to evade the immune response generated by the vaccine appearing.

I don’t think the scientist have much certainty on this.

IMO the government is betting way too much on those vaccines. We should plan and act on the basis that the virus will rapidly evade the vaccine.

I guess we'll have completed giving the first dose to the first cohort by mid February. I guess that would be the point at which we decide how best to proceed.

I don't know enough to say whether or not it's a good idea - but it's clearly a gamble, with many countries going the other way.

It's an attractive gamble with a very exciting potential payout - I can see why so many people are desperate to believe it's the right strategy - but there do seem to be quite a few ways it could go badly wrong.

It's happening now, so we'll just have to hope it does pay off.

Ever had a flu jab? They are only about 40/50% effective.

Based on that it is reasonable to assume that even with 2 doses nothing is " guaranteed".

As Whitty keeps saying we will be having restrictions for a long time.But people do not want to listen.

Here's the bit that nullifies the headline:
"...although the public health services head, Sharon Alroy-Preis, said that in most cases this was because the individuals had not built up sufficient antibodies after being inoculated before being exposed to the virus."

It's not really telling you anything if people are getting infected the day after the jab.
They, like us, don't have enough data yet because practically nobody was vaccinated more than a month ago.
 

No, I haven't - but that isn't comparing apples with apples, the 'flu jab has to try to protect against a range of different influenza variants (and will offer much better protection than that against some of them), the covid jab is rather more specific.

Sure. Nothing is guaranteed, but we do know that a course of the vaccine completed within a certain timescale does offer extremely good protection, the gamble is that we risk throwing that away by instead achieving much worse protection for a larger number of people.

It may be that things are currently so bad here that we might as well take that risk, that the only real hope of preventing a disaster rides on the success of the delayed second dose program. The government seems unwilling to lock down to the degree required to pursue virtual elimination, so I'm not sure what else is left.

The lack of data is what I've been pointing out all along.

It's a gamble. It might pay off; I really hope it does. But it also might not.

Norwegian scientists have suggested the same, that the uk could become a hotbed of vaccine resistant mutations. I'm not aware of other countries extending the period between doses. Worst case scenario is the uk becomes a global Eyam, so these are serious decisions the government has made. 

1369 deaths per day, average over the last week.

https://coronavirus.data.gov.uk/

I should have said 'the only real hope of ending the ongoing disaster', we're way past preventing it.

I think the next few days are key: vaccination rates have slumped and if they don’t pick up then we are no where near hitting mid Feb target. 
I really hope it is a data reporting issue. If is a vaccine supply issue then my worry is the large numbers vaccinated last week were because we had a big supply (because low numbers vaccinated in December and hence we had some ‘reserves’) which we have now used up so vaccination rates could stay the same or even go down more. Hope his isn’t the case l. 

Nearly all the current daily average deaths were December infections. As for risks post vaccination it takes a while to reach immunity. Rates published were based on average ages: we are vaccinating the most vulnerable first where the effectiveness might well be a bit lower.

You're exaggerating risk of the government plan for initial focus on a single jab. I think they really had little choice. If you think otherwise maybe you can try and explain why.

There's also the "gamble" that waiting a bit longer actually offers better protection long term. We don't know yet, but it is the case with plenty of vaccines.

Nobody's tried anything other than what was tried in the trials. Would anyone sensible bet that the gap between doses chosen in the trial (which was designed to get results fast) just happens to be the optimum one? No. Of course not.

The optimisation is yet to be done using data that are yet to be obtained. So it's not really any more of a gamble than gambling that the trial happened upon the perfect interval.
 

This is normally where Tom says something about "the tories"...

Hopefully the different data sources are being tied up to analyse infection rates vs time from first injection, so that the injection policy can be changed ASAP if needed.

That sort of longitudinal data isn’t in the public domain.

I don't know about you but what I'm gleaning from the actual information hidden between paragraphs of overhyped sensationalism, is that there is a huge supply of the AZ product but the batch testing and release is taking a long time. So right now it is a supply issue, but if what I understand is correct we should see a lot of product coming out the end of that process in the next week or two. Given that we have seen a lot of the infrastructure built up and people put in place ready to go, we could see things pick up immensely.
Or I could have interpreted wrong and we're hosed. One or other.

I would assume that as there are something like 12,000 different mutations so far that its reasonable to assume that most countries have all sorts of issues swirling around.Its just not identified.

The advantge in the Uk is that because of our genome sequencing  capabilities, in global terms 50% of the globes sequencing is done here.Even the USA is way behind on this capability.

Big article in the NYT about this last weekend.

Yep.

No - and I don't think anyone has suggest otherwise, have they?

There's uncertainty with every path. It's a common fallacy to imagine that means it's 50:50.

This has a long way to go globally imho.

close to 10,000 deaths in a week, sure we'll pass that terrible stat soon

I wasn't suggesting that the current death rate says anything about the vaccination program, sorry if it looked that way.

I was correcting myself where I'd said we were trying to avoid a disaster - by any reasonable measure, we've been having a disaster for some time now, we're trying to bring it to an end.

Wait a minute, I haven't tried to say what the degree of risk is - just that plenty of people who do know what they're taking about are pointing out some of them, and a great many other countries are choosing to go the other way.

I've also already said that there may have been no other realistic choice ("It may be that things are currently so bad here that we might as well take that risk").

There is far less uncertainty in using the vaccines in the manner they have been tested and licensed for. Anything else is speculative.

Indeed. Ignorance is bliss for many countries. Even Germany was quoting about keeping the British mutation out!! 

But a mutation for a person partially immunised is potentially a big problem than one not? 

Yep. A lot of countries have no chance at all of having an effective vaccination program.

Cases are coming down quickly, so I'd say the current lockdown clearly would be enough, it's just whether it's kept for long enough.

Hmmm, I didn't see a slump in rate when I checked this source last night. At least not a very significant one.

https://ourworldindata.org/covid-vaccinations

I calculated a vaccination rate of about 2.3% of population per week for the UK based on the last few days with just under 6.4% already given one shot. Assuming a slight improvement in rate as we get better at it we should reach 17% in about a month. IIRC the first cohort represented 17% of the population.

Also I wished we all stopped referring to these variants as « British variants » or « South African variants », it’s as stupid as talking about the « Chinese Virus »

Well, yes. And whether it even can be kept for long enough.

It's not really speculative because there is data on most vaccines that show immunity is developed after just one dose.  Also most of the vaccine's administered are the Oxford one for which there is data about delaying the second does (albeit only to 7weeks). There is also a certainty that many more people will die as a result of not having any vaccine if double doses within 3-4 weeks are given.

Rather more memorable than B-117 etc., so not stupid.

Blimey Rom, I agree!  

It's all covid, most flu strains aren't given special names with the odd exception like bird and swine. Even then swine flu was likely Mexican in origin, but at least we blame the pigs not the people. 

Agree. The British Society for Immunology have a position statement on the dosing schedules which is basically "it would be nice to have more evidence, but as a pragmatic decision under difficult circumstances this is probably okay":
https://www.immunology.org/policy-and-public-affairs/briefings-and-position...

Yes but if we want to talk about the different strains in general discussion, it makes sense to have names that are memorable. As far as I can tell the names aren't being used as thinly disguised racist slurs like Trump did with the "Chinese" virus.

If you didn't want to appear to be exaggerating then you might have read the article more carefully. The big problem in Israel is lax social distancing (esp large religious/social gatherings). The recently first dose vaccinated and subsequently infected were normally early after the jab. The reality is the recently vaccinated should never start acting as if they are immediately immune. What the UK is proposing should still work according to UK experts (providing most follow the rules).

Yeah but it can cause perception problems, just as we’ve seen asian minorities being picked on with the whole “Chinese virus” nonsense. It just makes things worse and helps no one.
 

Just so we're clear, could you please quote where you think I was exaggerating?

The graph you link is not up to date  

Screen shot from govt dash board  about 30% drop Friday to this Monday, but we had seen steady increases up to this point PLUS extra vaccination centres opened on Monday  TBH, I expected to see 350k vaccinations on Monday given the trajectory previous week. If it’s a data/lag issue then we should get a massive increase reported today. Or as others say,could be supply.

The cynical side of me wonders whether the govt are expecting big supply probs with Pfizer (revamping their factory plus demand from elsewhere) and they are recalculating whether to give more people the second jab now, rather than risk them having it too late (my father in law had his first jab this Monday, second scheduled 12th April, which is cutting it VERY fine so any delay could be a problem (he’s in Fife).

I had read the articles, but I've re-read them.

As far as I can tell, they don't say what you say here - could you quote that too, please?

(I do see the Guardian article saying they have a problem with this in the ultra-Orthodox community, but nothing saying that this is "the big problem in Israel" - Israel is hardly unique in having groups that are worse at observing distancing).

There's also the other variable that is the supply of the AZ vaccine. If things go well we could have an order of magnitude more doses of AZ to deliver than pfizer. If that is the case (big if) then suddenly the pfizer stuff will be small change so there will be no controversy in using it for second doses.

Thanks for this and the other reply. 

The delivery schedule for Scotland was briefly on the Scottish Government website before the Tories insisted it was taken down.  Presumably the schedule for England is roughly 10x this.

https://twitter.com/fatweegee/status/1351583237454389249

If you look at the deliveries for Pfizer you can see there's a few really large deliveries early on but twelve weeks out there is a much smaller regular weekly delivery.   If you push the whole of the initial deliveries into arms as first doses and do it as fast as possible like is happening in England there isn't new supply in twelve weeks sufficient to give those people their second dose.

Also, if you max out your vaccination capacity in week 1 then when you get to week 12 you are going to use up your whole capacity doing second doses.  If you start slower and aim to hit max vaccination capacity at week 12 you will be able to continue with first doses while also handing out second doses.

I'm not sure vaccine resistance occurs in the way that you are implying. Are you saying that a virus resistant to a vaccine is more likely to occur in people who have had 1 dose of vaccine and therefore only low levels of antibodies in the same way that antibiotic resistance can occur when bacteria is exposed to sub lethal doses of antibiotics?

Virus mutation occurs due to errors in transcription in the cell enzymes. It is independent of any external pressures such as vaccines or other antiviral drugs.

The absolute numbers of mutations in the virus population will depend on the absolute numbers of virus particles in circulation. So having more people with some immunity who potentially spread less disease (appreciate this in not proven yet but kind of makes some logical sense if they're not coughing evetywhere) should reduce virus mutation I would have thought.

Yeah, I have a concern about this.

There was a big, sensationalist, and somewhat dishonest fuss when it was revealed that the UK strategy would be to use a second dose of a different vaccine in some cases - it turned out that that was only to be 'in exceptional circumstances', which seems reasonable, contrary to the tone of the media reports.

I wonder, though, whether we might now arrive in a situation where a large number of people do find themselves in the 'exceptional circumstances' of not actually being able to get a second dose of the Pfizer vaccine in time.

As of yesterday, UK has ~630k live cases and a daily decline of ~14k (7 day average), so theoretically ~45 days.  November's lockdown saw a peak decline of ~10k a day with a base of ~300k live infections, so I guess a peak decline of 20k is what we're likely to see this time, which would give a month to eliminate. I doubt we'll see that though, vaccinated people will stop behaving sensibly and others will get bored of lockdown.

As far as I can tell it is well established that viruses evolve under selective pressure, either through transmission or within individuals.

In the case of the variants we are seeing they seem to have been adaptations that occurred in within specific individuals and took off from there. The theory is that these individuals probably had a chronic infection with the immune system not destroying the virus but putting huge pressure on it, forcing the selection of these mutations.

Probably over-simplified but I’m just repeating what I’ve collated from people worth their salt.

If we assume a direct relationship between cases and death rates, lockdown 1 shows the reduction is cases is fast to start with then slows off.  London/SE cases dropping about 40/50% a week from a very high number. Places like Grter Manc cases dropping about 20% a week. Given roads about 3 times busier than lockdown 1 (a good indicator of people going to work), then lockdown fatigue, vaccine euphoria,  people not giving two hoots and being too thick and irresponsible, I fear the reduction in cases will start to slow. Lockdown 1 took over 2.5 months to have the desired impact (deaths became very low in early July so cases became very low early to mid June) this could be a lot longer.  No real proof, just basic maths and human observations. 

Yep - it's loosely an exponential decay curve when r is below 1, just as it's close to being an exponential growth curve when r is above 1.

Real life doesn't follow such simple patterns, of course. Several countries have shown that the disease can be almost eliminated through early strong action, then kept at a very low level through a lesser set of restrictions (including strong restrictions on foreign travel, and requiring effective track and trace - which is at least easier to do when prevalence is low). We may still have to go down that route (greatly assisted by vaccinations), as covid won't be going away completely.

That's really, really not how this works

You rightly say risk doesn't mean 50:50 and fail to apply the same logic to exaggerating. You look at risks but not so much at mitigation. The big issue here is, thanks to misinformation, large numbers of people across the world are looking for reasons to maybe not take the vaccine and the significance of this latest news might be misunderstood and just move some of those on the border to make a bad decision. On the plus side it might make those who have been vaccinated remain careful with hands, face, space (as the rules require them to be).

I'll give another reason (on top of early infections, problems with social distancing/large meetings, and only having data from the most vulnerable) that might have changed things to make the vaccine look less effective than it is.... 'real world' also means people vaccinated know they are better protected and will very likely take greater risks. It's not a double blind experimental result.

It all depends how much immunity just one dose gives you. If it is too low then the strategy doesn’t work and you end up with loads of people who think they have protection but have none or little. As for the data coming from clinical trials, it’s coming with big confidence intervals.

I don’t think there is any certainty about what you are saying, most countries are not following the UK approach.

I am not convinced that it is the right time to sugest that. Most countries are in a different position to us on the availability of vaccines.so you really cannot draw any conclusions imho.  

It would be conventional to refer to it as Wuhan virus though.  As in Marburg virus, Norwalk virus (now norovirus), Ebola virus, Lassa virus etc, etc.

It's a bit tiresome being accused of exaggerating by you, when you appear to be unable to quote me doing so. I'll ask again, could you please either do so, or wind your neck in a bit?

In the meantime, since you appear to have skim-read and misinterpreted the article you accused me of skim-reading and misinterpreting, I'm going to go ahead and take it that you've misread what I've written too. I get it, you're busy and not paying much attention, that's fine but maybe cool down a bit? I'm not a covid denier, a lockdown sceptic, or an anti-vax idiot, and I'm not at all sure that the gamble of delaying the second dose is the wrong thing for the UK to do - it's just very clearly a high-stakes gamble rather than some genius strategy, and it's one that many other countries are going the other way on.

If the UK (a country that really, really doesn't seem to be good at making the best choices: https://news.sky.com/story/covid-19-uk-records-599-more-coronavirus-deaths-... ) screws up the vaccination program with this experimental approach, won't that dissuade people from taking the vaccine? Your argument cuts as well in either direction, just depending on which approach is actually best. And we don't know which approach would turn out best.

Yes, and potentially be put at greater risk too by others. But this is at least as much a reason not to delay the second dose, surely?

I don’t see how that is an argument against the suggestion that there is not much certainty that the current approach (delaying second doses) is the right one.

If anything, it’s an argument for. So I really have no idea what you are on about.

Not sure it was but went back and checked anyway.

Hopefully the format in the table below survives posting

Date   %population  Change from day before

19      7.47               0.51

18     6.96                0.31

17     6.65                0.34

16     6.31                0.41

15     5.90                0.48

14     5.42                0.48

13     4.94                 -

Which gives an average rate of vaccination over the past week of 0.42% per day so the rate is better than I said it was if you take a whole week into consideration instead of 16/17/18 which I originally used. So that's roughly 2.9% per week which is about 1.9 million people a week so just a little below the target of 2 million a week.

Let's hope supplies hold out.

No one is saying there is certainty it's right.

Well WHO has established best practice on how to name new infectious diseases. These things have been studied carefully believe it or not.

The WHO specifically recommends that place names are not used.

https://apps.who.int/iris/rest/bitstreams/724114/retrieve

But we’ve made so many right decisions thus far?🙄

The data for the 19th hadn’t been released when we chatted earlier and would have shoved your average up. Anyways, I think we are comparing slightly different things as the ‘slumps’ I referred to are visible in this screen shot and would have been worrying had they continued. However, today’s vaccinations looking good and yes, let’s hope supplies hold out. 

People make decisions on perceived risks for themselves, much more so than based on overall programme success (that's why antivaxers exist as the scientific benefits of vaccinations are clear).  The Pfizer single dose vaccination protection is way higher than 33% at two weeks as irresponsibility claimed by Sky news (the Israeli epidemiologists would back me up if you asked them and our own program would show multiple infections of the immunised by now if that were anything like true). The Israel scientists are highlighting genuine real-world issues but these are almost certainly behavioural problems more than vaccine problems. To be blunt too many of the vaccinated must have been being irresponsible with social distancing just after vaccination.

Everything around covid is a bit uncertain but some things are much less certain than others. You are focussing on the overstated grey area and missing the competing grey area factors (that I listed above), I see that as exaggerating (but far from hyperbolically so and with good intentions... hyperbolic comment is too often found here, and is very visible on this linked Sky joke 'analysis' https://news.sky.com/story/covid-19-analysis-shows-one-vaccine-dose-leaves-... ). One of the key factors missed in this joke analysis is for those in the clinical studies who did get infected  the vaccine very significantly reduces the impact of the subsequent illness.

Calling the UK position an experimental approach is true in a semantic sense but such statements can gain emotional attachment. What is important is the overall risks of this 'experimental approach' are felt to be low by actual experts and the risk of going at half speed very high by the same.

Yes they are not measuring the same thing. The clinical trial measure efficacy was based on symptomatic infection, not positive PCR test. 

I guess the only way we’ll see if this works is if hospital admission in Israel reduce significantly. So far not much signal of that happening, despite most older people vaccinated, but it could just be that we need to wait a few weeks to see it.
 

However bear in mind that most of the vaccines in the UK is the AstraZeneca, which has an overall efficacy of 62% with the current dosage regiment, with a lower 95CI bound at 41%.

And the range of uncertainty on first dose efficacy in preventing symptomatic infection  21 days after first dose is huge in the Astra trial. The lower bound of the 95%CI puts it below zero.

Hopefully it is bigger than that, but this highlights how much of a shot in the dark this is.
 

Some genuine hyperbolic exaggeration. It really is not 'a shot in the dark'.

Can't find confirmation of this anywhere. Do you have a link? Everything I can find says "laboratory confirmed... occurrence of..."

These are some slightly misleading cherry-picked numbers. The AZ 'efficacy' numbers are a known controversy. The more certain number is the complete prevention in the trial of severe cases. There was not a single hospitalisation in the vaccine arm of the trial. So.... would probably be better for everyone not to seed doubts about that, because there is none.

Also, nice move there calling out the centre value and lower ci bound. What's your motivation for doing that? Just 'forgot' to mention the other half of the confidence interval did you? The bit about how high it could be?
That's straight from the playbook of anti-vax wankers.

That's what people say when they start sentences with "I'm not an anti-vaxxer but..."
It's not a shot in the dark. It just isn't.

I don’t see how the data supports any other conclusion.

According to the data published in the Lancet, efficacy (in preventing asymptomatic infection), 21 days after 1 standard dose, was only 3.8% with a 95%CI between -72.4% to 46.3%

I am not saying it isn’t a short in the dark not worth taking.

WTAF? where?

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32623-4/...

To be clear this doesn’t mean the vaccine doesn’t work, it just that there is a huge uncertainty range on what kind of protection one first dose does.

Well said.

You need to stop picking the flakiest figures out of all these papers and ignoring the actual findings.

Boolean Overload

Absolute nonsense. I am not picking the flakiest figure, I am picking the one relevant to the specific topic of conversation, which is efficacy of the vaccine after one standard dose.

The only piece of data we have on that suggests a very high range of uncertainty.
I don't understand why people find it so hard to accept we don't have all the answers right now.

I am not anti-vaccine.  I am not against vaccinating as many people with a first dose as fast as possible. I simply don't know whether this will turn out to be the best approach or not, I guess we have to try something.

All I am saying it that at the moment there is no scientific data giving us any kind of certainty that it will work as we expect it to, and therefore we should plan for the worst case scenario.

That's it, that is the extent of my claim. Some on these forums need to stop jumping up and down pointing fingers and shouting "anti-vaxx" every time someone makes the mere suggestion that we should tamper our hopes until we have more data.

I'm mixing posts here to show you that you have.

What was the upper bound? Why have you chosen to highlight the bottom end but not the top end?

Why is asymptomatic infection "the one relevant to ..."?
It's not. We're not judging the success of this campaign by how many asymptomatic cases it prevents. Nor foes that CI suggest we should pay any attention to that figure. It even draws the question about whether that was just the false-positive rate of the PCR test showing through.

Just read the Pfizer paper :

https://www.nejm.org/doi/full/10.1056/NEJMoa2034577

The primary endpoint of the trial is the efficacy against "confirmed Covid-19 with onset at least 7 days after the second dose in participants who had been without serologic or virologic evidence of SARS-CoV-2 infection up to 7 days after the second dose."

They defined COVID19 as such "Confirmed Covid-19 was defined according to the Food and Drug Administration (FDA) criteria as the presence of at least one of the following symptoms: fever, new or increased cough, new or increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat, diarrhea, or vomiting, combined with a respiratory specimen obtained during the symptomatic period or within 4 days before or after it that was positive for SARS-CoV-2 by nucleic acid amplification–based testing, either at the central laboratory or at a local testing facility (using a protocol-defined acceptable test)."

They basically measure efficacy against COVID-19 (the disease) rather than mere presence of the virus. Which makes perfect sense TBH.

The efficacy number coming out of Israel are against positive PCR test.

That is why the two are not comparable, and why the Israeli data does NOT show a reduced efficacy compared to trials, as it is being claimed in some news outlets.

How is that not a PCR test?

Edit: This means symptoms AND a +ve PCR test. Rather than symptoms OR a +ve PCR test. Is this a source of confusion here?

I'm with you on this part

Why do the actual UK experts say something different based on some real science that you imply doesn't exist (they are confident the approach was the best available based on that science). There are real uncertainties but the UK problem here is more about transparency than likely efficacy. The bigger worst case scenario is many more vulnerable would have died or contributed to overwhelming hospitals if we stuck rigidly to Pfizer timetables.

https://www.bmj.com/content/372/bmj.n18

https://www.nature.com/articles/d41586-021-00045-8

I'm not defending the government here. We are only in this current mess because the government acted way too slowly on multiple occasions from September (and in that the leading government scientists abjectly failed to pursuade them). I'd even question strategy and will wait with interest to see the scientific basis on why they chose the route they did.... it always seemed to me those in care homes were way more vulnerable than older people capable of socially distancing at home.... and front line medical staff should have been protected up front in my view, given they knew before xmas that hospitals would be close to breaking point in January... I'm gobsmacked how well the NHS has coped under ridiculous pressure.

Morning, and thanks for that reply.

I certainly agree that there is some hyperbole and exaggeration in the articles, although I still don't see that I've exaggerated - I didn't write them, and I didn't go trawling for articles to push a view - they're simply two articles I read yesterday morning, from news sources I consider to be fairly reliable.

Which actual experts, though? Actual experts (not the 'experts' sponsored to sow misinformation) appear to disagree on this one, with some real concerns being expressed about delaying the second dose. And lots of other countries are avoiding delaying second doses.

I obviously can't say what approach is right - but I don't think you can either. The UK has repeatedly made high risk, bad decisions (or failed to take necessary hard decisions) throughout the pandemic, and appears to have done worse than almost any other wealthy country (except perhaps the USA, and maybe Sweden who started with significant advantages and squandered them).

So I'm really not inclined to trust UK decisions over those made elsewhere - and yes, my response is quite emotional, my home country has turned a crisis into a disaster and I really, really hope that they don't screw up the vaccination program, perhaps the one big thing where the UK has started off well with.

Finally, I don't believe that questioning the protectiveness of a single dose of one of the vaccines is going to put people off getting the vaccines. The safety of all three vaccines available here just now is good, and all offer greatly increased protection - this is about the risk of possibly not being vaccinated properly (not just the gap between the doses during which protection is lower than after the second, but also the increased risk of many never getting their second dose because it might not be available later). And if someone does decide to hold off getting their first dose of Pfizer in favour of one of the others, that's just more of the Pfizer for those who do want it - demand massively outstrips supply. Maybe some more people can even get their second doses on time.

I was in hospital in December, and there was a massive commotion at one point amongst the nursing staff - there was leftover vaccine from a batch being administered, and they'd been given the chance to get theirs early from it, and were practically falling over each other to get it done!

I am simply trying to highlight that there is a lot of uncertainty here and we need to manage expectations. Looking at the lower bounds of the CI is one way to do that.

I have quoted both the numbers for efficacy in positive cases and asymptomatic infection.
Stop cherry picking.

I agree. That was my very first point. Next time read properly.

Yes.

Also though, remember the pfizer vaccine is a real pain in the ass to deal with. So there were choices to make between going through the faff of getting it to a care home to vaccinate some people versus keeping it in the hospital and battering through a load more people. They were going to get a blast of sh&t from the papers whichever they chose. Going for more of the ever-so-slightly-less-vulnerable people was the only real option.

In reply to Alyson30:

So is looking at the upper bound.

But neglected the hospitalisations

I'm only filling in the gaps you've left.

At least you still have your sense of irony.

Many equally respectable international experts are taking a different view. Which the article you posted point out extensively. Sorry but it is wrong to say that there is scientific evidence that this is the best approach. We'll only know that much later down the line when we can make comparisons.

It's a judgement call, not a scientific certainty. And there is nothing wrong with making a judgment calls when we are dealing with uncertainty.

This is particularly important in this case, as we don't want people to start going out thinking they are protected when in fact they may not be. 
 

Well, no, because there is asymmetry in the impact of the error.

For example if I tell you you have a 50/50 chance of dying in a car accident, with a lower CI bound of 10% and a higher CI bound of 90%, getting it wrong thinking it is 50% when in fact it is 10%, isn't as bad for you as getting it wrong thinking it's 50% when it is in fact 90%.

That is why medicines agencies will typically not approve a vaccine if the lower bound of efficacy is too low, but won't refuse it if it is too high. 

I feel like I am stating the bleeding obvious here, but here you go.

I have not. Again, read properly.

Yes, in the trial it is a positive PCR test AND symptoms.
The Israeli data is only positive PCR test.

That is why they can't be compared (amongst other reasons)

The figure that is more worrying from Israel is that about 17 percent of the new serious cases observed in Israel have had their first dose. But again, can't jump to conclusions here, these people could have had it before they got the vaccine, and we know that immunity takes time to build after the first dose.

All this to say there is a lot of uncertainty and IMO we should act AS IF the vaccines won't work

I said it was conventional (in the sense that it was common, even usual, to do this in the past) to name new viral diseases after where they were first identified.  I didn't say it was politically advisable.  

The WHO recommendation from 2015 was also that new diseases shouldn't be named as 'equine' even if they occur in horses, 'bird' even if they occur in birds or 'swine' even if they occur in pigs.  There are good reasons for having a consistent viral nomenclature (as in SARS-CoV-2) but in the early stages of an unidentified, probably novel infection, especially one with a clear geographical focus, I suggest that using the name of the place is a pretty convenient descriptive shorthand, even if it's provisional.  Check out Reston virus as an example.

Of course, I bow to your expertise in this area, as on all things.   

Your reply to me implied that I was mistaken to suggest that using terms term such as "British variants" was a bad idea.

You are the one who pretends to have expertise in the matter and to know better than the WHO, instead of referring to their opinion, which is what I did.

Those other respected independent experts don't have access to the full information the government scientists have (including supply & logistics). That's why many call for greater transparency.

I'd accept that to an extent for Pfizer in care homes (even so, Scotland managed it in many homes) but it works the other way for most front line NHS staff. Now other vaccines are available, care homes still seem to be progressing slowly... lots of noise about this in the press.

There are many other details on government decisions on vaccines (and especially on restrictions) that I'd be very interested to see but I guess we might have to wait decades for a public view.

Thanks for (inadvertently) admitting that I wasn't wrong to suggest there isn't enough information out there to have much certainty as to whether the government strategy will work.

(but I don't think supply and logistics are the main source of uncertainty, though)

Are you crazy ? This would mean people in government being held responsible for their decisions. Never ! Better to hide behind the scientists !

Anyhow, by a truly weird coincidence, I’ve just watched a repeat of an old QI including a jokey exchange about the oddness of the exact 2015 WHO Best Practice guidance document you cited.

As you can imagine, the rest of the family was lost in admiration with my easy familiarity with the subject matter.

Well a GP is saying on the BBC news right now that there are supply and logistics issues; this includes specialist needles and sundry other items as well as vaccine.

I think its criminaly nuts we are slowing down a life saving treatment in some parts of the country because the government are worried about a postcode lottery.

The GP also said Public Health England risk advice has been clashing with GP views on getting into care homes. GPs want to go in ASAP if someone has covid as risks are very high for everyone else.

I think slowing down just means diverting the vaccine to another area. To be honest I think that is reasonable if it can be done .

on supply issues I read in the Guardian that Italy for example were scheduled to get 389OOO doses and only got 80k approx. 
 

until there are multiple vaccines and lots of them  there are clearly going to be real supply issues. 

This doesn't make sense though. You've got areas saying "why are we being punished for being quick" when they've vaccinated all their 80+s and want to get on with the 70+s but vaccines are being delivered to other areas that haven't.
If they got their way you'd have 80 years olds waiting for their vaccination because someone in a lower priority group had been given it somewhere else. What do people want to hear? You're going to see one of those stories all over the papers, with a headline carefully chosen to get everyone riled up. Which should it be?

This doesn't make sense either. If someone in a care home has covid you'd need to have vaccinated all the other residents 2 weeks ago to make a difference to the outcome.

Sure thing but from the point of view of whether delaying 2nd dose or not makes sense I don’t see how that would be much of a factor in the decision making. What counts is 1st dose efficacy / 2nd dose efficacy

I thought that convention had been dropped because it was needlessly stigmatising?

jk

Yes, I meant conventional in the conventional sense.  I think we've established that it's probably best avoided now.  Although some of the other recommendations about not using the names of the people who first described the disease or what animal it occurs in seem a little odd.  

To be fair, the GP may be saying this as the stories in the press are that GPs are "refusing" to vaccinate patients in care homes as there's covid, so a bit of deflection back to PHE. 

Doing the care hones first was the better option because:

a. mortality after a Covid infection is far higher in the care home population.   The numbers being vaccinated may be lower but the number of Covid deaths prevented is higher if you put the effort into doing the care home population first.

b. when you look at the delivery schedule for the Pfizer vaccine which was briefly published by the Scottish Government before Westminster forced them to take it down again it is pretty clear that you can't simply use all the initial supply for first doses unless you are either going to wait longer than 12 weeks or use a different vaccine for the second dose.    From memory the numbers for Scotland were something like 450k, 130k 130k to start and then out at week 12, it is a regular78k a week.

c. if you scale up to maximum vaccination capacity immediately what do you do at week 12 when you have to do second doses AND first doses.   You would need twice as many vaccinators and twice as much vaccine to keep the same tempo.

IMHO what Scotland and Wales are doing with a slower start and not burning through all the large initial delivery immediately and matching the tempo of first doses to available supply for second doses (probably assigning some of the initial supply for second doses to make it work) is what a professional person looking at the delivery schedule and logistics would plan for.

It is certainly a far more complex argument than the narrative the Tories are pushing and the press is taking up.  

I'm not sure I see what you see here, 450+130+130 = 710K, if delivered evenly over 12 weeks that's 59K/week which is less than 78K/week arriving from week 12 so you could potentially afford to front load delivery of dose one slightly, getting up to 78k/week done from week 1 until the initial batch runs out in week 9. If we did that the 78K done in week 1 get their 2nd dose from the first smaller frequent drop in week 12, second doses are delivered for 9 weeks then you move down the priority list and start again. It's messy having a stop start program and (I think) it makes lower (but still high) priority people wait longer for dose one than going a bit slower but I don't see it precludes anyone from getting a 2nd dose 12 weeks after their first. What am I missing?

You could do it in waves, stop delivering first doses at week 12 until new resources become available for the next wave. I'm not arguing we should but we could. In reality vaccine/staff/site capacity is still increasing, there needn't be a crunch here.

There's certainly more than one way to go about this and choosing the best will require both a clear objective and a clear estimate of the resources likely to be available some months into the future. It also requires a decision to be made on how to balance risks.

As much as I hate this government to the pit of my stomach I don't think it's clear they've bungled this or are being particularly reckless.

jk

This study is saying the vaccines - and especially the Oxford one - are not sufficiently effective to create herd immunity. 

https://www.uea.ac.uk/news/-/article/herd-immunity-may-not-be-achievable-ev...

This would mean that unless you are vaccinated yourself you are screwed when they lift the lockdown because there will be vaccinated people walking around asymptomatic but able to infect others.   The way the Tories are talking about getting back to normal there's going to be a lot of people not vaccinated yet at the point they start opening up.

Also, the Oxford vaccine the UK is betting on is pretty bad compared to the Pfizer one from the point of view of preventing spread from vaccinated people and they reckon that health care workers should be getting Pfizer so they are less likely to spread it to patients.

The problem is they aren't delivering it evenly over twelve weeks.  They are using it up as fast as they can get it into arms.

These are the actual numbers for Scotland, I assume England is 10x these.

https://twitter.com/fatweegee/status/1351583237454389249/photo/1

Yes, I agree you can devise a schedule which works.  But it's going to involve holding back quite a bit of the large initial orders, to smooth out the deliveries and providing some of the second doses from the first shipments.   If you simply inject the vaccine you have as fast as you can get it into arms so as to get headlines and prove you are 'world leading'  then you don't have the matching doses.

Yes, that's the logic.  Instead of a smooth operation doing 50% first doses and 50% second doses and gradually working through the population you get 12 weeks of all first doses followed by 12 weeks of all second doses.

When there's also a good medical argument about injecting smaller but harder to reach groups first and that approach also smooths out your vaccine schedule then it is a perfectly good strategy. 

I would have less of a problem if the UK government were honest about the tradeoff instead of using 'commercial confidentiality' to hide supply data.

That paper is making some fairly flaky assumptions and ignoring a lot of mitigations. It's had a mixed reception here: https://ramp-forums.epcc.ed.ac.uk/t/immunisation-asymptomatic-infection-her...

Yes, you're screwed if restrictions are lifted and the let-it-rip scenario happens, but that's not going to happen for reasons discussed many times over. You'd immediately fill the hospitals with the 0.5% of under 50s.

Yeah, you don't. Capacity ramps up.

I haven't found any evidence about the pfizer vaccine and asymptomatic spread yet. I thought the jury was still out on sterilising immunity for both vaccines, but would love to read about it.

I was under the impression the plan was to ramp up to more than 2x the jabbing rate by then, but could be wrong

The overwhelming necessity was to stop vulnerable people pouring in to hospitals by jabbing as fast as possible. That effectively took that strategy off the table. Tactical decisions on slowing down to make things smoother later had to wait.

I was going to congratulate you for writing your first post that didn't mention "the tories" in it there, but you just called them UK government instead.
I'm with jk on this. The strategic decisions seem to have been made by sensible people in places like JCVI and they don't look like bad ones to me.

Just been through the paper again and I can't find any evidence,  mentioned or cited, that the pfizer one is any better at preventing spread. If it's in there and I've missed it, ignore me.

I'm struggling to appreciate how it can be impractical when Scotland have done it.  Scotland did the most vulnerable and health service workers first where England went for easier to access groups and put more doses into arms to chase headlines.   

The consequences of burning through the large initial supply of Pfizer for first doses come in 12 weeks when second doses are due.

The consequences of going for 'Oxford' / AZ instead of Pfizer are also going to become clear in six months if, as the East Anglia paper predicts, the Pfizer jab is far more effective in controlling spread in the community.  

Be careful with that UEA paper Tom, its modelling based on lots of estimated sensitive values, ignores any action the government would take on prevalence data  and is not peer reviewed yet.

The main reason it's sensible to do things the Scottish way in terms of care homes and front line staff first is it maximises reducing risks of death and protecting hospital functionality to deal with current around/above capacity response. We don't know enough about England delaying the second dose (other than Scottish pressues being a bit lower gave more flexibility for them to make that choice)

"If they got their way you'd have 80 years olds waiting for their vaccination because someone in a lower priority group had been given it somewhere else. What do people want to hear? You're going to see one of those stories all over the papers, with a headline carefully chosen to get everyone riled up. Which should it be?"

You don't need to slow any areas if there is no major supply issue (which due to poor government transparency we don't know). Imagine how you explain to the family of someone in their late 70s in the NE who was scheduled for a jab, which was delayed and then in the meantime dies. It's just criminally mad to slow areas unless you need that supply elsewhere. Assuming supply is OK I'd tell the NE to get on with it and work on improving the system elsewhere to catch up. People being riled up versus people unnecessarily dying as a result of a go slow policy is a no brainer choice to me. Being generous I have to hope there is a supply issue (as otherwise the government will be killing people to avoid bad publicity).

It can be done (subject to the not moving it more than 4 times rule, and bearing in mind it's been moved twice before it arrives at its first UK destination), but the consequence is a lot fewer people vaccinated. It's a publicity win because scotland can say "Look at us, we managed to get one box of vaccine to a care home once. England didn't." but in the numbers game it's not a winning strategy.

It's as well as, not instead of.
It doesn't predict that, at best it postulates it.
That paper is really not worth reading too much into. Loads of good comments on the RAMP forums but I realise that's a faff to sign up for. Points like Offiwidth makes.
It assumes all the NPIs stop. It implies with NO EVIDENCE supplied that the pfizer vaccine would be better*. It assumes efficacy translates to effectiveness. It models a population after an immunisation programme is complete, so assumes an effectiveness across the population for (not) preventing spread, but then neglects to account for the relative impact when the immunised population is protected from severe disease.

I'm not sure what they're advocating. It sounds like they're pushing to wait for the pfizer vaccine, but doing so by shitting on the Oxford one without saying the pfizer one is any better, and ignoring the consequences of waiting for adequate supply.

*really, please do point me to any info on asymptomatic spread in the pfizer studies because I genuinely want to read any that exists.

I thought it was pretty clear supply is the limiting factor here....?
Obviously you don't need to 'divert' supplies if there's infinity of it. In the story I read it was between 70-year-olds in gateshead and 80+ in the south, and it was one or other.
If it could be both, well, then, I mean, yeah, of course you'd do both.

"I think slowing down just means diverting the vaccine to another area. To be honest I think that is reasonable if it can be done."

Does it mean diversion though? UK ministers keep saying there is no supply issue. If it is a supply issue why don't they tell us? It would certainly help justify the second dose delay for all those international scientists asking questions. It's very believable that this government would sacrifice lives with a go-slow in places like the NE to avoid bad publicity on the postcode lottery subject. PHE seem to be very poor in all this (ditto for battling with GPs on vaccinations in care home) .

All Hancock will say is supply is lumpy (meaningless waffle unless the average is below what they need).

There are good reasons why the deprivation in the NE justifies continued supply based on actual risk of hospitalisation or death.

https://www.hsj.co.uk/primary-care/exclusive-leading-regions-vaccine-supply...

This is what I thought you were referring to:
https://www.bbc.co.uk/news/uk-england-55755529

From that: "Vaccines minister Nadhim Zahawi later denied the claims and stated "no vaccine is being taken away from Yorkshire"."

Yeah I dunno what's going on here... seems like a massive non-story

Well I know of at least one care home in Manchester that have all (except those who are unable - allergies, etc) had the first jab and it will have been Pfizer because it was before Oxford had started. Their 2nd jab has been delayed beyond the 3rd week but the home is fighting to get it as soon as possible.

Given that this is coming from the government, I guess we can safely assume that the exact opposite is true then ?

..... it's not being 'taken' from Yorkshire it's being 'given' to the SE.

Doesn't look like that to me.  I posted this several times but the are actual official vaccine supply figures available for Scotland so this is not an unknown.  Presumably the numbers for England are the same except scaled for population so x10.  The number of doses of vaccine is not going to double 12 weeks from the start of the campaign.    

https://twitter.com/fatweegee/status/1351583237454389249/photo/1

I'm holding out for a better source than a Twitter link.

No need to presume: https://coronavirus.data.gov.uk/details/vaccinations

It already has doubled, from 200k to 400k. Available doses will increase immeasurably as the AZ stuff comes through testing (discussed above (or was it another thread? I forget)).

It's impossible to tell from those if there's a problem, most of the actual data is in one multi-week bin, the rest is projection. If that big bin of actual data from December starts slow and ramps up I don't think you necessarily have a problem. 

Jk

The Scottish Government posted it on their website and the Tories in Westminster forced them to take it down after a couple of hours citing 'commercial confidentiality',   But not before people had downloaded it and some kind person posted a picture of the relevant table on Twitter.

The Tories did not say the table was incorrect they said it was confidential.

The table doesn't show supply 'increasing immeasurably' it shows a surge at the beginning when they get 450k units of Pfizer and a few 300k orders of AZ and a few months out a regular supply which is flat at 265k units of AZ and 78k units of Pfizer a week.

So you're saying that injections spiked at the beginning of this month for the UK.

That's an interesting claim, do you think that will be true come March? 

Edit: if the news about supply issues are true this could well be the case. This is likely the commercial information that was being protected. 

I'm not convinced. I'd expect the Pfizer numbers to be divisible by the number of doses in a tray or in a box and they aren't. That doesn't on its own imply they're made up, but it does imply there's missing information.

That table, even if official, is someone's prediction. And unless whoever it is has a better crystal ball than "the Tories the Tories the Tories" it's yet to be seen how it plays out. I'm going to wait and see now because this argument doesn't really have a winner.

The table is a prediction by the UK government who are the people who placed the orders and who will be getting delivery information from their suppliers.

We know the Scottish Government posted the official numbers and the Tories got angry about it.  That's on the record.  Nicola Sturgeon called it a 'hissy fit' in parliament.  I actually clicked the link the Scottish Government posted but they'd already removed the document.

I have no reason to believe the guy that posted that table was lying.  Multiple people are saying they downloaded the document.   The numbers look reasonable to me - I'm not surprised they got a lot of Pfizer vaccine at the start because the UK approved it first.   Once other countries approve and start competing for supplies presumably there's less around.  

It will all be clear soon. We need to average 400,000 a day to meet the target but it is only a target, the local people on the ground really are doing very well and the large majority of the most vulnerable will have some protection by mid Feb. If supply is limited and the government is hiding that, I think there will be serious problems as many people at moderate risk (eg the overweight middle aged) but months from being near the top of the list will be worried and angry.

https://www.theguardian.com/world/2021/jan/05/no-data-to-support-uk-delay-o...
https://www.bbc.co.uk/news/uk-55777084

400,000 a day for 12 weeks of first dose only and then 800,000 a day (400,000 a day first doses and another 400,000 second doses).   

Seems like the UK is the only country in the world allowing a 12 week gap and the BMA is now arguing it should be 6 weeks rather than 12 weeks between doses.   But at the rate they are doing first doses, the question is whether they have enough Pfizer supply to do the second doses in 12 weeks.

https://www.independent.co.uk/news/health/coronavirus-uk-update-live-vaccin...

I'm saying the table of vaccine deliveries provided to the Scottish Government shows a large amount of Pfizer at the start 450k and two or three 130k deliveries but 12 weeks out it is a steady 78k unit delivery every week.   And I'm saying if you put all the initial deliveries into arms as first doses as fast as you can the smaller 78k deliveries won't allow you to do matching second doses in 12 weeks.

It's not a claim.  I'm just reading the delivery table the UK government supplied to the Scottish government for their planning.  

I would say that predictions are just as likely to be optimistic as pessimistic.  Maybe the vaccine guys will do better and the Tories are banking on that.  Equally, Pfizer have had production disruptions and AZ nearly had their warehouse flooded.  Things could equally well be worse than planned.

I suspect what they are protecting is that their vaccine delivery schedule 12 weeks out doesn't match up with their policy of first doses into arms as fast as possible.  They are rolling the dice and hoping they get more vaccine and the problem goes away.

Well that's a delivery table not jabs in arms. Your argument is predicated that there will be no increase of vaccines given, not the supply. 

That's true for all predictions. Let's hope we're being pessimistic. 

Well that's a conspiracy theory. Data on number of vaccines given is available, the commercially sensitive data is the breakdown of how many of each vaccine are being supplied at any given point. The news of supply difficulties is absolutely going to have an effect on the markets.

If you change over from first doses to second doses when you've had half the deliveries you can do the matching doses pretty much within twelve weeks. Due to the lumpiness and front loading of supply maybe start a transition a couple of weeks earlier than the half way point of deliveries.

Not a bad gamble when you have 1000+ deaths per day.

Using the inadvertently published numbers and playing with excel.

1.18M Pfizer doses delivered in the 9 weeks up to and including week beginning 29 Feb.
1.15M Pfizer doses delivered in the following 12 weeks beginning 7 Mar to 23 May inclusive.

If first doses only given in weeks up to and including week beginning 29 Feb there is enough supply in the 12 weeks afterwards to give second doses within 12 weeks without needing all Pfizer doses in last row of the table (13th week).

Some of the jabs already have been second doses which makes the problem easier.

There are plenty of ways to make it balance out.  But the Tory government stated policy and the one the Scottish Tories are trying to force on the SNP of getting vaccine into arms as fast as possible after delivery and not holding any back doesn't work with this delivery schedule unless you push beyond 12 weeks between doses or use AZ for the second dose.    The Tories are welcome to push their policy right up to the point they declare the official data which shows the gaping hole in it to be confidential.

That's true.  But the consequence is that you get a long period where no first doses are being done while all your vaccine is going into second doses.  So if this is the plan why aren't the Tories telling us 'oh by the way, nobody else is going to get vaccinated for a couple of months while we catch up on second doses'.

In Scotland second doses are showing up on the graphs of vaccinations done so a fair number of people are actually getting 2nd dose of Pfizer within about 3 weeks and it is presumably coming from the big initial order.   This all makes sense - especially for health workers.

In England we get press stories of Hancock threatening GPs who use any vaccine supply for second doses that their supply will get cut off.  Even if they are using supply which would otherwise be wasted.

https://twitter.com/SandraToFriends/status/1350842324608278529/photo/1

Good news from Israel regarding Pfizer's efficacy following a single shot dose.

https://www.ft.com/content/4d9fe80d-e604-4bbe-b0f8-fd4b8df9b7f1

Some concerns from the BMA, about the gap, being reported today.

https://www.bbc.co.uk/news/uk-55777084

If 2nd doses aren't allowed in England, how comes each day's stats have some (even if it's only 1 or 2 thousand) - who exactly is getting them?

Can you summarise it as it's paywalled.

''A single shot of the BioNTech/Pfizer vaccine produces a robust antibody response within weeks, according to Israeli data that could help inform whether scarce global supplies can be stretched by delaying second doses.

At the Rambam Health Care Campus in northern Israel, 91 per cent of the 1,800 doctors and nurses that received the two dose vaccine showed a major presence of antibodies 21 days after their first shot, before receiving the second dose, according to Michael Halberthal, chief executive of the hospital. A further 2 per cent showed a moderate presence of antibodies.

“If 93 per cent had a major response three weeks after the first injection, this raises a good question, that you might rather be using the first injection on more people” said Dr Halberthal.

At the Sheba Medical Center, similar serological tests at different intervals showed at least 50 per cent of staff with a level of antibodies “above the cut-off point” two weeks after the first jab, said Arnon Afek, the associate director-general of the hospital chain.

The UK will soon have its own data showing efficacy after the first dose for the different vaccines currently in use and any policy changes should await more robust data.

Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine The data from the two hospitals is based on individual antibody responses to the vaccine and does not a provide definitive assessment of the efficacy of a single shot. BioNTech/Pfizer’s clinical trials were based on two shots, 21 days apart, and did not measure antibody response. Pfizer said it could not comment on independent studies.

However, the early findings are likely to encourage those scientists who have argued that the time between the first and second doses of Covid vaccines could be extended in order to stretch limited supplies.

“This goes to what’s been in dispute right now in the UK, whether to continue giving just a first dose, so that people receive certain levels of immunity or to go to the second,” said Mr Afek''

Scotland's Chief Medical Officer Gregor Smith has stressed the second dose will be 'as or more effective' when delivered 12 weeks after the first.

So... The Scottish Chief Medical Officer selected by Scottish Government is advocating this approach. What do Scottish Conservatives have to do with anything? 

The reality is that nobody has an effing clue because it’s not been tested and there is no data. It’s only a guess.

So we just have to work with it.

Responding to the criticism, Prof Van-Tam said: "What none of these (who ask reasonable questions) will tell me is: who on the at-risk list should suffer slower access to their first dose so that someone else who's already had one dose (and therefore most of the protection) can get a second?"

Still waiting for any of the "it's a gamble"ers to address that point.

That's a non-question, designed to play purely on emotions - the answer is very obviously "whoever's just a little bit further down the priority list", what else could it be?

The "(and therefore most of the protection)" is also speculation, and ignores the fact that protection is not one-dimensional. It's very good for at least a wee while after it's bedded in - but how long does it last? How quickly does it decay? How does it affect transmission (rather than just symptoms)? How will those who've had one dose be treated, with regards to risk exposure?

In happier news...

https://www.echo-news.co.uk/news/19023188.illegal-rave-pensioners-queuing-j...

'Illegal rave’ in Southend just pensioners queuing for jab

Not at all. You quite clearly have to deny someone a first dose to give it as a second dose. And that someone is at considerable risk. Would you be prepared to stand between those 2 people and choose who to jab?

This is one of the few things that isn't speculation; antibody titres we're measured in the trials.

It's not ignoring that at all. It's clearly saying some is better than none.

Yes, absolutely, if I was satisfied that the prioritisation was made on the back of rational, evidence-based conclusions - and someone who wouldn't be, should not be allowed to make the decision.

And you're already standing between those two, and the next person on the list!

Yes, that seems to be absolutely correct (and I said so above - "It's very good for at least a wee while after it's bedded in") - but protection is not one-dimensional. (I won't repeat what I wrote again, it's just above if you want to read it.)

For the individual, at the point that they have some protection, it is undoubtedly true that having that is better than having none. That may, or may not, translate to better protection for a population over a longer period of time - for example, it could result in more transmission of the disease, or a period of vulnerability where those with high exposure lose their protection.

I get that you think this is the right way to do the vaccines, in the UK, just now - and it may very well be. What I don't get is the absolute certainty you seem to have about this, while there are plenty of well-informed people expressing concerns (no, I don't mean on UKC!)

On a personal level - would I rather my parents (in their 90s) got their second dose, or me & wife (61&60) got our first dose.

I think I'd go with them getting 2nd dose.

There are lots of well informed and better experienced people far wider spread than UKC expressing concerns, but none of them has said anything that starts with "it would be better to do it the other way because...". The only counter argument to what were doing is 'it hasn't been tried'. Expressing concerns is fine but saying it's wrong to do what we're doing without presenting a better alternative doesn't help much. It just erodes confidence, which is actually the worst plan.

There just isn't a watertight population-level argument for sticking to the short dosing interval while supply is the limiting factor. If you can find one let me know.

In reply to geode:

He's right, on both counts. 

Giving a person 90-odd percent protection makes a far bigger difference to the nation's immunity than topping someone else's up by 5%.

Publishing articles in mainstream media that wrongly cast doubt on the worth of vaccines, based on flaky data and caveated with 'might', is at best irresponsible and the most efficient way a media outlet could sabotage our recovery. Notably they haven't signed up to IPSO...

The question is more likely should your parents get a second jab or should it be another couple in the same or marginally lower risk group? 

Unfortunately you are more than three weeks behind your parents in priority.

I reckon you are 20 million people or 10 weeks at 2M/week behind your parents in the schedule.

https://www.bbc.co.uk/news/health-55045639

3 weeks or 6M behind your parents are nominally Health and Social Care staff or age 75+.

Sorry, that just isn't true. I've read arguments that it risks leaving high-exposure people more vulnerable in the meantime, risks those being given their first dose missing their second due to supply problems, risks allowing greater transmission, or risks encouraging new variants emerging. I fear you're being selective in what you're paying attention to (although, we probably all are).

I can't see a watertight argument either way, it looks very much like we don't really know and are making a judgement call based on UK-specific information that, for whatever reason, is not being released. And, unlike you, I don't trust that to be entirely altruistic, or even just correct.

It may be that we're likely to face absolute catastrophe if we don't roll out the first doses so really are best just going for it, but they don't want to terrify people in the meantime; it may be more career-based, from people who prefer making the 'might be quite good, might be really awful' choice over the 'almost certainly fairly bad' one, so that they at least have a chance of being seen to have done well; it may be something else entirely. I don't think that it can be that it's certainly better regardless, or a lot more countries would be doing it.

Quite right.

Some well informed people have expressed concerns about delaying the second dose, but the best informed people, AKA the JCVI, are telling us it’s the best way forward and no one has offered any evidence to contradict this.

Clearly the delay to the second dose is the best way to maximise immunity in vulnerable groups and the recent data coming out of Israel is validating the fact that there are high levels of immunity, which is having a positive impact on hospital admissions, after the 1st dose.

Yes, I'm aware of these risks, but the argument doesn't stack up when the alternative is running higher case numbers. They're all just as bad or worse if you have more virus in circulation. In the short term they are all better mitigated by getting the numbers down.

We sort of agree here. But again, in the absence of a good counter-argument I'm still close to the fence but definitely off the fence on the side of getting behind a strategy.

You're already seeing the early discussions in other countries. I don't think we'll be out there alone for long. Issue is right now very few other countries are in the position to be thinking about second doses.

OK - that isn't a stance I'd argue with!

I had formed the impression that you were more certain than that, but I suppose that's the danger of posting on forums defending a point.

Maybe. I think there may be a fair bit of just waiting to see how the experiment pans out here, before deciding - there should be a lot more real-world data available in the coming weeks...

On a personal level I'd be more than happy with a single dose. It would easily tide me over until we find the first escape strain and have to start all over again.

What I am certain of is that prevention of severe disease/hospitalisation in 2n people is better than any level of protection from mild disease in n people, no matter how complete that might be. And that the shortest realistic time for the effect to fade without a booster is long enough to make it moot.

Preventing collapse of healthcare is the motivation for everything we're doing. If one dose takes that off the table then I'm sold.

The less certain part is that I don't think the intricacies matter too much, but as we get more data we'll know for sure, and that won't be long now. We'll probably know enough soon enough to pivot if necessary.

In reply to geode:

You mean a union who:

- have a vested interest in getting their members a second dose

- don’t have access to data about supply

- don’t have access to all the data about the efficacy of the vaccines 

- aren’t experts on immunisation 

Quick question for you: why don’t you trust the JCVI’s advice?

I understand the reasoning behind delaying the second dose and whether this is correct or not is way, way above my pay grade but... one thing that was hammered into us at university was that in clinical practice you only deviate from established procedures, protocols and treatments as a result of good quality, peer reviewed evidence. Evidence Based Practice was not just held up as gold standard, the era of medicine without EBP was regarded with the same disdain as leeches and and butter on burns.

That all went out of the window in March when they downgraded everyone's PPE based on "guidance" rather than good quality evidence. Delayed second dose seems more of the same. Maybe it's the right course of action, maybe not. What isn't in doubt is that over two decades of clinical orthodoxy has been flushed down the pan.

In reply to geode:

Potentially. Don't know. Haven't seen the letter. Have you? Don't know what they said that they might be wrong about. The headlines said "BMA calls for...". That's not a right/wrong statement.

It seemed to be written after the first lot of unpublished rumour came out of Israel, but before it was debunked by the knowledge that loads of people were infected in the few days after the jab and also before more data came out to contradict. Does that change anything? Not sure.

This has been very much on my mind.

With PPE, they 

- had established advice on what was needed

- didn't have enough supply to meet it

- downgraded the advice to meet the supply(!)

- left key staff inadequately protected

- told complainers to pipe down (to avoid undermining the strategy/to avoid sabotaging their careers, delete as applicable)

I do appreciate that the situations are not identical and that many of the people advising are different, but it's hard to not notice the pattern.

It's a question that a scientific adviser should not be asking.  

Imagine you have 100 people to get off a sinking ship and a lifeboat rated for 20.

It is for the scientific adviser to say 'that lifeboat is rated for twenty people, maybe you could get 25 but it is risky as f*ck, if you put in more than 30 it is going to sink for sure'.  That's their professional competence.  

The question of which 30 people get in the lifeboat is a political/ethical one.   That's what the politicians get the big bucks to make.

You're probably about right with the delay between me & my parents. Maybe the question I should have phrased was "if I had aunts/uncles that were in their 80's/70's, would I want them to get 1st dose before my parents got 2nd dose?"

As I posed it originally, it was as I said on a personal level, better to reduce their high risk further than reduce my moderate risk - whether that would be best on a societal level is a different question that nobody yet has the answer to.

Countries like the US and Germany have at least as good advice on this as England.   The WHO and the vaccine developer Pfizer also have some pretty good people.  It's arrogant to think the JCVI is the best available advice.  Yes, they are smart people but are they smarter than the US CDC. the WHO and Pfizer?   Pretty much every other country in the world is against pushing it out to 12 weeks.  And plenty of UK experts have concerns.

https://www.theguardian.com/world/2021/jan/24/vaccine-experts-on-uk-12-week...

This policy is about how badly f*cked England is and the last reasonable roll of the dice rather than there being no reasonable concerns about delaying the second dose.  The difference between England and the rest of the world who are being more cautious on dose spacing is the death rate.

The problem in Scotland is roughly half the size of that in England and it isn't clear to me we should be following England's policy.

The other issue is that monitoring the program as it goes as is being recommended by UK experts is not necessarily going to be a solution.   If you've already pushed all the vaccine you have available into arms as first doses and your vaccine supply allows for a second dose after 12 weeks you can't necessarily bring that forward very much when there is a shortage of vaccine.

That’s not a point, it is a question. One that is not really relevant.

If course there is limited supply which means we have to distribute the vaccine sequentially. Following your logic to its absurd conclusion we should give everybody 1/100th of a dose so that nobody is waiting. 

 

The question is simple: which is the most effective waiting time between doses to maximise immunity with the at-risk population in the shortest amount of time. There is no data allowing us to say whether 12 weeks is better or worse than 6 weeks.

I don’t know which it is. Even experts don’t agree. Every other country on earth has decided to follow manufacturer recommandation, the UK decided not to. This could be a bad thing or a good thing, but the fact is, it is clearly a gamble and politicians should be honest about it.

There is nothing wrong about taking a calculated gamble, one I don’t blame them for making, but they need to be honest and take responsibility if it doesn’t work, that is it.

It's absolutely relevant. 

There's a compelling argument for giving 1/2 a dose of the AZ stuff if you really want to stick to the data...

No, it isn’t. The objective is to reduce hospitalisations and deaths as fast as possible, not to inject a first dose to as many people as possible as fast as possible.

You are losing sight of the objective. 

Well if you look at the data the uncertainty range for protection after one half dose is basically huge. If you want to stick to the data your answer should be « I don’t know »

Have other countries (besides Israel) got to the point where they need to decide yet (for any significant number of vaccinations)? And if so, are any of them at near crisis like the UK where they might have to make such decisions?

Agreed.

It’s a public health issue as I see it.  

When injecting 1,000,000-2,000,000 per week if there is a problem in delaying second jab beyond week 3 you find out about it in week 4* (or the same week in which it occurs). If delaying the second jab is an experiment it is hundred times bigger than a clinical trial and it generates data a hundred times quicker and you don't need to wait 12 weeks before changing policy.

*presumably anybody admitted to hospital will be asked about vaccination so we will know about problems extremely quickly.

Bringing forward vaccination during a peak (now) has a greater benefit than giving that same person a first jab after the peak when the risk is mostly over (and some of the unvaccinated will contract Covid and not survive to then).

Right now the CDC is in a bad way, having had a lot of politicisation - as with many other agencies - under the Trump administration.

Its just as well PHE isn’t being shut down and reopened with a new name and a clearly political leader rather than a public health expert...

That is a good point, and one can only hope that they they would indeed change policy rapidly if the evidence suggested we needed to.

We would need to make sure the evidence is being collected though.

It is inconceivable that doctors in general would not notice the hospital admission of vaccinated people. It's also inconceivable they are not aggregating and monitoring the data nationwide to look for the impact of the vaccination.

It's far from inconceivable they could f*** up again despite good information.

How have you got there??!! One dose to many reduces hospitalisations much faster than two doses to half as many. That is one of the few things we do know for sure.

Nobody thinks that if you go beyond three weeks before your second dose the partial immunity you got from the first dose suddenly goes to zero. 

It's more about how effective the second dose is at producing long term immunity if the delay between first and second doses is too long and it will take a lot longer to evaluate that.

Also, if you wanted to find out about infections immediately (rather than after symptoms develop and they get in contact with the NHS) you'd need to be giving people Covid tests every day.   Presumably they do have studies running where they are testing people who have had the jab every day but the numbers in those studies are going to be far smaller than the numbers being injected.

In reply to geode:

No, that one's a definite. We know vaccination is more effective than not vaccination in keeping people out of hospital.

No need for extra or daily testing. If hospital admissions amongst those vaccinated decline after single vaccination the vaccine is working. If that is maintained in week 4 then this confirms you can delay 2nd jab until at least 4 weeks for those vaccinated in weeks 2,3,4.

If reduced hospital admissions is maintained in week 5 then this confirms you can delay 2nd until at least 5 weeks for those vaccinated in weeks 2,3,4,5.

etc etc etc

If reduced hospital admissions is maintained in week 12 then this confirms you can delay 2nd jab until at least 12 weeks for those vaccinated in weeks 2,3,4,5,6,7,8,9,10,11,12.

If reduced hospital admissions is NOT maintained in week X then this confirms you can delay 2nd jab only X-1 weeks. Hence in week X+1 you need to consider switch to doing 2nd jabs.

Thread:

I'm seriously impressed with the rate of vaccination. Thankfully I was wrong to expect it to be screwed up, probably because the government has let those who know how to do it, do it, rather than phone sales executives . Hope supplies hold up.

It's fantastic. John Snow of Ch4 News filmed his vaccination. It's quite moving to see the joy and relief of those getting vaccinated and doing the vaccination.

In reply to geode:

How so. There have been trials involving 10s of thousands of people.showing just this.

In reply to geode:

You were just disputing it!

In reply to geode:

I'm not sure of myself. I'm sure of what is known for sure.

In reply to geode:

Lots of things aren't known, but some are. 

In reply to geode:

I'm pretty sure you're an alias for one of our regulars if that's what you mean...?

I think this abomination puts things into grim relief

https://www.theguardian.com/world/2021/jan/03/palestinians-excluded-from-is...

I thought that occupying powers had humanitarian obligations under international law?

Isn't this the same as if the powers occupying Germany after WW2 had fed their own troops garrisoned in Berlin and not bothered with an airlift?

In reply to geode:

You registered on 4th Dec. Well after Coel/pmp departed...

I think they likely named their original ego as a way of throwing people of the scent.

Its not Coel, he’s still here I reckon.  Created his new account the week before deliberately getting himself banned to martyr himself.

No, definitely not.

Interesting. Still posting?  I'll keep a keep en eye out!

In reply to geode:

Lucky you. But that's nothing to do with sock puppet accounts

Even if immunity did suddenly go to zero in week 4 did you wouldn't know that had happened by looking at hospital admissions in week 4.   New infections in week 4 aren't going to show up as a spike in hospital admissions until week 5 or 6.

Also, *nobody* thinks the level of protection from the first dose is going to fall precipitously in week 4.    Since there is a delay between getting the jab and it taking effect even if you got your second dose in week 3 any immunity in week 4 is presumably mainly from the first dose.

If we wait until week 12 before handing out second doses and second doses at week 12 are not effective at creating long term immunity we are not going to know that until some time after week 12.

Which all suggests you can pick up early precursors  (eg weeks 4 & 5 for your example) of anything calamitous (eg weeks 5 & 6 in your example) as individual immune systems etc vary.

I don't dispute this.

It's basically  a decision between the certainty of many dying due to being unvaccinated if we stick to 3 weeks or a uncertain but probably small reduction if vaccine effectiveness if a second dose is delayed, which could be rectified.  Given the situation, it doesn't seem a hard choice to me.  The British Society for Immunology have this

https://www.immunology.org/policy-and-public-affairs/briefings-and-position...

Good find

In reply to geode:

The mask is slipping!

Do we know how much more capacity there is to be rolled out in the vaccination. 480,000 vaccinations given yesterday, but I get the impression that there are more centres to open. In nine weeks when we will have to start stepping up the second jabs significantly, we have 40m+ first vaccinations done.

We don't, I guess, or the supply limits (although these are looking dubious).  2nd doses to those done or stick with one dose for more??

Good find.

The modelling data that’s referenced in the article is also really useful.

https://www.medrxiv.org/content/10.1101/2020.12.24.20248822v1.full-text
 

Things are looking quite bright by April/ May.

There is one scenario where things look awful by then.

It's the scenario where absolute idiots start clamouring for an immediate and wide-ranging removal of restrictions as vaccinations kick in and reduce hospitalisations, "to save the economy"

If we do that, the new SA variant, which appears to have little cross-immunity with older variants, will start to double on a sub 10-day timescale and will be almost impossible to detect and eradicate against the background noise of general cases running hot.  Then, before you know it, we'll be back to having healthcare overload due to a pandemic that's out of control, and the Oxford/AstroZeneca platform will have been "burnt" as people are now immune to the carrier virus.  Rather than saving the economy, this sends it in to more crippling lockdowns.

So, let's hope people have learnt their lessons over the last year.

You'll have to get up early in the morning to catch them out.

Still posting I think. Most recently having a special moment about BLM, Trump and how there's no racism in policing in the USA.  I assume this is some sort of over reaction to their departments Athena Swan or JUNO process; the kind of radicalisation Jonathan Pie prophesied.  

No, we don’t. It’s not been tested beyond the planned interval between dose 1 and 2 afaik (3 weeks). 

If you think we know, show me the data, happy to be corrected.

Well I am not aware of any coordinated effort to collect post vaccination data in a systematic and rapid fashion, maybe there is one, I just can’t find any.

Really? I only read the first bits and then looked at the tables & graphs but the overall impression I got was that (even with Tier 4 and 2m vaccinations/week) the peaks in most regions were going to happen later than I had expected; i.e. in quarter 2 of 2021 rather than in quarter 1.

The timing around opening up is a very difficult political decision that’s going to have to be made at some point.

I suspect public opinion will force an opening up of society once people feel that granny and grandad are safe and hospital capacity comes down.

The SA variant is a real worry, but there’s not a lot we can do really. Even if we shut our borders and did manage to contract trace all of the current UK cases, Southern Europe will reopen to tourism this summer and the SA variant will spread over there. We will continue to import food from Europe and in time it will spread here again.

Edit: If the DM are doing their political flying the kite right it looks like we will be closing our border. This should help a lot of course.

Hopefully if the SA variant has the same transmissibility as the old Covid strain and vaccine efficacy is only reduced by 30%ish, we should still be able to get close to herd immunity by high vaccine uptake, the Pfizer vaccine preventing spread, and minimal other measures in place (hands, face, space).

Herd immunity ? We don’t even know if the vaccines prevent transmission enough to make herd immunity possible.

I Where did you get that number from?  A reference or your imagination?

Some posters will advocate vociferously for it, I am sure.

We tighten control measures locally around any transmission zones to keep national cases below 1,000 a day with a highly responsive contact tracing system and don’t allow it to get out of control.

Do you have a basis for this or are you just pulling it out of your a... imagination?

Hence the word “hopefully” at the start of the sentence (I think there is some promising Israeli data on this though).

The new Covid variants are such an unknown at this point. 

mattmurphy has previously tested immunity theories by licking his brother [1] and whilst I can’t immediately find it, I think they advocated for getting covid as many times as possible to build a strong immunity.  

I struggle to tell if they’re a bad actor in this or just out of their depth.

[1] https://www.ukhillwalking.com/forums/off_belay/herd_immunity-725369?v=1#x92951...

"Published efficacy between dose 1 and 2 of the Pfizer vaccine was 52.4% (95% confidence interval (CI) 29.5 to 68.4%). Based on the timing of cases accrued in the phase 3 study, most of the vaccine failures in the period between doses occurred shortly after vaccination, suggesting that short-term protection from dose 1 is very high from day 10 after vaccination. Using data for those cases observed between day 15 and 21, efficacy against symptomatic COVID-19 was estimated at 89% (95% CI 52 to 97%).

The level of protection gained from a single dose of the AstraZeneca vaccine was assessed in an exploratory analysis. Vaccine efficacy from 22 days post dose 1 was 73% (95% CI 48.79 to 85.76). High protection against hospitalisation was seen from 21 days after dose 1 until 2 weeks after the second dose, suggesting that a single dose of the AstraZeneca vaccine will provide high short-term protection against severe disease. "

So one dose is closer to the efficacy of two doses than it is to that of zero doses. So hospitalisations come down quicker with twice as many singles. 

It was a figure Matt Hancock bandied about. I’ve no idea how accurate it might be.

Posters on UKC matter very little. The general public matters a lot. Their ideas about what’s the preferable course of events differ greatly from your own (there’s a link to a mumsnet post knocking about - it probably gives you a better idea about what the average women on the street thinks than UKC).

Easy(ish) to do in the summer, much harder to do next winter. People are also going to suffer fatigue. Compliance will drop, especially if cases are low. We can’t monitor people like China does.

https://publications.parliament.uk/pa/ld201719/ldselect/ldeucom/129/129.pdf
30% of our food comes from Europe. We can’t feed the country without it. It comes in lorries if you weren’t aware, and those lorries are driven by people (who can spread Covid).

Ultimately if the SA variant can evade the vaccine we’re going to need a new vaccine and additional production capacity ASAP.

I’m aware that a lot of freight is unaccompanied.  I’m aware that the remaining small fraction could be shunted on to and off ferry’s at either end, as is being done on Gurnsey and NZ right now I believe to avoid the lorry driver issue.

This stuff isn’t rocket science, and there’s plenty of time to fix it, but you’re always looking for every reason we can’t, it seems.

 Look at the rate of variant production.  Rising.  Lethality: Rising.  Transmissibility: Rising.  Cross-immunity: Falling.

 The only way to win this game is not to play it.

The watertight borders tactic buys time but it's not an endgame. They unfortunately never quite are. As we've seen in HK, NZ, China, even recently Guernsey eradication is fragile and it's definitely not a permanent solution. That's not too say we shouldn't try to cut down the number of times bad things are seeded, but we need a better playbook. Not least because we'll uncover escape variants everywhere that vaccinates, since when you wipe out the susceptible strains, what's left?

Therapeutics and adaptable vaccines are going to have to be the future.

I agree, but buying time is one of the most important thing we can do right now.  

Yet, in each of those places, the quality of life, the economic disruption, the disruption to the education of children etc has been less than in the places that didn't do it.  That alone is worth it IMO.  

Eradication is only really possible if it's global - and I fear this virus will drive global division rather than be subject to global eradication. 

They are, but neither are there yet.  

• Repurposing existing compounds through a crash priority set of trials has given therapeutics a boost, but the "breakthrough" gains that stop this virus from being able to overwhelm healthcare will come from understanding how the virus mucks up immune responses and designing new approaches to target that.  This is going to take a lot more time than throwing existing compounds at patients and seeing what helps.   So, we have to make that time.
• Vaccines - you raised the immunity to carrier virus problem on another thread; it's clear the synthetic vesicles + mRNA ones don't have this problem, but it also seems clear more time is needed to be able to scale them sufficiently.  So, we have to make that time.

We have to get to the endgame intact.  Every country you listed has proved that watertight borders and local eradication minimise the following:

• Damage to the economy
• The number of people killed
• The number of people with life limiting health damage
• The number of medical workers killed
• The number of medical workers with PTSD
• The education of children and young adults
• The net total curtailment of individual liberty

Just because it's not the solution does not mean it's not the best way of treading water to allow us to work on the solution.  I don't think we need to go for eradication or "zero covid" but for a low level of covid so that we can't be blindsided by new variants taking us to crisis point again. 

Mattmurphy thinks we shouldn't try because he can't conceive of a way to stop lorry drivers spreading it in from Southern Europe.  Myself, I prefer to think that a species who can put people at the bottom of the ocean and on the moon can solve a problem like how to move lettuces around without spreading a virus

I fully agree with all of that

You need to re-read carefully: none of the figures you have posted show what happens after week 3 with only one dose, which is what I have been asking you for, and what is relevant  to the question of extending to 12 weeks.

Hint: you won’t find it because it does not exist.

It doesn't alter anything regarding "One dose to many reduces hospitalisations much faster than two doses to half as many. That is one of the few things we do know for sure."

Now you're just changing what it is you were arguing about.

It's a fantastic solution if everywhere aims for elimination.  You can only import cases from places that have the virus, so if everywhere eliminates then that source of importation disappears.

That's the one future out of all the possibles that I would confidently bet against coming true.

So disingenuous. You know full well that we were talking in the context of a 12 weeks extended delay between 1st and second dose. That’s what was being discussed and you know this, and when I asked you for this data I was specific:

 « No, we don’t. It’s not been tested beyond the planned interval between dose 1 and 2 afaik (3 weeks). »

Since you are now starting to engage in intellectual dishonesty instead of simply admitting you don’t have the data you claimed to have, I think I’ll leave it there.

Let's have a good old recap:

Me:

.....

everyone has an occassional lapse into wishful thinking.

You know the evidence is against that.... multiple observational studies (admittedly, although actions might have been random and blinded, I don't think that counts as a designed study but the reproducibility of the outcome is convincing) have failed to show that. If we are working on objective evidence no lessons will have been learnt.

I was just winding myself up for a long post about this but, fortunately for all of us, I don't need to bother.  The BSI statement is pretty much exactly what I was going to say.

Not that I'm surprised, I only let my membership lapse last year when I finally accepted it had been quite a long time since I could describe myself as a professional immunologist, but my long-term memory and anamnestic responses remain.  

Edit: to get my words in the right order!

I'm not a medical professional, but I think that's a well written piece that sums up the reasons (and necessary actions alongside it) well and I completely agree with it.

Your « recap » contradicts your own claim...

Now you are telling us a vaccine protocol with an effectiveness of zero would reduce hospitalisations.

You have reached peak absurdity I think.

You're gonna have to explain that one

No, I'm not. Can you actually read?

You can see in your "recap" that I was quite clear about the data I wanted you to present to support your claim:

"There is no data allowing us to say whether 12 weeks is better or worse than 6 weeks"

"It’s not been tested beyond the planned interval between dose 1 and 2 afaik (3 weeks). If you think we know, show me the data, happy to be corrected."

I am still waiting for this mythical data.

Quote : "if effectiveness drops to zero on day 22, you still reduce hospitalisations faster"

Do I really need to explain why a vaccination protocol that brings effectiveness to zero will not reduce hospitalisations ?

It's mythical. I'm not sure why you're asking for it or where, as you suggest, I claimed to have it.
What I did say is that it's irrelevant.

It's often important to read whole sentences. I see you struggle with that.
 

There are a few of us who have discussions like this with Alyson and his previous Alias,Rom. Best advice is just to ignore and not take it any further after a few posts. Everybody who regularly posts will understand 

More good news.

Israel Data shows a 60% reduction in over 60's cases following a single dose of the Pfizer Vaccine.

https://twitter.com/segal_eran/status/1352696337477890049


Canadian researchers find Antibodies last for months, if not years.

https://globalnews.ca/news/7589668/canadian-researchers-coronavirus-antibod...

Let's keep the good news coming!

Appreciate your concern; yeah I know. Been round before.
This one should fizzle out soon.

The reason I was asking for it is because it is needed to evidence your claim.
Thanks for finally admitting after many roundabouts that it doesn’t exist.

It took you a while to admit the bleeding obvious. I don’t get why it was that hard.

I have read the whole sentence, you are clearly stating black on white that a vaccine protocol with zero effectiveness after 21 days would reduce hospitalisations faster...

if that is not what you meant, clarify it, instead of accusing your interlocutor of misreading.

Think you're confusing him with Pan Ron, the guy whose one and only opinion is that everything is the fault of THE LEFT. Especially anything that the far right does. 

No, it isn't.

You clearly haven't then. There's an important bit that precedes that.

"One dose to many reduces hospitalisations much faster than two doses to half as many. That is one of the few things we do know for sure." is the point under debate, no?

200 people given even short-lived immunity brings down hospitalisations faster than 100 people given immunity. How are you struggling with that?

Ah f*ck it, neil was right. You know what, sure. The sky is red and the earth is flat.

I admit to having a disproportionate aversion to bullshit. It always served me well though.

Yes. 

That is why I have asked you to produce evidence of that it is the case.

I am really puzzled as to how you are NOT struggling with that.
Everything else being equal, if you vaccinate 200 people and their immunity expires, why would you see a reduced number of hospitalisation in that group over that of a group of 100 people with immunity ?
At best, hospitalisations in the 200 group would be delayed, but not reduced.
 

I did. I gave you the evidence that one dose is a shitload more effective than no doses.

Again: "One dose to many reduces hospitalisations much faster than two doses to half as many. That is one of the few things we do know for sure.".

Reduced. Because the halving time of case numbers is shorter than immunity lasts. So by the time it wears off there's less than half the chance of ending up in hospital. So fewer people end up in hospital. F&ck me. Is that clear enough or do you want it in skywriting?

No, you gave you the evidence that one dose is a shitload more effective than no doses before the 2nd dose in the trial is administered.

The whole crux of the argument is whether it is true beyond that period. That is the evidential gap that I pointed to (and so have BMA and the WHO)

It is clear now.

I can see that you are trying to save your argument by adding a key assumption. 
The assumption is that during the vaccination campaign we are in a period of case reduction that is sufficiently fast and can be maintained, as such even short-term immunity provides a benefit.

In that case, yes, that would a logically viable argument.

Obviously you hadn't mentioned this assumption in the first place, and it is also moot: if we could maintain a fast case reduction over time we wouldn't be having a need for vaccines in the first place...

I did wonder about that, but I'm pretty sure this is CH and not PR.  There's so many people prating about under false and multiple accounts that it's getting silly.

I did make the fantastical and off-piste assumption from the start that we were talking about reality, not some random alternative universe.

I don’t know in which alternative universe you live, but in mine I have no crystal ball telling me what the halving rate of the pandemic will be in the future - beyond the next few days.

We keep doing the yo-yo with it, so if history is any guide, the pandemic will start growing as soon as we lift restrictions. There is no reason to think that the current halving times will keep as they are forever. I suggest you refer to the excellent Friday COVID plotting Wintertree posts for context...

Sure.
You get yourself a pencil and work out what scenario, in terms of halving/doubling time and efficacy after 21 days, would mean it's better to do two doses to half as many. Then come back here and start and argument that that's what you meant all along.

You are the one who made this claim, and you are the one who modified it. All I have asked is that you provide evidence for it. The onus is you, not me.

No you modified it

No, I have not, you are the one who has added an halving times assumption.

Notwithstanding that , "One dose to many reduces hospitalisations much faster than two doses to half as many" is your claim, not mine.

I have never said it was wrong, I am not seeking to disprove it in any way.
I have simply asked you the evidence for it. The onus is on you to provide it.

I haven't added any assumptions. You threw a tantrum when I referred to the reality clause.

What is the reality clause again ? The one where you pretend to be able to predict halving rates of the pandemic in the future ? Or something else ? Be specific.

The one where I've been talking about the world we live in all along.

Specifically ? What was it ?

Whilst not wishing to take sides here, I would like to see a mathematical model that demonstrates which is more effective at keeping people out of hospital.

I started to play around simplistically in Excel and realised that it's actually more complicated than it initially seems; relying on various assumptions. So whether 3 or 12 week gap is more effective will almost certainly depend on what those assumptions are - in which case what are those assumption "tipping points" and where are we at the moment relative to them.

Now of course I may be wrong and there may be a simplistic model that I've missed that demonstrates this one way or the other - in which case I'd be very happy to see that model.

You are absolutely right, it's pretty complex and depends on a lot of assumptions, many of which we don't have sufficient data for anyway.

Hence why I am very suspicious of any claim of certainty on the matter...

2x > y when x (single dose efficacy) likely to be greater than 0.5 and y (two dose efficacy) less than 1.

Yes, but if the result is that the second dose isn't effective at producing long term immunity then all you have done is half-vaccinated someone and kicked the ball down the road.   Maybe you will need to retrieve the situation with a third dose at an appropriate interval after the second.

"second dose isn't effective at producing long term immunity" - has this been shown to be an issue for any previous vaccine or is it that the immune system doesn't work that way?

"kicked the ball down the road" - at the peak of infections this is useful

"Maybe you will need to retrieve the situation with a third dose at an appropriate interval after the second" - has this ever been necessary or is it that the immune system doesn't work that way?

So what? Fewer people die in the meantime and we.get.out sooner.

If only it was that simple - I don't believe it is. For a start, that's just considering those that have been vaccinated and ignoring those that haven't yet been.

You'd have to make assumptions - here are some:

1. Vaccine is immediately effective to x% after 1 shot and y% after 2 shots.

2. Proportion of people getting ill enough to be hospitalised in the un-vaccinated stays constant at z% day - or maybe it gradually decreases making the modelling more complicated (but obviously the unvaccinated population size goes down every day), and the number of people getting vaccinated/day is W. So on day 22 (the first that will be different) the 3 & 12 week daily amounts going to hospital (ignoring the delay before they get ill enough to get there) are: 

(population - W*22)*z + W*21*z*(1-x) + W*1*z*(1-y)      v     (population - W*22)*z + W*22*z*(1-x)

etc, until end of week 6, then 2nd batch of 3-weekers starts.

Now I'm sure what I've said above is full of errors (it's just a quick illustration of the possible complexities), but I would be gobsmacked if the real problem over a 24 week cycle reduced down to 2x > y.

Of course it doesn't! But as a conceptual illustration of the issue, it's pretty good.

The basic question is, clinically, does it actually make very much difference in the long term between receiving your booster second inoculation at 3 weeks, 6 weeks or 12 weeks?

1. There are some data from people in the clinical trials who, for various reasons, received there second shot late - I think out to 26 weeks from memory.  
2. The 3 weeks' gap is itself a fairly arbitrary choice, basically the shortest sensible gap, I'd guess because, for fairly obvious reasons, everyone was in a bit of a hurry to get to a usable end-point for the trials.
3. Nobody believes there is likely to be any sudden cliff-edge reduction in the primary response rendering the secondary response ineffective.  This is based on the experience of lots of people with loads of experience of administering antigens to humans and animals in various ways (orally, nasally, subcutaneously, intradermally, intramuscularly, intraperitoneally, intravenously; by scarification, with or without a variety of adjuvants, excipients, lipid nanoparticles; soluble antigens, precipitated antigens, protein antigens, carbohydrate antigens, with or without haptens, nucleic acid-encoded antigens, live viruses, killed viruses, attenuated viruses, subunit vaccines.  People even use similar techniques to generate the opposite of vaccines - they try to tolerise patients to things they shouldn't be reacting to.  

So, you're right in that there are some uncertainties with the approach of extending the time between shots, but there's no mystic significance to 3 weeks or 4 weeks or 6 weeks.  Even if there were, even if there was a complete drop-off after, say, 8 weeks, and even if those people never got a second shot as a population we might still be better off having twice as many people with temporary immunity during the height of the crisis than half as many with long term immunity stretching long into a period when there is no circulating virus.  Not desirable, not recommended and not going to happen, but in desperate times sometimes you just have to deal with what's happening right now.

Personally, I'd be quite surprised if, even after one one shot, there wasn't a clear rapid anamnestic response in most people to a challenge (either a second shot or exposure to the virus) in a year's time.  Not maybe enough to prevent some symptoms, but enough to prevent serious illness in most cases.  Not suggesting it as a population-wide experiment, but memory cells are real, even if there are zero circulating antibodies. 

I presume longitudinal data on detected infections and hospitalisations is being recorded and evaluated continuously as a priority.  Given the expert views, the sheer number of people being vaccinated, the bonkers levels of infections right now and presuming real time surveillance of the outcomes, we will very rapidly determine the efficacy of this approach to a far higher degree of certainty than the clinical trials, which had really quite low numbers of people being infected with Covid in the vaccine arm, thus limiting the confidence intervals on their findings.

If this isn't working, we'll know soon enough and can change the plan.   If it is working, the information so gleaned could save a lot of lives in a lot of other countries that could soon be staring down the same abyss as the UK.

Some times you have to roll the hard six.  I'm ******* grateful that I'm not the person looking at the different scenarios and making the decisions.    

I've said it before, and I'll say it again.  The effect of an efficient procurement round and of pouring resources into existing national, regional and local public health infrastructure has achieved something phenomenal with the vaccine roll out - and it's still ramping up.  

Perhaps we should do the same for a rebooted test and trace.

A point that often springs to my mind when people state that "There's no evidence the vaccine reduces transmission" in a way that implies it won't.  Their statement is true, because the trials were not scoped to capture that information for obvious reasons of expediency and difficulty.  However, the experience of vaccinating people against myriad different diseases over the years does have a lot to say on the general subject...  As does a bit of first order thinking applied to the whole business about what vaccines do and how they work.

I had to look that one up.

This is perfectly correct however I do think one should plan in the expectation that the vaccine will not reduce transmission.

IMHO we should plan pretty much as if the vaccine would not work at all. Now we are betting everything on the vaccine working as we expect it to but it may well not.
We should shoot for eradication with known methods, and if vaccines work it will be a great bonus.

Problem is that when you say that we should aim for eradication you are immediately branded “paranoid” or “pessimistic”...

What's the problem with that *if* it's the case? We have a very pressing problem here, kicking it away down the road is probably good enough for now.

Jk

thanks for this.

I agree with everything you have said, my only point is that there are  no certainties here just good guesses, and there are undoubtedly risks to any untested strategy.

A lot of this stuff is informed guesswork and involve weighting risks, and that is fine, but the gov needs to be honest and say it is, and  take responsibility if it fails.

Instead they have a tendency to present things a scientific certainty, not publish their working and silence any criticism or question as “undermining the vaccination effort”

You could try to include a decay function for immunity.

But that’s only the start of the problems... You’d need to take into account how immunity with one dose works in elderly people - which are your priority group, then you’d need to understand if a 12 weeks delay will reduce (or increase) the booster effect of the second dose.

Not much data on all of that...

Well after doing a bit more Excel playing I'm a bit stunned and must apologise to "elsewhere" and maybe others.

Assuming that the %age of people that get hospitalised is a constant proportion over time of the unvaccinated population (and a lower constant %age for people vaccinated with 1 shot & even lower with 2 shots) then 12 weeks ALWAYS produces less hospitalisation than 3 weeks as long as the 2nd shot protection is less than twice as good as 1st shot. So if 1st shot is 60% effective and 2nd shot is 90% effective then 12 better than 3. If 1st is 40% and 2nd 90% then 3 better than 12. The break even point is when 2nd is twice as effective as 1st - hence the 2x > y appears to be spot on.

With some "realistic" figures; population 50,000,000, vaccinations/week 3,000,000, 1st shot 60% effective, 2nd shot 90% effective, 0.05% of population/week need hospitalisation (starts at 25,000), then after 24 weeks 12 weeks results in approx 24,000 fewer hospitalisation (379k rather than 403k).

Factors that affect things; higher %age hospitalisation makes 12 weeks relatively better, more vaccinations makes 12 weeks relatively better (the obvious one), smaller gaps between 1st and 2nd shot effectiveness makes 12 weeks relatively better (another obvious one). Overall population size doesn't make any difference as long as some are unvaccinated after 24 weeks.

Edit: Just realised I've assumed that protection remains constant (once you've had 1st & once you've had 2nd shots) over the 24 weeks, oh and I assumed number of vaccinations remains constant.

Extra bit - weekly decay in %age that need hospitalisation - decreases the "advantage" of 12 weeks over 3 weeks.

And if the prevalence %age is rising, the advantage increases.

Edit: if the 1st shot effectiveness only lasts 3 weeks (and 2nd shot is ok until end of 24 weeks) then 12 weeks gap is NOT better than 3 weeks gap.

You don't half talk shit. No one is talking about certainty.  Whitty, while standing next to the PM:

'"Prof Whitty, pressed on whether the delay could give the virus time to mutate and work against the protection afforded by the first jab, added the decision to delay the second vaccine doses was based on "a balance of risk".

"I think most people would agree that the risk that was identified was a relatively much smaller risk than the risk of not having people vaccinated, which essentially was the alternative," he added.''

I suggest you read properly. The question was on the risk of mutations. Different issue.

In any case it’s all very nice talk but they aren’t publishing their analysis either...

That’s governments for you.  Scientists are comfortable with p values and confidence intervals.  To be fair, governments are often required to present certainties or very absolute choices.  You (and I) might want to the know the facts.  At the very least, even if we don’t understand the details, we want to be convinced that the people in charge do.  Many people, if they are honest, just want to be told everything is going to be ok.

Well I know someone in SPI-M. she is very tight lipped about what is going on as they have strict confidentiality instructions, however I do get the occasional « insight »,  and it usually is along the lines of « a lot more things can go wrong than you may be led to think »

To be fair I think this whole discussion around effectiveness at 3 or 12 weeks is a bit of a sideshow, the big elephant in the room I see is whether the Astra vaccine, which is the one we’re putting in millions of arms right now, will actually work.
People don’t realise how little data there is especially in the older age groups. I wouldn’t be surprised if there are disappointments...

Re 3 v 12 - I think you may be right, my noddy modelling showed about 6% reduction in hospitalisation - and whilst that's a big deal for that 6% it's not a game changer.

I am not sure how I could be right though, I made it clear that I have no clue as to which is interval is best....

I for one am shocked to find out that the government have been downplaying the risks of this pandemic from the start.

Shocked, I tell you.

In reply to Dave Garnett:

Nail on the head.  The government messaging isn’t targeted at thee or me.  I’ve found the last year very uncomfortable as I try and second guess the data and implications behind the messaging.  I’m very grateful that we have as much openness in government as we do - SAGE and NERVTAG minutes online and open access, and the data dashboard (without that and it’s API I’d have to find a new hobby for Friday nights).  We don’t see the lobbying that goes on behind closed doors, which is a significant part I think of the equation.  Now more than ever I think lobbying organisations and lobbyists should be required to be listed on a central register, along with all ministerial interactions,

It's a problem if - as looks to be the case - vaccine supply is the limiting factor.  You are using the limited supply less efficiently.   You pay for giving some people 3 doses by not being able to give someone later in the queue their first dose when they should have got it.  

I meant you may right about 3 v 12 being a bit of a sideshow.

Ha yes, well probably true, especially we don’t even know if this thing really works as we want it to in the first place anyway... a lot of uncertainty.

Efficacy tells you none of that as it's based on only about 100 people getting Covid. That was true for all the approved vaccines because as soon as they had the required statistical significance they went for approval. 100 cases in unvaccinated control group vs 10 cases in vaccinated group is enough to tell you the vaccine works on average over a few months from start of trial.

Spreading out the Covid cases over the few months of the trial, after a while you might be able to say "In the nth week after an individual's first jab, ten people got Covid and zero or one of them had been vaccinated".

10 vs 0 or 1 is not enough to say how good the vaccine is that week after vaccination. 

Anyway, simple maths 2x > y is enough when you only have such simple information.

Earlier this week data from Israel about the impact of mass vaccination in the general population came out. UK data can't be far behind. That could be politically tricky if it detects two jabs per individual better than one jab per individual even if one jab each for two people saves more lives.

Agreed, my noddy model basically showed me that 2x > y was "valid" and also how altering some values/assumptions might affect things. Of course it was making so many assumptions about things that we really don't know in enough detail yet that it's not really of any use beyond that.

Except that it does give "ball-park" figures - and what stood out for me was that we've still got over 100,000 hospitalisations to go, more likely to be 200k & quite likely 300k or 400k - however you look at it, that's a lot.

I really hope you are wrong there but looking back to spring summer I think we can expect 100,000+ in the decay (we are past the peak but the peak was higher). 

date            daily    cumulative
06-04-2020    3,046    42,200 (peak daily admissions)
22-08-2020    72        134,652 (low daily admissions)

https://coronavirus.data.gov.uk/details/healthcare

However Israeli data suggests vaccination works.

"~60% reduction in infections among 60+ years old 13-23 days after first dose"

https://www.ukhillwalking.com/forums/off_belay/delaying_the_second_vaccine_dos...

Hospitalisation is 5 days (average) after symptoms and 10 days (average) after infection. Hopefully they'll find (this week!) that vaccination offers greater than 60% protection against hospitalisation as seemed to be the case during the trials.

Actually if you look at the same guy on twitter then you will be cheered up!

https://twitter.com/segal_eran/status/1353811878208745473

https://twitter.com/segal_eran

Delicate question - did you say you are Jewish at some point and if so, can you read the Hebrew on the graphs?

Supply is only limited in the short run. Longer run we can make as much as we want. Anyway I don't see any cause to suspect we're talking about first dose efficiency rolling off significantly within weeks, more that it's not very well defined. Our current crisis should be passed and prevalence low again within a couple of months, if we need to start some people's vaccination again then it's not the end of the world. I suspect we're into a rolling program of vaccination anyway for a few years. While until global prevalence remains high we'll be working fast to keep pace with evolution.

It's not obvious what the right answer is here, the data isn't great, the objective differs slightly with perspective and the situation is evolving but it is not at all obvious we've chosen the wrong option even if it ultimately yields higher costs and greater delays in vaccinating the lower risk population that may still be preferable if it gets us out of winter on our knees at least.

jk

Yes, I am Jewish, the Hebrew on there isn't vowelized so it stops me (having said that although I can read vowelized Hebrew I understand very little, I only really learnt that as a child for synagogue; never got very far learning it as a language - and too many in Israel just answer you back in English 😁) - I've used Google translate on the Israel dashboard - https://datadashboard.health.gov.il/COVID-19/general - the funniest bit (sic) is the translation of the total number of deaths to "Cumulative get rid of". The translate misses graph axis labelling but it's pretty understandable.

Edit: I usually open it from Chrome, just done it from Edge so presumably Bing translate (or whatever) - gets it right with "Cumulative deceased".

Thanks. That Google translate is a tad insensitive!

I guess the results from Israel will be in the UK news pretty quick.

Thanks for that. I’ll keep an eye on it.

We should hopefully see the number of severe cases dropping quite dramatically within the next few weeks if the 1st doses are effective, given the very high proportion of the older population vaccinated earlier in the month.

Very, very, good news : https://www.timesofisrael.com/vaccine-found-92-effective-in-israel-in-first...