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Pfizer Moving Goalposts on COVID-19 Vaccination Endpoints for Toddlers Tanked Their EUA Big, But it's Par for the Course. How it Relates to Pfizer Vaccine Immune Suppression. Plan B.
Someone thought it would be a good idea to move to a secondary endpoint mid-review. That told us a lot about how bad Pfizer's data must be for their vaccine in children and why they pulled their EUA.
Remember back in the beginning when COVID-19 vaccine “efficacy” was defined as “ability to prevent transmission”? And then it became “ability to reduce death and serious illness”? And then it became “ability to produce neutralizing antibodies”? And then it became “ability to produce antibodies”?
The data leak Pfizer did to the New York Times backfired, revealing the weakness of the data to be reviewed by FDA. As Toby Rogers put it, “We Did It!” - but in reality, Pfizer and the other vaccine manufacturers - and their friends in the FDA - did it to themselves by changing the goal-post of success mid-study, after data peeking - which has been par for the course in post-marketing vaccine studies. Now we see it in pre-approval vaccine studies, and it’s never going to fly in that regulatory context.
Vinay Prasad, a pro-vaccine MD, MPH, published a YouTube video entitled “FDA flip flops on Kids Vax 6 mo to 4 years old | Worst day for the agency in 20 years | Reputation” in which he decries the same issues I published in my article calling Pfizer and FDA to task for the clear flaws in Pfizer’s pending data.
I strongly disagree with Prasad on his concern over anything that would cause people to bring all of childhood vaccinations into question. His position is based on the false premises that safety is assured and that efficacy has not waned in those vaccines*, his clear frustration at the process used by the Pfizer/NYTimes/FDA team that effected the fiasco is worth watching and hearing. (*Fudged retrospective studies cannot assure safety, and evidence of childhood vaccine failure abounds, all reviewed at jameslyonsweiler.com and elsewhere). Formal skepticism is a fundamental part of objective science, and all things must be questioned for Science to even exist.
Prasad and I also differ in that I understand that the implosion of the current regulatory fiasco is actually long overdue, whereas he (ostensibly anyway) would like to see it continue as-is. The FDA’s (and CDC’s) reputation has been propped up by fudged and manipulated retrospective studies that are incapable of determining the causality of adverse events. Also, remember, from Study 1 from Moderna, efficacy was never 95%; it was 75% due, and inflated due to their dropping patients who got COVID-19 before the second dose.
Now we have evidence that COVID-19 vaccine can lead to immune suppression via lymphocytic reduction (see Dr. Mobeen’s lecture on this, below) - meaning those who got COVID-19 after the first dose may well have been temporarily immunocompromised. That would change everything.
I cannot tell if Prasad is as upset with those involved for data results peeking and moving the endpoint goal post as he is that they did it in full view of the public. I’d like to talk with him on my podcast, but it’s not clear he’ll be responsive to invites: long ago, he blocked me on Twitter. So he’s not ready for the message that objective science comes first in all matters related to science, medicine, and public health.
Nevertheless, Prasad’s video is filled with very important points. So, I’ve placed the grammar and spelling-corrected transcript of Prasad’s video, edited only for readability. I believe his concerns are well-placed and that he reveals some critical flaws in the regulatory and economic processes and what I consider to be illegal activities. I understand, and the public should understand that those involved who have colluded to mislead the public brought this upon themselves; that the failure of the Regulatory State was? is? all but inevitable because like all false paradigms it must, in the end, be reconciled with reality.
If I were in charge of the FDA, every single efficacy calculation for COVID-19 would be re-calculated, and the program re-assessed. mRNA vaccines would reclassified as “new drugs” and everyone would start over, comparing efficacy to early interventions and treatments with inexpensive, widely available drugs and therapies.
And I would begin to deconstruct the entire regulatory framework and help the Senate build Plan B.
This post will get you thinking, so grab your coffee, tea or other, grab a notebook and jot down your thoughts. I’d like to hear from you in the comments - your thoughts and reactions to Dr. Prasad’s concerns are important!
As always, please share everywhere to get around the know-nothing censors.
Transcript (editing by JLW for legibility, any meaning change is unintentional):
“Huge news today the FDA has announced that next week's advisory committee looking at the EUA of the Pfizer beyond tech vaccine from six months to four years old is on hold we're going to put it off two more months until we get the antibody data from the third dose this is an astonishing series of events over the last two weeks and represents I think so many things about regulatory science that we need to talk about.
So what happened well as you know and I’ve talked about on this channel before the standard of the randomized control trial in the six-month to four-year-old age group was to show non-inferior geometric mean antibody titers to show that the kids can get at least so much antibody and that was the primary endpoint of the study they shot with two doses of a three microgram dose one tenth the adult dose and they fell short after that study was run it's been reported New York Times today that they had 60 of the target antibody levels they're not quite where they need to be now what might a drug company have done I think under many times a drug company might have gone back to the drawing board came back with maybe a six microgram dose tried it again but what the company's done in this case is just added on a third dose which would make it go faster they've added on the third dose and we're waiting for the antibody levels.
Then all of a sudden, two weeks ago many people on Twitter started getting the bright idea perhaps even seated by the White House we don't know where this idea comes from that we should proceed with the evidence we have now which is not quite meeting our antibody level but maybe there's some suggestion of different symptomatic stars cove two cases in this trial and take it to EUA two doses now and let's try to get the third dose later down the road and they advertised this in the news and it was talked about as if it was a done deal.
I think I saw news coverage saying that different locations are being told when they will get the shipment of this vaccine and how they will be able to administer it.
So they were getting ready to do it then all of a sudden today they announce that the meeting is off they're not putting out the packet and we're on hold until April wow I don't know what to say I’ve been following regulatory science throughout my whole career for about 15 years now in biomedicine and I have also studied the history of regulatory science I’ve never seen anything quite like this.
This is unprecedented.
We've had a series of unprecedented things happen in this space.
Number one, I think we got to go back to the beginning many people were worried that Donald Trump would put the heavy hand of politics on the FDA and try to push an approval a quote-unquote October surprise and I think I was among the people who (were) concerned about that that might happen and that would delegitimize the FDA well it turned out that didn't happen we didn't have the October surprise in that election year but what you're seeing now is what many people feared
I think the heavy hand of politics playing a role in the FDA over the course of the last year we have seen Marion Gruber and Phil Krauss the director and deputy director of the vaccine products division resign they're resigning it's widely reported under pressure from the white house to approve a boosters one-size-fits-all policy we now in this country boosting anyone over the age of 12. they were reluctant to pursue that strategy they have written now a number of op-eds critical of that strategy joined by Paul Offit who he himself is on the vaccine advisory committee and I think the question here is an important question it isn't “do boosters benefit older people?”.
I think the answer is clear: they do benefit older people. I think the question is “do boosters benefit younger people?” and I think it's a very different question and even though we keep seeing more and more data.
I have not yet seen persuasive data that a young healthy person between the ages of 12 and let's say 40 even or 50 even that by giving them the additional dose that third dose you have further reduced their rate of severe disease and hospitalization I haven't seen that data I look forward to seeing that data but I haven't seen it to date and I think that's what Paul Offit says and that's what these now resigned FDA reviewers have said and that's why they were reluctant there the other thing they did before they left
Was they expanded the sample size of the five to 11-year-old randomized control trial but we don't know all their thinking in that space and they have never made it public and so again I encourage media outlets you need to track these two people down and conduct an interview that's still not happened to my knowledge I’ve not seen any major media network track these two people down and ask them what are your thoughts on these other issues so enter this decision I think obviously the administration's under a lot of pressure to make available a vaccine for pretty much everybody especially this age group that currently doesn't have an available vaccine.
They announced two weeks ago that we're going to do that with the data at hand now I outlined a number of concerns which is one the moment you start looking at non-primary endpoints you introduced some challenges in a regulatory space the one is it wasn't what the trial set out to look at.
The second thing is how many times did you look at the data before you're analyzing the data now in clinical trials as a general rule you have to pre-specify when you actually look at the data and account for the number of looks on data the more you look at the data you have to correct for the fact that by looking many, many times by mere chance alone there may be deviations in the number of events in both arms so you need to adjust for that and they're complex statistical methods to do that, but it typically is something pre-planned and well well-orchestrated I mean this is not something that's an unknown territory this is tried and true territory so the moment they say we're going to look at the secondary outcome it's unclear if they've done all that the next thing that's unclear is what were the cases that they are detecting.
It's being reported by the New York Times that there are 50 events that occur in this age group in this randomized control trial and the denominator is roughly you know in the three to four thousand ballpark 50 events and they're saying they have a 57 reduction in uh and stars cove two cases in this group but what's the confidence interval around that 57 percent and when you start getting down to 50 events it's quite possible that confidence interval is very, very large possible it's as low as 27 to 75 as some statisticians have calculated but it depends, nobody knows exactly what the confidence interval is because this is the time to event end point and you actually need the time part of it to know for sure, and so these are all kind of best back of the envelope guesses but this is a good this is a good statistician, who has posted this and I think she's probably in the right ballpark, but that's important because the FDA had said earlier that we would only accept a 50 more reduction for vaccines if the lower bound of the 95 confidence interval does not dip below 30 percent and it's possible it dips below that here.
But I’ve also pointed out that even thinking down this road is kind of misguided because this is all assuming that this was the primary endpoint of the study which it is not it is a secondary endpoint of the study and secondary endpoints are known to be more subject to the vagaries of chance than primary endpoints particularly when you don't pre-specify all these things.
So, this would insert a lot of complications into the data set I think the next big complication is how many of the cases are going to be delta and how many are going to be omicron remember we're dealing with omicron now so I think we're going to put less stock in delta cases.
I think the third thing will be how durable is this? Is this a short-term reduction in SARS-CoV2 (infection) or is it durable? There are now a host of data from a number of different countries suggesting that vaccine effectiveness is lower for Omicron than Delta.
That's known, after all this is an ancestral mRNA sequence that's in that vaccine so it's natural that the deviations from that sequence would maybe not be covered as great but the other thing is it's waning the vaccine effectiveness is waning with time and that's an important factor so these are all concerns that were floating in my mind.
I made a video of this before and actually got some feedback from some very top people who thought that those concerns were reasonable but I was most concerned with the fact that you've lost your director your deputy director and it feels as if politics is now running the FDA that was my biggest concern and then lo and behold today just on the precipice of making this advisory committee hearing and the precipice of releasing the documents they have walked it back.
So we're going to do it again in two months and some people online say well you know it's better to do it right than to rush it and this is the right call but they're missing the forest for the trees this is like somebody who created the problem and then (the same person is) defusing their own problem.
They didn't have to go public and say we're going to push this through they did that two weeks ago and now they're walking it back.
It's a political fiasco it's a total fiasco I don't even know how… how much I can state how bad this is.
You do not want to be playing flip-flop games with the public around vaccination more is at stake than just this vaccine all confidence in all vaccines is at stake that's part of what's going on right now we are living in a very important time where the fate of future vaccination campaign is being dictated by the choices we're making right now.
I don't want to live in a world where people lack confidence in routine childhood immunization I believe that it is a huge good and many of the programs that have promoted that are a huge good and I worry that the backlash to these FDA fiasco decisions is going to affect the things that have been done and tried and true for many, many decades.
That's not some theoretical worry that's a real practical worry we already see legislation in some states trying to peel back routine immunization requirements and that's not something that I would support.
I think the problem is you've lost people with experience and I don't know who's making the call within the administration but I suspect it's somebody who lacks experience and they lack experience with regulatory matters with evidence with these kinds of questions the other thing is they're they don't care as much about long-term reputation they don't have the incentive in a transient administration to care about the reputation of the FDA itself over the long haul but the reputation of the FDA itself.
Over the long haul is the greatest thing the FDA has going for it that's the entire thrust and strength of the FDA is their reputation and if you don't believe me you can read the book by Dan Carpenter I think it's called “Reputation and precedent” (it’s Reputation and Power) at the FDA it's a nice 700-page tome but it is a brilliant account of what made the FDA the one the greatest agencies.
Now I think as somebody who studies cancer drug policy that in recent years and decades that they have largely lost a lot of that prestige but these decisions in the vaccine space are hugely influential they're going to be seen by so many people and they can throw away more reputation in a short period of time than they can ever earn back it will take decades to rebuild trust after these kinds of decisions.
This is not a good call it's not good to see the light at the 11th hour you didn't have to go out there publicly and say you were going to do this that was your opportunity to make the right call I don't know what to say everything I know about this six month to four year-old decision I am learning from leaked information leaked information on the Sunday talk shows from the New York Times.
I don't see the data (and) this is unacceptable that you have scientists clinging to bits of information we hear in the grapevine or we see in a news story to make a decision or to think about this question they have an obligation to put this information first this is not how the FDA works the FDA doesn't make decisions by trickling out and leaking to reporters you know I think it's 50 events I think the denominator is this I think it's 57 that's not how the FDA works they carefully meticulously look at the data have pre-specified rules for what will count for approval and then make the call that's all being violated in this case ironically the thing people feared that Donald Trump would do is actually happening right now.
It's the heavy hand of politics influencing FDA decisions people are playing with the FDA's credibility.
It's not their money to play with they're playing with it like its monopoly money it's not going to go well.
I worry we're going to enter a situation where we have both made some bad calls, we are boosting people who we don't have good evidence to boost, and it may not be the right call to boost them we may be making choices around kids vaccines that are not consistent with European nations and may not always be in someone's best interest particularly a healthy kid who's already hadn't recovered from COVID-19.
And (I also worry that) we're not doing the things we ought to be doing like making sure everyone over there is 65 is boosted that's one, two (dose) for the people who are older who don't have documented natural immunity (because) at least one dose would be much better for them than to walk around with no doses at all have some vaccine coverage even one dose so that would mean acknowledging natural immunity and making some sort of compromise with people I think and that would also be much, much better but focusing so much on the youth on young people for (vaccination) with this kind of age gradient just doesn't make a lot of sense and playing with the credibility and reputation of the FDA makes no sense at all.
This is bad times I worry that we're going to end up in a terrible situation where there is widespread loss of trust in the FDA.
There's going to be a backlash that affects really legitimate programs, I don't I don't want any of this.
I don't want to see loss of confidence in vaccine programs I don't want Paul Offit to disagree with mandates I think that when you lose Paul Offit you've lost a lot the man makes vaccines he's been a crusader for vaccines and you lost him that should give you some pause I don't want politics to set FDA policy it should not be after this is done we need some firewalls between the white house and the FDA and ironically it wasn't trump that led to that it was this administration which is exactly the opposite of I think what many of us feared.
This is bad this is just terrible them walking it back the flip-flops the public messaging around this even the booster fiasco before where the advisory committee said no even though the President himself had promised it.
This is just terrible for the public faith in the FDA and for the faith and vaccination I don't know what to say there should be culpability for this I think people should demand some accountability for this who made this call and that person's got to go I think that's a clear standard but we don't know who makes this call that's part of the problem.
I have proposed a bit tongue in cheek but I sincerely believe it that I believe (the Biden) administration should issue an apology to Gruber and Krause apologize to these two people they were in the right next you need to rehire them maybe as a temporary employee but you need to make it worth their while to rehire them you need to make a public promise that you're going to let them make all the calls it's up to them they can decide what the sample size of the study is they can decide the endpoints they can push on the companies whatever they want and you will not touch this issue again you need the administration to promise and not to touch this issue again they have to get out of the FDA and get out of the vaccine business.
This is going to end poorly there will be no winners here there's only going to be losers I think I have never seen anything like this I think if you had consulted people who have followed the FDA for a long time you wouldn't have ended up in this fiasco, and I think uh if the institution suffers a loss of trust, we will have lost so much.
So, I really disagree.
And then the last thing I’ll say is you know there (are) some Twitter accounts who purportedly are experts they all say the same thing as if they are in cahoots as if they're synchronizing their messaging.
I think that's problematic we need independent experts to be independent to make up their own mind and so I wouldn't go on twitter and say the FDA made the right call.
That's a false narrative the right narrative is what the hell did you do two weeks ago when you advertise this and who made that decision and why? And this reversal is a huge error and blunder, and someone needs to be fired as a result of that.
That's what I would say and similarly, you don't need the president to go on tv and say when boosters are ready for all you need the US Food and Drug Administration to say when their efficacy and safety standards are sufficiently met.
And I think we have a big problem, so I encourage reporters to interview these two people and two FOIA documents because I think you need to foil some emails you'll see what's going on over here.
And I think this was a colossal blunder a huge blunder and I think when Dan Carpenter writes his sequel to the history of the FDA I suspect he'll write a 100-page chapter on this episode.
And I worry that we may have already done the damage.
So those are my thoughts on this new FDA decision as someone who has written a few papers you can go pull up my PubMed and all the papers I’ve written about FDA drug policy drug regulation law etc. so this is what you get on this channel and also, I was kind of annoyed so I must admit a little more annoyed than usual.
Because this is such a fiasco what are they doing God what are they doing?
I don't think it's controversial to say we want regulators to be separate from politicians nobody wants a politician to be deciding what things should be approved or not that's why this is a separate agency they need to get out of this business they need to stop entirely make a promise I think reporters should ask them to promise not to interfere with the FDA's actions ever again.
And well I don't know what to say.
I’m saddened to see this.
Until next time.”
Prasad has many times called for increased independence of scientists studying vaccines, and seems a bit naïve on the fact that the LMO answers to Pharma due to direct-to-consumer marketing via Pharma ads. It’s the #1 source of revenue for LMO. If he understood that, he would not seem so naïve and call for the media to hold the FDA accountable.
Here is Dr. Mobeen’s review of immune suppression from Pfizer vaccination:
And here is the link to my peer-reviewed proposal for Plan B.