Covid-19: Researcher blows the whistle on Pfizer vaccine trial data integrity | Hacker News Reader

Covid-19: Researcher blows the whistle on Pfizer vaccine trial data integrity

bmj.com

104 pointsAndrewBissell81 comments

What I still can't wrap my head around is that they vaccinated the control group after less than a year and got away with it. Here we are, with a novel coronavirus, a novel vaccine technology and a novel vaccine, and we can't even do a 2 year longterm study.

> "During that visit we discussed the options, which included staying in the study without the vaccine," he says, "and amazingly there were people — a couple of people — who chose that." He suspects those individuals got spooked by rumors about the vaccine. But everybody else who had the placebo shot went ahead and got the actual vaccine. So now Fierro has essentially no comparison group left for the ongoing study.

https://www.npr.org/sections/health-shots/2021/02/19/9691430...

That's an alarming detail I didn't realize. Without a control group maintained over some lengthy period (10+) years, is there any other methodology to identify and attribute any potential long-term side effects of a vaccine? I'm not worried about this all that much, as someone who opted for an mRNA vaccine, but I think we should still be rigorous in studying it just in case.

Side effects from vaccines almost always occur within a few weeks of getting them, if they occur at all. It would be exceptional if side effects occurred months or years down the line. It’s obviously not impossible and I don’t want to give the impression that I think it is, but it’s just not considered a likely outcome. Plus, anyways, we know that SARS-CoV-2 is far more dangerous in both the long and short term.

Dangerous? I think you need to be a great deal more specific than that, since the risk tranches of Covid-19 are highly variables based on obesity, comorbidities, and age.

At a very young age, mortality from vaccine side effects (~200 to ~700 peri/myocarditis per 1M) is greater than mortality from covid itself (1 per 1M for a healthy young male no comorbidities 18 yo not obese), depending on comorbidities.

This violates do no harm.

> At a very young age, mortality from vaccine side effects (~200 to ~700 peri/myocarditis per 1M) is greater than mortality from covid itself

Do you have a source for that number? All I have seen indicate that the cases are mild to intermediate, but no actual deaths directly linked to myocarditis.

Pfizer's 5-11 covid vaccine FDA application estimates a bunch of numbers that roughly match the OP numbers in Table 14, page 34. Though we should not confuse myocarditis in boys 200/M with myocarditis mortality, which is 0. And, of course, grain of salt for Pfizer estimation, probably the real numbers could be marginally worse. https://www.fda.gov/media/153447/download

> Post-EUA safety surveillance reports received by FDA and CDC identified increased risks of myocarditis and pericarditis, particularly within 7 days following administration of the second dose of the 2-dose primary series. Reporting rates for medical chart-confirmed myocarditis and pericarditis in VAERS have been higher among males under 40 years of age than among females and older males and have been highest in males 12 through 17 years of age (~71.5 cases per million second primary series doses among males age 16-17 years and 42.6 cases per million second primary series doses among males age 12-15 years as per CDC presentation to the ACIP on August 30, 2021). * In an FDA analysis of the Optum healthcare claims database, the estimated excess risk of myocarditis/pericarditis approached 200 cases per million fully vaccinated males 16-17 years of age and 180 cases per million fully vaccinated males 12-15 years of age * .44 Although some cases of vaccine-associated myocarditis/pericarditis have required intensive care support, available data from short-term follow-up suggest that most individuals have had resolution of symptoms with conservative management. Information is not yet available about potential long-term sequelae and outcomes in affected individuals, or whether the vaccine might be associated initially with subclinical myocarditis (and if so, what are the long-term sequelae). A mechanism of action by which the vaccine could cause myocarditis and pericarditis has not been established. Myocarditis and pericarditis were added as important identified risks in the PVP and included in the Warnings sections of the vaccine Fact Sheets and Prescribing Information. The Sponsor is conducting additional post-authorization/post-marketing studies to assess known serious risks of myocarditis and pericarditis as well as to identify an unexpected serious risk of subclinical myocarditis.

I pulled out the text from your link which is the applicable text with most apropos italicized

Given what we know thus far I think it is consistent with the research to say that this is likewise, potentially caused by intravenous injection of the vaccine, rather than intramuscular as properly indicated. This is also partially caused by modern vaccine procedures which rarely involve aspiration, therefore, the medical provider has no clear indication of whether or not they are injecting into muscle or veins.

As someone that considers himself vaccine-hesistant, I consider this to be a big potential victory in addressing arguably one of the most concerning side effects with mRNA based vaccines, and reducing my concern level if I am required to get the vaccine.

The source for that is a number of studies I have read, and that is why I am using such a huge range. For example, the numbers in [1] are quite bleak from a % basis, more so than other studies.

On the other hand, myo/pericarditis are known side effects of vaccination in general. In general I don't think that dissuades us, because the rates are usually low. Not in this case though.

Fortunately, I believe some researchers have already identified a partial cause, that being intravenous injection of the vaccines rather than intramuscular [2], and related [3]

[1] https://pubmed.ncbi.nlm.nih.gov/34341797/

[2] https://pubmed.ncbi.nlm.nih.gov/34406358/

[3] https://pubmed.ncbi.nlm.nih.gov/34453510/

If aspiration is such an obvious solution why isn't this information immediately broadcasted to all the doctors and nurses, as many of these are still mind boggled when you ask for aspiration?

you completely misunderstand the concept of "do no harm" (which in itself wasn't a particularly good concept).

I'm not even going to comment on your claims about mortality rates for vaccine in young people.

In the 50's 10-30% of the polio vaccine was contaminated with Simian Virus 40 (SV40), a virus shown to cause cancer in animals. There was much concern that the contamination would lead to increased cancer risk in humans, though results from studies were mixed. I believe this meets the definition of long term damage from vaccines.

You're comparing mRNA vaccines to traditional vaccines.

Unlikely outcome sure. So is getting autism from a traditional vaccine but the warning still appears on the MMR vaccine insert.

"It would be exceptional if side effects occurred months or years down the line"

If you dig into the sources of such claims, you find they're unfortunately based on circular logic. As is so often in the case in public health. Specifically, circular logic of the form "we can't prove beyond doubt a nasty thing that happened ~3 weeks later was due to the vaccine and we're not inclined to look, so it won't be reported as an AE, therefore there are no AEs after that point, therefore it's exceptional for vaccines to cause long term injuries, therefore we won't blame vaccines for anything happening after 3 weeks because it doesn't happen".

Except in the case of the COVID vaccines a few weeks became 7 days. Literally any event that happened after 7 days was considered not vaccine related in the trials. That's not very long especially given the nature of heart damage.

Also, you have to distinguish between side effects happening, and side effects being recognized by public health. It took five years for the system to accept that Pandemrix had maimed teenagers (to protect them from Swine Flu, a disease so mild everyone had forgotten about it by the time this fact was recognized). It also took lawsuits and a very slow moving process to even get the pharma firms to cough up the data showing they knew about the problem much earlier.

Finally, actually, no, we don't know that SARS-CoV-2 is much more dangerous. The data and science quality on this topic is so poor that almost nothing can be said for certain except at the extremes.

> Side effects from vaccines almost always occur within a few weeks of getting them, if they occur at all.

According to what? Studies where control groups were eliminated after a few weeks?

Many anecdotal reports coming in where people start experiencing side effects 3+ weeks after the vaccine.

But anyway, of course you can't link any of this back to the vaccine. Especially without control group.

This is a nothing burger.

>Pfizer’s vaccine at several sites in Texas during that autumn, speed may have come at the cost of data integrity and patient safety. A regional director who was employed at the research organisation Ventavia Research Group has told The BMJ that the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase III trial

While concerning, this was only a few sites in Texas.

I'm not that concerned about the irregularities in the original article, which are reported for some sites in Texas, though they are signs of rot.

I am concerned that we promote, even mandate, mass vaccination for a novel coronavirus with a novel vaccine technology and a novel vaccine and no longterm controlled study in place.

Back in the old days of vaccines we made do with a lot less

Back in the old days we used to do long term vaccine controlled studies. Cursory Google search finds:

> A long-term follow-up study on the efficacy of further attenuated live measles vaccine, Biken CAM vaccine, S Isomura & all, 1986

> Antibody persistence was measured in 39 children in an open community 12-13 years after immunization against measles with further attenuated live vaccine, Biken CAM. [...] For evaluation of the protective efficacy of the vaccine, matched controls were studied during the same period. Serological examination revealed that 97.5% of the controls were infected with measles and contracted the disease.

https://pubmed.ncbi.nlm.nih.gov/3778422/

A quick glance at your post history and almost everything you post is antivax covid junk.

I think you're too biased.

Gaze upon the forest and not on a single tree.

Gaze upon a forest and realize trees never fall the sun never fully shines and its always misty and cool.

The alternative is to knowingly let people get infected. Almost everyone will get exposed. The vaccine is safer than infection, both in the short and long term. Saying “they got away with it” makes it sound like a conspiracy.

"Got away with it" in the sense that it went under the radar of most media and average people. I only found about it recently, and it was quite a bit of surprise, especially in the context of "science" being thrown away so liberally during this pandemic.

they were very up front about it.... 'operation light speed' they were explicitly removing barriers to speed up development and deployment.

I recall this being reported in several reports some months ago. It just wasn’t being treated as some failure or conspiracy.

The alternative is having the control data originally plotted out.

It's dissonance inducing to say "both in the short and long term" when the point of the trial is to determine long term outcome.

> The vaccine is safer than infection

Not for everyone, sadly:

Boys more at risk from Pfizer jab side-effect than Covid, suggests study https://www.theguardian.com/world/2021/sep/10/boys-more-at-r...

> US researchers say teenagers are more likely to get vaccine-related myocarditis than end up in hospital with Covid

Why COVID-19 Vaccines Should Not Be Required for All Americans https://www.usnews.com/news/national-news/why-covid-19-vacci...

> Dr. Marty Makary, a professor at Johns Hopkins University School of Medicine and editor in chief of MedPage Today, argues that mandating vaccines for "every living, walking American" is, as of now, not well-supported by science. ... The risk of hospitalization from COVID-19 in kids ages 5 to 17 is 0.3 per million for the week ending July 24, 2021, according to the Centers for Disease Control and Prevention. We also know that the risk of hospitalization after the second vaccine dose due to myocarditis, or inflammation of the heart muscle, is about 50 per million in that same age group.

Thanks, I wasn’t aware of that pediatric study. In hindsight it’s not surprising that children might need a different quantity of vaccine than adults to tilt the balance further away from the harms caused by rare reactions.

> it’s not surprising that children might need a different quantity of vaccine

Or perhaps none at all, given that the survival rate for unvaccinated children ages 0 to 19 is 99.9973%:

Infection fatality rate of COVID-19 in community-dwelling populations with emphasis on the elderly: An overview https://www.medrxiv.org/content/10.1101/2021.07.08.21260210v...

Yea but children live among the rest of us.

And they are no different in relation to risks of transmission than what we know are between 40% and 60% of vaccinated susceptible to asymptomatic breakthrough cases.

Are you saying we should hurt the young to protect the old nevertheless, which would be the result of such a policy ?

It’s not clear to me what your position is. We are talking rare harms, perhaps dozens per million, and no deaths that I know of. So I’m unconcerned. As more data comes out maybe my mind will change and I’ll agree with you. But you seem to be nipping for a fight and I don’t really care to engage.

You don't know of any deaths because most physicians and the media steadfastly refuse to attribute any to the vaccine. There are thousands of reports in VAERS, many of them of deaths in very young, healthy people hours or days after getting the vaccine.

It's not the Pfizer vaccine, but the AstraZeneca vaccine has been publicly acknowledged as the cause of BBC presenter Lisa Shaw's death.

If you even want to cite VAERS as a reliable source of _anything_ it means you don't even know the first thing about the topic.

It is not reliable, for sure, and we don't know by what factor or which way the error goes.

It might show ten times the real number, or half the real number. That would be either 1'700 people or 34'000 dead in the US alone.

I wouldn't discount the lower limit either, 1'700 is still a lot and far from a small risk.

You've essentially admitted it's an unreliable source that can be complete fiction for all we know. It's not validated by any medical institution, no one has jumped to defend it, none of the claims can be independently validated. I might as well just take my pandemic advice from a radio talk show host.

You're just robotically repeating fact-check talking points. Lots of young healthy people have been killed by the Covid vaccine and, for all its problems, the reason they're waving gigantic "DO NOT LOOK HERE" signs around VAERS is to give people like you an excuse to keep your heads firmly planted in the sand.

> Lots of young healthy people have been killed by the Covid vaccine

Cite your sources, you have a wildly outlandish claim that is beyond the expert consensus on the topic.

> It’s not clear to me what your position is. [...] As more data comes out maybe my mind will change and I’ll agree with you. But you seem to be nipping for a fight and I don’t really care to engage.

I am a big proponent of the precautionary principle when the health of the young is concerned. I also believe that such things ought to be held sacred (whether you are religious or not).

While precautions must of course be taken to protect those at risk, one of the consequences of my positions would be that yes, even as childless as I am, I'd rather lose vaccinated > 40 y.o. people to a breakthrough infection than risk hurting a child in the short or long terms.

This is why I'd rather wait for data to come in before vaccinating the young than the other way round.

Survival rate is not the only measure. COVID survivors exhibit numerous lingering problems including myocarditis. The aim of the vaccine is more than just keeping people from dying.

There are similar studies for adults.

The reality is, nobody knows how dangerous the vaccines are relative to COVID because the trials weren't sufficiently reliable or well powered to show it, the data on COVID is corrupted by people being reported as died of/with COVID or hospitalized with COVID when the true causes were different, and all data on vaccines then is horribly corrupted by swivel-eyed hatred of "anti vaxxers". meaning reports of people being seriously injured or killed by the vaccines are constantly being swept under the carpet.

Anyone who thinks they have a clear picture of this, or that they understand the tradeoffs, just isn't aware of how useless the data has been (deliberately) made.

> Boys more at risk from Pfizer jab side-effect than Covid, suggests study

That study (which was still a pre-print, not reviewed) was retracted.

It didn’t make any sense for the authors to compare the risk of myocarditis (most of which is benign) after receiving the vaccine to the risk of hospitalization from a COVID infection. Comparing two different outcomes against each other is deliberately misleading.

COVID infection is also well-known to cause myocarditis at high rates, but the study conveniently ignored that.

> That study (which was still a pre-print, not reviewed) was retracted.

That study wasn't retracted. It's still here:

https://www.medrxiv.org/content/10.1101/2021.08.30.21262866v...

Maybe you're confusing it with another one. There was a Canadian preprint on myocarditis (sample size: 32) that got retracted by its authors:

https://nationalpost.com/news/canada/university-of-ottawa-he...

To make the confusion complete, there is a study on myocarditis that got peer reviewed and accepted for publication in an Elsevier cardiology journal, only to be "temporarily removed":

> The Publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated.

https://www.sciencedirect.com/science/article/pii/S014628062...

The study was not retracted:

SARS-CoV-2 mRNA Vaccination-Associated Myocarditis in Children Ages 12-17: A Stratified National Database Analysis https://www.medrxiv.org/content/10.1101/2021.08.30.21262866v...

and the CDC itself supports an even more "radical" conclusion:

Why COVID-19 Vaccines Should Not Be Required for All Americans https://www.usnews.com/news/national-news/why-covid-19-vacci...

So, I know people involved in COVID vaccine trials (I can't remember which, I think it was Pfizer or Moderna), and also work with people who have been involved with other sorts of trials involving sensitive populations.

Awhile ago, we had a conversation about the issue you're referring to. Basically what was happening was that people in the control group were getting vaccinated, increasingly so, after the trials showed efficacy. It wasn't even so much they were leaving the study, they were just violating the inclusion criteria.

They were very aware of this, and discussed all sorts of ways of trying to get around it, too many to note here, including some weird designs with a new sample that at the time didn't really make logical sense to me from an efficacy RCT standpoint, but did from an ethical standpoint.

There were at least two things on their mind. First, you can't force participants to remain in the trials long-term. So if they want to go get vaccinated, they're going to get vaccinated. You can't keep them from doing that. So if you lose 95% of your participants to that, and your power goes through the floor, what can you do?

Second, there's a strong argument to be made that if you show strong efficacy of an intervention that prevents a world-crippling disease, it is highly unethical to keep the intervention from the control participants. It's not just unethical to encourage them not to get the vaccine, it's unethical to not offer it to them. There are many RCTs my colleagues have been in, of much more inconsequential treatments, where they ended up giving the treatment to controls because of this issue. So what about a COVID vaccine?

Yes, long-term findings are necessary and/or desirable, but this can't really be done while circumventing ethical issues about withholding a highly effective intervention. There's lots of scenarios where this happens all the time -- where you'd like to get more and/or any RCT data but doing so raises ethical obstacles that are difficult to overcome.

Maybe you could scrounge together enough people across trials but then you run into another issue: are the people who choose to remain in the control group long term really comparable to treatments on average anymore? You lose your randomization in an important sense, so it's all moot anyway.

It's a difficult issue.

How do you make sure we don't inadvertently fuck over a huge population in a black swan event?

It's like the establishment is using small scale tactics at totality scale which is certainly a critical point to be concerned about.

Watch the elimination of the control group. With a control group, it is easy to see the adverse effects.

Thanks for taking the time to write an in-depth informative mini-article. It is a difficult issue.

Usually the following would be none of my business, but we are in a pandemic that affects billions of people around the world. It is uncomfortable to navigate uncharted waters without a depth line. A lingering unclarity is that in practice there is no shortage of people willing to weather covid with no vaccine. I suspect such people are unlikely to participate in a RCT, but perhaps the recruitment process can be adjusted to attract more conservative (in the psychological sense) types.

There are more than enough people who don't want to take the vaccine for pre-existing reasons that they could have formed a control group who promised not to take it, and would stick to it.

For a double blind randomized trial, no one can know who's in what group. If an individual isn't willing to get the vaccine then they'd be excluded by default.

While a blind trial is preferable, we can and should still gather data based on unblinded trials. Using the voluntarily unvaccinated in trials as a control group will yield meaningful data at scale, just not as good as it could be. For example, are they being diagnosed with heart problems less often? That is not likely to be placebo.

Have you carried out clinical trials before, done any sort of public health research, or worked in any way in science that involves people?

When you say "got away with it" it sounds like you think they were intentionally carrying out a conspiracy theory. The reality is far more banal.

I did for non-invasive devices that were mostly class I + II. Even for those 1-2 years is very fast. Larger manufacturers might be quicker, but it is the time you should calculate with at minimum.

I think the state of emergency allows to cut the time short, because these are very short time frames for clinical trials.

Somebody was kind enough to explain in a fair amount of detail how the process goes. It is an difficult ethical question. Mine is also an unfortunate formulation, perhaps "went under the radar" reflects the sentiment better. Here we are, managing a deadly pandemic with a novel technology and no depth line. All of this to say, given that there is no shortage of people willing to weather covid without a vaccine (17% of adults "definitely not" or "only if required" as of July 2021), perhaps there is a way to ethically design a study of the vaccines that doesn't lose its control group after less than a year.

To risk "conspiratorial thinking" charges, what are the odds that in a country with 31% unvaccinated adults, only 2 participants in the control arm of a critical RCT didn't want to take the vaccine as soon as it was offered?

https://www.nytimes.com/2021/07/31/us/virus-unvaccinated-ame...

Edit: The study the NYT article references:

https://www.kff.org/coronavirus-covid-19/poll-finding/kff-co...

Edited the numbers to reflect the original source.

I recommend that instead of postulating things on hacker news, you go read up some more, and then temper your comments.

Really, large numbers of highly educated people who do this for a living have been arguing about this. We want to do better but we're restricted by human ethics and public opinion.

I would be grateful for a handful of links to the highly educated people arguing about this, if the discussion happens to be public. I did speed read a few top academic Google hits on RCTs, but none of them tackled the particular issue of long term followups.

Edit. Really, the only point I want to convey is that perhaps the highly intelligent and educated people could reflect on why RCT population of the covid studies don't seem to reflect the country population for the particular dimension of taking the vaccine as soon as the RCT ended. Perhaps this can be fixed somehow. This is as kind of a suggestion as I can muster. Perhaps they already do, and then all of this is moot.

3 years isn't enough. People need to spend at least a decade working in human health before they can really contribute significantly towards improvements.

Incidentally, I originally wrote 10, but then I cut it down to 3. More than happy to accept your correction. [This refers to paragraph I ended up editing out because it was not constructive enough, sorry for any confusion. Sometimes I wish HN had DMs.]

Why are we suddenly pretending that the same industry that gave us the opioid crisis (in addition to dozens of other serious unethical practices for which they've been sued) is suddenly above shady research and massaging of results? Particularly when they have been legally absolved of liability and stand to gain tens-hundreds of billions of dollars?

It doesn't take a conspiracy. Just a little pressure from upper management. People don't want to lose their jobs and usually the way these things go only a handful of employees are actually involved in fraud while the rest are unaware or look the other way when confronted with suspicious circumstances.

This pandemic is not an excuse to give pharmaceutical companies the free reign to rake in cash with no accountability. And that accountability comes not just from government, but from laypeople too. It took five years to discover that thalidomide was causing severe birth defects in children, and the covid vaccines are based on an untested technology. I'm not being "anti-vaxx" here, just trying to offer up some common sense: when money is involved, there is no limit to what executives and unscrupulous employees are willing to do if they think they can get away with it. And in a complex system with so many moving parts, a handful of seemingly innocuous violations of good practices can combine to produce a serious outcome.

We should all be far more critical of this entire rushed process, especially in light of not just financial but political pressure to produce evidence of a working vaccine.

Edit: I didn't even bring up regulatory capture that we've also suddenly forgotten all about. The former FDA commissioner is on Pfizer's board of directors. As is the CEO of Reuters. Our economic system is ethically sick, the pandemic did not suddenly fix it.

The alleged issues apply to only a small subset of the clinical sites/volunteers in the trial:

> In her 25 September email to the FDA Jackson wrote that Ventavia had enrolled more than 1000 participants at three sites. The full trial (registered under NCT04368728) enrolled around 44 000 participants across 153 sites that included numerous commercial companies and academic centres.

Ventavia looks sketchy, but this affects 1/44th of the patients and 3/153 of the sites. There's nothing to suggest they fudged the numbers in Pfizer's favor either, only that they were sloppy.

The greater cause for concern is the fact that the whistleblower submitted a report to the FDA which was ignored, and was then fired in retaliation. That suggests the possible presence of systemic weaknesses with much broader impact beyond Ventavia.

The inability to swab 477 trial participants to test for SARS-CoV-2 infection is also pretty bad given that confirmed symptomatic cases of COVID were the metric used to establish the efficacy numbers in the trial.

did someone in the FDA disclose the whistleblower's identity to Ventavia? or did they figure it out on their own? retaliation either way, but I didn't see any evidence of conspiracy in the article.

Yeah the article doesn't make it clear. In my own reading I had assumed Ventavia figured it out on its own.

There's countless of other questions and concerns this article brings up in my view. You must really give benefit of the doubt to Pfizer to not expect there to be something wrong with the final data.

> Since Jackson reported problems with Ventavia to the FDA in September 2020, Pfizer has hired Ventavia as a research subcontractor on four other vaccine clinical trials (covid-19 vaccine in children and young adults, pregnant women, and a booster dose, as well an RSV vaccine trial

meanwhile:

Today in the WSJ: CDC Advisers Consider Pfizer Shot for Young Children

Not to worry, that trial was so small and underpowered there's almost no data about which to have any integrity concerns.

And the one child with adverse effects was removed from the study, so general public doesn't have to worry.

Most trials fail. But many of those failures are preventable. The Lean Trial is a new approach being adopted across the globe, changing the way companies perform medical research.

The Lean Trial approach fosters companies that are both more capital efficient and that leverage human creativity more effectively. Inspired by lessons from breakthrough healthcare startups, it relies on improving data ("Falsify Until You Qualify®"), employing Pareto-trained® workers (80% of knowledge comes from 20% of training), as well as a number of counter-intuitive practices that measure actual progress without resorting to vanity metrics like adverse event reports. It enables a company to pivot with agility, deviating from protocols inch by inch, minute by minute.

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