British Medical Journal: “Researcher blows the whistle on data integrity issues in Pfizer’s vaccine trial”

So far, no major US or UK press outlet has taken up an article at the British Medical Journal that calls the integrity of the Pfizer clinical trials for the Covid-19 vaccine into question. At a minimum, the results for 1 000 of the roughly 44,000 participants were compromised.

(Article by Yves Smith republished from NakedCapitalism.com)

IM Doc, who was the first of several to send this link along, said it was also discussed at a conference yesterday. A participant told him a speaker said: “If true, this is terminally damning and none of the data of that trial can be believed.”

The BMJ substantiated the claims of a former regional director and trained clinical trial auditor Brook Jackson of Ventavia Research Group, which was running a portion of the Pfizer Covid-19 clinical trials in several sites in Texas. In the two weeks she was involved, she saw data falsification, unblinding, poorly trained vaccinators, negligence via not following up on some serious adverse events, and large scale failure to complete test on participants who reported Covid-type symptoms. Jackson first escalated internally, and when that got nowhere, reported to the FDA. She was fired the same day.

The BMJ published this list of half the concerns Jackson reported to the FDA:

Participants placed in a hallway after injection and not being monitored by clinical staff

Lack of timely follow-up of patients who experienced adverse events

Protocol deviations not being reported

Vaccines not being stored at proper temperatures

Mislabelled laboratory specimens, and

Targeting of Ventavia staff for reporting these types of problems.

Jackson received a follow-up call from the FDA but there was no indication the agency took action. In fact, 11 months later, when the Pfizer vaccine received full approval, the FDA had peculiarly not inspected the Ventavia research sites despite the company fully expecting an inspection and being in fear of it before Jackson filed her complaint. From the BMJ:

… after the full approval of Pfizer’s vaccine, the FDA published a summary of its inspections of the company’s pivotal trial. Nine of the trial’s 153 sites were inspected. Ventavia’s sites were not listed among the nine, and no inspections of sites where adults were recruited took place in the eight months after the December 2020 emergency authorisation. The FDA’s inspection officer noted: “The data integrity and verification portion of the BIMO [bioresearch monitoring] inspections were limited because the study was ongoing, and the data required for verification and comparison were not yet available to the IND [investigational new drug].”

Allowing Pfizer to withhold data is simply outrageous. As IM Doc said by-mail:

This is exactly why I spent so much time in the original Pfizer research guest post about the fact that my mentors would have literal carts full of binders of just the kind of data being discussed in this BMJ report. That was back in the day when peer review meant just that. They would have gone over these data in fine granular detail. This kind of thing would have been caught.

I am not sure that level of access was even provided to the peer reviewers in this case – or pretty much most anything these days – it is all proprietary. And as I pointed out in the guest post, Dr Rubin a member of the FDA committee admitted in the radio interview that he had not even bothered to look at the material for Moderna just a day or two before the vote. This BMJ article is bringing to light what happens when people just simply do not care and do not do their jobs. But gladly accept paychecks and favors for their companies or interests.

We pointed out late last year that STAT, which is hardly an anti-drug company publication, had criticized the FDA for obvious and grotesque corners-cutting on its data validation when the Emergency Use Authorization was issued. STAT came down on the FDA because it assumed the FDA had not allowed enough time and had not assigned enough manpower to the task. Reading between the lines with the benefit of the new BMJ report, it instead appears the FDA let Pfizer provide very little data and the FDA tolerated that and hence didn’t have much of a data-scrubbing/testing task. From its Did the FDA understaff its review of the Pfizer/BioNTech vaccine?:

In what is arguably the most important decision the Food and Drug Administration has made this year — its emergency use authorization of the Pfizer/BioNTech Covid-19 vaccine — the agency apparently assigned only a single reviewer in each of two key scientific disciplines (clinical and statistics) to do the work in three weeks that usually takes months to do….

Unlike its counterparts in other countries, the FDA is believed to be the only drug regulator in the world that consistently receives and reviews patient-level data from the clinical trials that underpin drug and vaccine approvals. To perform such rigorous analyses, the FDA typically spends around 10 months (a mere six months for applications given “priority review” designation) in an effort that involves reviews by experts representing various scientific disciplines: clinical medicine, statistics, pharmacology, chemistry, pharmacovigilance, and more…

Given the urgency of the pandemic, the review of the Pfizer/BioNTech vaccine was conducted far faster than usual. The centerpiece of the analysis was data from the company’s 44,000-participant Phase 3 trial. FDA reviewers had just three weeks, from Nov. 20 to Dec. 11, to complete their analyses. It was a monumental task, which raises the question: Why didn’t the FDA devote additional reviewers to it? According to the FDA’s review memo, some scientific disciplines, such as pharmacovigilance, had multiple reviewers involved. But the two disciplines tasked with examining the clinical trial data and results, the clinical and statistical reviewers, were seemingly left to do their work solo.

This seems wholly inadequate on at least two levels. First, without additional reviewers it is hard to comprehend how the work of several months could be squeezed into a matter of 22 days (including Saturdays and Sundays). In-depth review calls for examining patient-level data — a large feat that involves auditing and reviewing individual case records as well as independently rerunning analyses on the raw data.

I find this section the most troubling:

After Jackson left the company problems persisted at Ventavia, this employee said. In several cases Ventavia lacked enough employees to swab all trial participants who reported covid-like symptoms, to test for infection. Laboratory confirmed symptomatic covid-19 was the trial’s primary endpoint, the employee noted. (An FDA review memorandum released in August this year states that across the full trial swabs were not taken from 477 people with suspected cases of symptomatic covid-19.)

477 missed test results out of 40,000ish participants may not sound like much until you recall the very small number of infections that served as the basis of Pfizer’s efficacy claims. From the New England Journal of Medicine paper on the Pfizer clinical trial:

Among 36,523 participants who had no evidence of existing or prior SARS-CoV-2 infection, 8 cases of Covid-19 with onset at least 7 days after the second dose were observed among vaccine recipients and 162 among placebo recipients.

I don’t see how anyone can believe the efficacy claims in light of the much larger number of possible Covid cases that Pfizer never bothered to diagnose.¹

The BMJ report also warns that the unblinding that took place at the Ventavia sites could have been a large-scale problem:

Early and inadvertent unblinding may have occurred on a far wider scale. According to the trial’s design, unblinded staff were responsible for preparing and administering the study drug (Pfizer’s vaccine or a placebo). This was to be done to preserve the blinding of trial participants and all other site staff, including the principal investigator. However, at Ventavia, Jackson told The BMJ that drug assignment confirmation printouts were being left in participants’ charts, accessible to blinded personnel. As a corrective action taken in September, two months into trial recruitment and with around 1000 participants already enrolled, quality assurance checklists were updated with instructions for staff to remove drug assignments from charts.

As Lambert tartly observed: “If so, we don’t really have an RCT at all.”

As IM Doc summed up:

This is exactly the reason I recoil from “evidence based medicine”. As a profession, we no longer understand that the “evidence” is literally just what Pharma wants you to see. I learned that the hard way with Vioxx and also the opiates. The scales fell off the eyes when it became clear how much they had lied and manipulated.

This Pfizer research is “pristine” in the eyes of the evidence based medicine folks. It has been peer-reviewed. It was an RCT. It had more than sufficient power. It was accompanied by an editorial in one of the world’s leading medical journals describing it as a triumph. EVIDENCE – on a grand scale. Nobel potential. And yet – it may have been fatally compromised by laziness on Pfizer’s part and everyone that reviewed it. And the motivation of these independent research companies is to keep the cash coming – no matter how sloppy they do their work. I have been involved in more than one complete audit of trials in their hands that have gone bad like this. This is why I have a problem with “evidence based medicine”. EBM is nothing more than Pharma’s way to control the minds of physicians.

No one who has been paying attention should be surprised that vaccination rates have no correlation with Covid case levels. These vaccines were falsely sold as magic bullets for the pandemic. Politicians desperately wanted a solution. Medical professionals and investigators had long accepted Big Pharma giving them the mushroom treatment. So we have vaccines that do have utility in protecting individuals from the worst outcomes, but don’t do much good in preventing contagion.

And this mis-selling of what the vaccines do is of critical importance. GM has made this argument repeatedly:

The existence of vaccines will kill more people than vaccines will save directly.

Because it gives the politicians the excuse to let it rip.

Without vaccines the daily death toll becomes unacceptable and someone has to do something about it and contain the contagion. Which we know how to do, we just don’t want to.

With vaccines it either becomes “tolerable” (even if it is nothing but; see the UK) or even if it does break hospitals (as happened in many states in the US in August and is still happening in various places), it can be ignored by blaming the “anti-vaxxers”.

But in the long term it is the area under the curve that matters.

Welcome to a world run for the benefit of Big Pharma.

_____

¹ And remember, before you say, “Oh, Pfizer couldn’t have done anything nefarious,” we pointed out last December that the study was effectively unblinded to the participants and the study nurses who kept on top of reactions and were tasked with determining if someone who reported Covid-like symptoms needed to be tested. They could identify a fair number who’d gotten the vaccine by virtue of the high level that had bad reactions to the first and even more often to the second shot, the prototypical feeling really sick for 6 to 48 hours. As we wrote:

Epidemiologist Ignacio had already raised another concern: that the high frequency of strong adverse reactions meant the study was unblinded to those patients:

First and foremost, we are looking to very transient results obtained in a period too short to be relevant to evaluate the efficacy of the vaccine. It is well known that vaccines induce antibody peaks just about 12 days after the second shot. We are looking at this peak. Very relevant regarding the possibility of some short lived sterilizing protection in the upper mucosa.

Second, the high reactogenicity of the vaccine, way higher than the placebo, removes one of the blindnesses of the trial. You know if you are a recipient of the vaccine. As IM Doc says, the reactogenicity is way above what can be considered normal or standard and with potential to be problematic, and a behaviour changer in the recipients which can have very significant effects in the numbers observed obtained in so short times after vaccination. This effect will be diluted by time in later reviews but it can be quite important in the first review.

STAT agreed that the effective unblinding was a concern:

One of us (P.D.) raised questions about potential unblinding in the trials through the vaccine’s side effects, as well as about the confounding effects of fever- and pain-reducing medications, which participants in the vaccine arm took three to four times more often than those in the placebo arm. Yet the FDA’s review shows no evidence that any of its scientists investigated either of these issues, and without more scientific staff devoted to the task it is hard to imagine how they could.

Read more at: NakedCapitalism.com