Lesson to learn from Israel. Pfizer vaccine less effective than announced

[Cormoran]

www.theguardian.com/world/2021/jan/19/single-covid-vaccine-dose-in-israel-less-effective-than-we-hoped

It is known that a single dose doesn't guarantee whole protection, but Israel's numbers are showing that delaying the second dose might be a losing strategy.

So if any of you has received the first dose but not yet the second, keep acting as if you had received none and stay safe.

What we won't get from Israel is data on what happens after 21 days following a single dose (as they are giving the second dose on day 21 as was done in the phase 3 trials). So we will have to wait for the UK data on that.

I still wonder why Pfizer have calculated it one way and the government scientists have chosen another

Pfizer designed the trial around 2 doses 21 days apart. The data was obtained during the trial. The data clearly supports the 21 day interval as intended, but it also strongly suggests that the response is very good after the first 12-14 days.

The authorisation was given by the MHRA to Pfizer in response to their licence application, which included the 21 day interval. The MHRA will refuse to authorise, or may modify the conditions of authorisation, but are unlikely to interfere with something like a dosing schedule where the evidence is good.

Once authorised (temporarily in this case) the marketing authorisation holder is bound by the tens of the authorisation and is not allowed to make recommendations or claims that deviate from it.

In normal times, there would be no good reason for anyone to want to deviate, but these are not normal times, so this has been judged by the JCVI etc. to be the least worst option.

There will (and should be) dissenting voices, and the second dose must not be allowed to be delayed beyond the 12 weeks.

tens = terms. Fat fingers.

The WHO were reported yesterday as coming out saying that although it could be delayed 4-6 weeks if necessary, it should not be longer than that.

@Haffiana I think you’re nitpicking tbh, because I quite clearly said that what happened after 21 days is not known. But if it makes you feel better:

Between 12 and 21 days after a single dose of the Pfizer vaccine, the reduction in risk of infection is 90%.

How’s that?

We do not know what happens after 21 days if a second dose is not given then. I have seen reports (didn’t save them, can’t reference, sorry) of immunologists and virologists saying it is highly unlikely that immunity will fall off a cliff at day 22. Or day 23. That is not evidence, I agree. It is educated opinion (and not mine.)

I’m off to look at a video I just spotted on the Zoe page on “what we’ve learned from 100,000 vaccinations.”

Very interesting piece by leading UK immunologists in the BMJ on deferring doses:

“The current UK strategy with the Pfizer mRNA vaccine is, in our view, a non-randomised, uncontrolled population experimental study without pilot data. The Joint Committee on Vaccination and Immunisation (JVCI) and Public Health England should be prepared to revisit and, if necessary, reverse their decisions based on emerging scientific evidence.”

blogs.bmj.com/bmj/2021/01/20/revisiting-the-uks-strategy-for-delaying-the-second-dose-of-the-pfizer-covid-19-vaccine/

What @PuzzledObserver said.

Quite rightly, there is a lot of regulation around intended use of drugs, dosing etc. Just because Pfizer or AZ recommend a certain regimen does not mean it’s totally ineffective to change it; it means it wasn’t tested for that and there may be insufficient data. They can only provide a confidence level of X% efficacy based on the known and tested conditions. What we in the UK consider worth the risk is relative to the death rate and broader impact of lockdowns.

As we know from the AZ-Oxford vaccine, due to an error in dosing during the clinical trials, it was discovered the efficacy actually INCREASED from 60-90% (correct me in the exact numbers) by changing dose in that instance, not intervals.

If you’re Pfizer regulatory dept of course you will be closely sticking to the line of “our recommendation is X” as you can’t do otherwise. I take an anticoagulant that is new(er) to the market and not yet tested for long-term use. Risks outway the benefits for me and data is coming out all the time.

I understand people’s concerns but think we have limited options, the alternatives are worse so I’ll keep an open mind.

In normal times, there would be no good reason for anyone to want to deviate, but these are not normal times, so this has been judged by the JCVI etc. to be the least worst option

Thank you again for explaining it so clearly, JanetWeiss, and yes - the bit above is how I understood they'd come to the decision

It's just that I worry what'll happen if it turns out to be the wrong one

@Em777

Having only skimmed the BMJ article my comments are its a valid view - if viewed purely through the lens of a scientist/medical professional with that view point :)

Politicians (as much I dislike them) are balancing far broader socio-economic implications so I think it’s complex. This week will likely hit 2k deaths per day. Wonder what choices any of us would really make in that situation.

It's just that I worry what'll happen if it turns out to be the wrong one

That is understandable. What will happen is that they will change the strategy.

When my mother was in her thirties, she had a duodenal ulcer. The standard treatment in those days was to surgically resect it and cut part of the vagus nerve - this has left her with a tendency to diarrhoea for which she needs to take Imodium on a daily basis. These days, she would be treated with a course of antibiotics.

The history of medicine is one of trial and error, learning and improvement. Sometimes people do things on a hunch which proves to be right and saves untold suffering. And sometimes they are wrong.

The gamble (yes, it is a gamble) in this case is that if they are right, it will save thousands of lives. If they are wrong, it will cost some - but it is unlikely to be anywhere near as many as will be saved if they are right.

Many decisions to treat are a gamble. Every general anaesthetic carries a small risk of death. The reason that elective surgery happens at all is that the benefit of successful surgery is so much greater than the small risk of death.

I just read the BMJ piece and see that they are calling for 1/4 of recipients to receive their second dose at 21 days so they can be compared with those having the second dose delayed. There are already over 400,000 people who have had the second dose, they could be used as a comparison group to do the analysis....

Separately - some people were scheduled to have their second Pfizer jab after 4 weeks, not 3. So Even before the “delay to 12 weeks” strategy, the 3-week interval was not being universally followed.

[quote PuzzledObserver]@Haffiana I think you’re nitpicking tbh, because I quite clearly said that what happened after 21 days is not known. But if it makes you feel better:

Between 12 and 21 days after a single dose of the Pfizer vaccine, the reduction in risk of infection is 90%.

How’s that?

We do not know what happens after 21 days if a second dose is not given then. I have seen reports (didn’t save them, can’t reference, sorry) of immunologists and virologists saying it is highly unlikely that immunity will fall off a cliff at day 22. Or day 23. That is not evidence, I agree. It is educated opinion (and not mine.)

I’m off to look at a video I just spotted on the Zoe page on “what we’ve learned from 100,000 vaccinations.”[/quote]
Yes that is a bit better although still not entirely correct.

It matters.

Not because it makes me feel better or because I want the last word. It is not personal.

In science there is a HUGE difference between what you first posted and what the actual data shows. It doesn't matter that you 'knew' or that it was was you meant really, it was simply not correct.

Nothing to do with 'nitpicking'.

You actually stated:
So if instead of asking “what percentage protection do you have from one dose?” and count all the cases, you ask “how much protection do you have from 12 days after one dose,” the answer is 90%.

Which is incorrect.

How unlikely or not some scientists consider that the immunity will change after day 22 is opinion, as you say. In part that opinion is the basis of the Government decision to vaccinate with a 12 week gap, but ONLY in part. The other part is because the situation is desperate and therefore the advice and decision is pragmatic rather than purely science-lead. That is OK and how it is.

Nevertheless the opinion may be incorrect and the advice may not be good advice. Plenty of scientists have a different opinion, but all scientists can only work with the available data.

In the next few months there will be much more data and the figures obtained in the trials will be superseded.

Well Israel has now made a statement saying the minister was miss quoted and it is to early to say what the is happening.

All the posters that were explaining this were right. It is a total no news story.

Check it out on the BBC news site

@Haffiana

Yes that is a bit better although still not entirely correct.

How is it not entirely correct? How would you modify it to make it entirely correct?

It could also be the case Pfizer told them to shut up. It's not going to do them any good publicity wise if their vaccine is said to be less effective before it has a chance to reach peak effectiveness (and they've sold a heck of a lot more).

The pfizer vaccine was only ever a stop gap until the astrazeneca / oxford was reviewed and production ramped up in India. Eventually I have no doubt everyone who has had a pfizer vaccine will need to be vaccinated again no matter how many doses they have

We will have more than a million people who have had the first dose more than 21 days ago soon in the UK. Then we will have some good data on effectiveness. I don't think we have to wait long.

@GrumpyHoonMain

The pfizer vaccine was only ever a stop gap until the astrazeneca / oxford was reviewed and production ramped up in India. Eventually I have no doubt everyone who has had a pfizer vaccine will need to be vaccinated again no matter how many doses they have

I agree it was something of a stop gap but because the AZ is much cheaper and much easier to store, transport and administer. Why would people need to be recalculated though?

*revaccinated

Apologies, not read the full thread. Wanted to post the second half of the Israel data update as the first bit (about the first dose comment) has been so widely circulated, but the second more positive data has not...

Times of Israel link
Israeli hospital: 98% of staff who got 2nd shot have high-level COVID antibodies

@GrumpyHoonMain

The pfizer vaccine was only ever a stop gap until the astrazeneca / oxford was reviewed and production ramped up in India. Eventually I have no doubt everyone who has had a pfizer vaccine will need to be vaccinated again no matter how many doses they have

Interesting assertion. What’s your reasoning?

As we know from the AZ-Oxford vaccine, due to an error in dosing during the clinical trials, it was discovered the efficacy actually INCREASED from 60-90% (correct me in the exact numbers) by changing dose in that instance, not intervals.
AZ-Oxford vaccine is designed differently though. It has a "carrier" harmless virus (one of great apes' common cold viruses, I think), which is engineered to carry important bits from SARS-CoV-2. From what I understand, the explanation about why a half dose was suddenly more efficient than a full dose, was due to the human body developing an immune response not only to the coronavirus, but also to the "carrier" virus. So with a full dose, the immune response to the "carrier" virus was too strong and actually destroyed it before the cells could replicate enough of the coronavirus bits, while the half dose slipped under the radar, so to say. I think this was the reason why they wanted to combine it with another similar vaccine, which uses a different type of "carrier" virus - I think some trials with Russia's Sputnik were planned? But I am not following this topic very closely.

@Haffiana you are totally right about there being no independent data for days 21+ in the current situation (and that no conclusion could be made with respect to whether the current UK strategy of delaying is right or wrong), but the fact, from what I read, seems to be that the efficacy observed in Israel for the interval between the initial shot and the booster is indeed not very well aligned to the one observed for the same interval in the original Pfizer trials.
It could be, for example, an issue with storage and distribution though, not some sort of a deliberate misinformation. This vaccine has to be stored and transported at very low temperatures, and I am not sure how well the quality assurance works for the whole logistics chain here. It's like with condoms, you have "perfect use" efficiency (~trials) and "typical use" efficiency (~actual vaccination process).