The finance minister for Canada’s most populous province has resigned after going on a Caribbean vacation during the pandemic and apparently trying to hide the fact by sending social media posts showing him in a sweater before a fireplace.
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Quote:
Originally Posted by Aimless
Unknown.
The data shows it to be highly efficacious from 10 days after injection until the second one is given so far. There seems to be little reason to believe protection will overnight drop from highly efficacious to completely ineffective in the extra 9 weeks proposed. But it will be completely ineffective for those not given a vaccine if they aren't given one.
The reality is we are talking a marginal increase in communal efficacy for half as many people - or a massive increase in communal efficacy spread across twice as many people.
The NHS and the vaccine rollout is about what is best for the community, not just the individual.
Between the first dose and the second dose—administered with a 21 day interval—the efficacy at group level was estimated at 52% compared to placebo. It's not "highly efficacious", and it's not "overnight". During this period of inadequate protection, the UK will have extremely widespread community transmission—perhaps entailing a higher baseline risk than was seen in the study. The evidence does not support delaying the second dose for an additional 9 weeks, and certainly does not seem to support doing so for the most vulnerable groups. You cannot speculate about the extent and duration of protection at the community level with the proposed strategy on the basis of this data. The modeling that has been conducted to justify the decision has not undergone external scrutiny, and might be sensitive to unforeseen developments wrt eg. the spread of the new lineage.Quote:
Originally Posted by RandBlade
Saying that something is about "the greater good" doesn't magically justify a questionable decision-making process.Quote:
The NHS and the vaccine rollout is about what is best for the community, not just the individual.
Not entirely true. The data shows that there is negligible protection on the day you get the injection or the days after it, but that is not the case from about day 10 onwards.Quote:
Originally Posted by Aimless
Yes you can get the injection and then later that day or the next day become positive - but then its entirely possible that is because you were already positive before you got the injection, it just wasn't showing up yet. Hence looking from days after the injection and the data shows extremely high efficacy from day 10 onwards - you have only got it down to 52% by including days 1-9 in the pool of days 1-21 which is distorting the data.
The Pfizer vaccine from day 10 onwards gives close to 90% efficacy with just a single dose, not two doses. From Day 14 to Day 21 is virtually a flat line.
https://wp.technologyreview.com/wp-c...NEW.png?w=1800
https://wp.technologyreview.com/wp-content/uploads/2020/12/PFIZER_CHART_NEW.png?w=1800
This is not how immunology or clinical trials work. Immunology is fiendishly complex and the exact mechanism and extent of immunity can be greatly affected by route of dosing, dosage, vector, and dosing frequency/timing.Quote:
Originally Posted by RandBlade
Is it possible that a single dose of a given vaccine will give long lasting and effective protection? Sure! But without a clinical trial to prove it, you're essentially gambling based on very incomplete information. Several pharma companies have specifically started additional trials to prove just this; they start with a 2-dose regimen because it's most likely to succeed, but follow on with a single dose trial to see if they can reduce cost/complexity. Without that data, however, you're just guessing.
I sincerely hope that it works out for the UK, but do realize that if it does this will not be a 'vindication' of their strategy. It will just be that they got lucky. This is not how evidence based medicine works.
On a broader note, I don't think that people outside of the medical or biotech world understands that these vaccines are not in fact 'approved'. We don't have adequate data to really know the full safety and efficacy of these vaccines. These are being authorized for use on patients under an 'emergency use authorization', which is essentially the FDA saying 'it looks like it's probably okay and the risks are lowish, so go ahead and start using it because the need is so pressing'. But everyone who's getting this vaccine (at least in the US) is essentially being enrolled in a Phase IV trial to track the outcomes and make sure the EUA wasn't mistaken. This whole process has been at breakneck speed, and while few corners have been cut (outside of the badly botched AstraZeneca trial), there are still lots of unknowns. This doesn't mean we should refrain from taking the vaccine - it is precisely the people who understand the ramifications of the EUA and this technology who are lining up to get it first, and I will gladly get vaccinated when it is my turn - but it definitely means that going off half-cocked on the basis of very thin to nonexistent data is just asking for trouble.
I'm not sure if you wrote that before seeing the chart I posted in my subsequent reply wiggin but absolutely it is a gamble. But that is part of the point, this isn't a licensed medicine yet (and even if it was then off-licence use of medicines do exist) it is an off-licence emergency authorisation using pre-existing emergency authorisation procedures. And we are indubitably in an emergency right now.
That chart is one of the most compelling pieces of evidence I have ever seen. My background is economics and business rather than epidemiology and medicine but that is a very clear chart to read.
Yes it is a gamble. But it is literally a gamble that could and probably will literally save tens of thousands of lives. The JCVI, MHRA and all four countries CMOs unanimously all think it is a gamble worth taking and I agree.
RB, I have seen every public scrap of data on these trials. 10 days of a reduced incidence of events doesn't tell you shit.
I wish the UK luck.
It does tell you something. It tells you that efficacy was over 90% for those 10 days.Quote:
Originally Posted by wiggin
It doesn't tell you that the efficacy will remain over 90% from day 22 to day 84, of course it does not, but it is an educated guess and gamble that it will remain high.
There are two separate concerns here:Quote:
Originally Posted by RandBlade
1. We have no data on the duration and extent of efficacy between the first and second doses if the second dose is given late. The data is extremely thin in the brief period between the first two doses on a normal schedule (only a handful of events and no ability for long term followup), and nonexistent otherwise. They are using a booster dose for a reason.
2. We have no data on the duration and extent of efficacy of a second dose after an extended delay outside the scope of the original trial. Immunization boosters are not well understood and their timing can be critical depending on e.g. vector design.
So, not only might the people be vulnerable until their second dose is administered, they might be vulnerable after the second dose is administered. They might be fine, too, but we simply don't know. Without data it's speculation.
(double posting but totally different topic)
There was an amazing article about my town in Slate a couple weeks ago. I have fortunately avoided this drama because our daughter is not attending the local schools, but I've seen the trend in local elections for some time - there's a clear fault line in the community on the issue of schooling (which drives most of the town's budget), with a traditional labor-supporting progressive wing at odds with a more technocratic leftism. At the higher levels of power in the town, the more dogmatic lefty candidates have not fared all that well, despite the overwhelming blue lean of the town.Quote:
Originally Posted by wiggin
Seeing this tension play out on the context of Covid is fascinating. And it's also a mildly hilarious profile of the super weird place that I live.
Quote:
Originally Posted by wiggin
Indeed it is speculation, but it is well reasoned speculation. Just like emergency authorisation itself - the potential for saving tens of thousands of lives makes it seem worthwhile to try this route during the pandemic.
There are data and empirical justification for an EUA. There are not for a substantial changes to dosing schedules.
Well reasoned speculation is still only speculation.Quote:
Originally Posted by RandBlade
There are countless hypothesis which make a lot of sense. And which are then proven wrong. Especially in the areas of biology and medicine.
No, it does not tell you that at all. The image you provided has been cropped, and lacks the most important part of the original image, which shows a very wide confidence interval for estimated efficacy between the first and second dose—roughly 30-70%. Most likely, some of the participants had relatively good protection, while others did not, but you cannot determine the extent to which protection was conferred on the basis of this figure. Moreover, you cannot determine the extent to which the most vulnerable people will be protected after a single dose, on the basis of this figure and this study.Quote:
Originally Posted by RandBlade
Even without taking differences in baseline risk into account, this is problematic. There has been some simulation-based work done on the issue of single-dose vs. 2-dose regimes in the context of a hypothetical (influenza) pandemic, and it seems likely that the risks and benefits of either approach depends to a great extent on the magnitude and duration of the primary response—which is unknown for the interval that's now being discussed—and the transmissibility of the virus—which is unknown but probably rapidly changing, due to the new lineage. This is without taking rapidly shifting baseline risk into account, and assuming homogeneous transmission. The curently available data on the Pfizer vaccine and on covid do not clearly support the decision to greatly delay the booster dose; it's likely the experts involved have based their recommendation on at least some rudimentary modeling, but it's crucial that they show that work and let it be subjected to critical review by other experts.
Conversely, it might be a gamble that will end up having the opposite effect. The basis for the gamble should be made clear and subjected to critical (external) appraisal.Quote:
Yes it is a gamble. But it is literally a gamble that could and probably will literally save tens of thousands of lives.
One interesting side effect of this pandemic is that suddenly everyone is an expert - from statistics to immunology, I find it amusing how lay people are correcting experts, even in this thread.
For what it's worth, at least I know enough to say that immunology is complex as shit so I will refrain from thinking I can make sound judgement, and leave it to experts. I hope the UK gets lucky with their gamble, but do realize it's not really based on much and that it could affect efficacy after the second shot as well. So, fingers crossed.
Yes, that is certainly a popular talking point—one that has been weaponized in Sweden, the UK and, indeed, in the Netherlands, with the intent of stifling legitimate criticism of dubious contrarian policies. It has no place in a discussion forum. Nor does it confer any advantage to the broader public debate.
The JCVI, MHRA and CMOs are independent extermal experts and not politicians. Providing critical appraisal is literally their job.Quote:
Originally Posted by Aimless
I have no idea how you failed to understand from my post that I was speaking of experts outside the group that developed the models and reasoning underlying this decision.Quote:
Originally Posted by RandBlade
They weren't the ones that came up with the reasoning underlying this decision, it was proposed previously by others including former Prime Minister Tony Blair, for example this was produced 22/12.Quote:
Originally Posted by Aimless
https://www.independent.co.uk/voices...-b1777845.html
They are the independent experts who need to make approvals (MHRA) and advice (JCVI) and have independently reviewed the proposal made by others.
Are you telling me Tony Blair develops complex epidemiological models on the side, RB?Quote:
Originally Posted by RandBlade
No.
I am saying others have made proposals and the appropriate, statutory, independent regulatory bodies have done their job.
Are independent regulatory bodies supposed to outsource their work to others?
Is hugely important scientific work supposed to be conducted unsystematically, by a small group of people, in secret and without scrutiny? Please re-read what I wrote a little more carefully so that you can understand why your response about Tony Blair missed the mark.Quote:
Originally Posted by RandBlade
No. The work has been done by Pfizer and AZN etc and they are scrutinising it and coming up with the best response. They are the scrutiny.
Plus all their reports will I believe be put into the public domain.
That is incorrect. Pfizer has not modeled this public health policy. Moreover, Pfizer has explicitly stated that the evidence does not support the proposed deviation from their protocol. AZN has tested a protocol not too different from this proposal, but they have not produced any applicable epidemiological work. I'm not sure how you managed to get so confused about this, but what's at issue here is the decision to delay the second dose by three months, and it's that decision that must be based on evidence and models that can withstand scrutiny. That is why your comment about Tony Blair missed the mark—Blair has not produced any scientific results that can answer this question. Presumably, the group of experts that have decided to support this decision have developed models that they believe show the tradeoff to be worthwhile. That work needs to be able to withstand scrutiny—now, not when it's too late. Such models are often sensitive to changes in key parameters or reliant on key assumptions. Some of the most likely key parameters are not known, and it's important to see how they've dealt with that limitation—the range of assumptions and scenarios under which the decision to greatly delay the second dose results in a net benefit. What is happening here is the exact opposite of scrutiny. They're making guesses based on eg. the data from the Pfizer trial; those guesses must be seen to be able to withstand critical appraisal by other experts.Quote:
Originally Posted by RandBlade
Lol
Twitter Link
Oh God. Frankensteining vaccines and making it up as they go along?
Seriously?
the fuck are they doing
Reports of GPs ignoring the Clown Circus and administering the second dose as scheduled to those who'd made second appointments.
What a joke this has quickly become.
At this point, anyone advising the British and Swedish governments about Covid needs to be kept away from hot stovrs let alone life and death decisions.
Well let us see in 3-4 months, and this time next year.Quote:
Originally Posted by Loki
Currently over a million people have been vaccinated. If by the Spring tens of millions have been and it works then good.
The French are surely handling vaccinations far, far worse yet that doesn't get a look in from you Anglophobe obsessives.
Unsanctioned human trials.Quote:
Originally Posted by Steely Glint
What the actual fuck.
Even the initial plan (single dose for more people) is a gamble, there's no other way putting it. And it is not "well reasoned" - though, to be fair, it can't be called outright stupid, either, IMO. It's a desperate move, which in best case scenario, provides reasonably good immunity to large parts of population quickly enough to significantly limit the pandemic, and in worst case scenario, renders the whole immunization effort moot. And there is no solid data to suggest with any level of confidence which of these outcomes is more likely.
The "mix and match" lunacy, though, is not too far from "those who are afraid of needles will be allowed to just drink the contents of the vial and hope for the best".
The Dutch government's stance of 'we may be slow, but we want to make sure we do it right' is starting to look less idiotic.
Because slowness isn't as interesting to discuss as a govt. sloppily conducting unsanctioned medical experiments on millions of people.Quote:
Originally Posted by RandBlade
That's not how science works. And it certainly shouldn't be how science works when tens of thousands of lives are at stake.Quote:
Originally Posted by RandBlade
Seeing a number of colleagues and other HCWs across the country saying that we/they should be prioritized over nursing home residents when it comes to initial vaccine rollout. They do not seem to understand that the Pfizer trial data do not permit us to rule out asymptomatic transmission. They do, however, let us assume that we can protect nursing home residents from symptomatic illness by vaccinating them. There's no way in hell all nursing home staff will accept the vaccine, so the risk of getting covid into our nursing homes will remain very high. We can, however, vaccinate almost all nursing home residents, protecting them from symptomatic illness. Disappointing moment in Swedish healthcare.
2020 is the year we found out how people really feel about grandma.
For sure, but I think this might (partly) be chalked down to not knowing what the Pfizer trial actually showed vs. did not show.Quote:
Originally Posted by Loki
Not surprising. The govt. is asking them to violate core principles of medical & research ethics.Quote:
Originally Posted by Timbuk2
Florida just reported 31k+ plus new cases today. The previous record was 17k, which happened earlier this week.
Universal theme park hit capacity 10 minutes after opening.
We are so fucked.