Earlier this week, we posted An Internal Medicine Doctor and His Peers Read the Pfizer Vaccine Study and See Red Flags [Updated]. Most readers responded very positively to the write-up by IM Doc, which included the reactions of the eight other members of his Journal Club who reviewed the article and its editorial, as they have done regularly with important medical journal articles. We have embedded the Pfizer article from the New England Journal of Medicine (NEJM) below; the link to the editorial is here.
However, some took issue with IM Doc noting that two nurses in the UK had suffered anaphylaxis, a severe, potentially life threatening allergic reaction, after getting the Pfizer shot. IM Doc criticized the paper and editorial for not including or adding a discussion of any exclusion criteria, particularly since Pfizer’s proxies admitted that severe allergies were an exclusion criterion. From MedicalXpress:
Moncef Slaoui, who is the chief advisor to the US program for COVID vaccine and treatment development, told reporters, “Looking into the data, patients or subjects with severe allergic reaction history have been excluded from the clinical trial.
“I assume—because the FDA will make those decisions—that tomorrow this will be part of the consideration, and as in the UK, the expectation would be that subjects with known severe reactions, (will be asked) to not take the vaccine, until we understand exactly what happened here.”
Slaoui is the co-head of Operation Warp Speed and previously head of GlaxoSmithKline’s vaccine department. Other media outlets and professional medical writers (see here and here for examples) picked up his statement that subjects with severe allergic reactions were excluded.
If you look at the article below, you will see that it is not searchable. That indicates an expectation that it would be read as a print out only. You will find it make no mention of “exclusion criteria”. Neither does the the separate editorial by NEJM editors. The article does does mention “protocols” in the text, twice, but does not have a link to where to find them, does not have a written URL, nor does it provide a name or location to assist in finding them.
Some critics argued that the protocol (which you need to search through to find the selection process for candidates, including the exclusion criteria, for the Phase III trials) could “easily” be found in the Supplemental Materials and further asserted that any regular reader of medical papers would be able to find then. The fact that IM Doc, who has been reading medical papers for 30 years, and his eight colleagues did not locate them is already significant counter-evidence, particularly since the NEJM’s media kit lists the publication’s audience solely as physicians. No doubt scientists read it too, but the eyeballs advertisers really want to reach are doctors, academics or scientists in the employ of competitors.
IM Doc could not find the Supplemental Materials because the PDF that the NEJM generates does not include them. It is in the online version, and opens up to a dropdown menu, with the first item “Protocols” which takes you to a document via an external link. Since readers have every right to assume that online and PDF versions of the same article are identical, there was no reason for him to look further.
It turns out that the data waters appear to have been muddied by the NEJM itself. IM Doc and his colleagues found and read the Pfizer paper late last week. It was then on the first page of the site. He sent me his write-up on Saturday the 12th. I went to look at the article and charts on the NEJM site. It was then on the front page of the site. I experienced rendering issues in Firefox but nevertheless was able to look at the article, along with the separate tab in the header area for “Figures/Media”. I also noticed a “Supplemental Appendix,” which I opened. It was a bit of a hodge podge but didn’t contain anything that related to IM Doc’s observations. I did not see any tab with “Supplemental Materials.”
IM Doc did a big revision of his draft on Sunday, which I edited that evening. IM Doc was a bit freaked out Monday AM when the Pfizer article has moved off the NEJM front page, but he quickly located it on the site. I looked quickly, simply registering that I could find it and see the charts, but I did see that the rendering problems were no longer occurring.
I was not the only person who recalls seeing the “Supplemental Appendix” (notice NOT “Supplemental Materials”) as a stand-alone document with a link to it in the top area of the NEJM site before December 12 (sadly, the Wayback Machine allows publishers to suppress older versions of articles upon request, so there is no image of the article as it initially appeared on the first page of the NEJM site).
Fortunately, reader KLG harrumphed about the Supplemental Appendix in comments. KLG is a professor of microbiology and has been doing basic research for 30 years, so he can’t be dismissed as inexperienced in reading scientific papers. I asked for his recollection of what he found when he went to the Pfizer article:
Here is how I remember finding the paper, after seeing the post from IM Doc yesterday. I apologize if this is TMI, but I want to be as clear as possible:
(1) I clicked on the link while in my office and gained direct access through our medical library, downloaded the pdf, and printed it on a high-resolution color printer, which is my standard, old-fashioned practice. I then read through the paper fairly quickly, and thought it was OK/promising but not necessarily complete.
(2) I saw no obvious (printed) link in the pdf to any supplementary materials, so I went back to the online link to the paper through our library (full access to most medical journals). I saw the link to the 12-page “Supplementary Appendix” with the 4 pages of names and downloaded and printed it. This link was on the right side of the screen/page, near the top. This link was not at the bottom of the single page of the paper as I see NEJM.org from home this evening, along with the other links, including Protocols, Disclosure Forms, etc. I am not accessing the journal remotely through our library tonight and would be seeing it as “outsiders” do. The point for me is this: One link to supplementary material should go directly to all supplementary materials. This has been what I have been accustomed to for years. Sometimes the files are ridiculously large and there may be 10-15 of them, but they are all there and easy to find. If one link cannot be managed, then all links should be in the same place on the webpage, listed one after another as S1, S2, S3, etc.
(3) Still, I may well have missed these other links, because while I am very skeptical of “science” direct from Big Pharma, my forensic antenna were not fully deployed until the usual suspects showed up later in the day as I checked back in to see how things were going.
(4) But more importantly, I do not believe for a second that IM Doc and his like-minded journal club (a common mechanism for all biomedical scientists and many clinicians to keep up with current developments) would have missed these materials, if the links were properly displayed as they should have been on day-one. As I mentioned in my previous email, so-called supplementary material has become a thing, for good or ill, in biomedical publishing, and in my experience the links are prominent in strong journals (and NEJM is definitely that, or certainly was when Marcia Angell was editor). Moreover, IM Doc undoubtedly has a subscription to NEJM, which should have displayed the links prominently both in hard copy and online. Based on his every contribution to NC, IM Doc seems uncommonly attuned to both the practice and science of medicine, going back to the beginnings of the HIV/AIDS epidemic, which made a deep impression on all of us who were there, clinicians and non-clinicians alike. That is when we learned to parse the literature and separate the wheat from the chaff. And there was a lot of chaff in the HIV/AIDS literature from ~1983 until triple-therapy was published in 1994 IIRC and AIDS became a chronic, manageable condition for most of those infected with HIV.
Let us stress again, as you can see from the PDF below, which I downloaded Monday morning: In the PDF, there are no Supplemental Materials nor any reference to them. The Section is completely omitted. This is where the link to the Protocol would be found, were NEJM to have followed its usual practice in other articles.
In other words, NEJM initially either did not present the Supplemental Materials tab at all or through terrible design, directed reader attention away from it by having a prominent Supplemental Appendix link at the top, which experienced readers would assume contained all of any additional documents, save any others mentioned and/or linked to in the article proper and/or the editorial. And even when it cleaned that up, NEJM did not update the article to include a link or printed URL, or a reference.
In addition, even after readers in comments had pointed out where to find the exclusion criteria (in the Supplementary Materials, in Protocols, meaning two clicks and a search, when it should have been easier to find), other had difficulty finding it and also deemed the material to be poorly presented:
Thank you for highlighting the exclusion criteria. When I looked at the NEJM article, I was also unable to find them. I noticed that a reader has since posted them, and you updated the post. I also found the on Pfizer’s website. https://www.pfizer.com/science/find-a-trial/nct04368728-0
My wife is a graduate of Stanford Medical School and is a subspecialist in Internal Medicine. Not infectious disease. She was at the top of her class. She graduated a bit more than 10 years ago. I was so intrigued by this doctor’s post that I wanted to do a little test, admittedly with just one subject. As you can see I was an early commenter and have skin in the game because I live with a doctor.
I wanted to see if she could identify quickly the exclusion criteria just like this doc has now admitted was confusing but actually there. She could not do so quickly – and it took her about 45 minutes to do so and then she stated to me when looking through them how recklesly they were spelled out. She was surprised. Phase 1 stuff all mixed in with the others. She was also very concerned about the fact that there were so many common conditions that had not been studied or included in a wide population impact drug like a vaccine. Concerned about why these are not being more publicized given the fact that we will be trying to vaccinate presumably everyone. Should this not be publicized more with both docs and patients.
This discussion should put the question of the adequacy (not) of the NEJM presentation of information about the Pfizer vaccine to rest. It was incumbent on the New England Journal of Medicine to provide a concise overview and ready access to details important to practitioners to help them assess a medication intended for the entire population, yet developed and approved on a corner-cutting basis. They fell short.
Lambert, who in a prior life was a document analyst and developed schema for medical journals, was taken aback by other data presentation failings in these pieces. He intends to discuss them in the near future.
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine - NEJMoa2034577
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The European FDA equivalent is poised to issue an statement of approval for the Pfizer candidate next Monday and the Comission states that it will subject the approval to conditional but ultrafast commercialization procedures under pressure from German authorities now seeing, not overwhelming but high hospitalization and casualty numbers.
Rather than in the NEJM publication I wish that all statements by the Agency and issues are treated with the required transparency. We will see.
You cannot really have transparency if you need to be a fully accredited MD with virology or similar specialization.
We cannot all study for >10 years simply to understand some Pfizer very carefully massaged text, just like those MDs cannot actually understand how their new expensive gene sequencing machine actually works: lack of electrical engineering knowledge.
Human subjects research boards are required by regulation to have a non scientist member (or at least someone whose primary day job is not in a scientific area.)
So these human subject research protocols are supposed to have at least a modicum of concern “for the layman”. This one falls somewhere in the middle for me, as a non scientist. It’s just clear enough to show that it has uncertain outcomes and is understudied.
But you can explain in plain words if there are:
1) Identified risks and contraindications. Their frequencies and populations at risk if known. And the uncertainty associated if these are not known.
2) If the assessment for risks and contraindications is, or isn’t, complete according to current approval procedures, indicating what legal procedure (emergency or so) is applied for such ultrafast approval and what are the conceivable uncertainties about the vaccine and potential risks that have been detected in the past.
3) Ensure that during deployment everyone will be informed in the most comprehensible manner onhow these uncertainties could matter, with the potential for yet unidentified adverse and severe adverse effects of the vaccine that could appear later on but have not yet been identified. Indicate that this is the first time that RNA vaccines are deployed with additional uncertainties on performance and risks.
4) What are the criteria for eligibility of subjects for vaccination programs and what kind of risk/benefit assessment recommends such application.
5) What happens and who is responsible when and if adverse or severe adverse effects appear unexpectedly.
This is very important when emergency procedures are being used. Subjecting yourself to a vaccination program approved under emergency measures with so many uncertainties regarding performance, duration and risk requires at least being informed of their existence. This is not like an aspirin.
Yesterday a commenter talked about the protection instinct. It shouldn’t make us run blindly for the vaccine.
Very much like the participants in a trial must be informed, notice their understanding of the risks and sign the informed consent form. We are still on trial.
All scientific information of public interest should be communicated in a ‘layered’ manner if it is to be fully understood and accepted.
There is nothing new about this, and its frequently set out in law. For example, under the EU Environmental Assessment Directive, information on the public record should include a full documentation with three parts – a ‘non technical summary’ for the public, a main Statement for regulators and the scientifically literate, with additional full appendices for peer review by peer specialists.
Unfortunately in medicine there doesn’t seem to be such a clear distinction, leading to information released which is often either dumbed down too much, or is too technically complex for the average busy doctor to be able to critically review.
Everyone on this site will recall Edward Tufte’s “PowerPoint Kills” (not his title), where he demonstrates how NASA’s slavish misuse of the software doomed the Columbia astronauts. One might wonder if this is a case of “Adobe Acrobat (or whatever software used to generate the materials in various formats) kills”? Clearly the differences in content between the web site and pdfs are unacceptable, and at par with the deadly technical hubris shown in the Columbia disaster. Decades of experience in IT systems tell me these failings could have been avoided, and in a serious enterprise would have resulted in heads rolling: unless it was deliberate, in which case we may have at least a case of felony computer fraud.
Wow! This whole thing smells a lot like the Boeing 737 Max debacle, except involving a potentially greater number of corrupt parties and having even farther reaching consequences. I think there is a very high risk of serious problems emerging from the Pfizer vaccine and some kind of scandal erupting, and even ignoring the direct damage done, this could completely poison trust around the roll-out of a later-arriving but competently developed vaccine.
More generally, a major failure here could seriously harm the reputation of the FDA much like the 737 Max harmed the FAA. I mean before the 737Max happened, if you’d ask me personally whether I trusted the FAA or the FDA more, I’d probably have said FAA with little hesitation, so what am I to make of things now?
Also, if not already in today’s links:
U.S. quarantines Pfizer vaccine shipments in California and Alabama after transit ‘anomaly’ left vials too cold
Rapid scaling of cold chains is hard.
Please turn down the alarm a bit. The whole combo plate, novel + never deployed in humans at any scale technology, rushed approval, boosterist presentation of findings, and fussy deployment, all bear watching. And I’d love to have the biomedical engineers in the house weigh in on the “too cold” issue. But we need to see what falls out.
Not a biomedical engineer, but having run validations on all aspects of product manufacturing, my review is generally about how Chemistry Manufacturing Controls (CMC) are being followed to assure the quality, efficacy and safety of product delivered to the patient is maintained.
Limits are set in the CMC for all aspects of manufacturing and distribution beyond which a product can be considered adulterated. People are generally surprised to hear that a significant contributor to adulterated product are errors in label printing. The product may be perfect, but mislabeling can lead to the destruction of entire batches. That is life in a highly regulated environment.
Exposure to temperatures outside the range of studies is a nonconformance to CMC, and in the regulatory environment no amount of justification is allowed for the use of those units. I am also concerned when the FDA states that 2 extra doses are included in vials. So, I ask whether or not this was within the specified fill volume or an issue with control of the fill line.
When one audits a manufacturer, I consider a violation of CMC as a window into their processes and the possibility that other nonconformances may be allowed to impair quality, efficacy and purity.
So, I am of the mind that the exposure to temperatures that are not qualified for distribution cannot be excused.
“I am also concerned when the FDA states that 2 extra doses are included in vials. ”
That does seem like a pretty basic calculation does it not? How much does this bottle hold?
And then… are all the calculations about how much vaccine is available based on this?
Would Coca Cola put out a 16 ounce bottle that they advertised as holding 12 ounces? Shouldn’t a major drug manufacturer be as good at basic arithmetic as Coca Cola?
Cola Cola would certainly put 12 oz in a larger 16oz bottle to deceive the consumer; consumers rarely read the label! However they would make sure it’s not well advertised as 12 oz.
Today’s tricks are to keep the size of the container the same but put in less of the product.
In my experience over 40 years of pharmacy, injectable pharmaceuticals packaged in a vial are usually “overfilled” by some amount (around 10%). This is to account for the potential lost product due to manual withdraw and manipulation to prepare the syringe for injection. With good pharmacy practice and aseptic technique the overfill can be used so as not to waste product and potentially decrease costs. As I have not seen the Pfizer vials I am not aware of the labelled volume compared to the measured volume to determine the percentage overfill and how many doses this represents. Just wanted to share that this overfill is not unexpected.
The Chemical Manufacturing Controls submission for a process will usually state the specified volume as X +/- 10%. All fills must conform to that spec.
Title 21 Code of Federal Regulation, Chapter 9, Subchapter V, Part A, Section 351 states A drug or device is deemed to be adulterated “. . . (B) if it is a drug and the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this chapter as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess; . . .” Fill volume is a quality attribute.
Just as a label misprint renders a drug adulterated (people are surprised that this is the cause of many scrapped batches), failure to meet fill specifications in the CMC renders the product adulterated.
No 40 years here, but 21 CFR as well as regulatory guidance was the waters I swam in working Validation/Regulatory.
Thanks to both. I, too, had wondered about the fill tolerances.
I invested in a pharmaceutical UNpackaging machine early in my VC career. It was a wonderfully Heath Robinson affair, unpacking foil backed blister packs by presenting them to a fast moving roll of sticky tape! The engineering is harder than it sounds. The tape was a consumable.
The value of mispackaged tablets was high enough to merit keeping a fleet of these handy beside the blister packing lines because there was only a narrow time window in which they can be unpacked and repacked.
This is starting to get frightening this. Vital information deliberately buried in a maze of links. I am given to understand that when a company comes out with a financial statement, that embarrassing figures are buried deep in the accompanying notes which you have to dig through tofind. This sounds more of the same but with dodgy methodology buried in Supplemental Materials that even an experienced person has to hunt for to find. Seems to that when such an obscure document appears, it should be downloaded/printed immediately before something “happens” to it.
When you consider that the FDA has shifted much of the responsibility of whether an individual should get the vaccine to the individual and their family doctor, it’s even more important to make whatever information exists about the vaccine’s contrindications easy to access and understand.
I can dig it. I don’t think that any of our resident commentariat doctors or medical professionals are in the wrong for having missed these docs. Supplemental info is standard these days so it should be there every time.
What’s amazing, if unsurprising, is that I feel like this blog is the only media outlet that’s even bothering to look at them. Has anyone else even heard of another media outlet reading the protocol?
+1,000
A thousand thanks.
This point is CRITICAL.
Crickets
We may indeed have one of the finest products of modern medical technology ever developed in our hands.
MAY,
But the failure to approach this with careful questioning and TRUE transparency shuld be cause for alarm by us all.
Apparently the raw data IS NOT available for independent groups to analyze.
I wonder how many people know that Pfizer are not liable for any bad consequences resulting from this rushed novel vaccine. I only learned the above recently & am concluding that the only skin in the game for them seems to consist of making lots of money.
Neither is anyone who “administers” the vaccines, as in a doctor or pharmacy. However, all of these employers who are considering requiring employees to get a vaccine as a condition of employment are putting a big liability target on their backs. They can definitely fire people for not taking the vaccine; sadly, unless you have a strong union or other employment agreement, you are an employee at will. An employer can turf you out freely unless you can make a case it was as a result of discrimination or whistleblower retaliation.
However, if someone is coerced into taking a vaccine, and the threat of being fired sure sounds like coercion, and Bad Shit Happens, the liability exemptions, based on my layperson reading, don’t give the coercer an out.
I cannot say with certainty but according to the Spanish law the administration of a vaccine will always be voluntary, so a company cannot force vaccination or coerce the employees for administration. There is special regulation for sectors exposed to high biological risk such as Health Care but in these cases, vaccination is still voluntary. Yet because emergency, some are demanding that companies could force vaccination but this would require judicial mandate and I wonder if judges are prepared to deal with this.
Here in Germany it is not Pfizer, that is rolling out the vaccine but a small company called Biontech. Biontech actually developed the vaccine but Pfizer is manufacturung it. The beauty from the point of view of Pfizer is that Biontech will be liable for any damages.
But things are even worse than that. Dr. Wodarg, a medical doctor and former member of the Bundestag for the Social Democrats who was a well known critic of the pharmaceutical industry has teamed up with the ex-Pfizer head of respiratory research Dr. Michael Yeadon to warn the public that the vaccine is highly dangerous. They have filed an application with the EMA, the European Medicine Agency responsible for EU-wide drug approval, for the immediate suspension of all SARS CoV 2 vaccine studies, let around the roll out of the vaccine.
They demand that it must be excluded, e.g. by means of animal experiments, that risks already known from previous studies, which partly originate from the nature of the corona viruses, can be realized. The concerns are directed in particular to the following points:
“1. The formation of so-called “non-neutralizing antibodies” can lead to an exaggerated immune reaction, especially when the test person is confronted with the real, “wild” virus after vaccination. This so-called antibody-dependent amplification, ADE, has long been known from experiments with corona vaccines in cats, for example. In the course of these studies all cats that initially tolerated the vaccination well died after catching the wild virus.
2. The vaccinations are expected to produce antibodies against spike proteins of SARS-CoV-2. However, spike proteins also contain syncytin-homologous proteins, which are essential for the formation of the placenta in mammals such as humans. It must be absolutely ruled out that a vaccine against SARS-CoV-2 could trigger an immune reaction against syncytin-1, as otherwise infertility of indefinite duration could result in vaccinated women.
3.The mRNA vaccines from BioNTech/Pfizer contain polyethylene glycol (PEG). 70% of people develop antibodies against this substance – this means that many people can develop allergic, potentially fatal reactions to the vaccination.
The much too short duration of the study does not allow a realistic estimation of the late effects. As in the narcolepsy cases after the swine flu vaccination, millions of healthy people would be exposed to an unacceptable risk if an emergency approval were to be granted and the possibility of observing the late effects of the vaccination were to follow. Nevertheless, BioNTech/Pfizer apparently submitted an application for emergency approval on December 1, 2020.”
Here a link to the only English language article about the petition that I could find:
https://2020news.de/en/dr-wodarg-and-dr-yeadon-request-a-stop-of-all-corona-vaccination-studies-and-call-for-co-signing-the-petition/
(tinfoil alert)
dern…that’s pretty chilling…and in line with what my spidey senses have been tingling about since all this began.
hypercynicism trends into tinfoil, sure…but the fundamental problem humankind faces is overpopulation…it’s at the root of all the other problems.
eugenics has a long history in the Versailles of the world, after all…and what a perfect opportunity a badly managed pandemic provides.
“Thin the Herd” has been running on track 3 of my mind since march.
I hate that(unprovable, etc), but there it is.
it’s a testament to how little i trust those in power: ie: they can’t be trusted with a fork.
hats off to whomever called the pfizer/moderna vaccines “Darwin Filters” yesterday.
that’s where my vibe antennae and prophet’s beard have left me….and the PTB sure ain’t doing a good job of dissuading these worries.
(tinfoil off)
The thought that occurred to me was “Gaia decides it’s time to cull the herd”
Re: the possibility of auto-reactivity to placenta — the “vaccines for sterilization of minorities” meme would become immortal, with justice.
Does ADE arise after natural exposure to coronaviruses? Is there any way to pre-emptively down-modulate this response?
well, from Gaia’s perspective, us pesky Fire Monkeys have learned to thwart her usual go-to herd management tools…with sanitation(sewers) and modern medicine(antibiotics and vaccines).
add in energy dense tools, like oil and coal, and we’ve managed to overshoot carrying capacity more than the st matt’s island Deer ever could.(i’m guilty of conflating st matthew’s reindeer with plum island foot and mouth at times, mea culpa,)
I remember, prolly 15+ years ago, the trope in my doomer/peak oil circles was that if everybody on earth lived like a moderately poor us citizen, we’d need 5 additional earths.
my wife has often said that she thinks of global warming as Mother Earth having a fever to knock down the human pathogen.
Well, if one drills down into Eldridge and Gould’s Punctuated Equilibrium addition to Evolutionary Theory, some evolutionary changes to highly successful species occur when there is population reduction and isolation of remnant populations that allows new characteristics to become “fixed.”
In this current extinction we will test whether or not genus Homo will undergo another round of speciation. But then, I look upon humans as a geological agent.
“humans as a geological agent.”
+10
anthropocene, and all.
instead of a strata of ash, there’ll be a strata of microplastics marking our passage.
Previously I lightly joked that in the sedimentary record we will be known as the band-aid civilization from all the band aids lost while swimming in lakes.
Yes, ADE occurs after vaccination (or natural infection), with exposure then to the wild virus. This is the catastrophe that occurred (and killed children) in the Philippines after the mass rollout of the Dengue vaccine.
The fact checkers have been out saying that the bit about female infertility is fake news.
However if you read the trial, women who are involved with the trial need to be on birth control and no pregnant women were involved. So it’s inconclusive and it’s on Pfizer to prove that this is not harmful to fertility.
Dr. Yeadon has been discredited for statements he has made in the past that were patently false, so I would take whatever he says about the Pfizer vaccine with many grains of salt.
Can you back up that accusation? Links and facts please.
From a 15 minute inspection, this news source ‘2020news’ strikes me as unreliable and untrustworthy (a source that boasts of its own objectivity is almost always a red flag). Do you have another? auf Deutsch would be fine.
This is something that really concerns me. Its logical to provide some sort of partial indemnity given the urgency, but the type of blanket indemnity provided seems to me to be a recipe for providing exactly the wrong incentives to the drug developers. You need at least some skin in the game, as you put it.
If I was to use an analogy, if you wanted to build a house built, and did it by providing an absolute indemnity to the architect and construction company for any and all faults or construction regulation failure, nobody would be surprised if it collapsed around your ears in the first storm.
They have transferred the responsabilities totally to the Public Administration. It is the P.A. who decides whether to approve or not the vaccine and there is where responsibilities lie. Any bad outcome will lie in their back and I think this is correct since it is political pressure what is speeding the process so much and breaking the normal procedures.
It is ultimately the regulators who are responsible, but I think giving the companies a full indemnity provides an incentive to those companies to, at the very least, fudge data.
To a certain extent, the authorities can only go on the data provided by the drug companies and overall commentary provided by independent scientists. The companies have a lot of control over what information is provided to the regulators and the scientific community. The immunity in my opinion provides a strong negative incentive for them to, if not commit fraud, then at least modulate the information released to favor a positive response .
In theory it is not the company who monitors the trial, they are supposedly firewalled from it. There is an external board, which is supposedly shielded against pressures, designated to monitor the data and the safety procedures of the trial. So, the company couldn’t be blamed for data fudging but the board.
I don’t get it?
Go to the article – https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
Scroll down to the supplementary material and click Protocol – https://www.nejm.org/doi/suppl/10.1056/NEJMoa2034577/suppl_file/nejmoa2034577_protocol.pdf
ctrl-f “exclusion” and there you are.
What’s the big deal? It’s completely normal for the supplementary material not to be included in the article pdf. In this case it runs to 376 pages.
All of this information has also been available on the clinicaltrials.gov listing for months – https://clinicaltrials.gov/ct2/show/NCT04368728
By all means ask the question whether people with severe allergies should have been excluded from these trials. Like everything it’s a tradeoff, in this case made more difficult by the obvious need to get an answer on these vaccine candidates as soon as possible. Delaying the trial by a week, or even a few days, would have led to far more preventable deaths from covid-19 than could ever occur from anaphylaxis.
You appear to be new here. I suggest you read our site Policies before commenting again, since by commenting you have consented to them.
They require that a reader have read the post in full before commenting. You either didn’t or are choosing to pretend to be obtuse, which is arguing in bad faith and a different violation of our Policies. Violations put you on a fast track to having your commenting privileges restricted or revoked.
First, as the post explains, there is strong reason to believe, even though we cannot prove it due to the state of the Wayback Machine, which does not display the article and editorial as they were presented initially, on the front page of the NEJM site, that nine doctors, one biomedical professor/scientist, one interested reader and I did not see any Supplemental Materials. Some (I presume most/all, I haven’t asked IM Doc for more detail from his fellow Journal Club members) DID see a prominent (as in the header area) “Supplemental Appendix” link and checked it out to see that it was an informational nothingburger.
The nine doctors and the professor have all been reading medical papers for decades. The fact that they didn’t find it despite a lot of looking (in IM Doctor’s case, over several sessions since he kept checking over the weekend, before the paper was moved off the front page) suggests it was not there or not placed properly. This is consistent with the PDF having bizarre formatting problems and my finding that the site was having rendering problems when using a not-current version of Firefox on the Mac (these went away when the article was moved off the front page of the site). At best, the prominent position of the Supplemental Appendix (before the article was moved off the first page) deterred some (many) from looking for the Supplemental Materials.
Second, you are completely wrong in your assertion about the PDF, and your posture confirms that Lambert’s post on the information deficiencies is badly needed. The failure to mention in the PDF where to find the protocols after referring to them is a violation of the AMA style guide.
Follow me…doctors and scientists and their employers pay big bucks to publishers like the NEJM to present information clearly and completely. If readers have to go on a treasure hunt to find important data, the institution has blown its basic mission (or perhaps more accurately, its strategy for commanding enough attention from medical professionals to be an important venue for advertisers). The need for publications to be respectful of their readers’ time and organize their information well is even more important given how stretched front line doctors are due to Covid.
As IM Doc said, and you chose to try to talk over, the article and/or the editorial should have EXPLICITLY discussed the exclusion criteria, even before the allergic reactions by the 2 UK nurses put a spotlight on this issue. The Pfizer vaccine deploys a technology that has never been used on any scale in humans, and due to the expedited trial process, none of these mRNA vaccines were tested in animals. And they are now about to be deployed in the population at large, unlike most medications that target much smaller groups.
Doctors have every reason to know who got the vaccine. Recall also IM Doc’s related concern that there may not have been many old people in the trial. The age distribution could easily have been heavy on 55 to 60 and have had just a handful of oldsters. That would fit with the little that Pfizer presented.
The PDF did not discuss or even mention exclusion criteria, which IMHO in and of itself is a fail. The second fail is that it mentioned the protocol twice, in passing, without telling the reader where to find them. You don’t pay for a fancy article to go have to do Google searching to locate essential material. Any mere grad student who did something like that in a paper would have been dinged.
“…wasn’t even tested in animals.”
I missed this tidbit, somehow.
that makes it all even worse.
have a link handy?
That’s one reason the vaccines could be approved so quickly. See below, previous attempts with other mRNA vaccines for other diseases for the most part didn’t make it out of the animal trials. A reader claimed there was a mRNA vaccine for Zika tested only on 120 people but I didn’t see a link. Needless to say, that wasn’t approved.
This is in narrative form and doesn’t give timelines. Sorry not to provide more but I really need to turn in. But you can see animal testing is the next stage after in vitro testing.
https://www.fda.gov/drugs/information-consumers-and-patients-drugs/beginnings-laboratory-and-animal-studies
Yves: previous attempts with other mRNA vaccines for other diseases for the most part didn’t make it out of the animal trials.
There’s a central point you’re missing.
You’re assuming the mRNA vaccines were developed as vaccines against infectious diseases and there were previous attempts to use the technology against infectious diseases (besides the Zika virus).
Certainly, in the case of the Moderna mRNA vaccine technology, that’s false. Moderna never made any such attempts because — as Patrick alludes to — over the ten years that company has existed their mRNA technology was being developed entirely as a platform for a cancer vaccine.
That is, the aim was a personalized medical treatment whereby an individual cancer patient’s specific cancer would be sequenced and a ‘vaccine’ would be created so the individual’s immune system would be ‘taught’ to recognize that specific cancer and fight it.
I can’t speak to the Pfizer vaccine’s history and what else those who developed it might have strategized or intended or tried. But the ‘cancer vaccine’ angle presumably would have been primary there, too.
As regards the burying of the exclusion criteria for the Pfizer trials, IM Doc is right to raise objections.
If a novel biotechnology is introduced on a mass basis, every effort needs to be made to explain what it is and how it works, because otherwise it’ll be incomprehensible to most normal non-biotech-aware people — which definitely includes most of the doctors and nurses who’ll haveto administer these treatments — and incomprehension naturally leads to fear. As here.
As I mentioned, mRNA technology was also used for a Zika vaccine and it did not wind up winning approval. Nature says it has been in development for other infectious diseases. This is from a 2018 article:
https://www.nature.com/articles/nrd.2017.243
This 2019 article has an extensive discussion of the efforts to improve mRNA technology and develop vaccines. It seems it is/was further along with animal vaccines. For instance:
https://www.frontiersin.org/articles/10.3389/fimmu.2019.00594/full
Interesting.
Well, I apologize. I only knew Moderna’s history.
The claim that this vaccine was not tested in animals is not true.
The mouse and macaque studies on BNT162b2 were published as a pre-print in September and in NEJM in October. You can read the manuscript at https://www.nejm.org/doi/full/10.1056/NEJMoa2024671 or on medrxiv at https://www.biorxiv.org/content/10.1101/2020.09.08.280818v1.
There are decades of research in other non-human animals underlying this work. There have also been previous human trials of mRNA vaccines for cancer, which were safe but not shown to be effective.
As I read this, these were efficacy studies, not safety studies. The usual sequence, as I understand it, is animal safety studies are the next step after in vitro, not animal efficacy. It looks as if the animal safety step was skipped unless you can provide a link indicating otherwise. The focus here is safety for very broad populations.
And reading between the lines of the Moderna hype, the well tolerated mRNA vaccines were not effective precisely because they didn’t elicit much of an immune response. And the blurb also makes clear mRNA vaccines are or can be highly tailored; Moderna’s original raison d’etre was personalized cancer treatments. So any past safety findings would seem to be irrelevant for any vaccine that didn’t make it through due to lack of adequate immune response.
https://www.nature.com/articles/d41586-019-03072-8
So please show me the safety, as opposed to efficacy, study. I’m prepared to stand corrected. I must note the mice study had only 8 per group, which seems awfully small. The NEJM site is not responding so I can’t look at that study.
The comment from Dissent Voice below, which is left wing and hence not in the knee-jerk “medical freedumb” camp, summarizes the history very differently than you do. Cribbing from the extract below:
https://dissidentvoice.org/2020/12/from-tmap-to-warp-speed-how-big-pharma-algorithms-fast-track-unapproved-drugs-and-vaccines/
I’d also like KLG to weigh in, since this is his area of expertise.
I’m no expert on preclinical nonhuman vaccine studies, but I’m not sure I understand your distinction between safety and efficacy trials in this context.
Are there specific safety experiments you think should have been done which aren’t reported? I don’t know of any animal model which will provide information beyond what we see in 43,000 patients worth of phase I, II & III data.
As to your link above, I don’t follow.
Previous animal studies with different vaccine platforms did indeed show evidence of antibody dependent enhancement in SARS-CoV-1 and MERS-CoV. This has definitively not been seen with the Pfizer/Biontech vaccine or any other SARS-CoV-2 vaccine which has been reported on to date. It just doesn’t seem to happen with this virus or at least with the platforms reported to date, which is a happy accident of biology.
By the way, the name for what you’re doing is ‘moving the goalposts’.
I read the articles. I thought the author made a few interesting points, but I wasn’t convinced by today’s follow-up hence my reply.
I am a doctor and I read clinical trials all day. Unfortunately many trials are poorly reported and I am used to spending a lot of time ferreting out pieces of information that companies try to bury. I completely agree that this is a problem and needs to be addressed with iron-clad reporting guidelines.
re: your comments – If the supplementary material was missing when the NEJM article was posted that’s an interesting observation, but there’s no evidence of that presented here and it doesn’t seem to have been noticed by anyone else. As it stands it’s available now and has also been available for months on the clinicaltrials.gov record.
I don’t really know what else to say other than that I found the data without any trouble, and I’m not sure what all the fuss is about. If I wrote the manuscript I would have put the exclusion criteria in the final flow diagram, but all of the data is there, with no paywall, for anyone to see. In the grand scheme of pharmaceutical company shenanigans this is nothing.
On your comment that ‘none of these mRNA vaccines were tested in animals’ – the non-human primate studies on BNT162b2 were published as a pre-print in September and in NEJM in October. You can read the NEJM manuscript at https://www.nejm.org/doi/full/10.1056/NEJMoa2024671, or the preprint on biorxiv at https://www.biorxiv.org/content/10.1101/2020.09.08.280818v1 . This work is supported by decades of work in other non-human animals, and previous trials of mRNA cancer vaccines in humans.
p.s. I’m a bit taken aback by the tone of your initial response. I don’t think I’ve done anything that contravenes your policies, and I get the sense that you’re attributing motives to me that I don’t hold. I was just trying to add to the discussion – if that’s not how things work here then I’m happy to go somewhere else.
I’m curious as to your thoughts on the state of play with the vaccines in general.
They’re the real deal. The trials have all been well run (dosing snafus aside) and the side effect profile is mild. It turns out it’s much easier to make vaccines for this disease than we thought, which is a great result. mRNA vaccines are probably going to be a major part of medicine going forward, which is fantastic.
Remains to be seen how effective they are in reducing spread as well as preventing severe disease. There is an encouraging signal in the Oxford/AZN trial, but the trials done to date can’t answer that question conclusively and we will need to wait for a much larger sample.
My sense is that some countries are itching for any sign that they can declare victory and move on from COVID-19, and even if there was no effect on spread then that might be good enough for them. Countries in Asia which have managed to eliminate or suppress the virus are in a more precarious position (though obviously still an enviable one), because I think they’re going to be much less enthusiastic about opening up completely if we have a vaccine which prevents disease but doesn’t wholly prevent spread.
So, short answer – great news, we’re not out of the woods yet but we are now in a much better place than I and most others thought we would be. I’ll be very happy to have whichever vaccine is available when my spot comes up in the queue.
I’m sorry, but your comments don’t give me confidence – rather the opposite. I’ve never heard a doctor cheerlead for any drug as much as you are for this vaccine and I have to wonder why, especially since this new type of mRNA vaccine is still experimental and mRNA has not had much success in the past being used for anything else.
Second, you read clinical trials all day – do you ever see patients? I called my doctor about this vaccine since it is becoming available – I wanted to know if she would recommend it for me given my health issues – and she is not very happy with the Pfizer’s study right now. She doesn’t have time to read clinical trials all day and she wants to see the things she needs to know – like contraindications – highlighted in some manner – much like what she sees with other medical studies – she doesn’t want to have to dig around for them. She is not recommending the vaccine until she can sit down and read the Pfizer articles thoroughly, and she is so busy right now she doesn’t know when that will be.
I agree. I thought Patrick’s initial points were intellectually honest and I was intrigued to see where this may lead, but this last comment reads like a Big Pharma advertisement.
In Patrick’s defense, the potentials of the mRNA vaccine technology are exciting, as he says elsewhere. Its application to COV19 are just the tip of the iceberg.
Maybe – and then again, maybe not.
https://www.statnews.com/2020/11/10/the-story-of-mrna-how-a-once-dismissed-idea-became-a-leading-technology-in-the-covid-vaccine-race/
I made a longer reply which seems to have been deleted by somebody or removed by the spam filter.
Short answer – they’ve exceeded expectations, which is fantastic. Turns out it’s easier to make a vaccine for this virus than we thought, and that the serious side effects which were problems in previous coronavirus vaccines are either not an issue with this virus or with these vaccine technologies.
The trials were well run and there are no significant safety concerns. There will be reports of rare and idiosyncratic adverse events, but I expect most of this to be the inevitable noise which occurs when millions of people receive a drug. If there is a late safety problem it will be detected by the vaccine surveillance systems in place around the world.
Different countries will respond in different ways depending on how effective the vaccines turn out to be in preventing the spread of disease (in addition to preventing people becoming seriously ill when infected). I suspect European states are itching to declare victory and move on, while countries in Asia which have achieved suppression/elimination will be less enthusiastic about a vaccine which only prevents disease. Time will tell.
And I expect that mRNA vaccines will have an enormous impact on medicine more generally. Exciting times!
The future of this vaccine is so bright that I need sunglasses.
Seriously, your post reads like a pharma blurb. Not helpful at all; really worse than not helpful. When I read this sort of thing it confirms to me that I am being fed pablum.
This is a contradictory mess of “if this, then that.”
(1) Expectations have not been exceeded. It is unknown if this vaccine will work long-term (based on known coronavirus pathobiology, probably not, but I am not a virologist). Does it prevent transmission? If it requires a yearly booster, fatigue will set in quickly, especially if it “hurts.” The annual flu vaccine works, sort of, but for healthy people influenza does not kill nearly as often as Covid-19, nor leave many people damaged after apparent recovery. And yes, it is theoretically “easy” to make any mRNA vaccine, not only for this novel coronavirus. The molecular cell biology of this is very simple in principle. Sometimes simple principles lead to successful clinical interventions. More often, however, they are simple minded. But just as often they can lead to incremental advances, which are not to be denigrated.
(2) By no means has it been determined that serious side effects have been avoided. This is conceded by Patrick: “If there is a late safety problem it will be detected by the vaccine surveillance systems in place around the world.” A “late safety problem” could be horrific. No one is assuming this will be the case, but thalidomide was thought to be just a tranquilizer and cure for morning sickness. I realize comparing this vaccine and a drug border on a category error, but “rare and idiosyncratic” are in the eyes of the beholder. Because of late, great Frances Kelsey of the FDA, thalidomide was not the disaster in the US as it was in Europe.
(3) If expectations have been exceeded, then “how effective the vaccines turn out to be in preventing the spread of disease (in addition to preventing people becoming seriously ill when infected)” are not an issue! And since this vaccine must be kept at -70C from manufacture to the site where people are vaccinated, this product is for only what was previously called the “First World.” A supply chain that meets this requirement is not possible in most of the world. This has been discussed at NC and no one has come up with a solution. (My small institution has a bunch of these freezers and that might mean we are a depository site. I have such a freezer full of priceless, i.e. irreplaceable cells, reagents, and yes, RNA, which I am not looking forward to losing. Even if I am likely to never use them again ;-))
(4) “And I expect that mRNA vaccines will have an enormous impact on medicine more generally. Exciting times!” mRNA vaccines are as likely to revolutionize infectious disease prevention as angiogenesis inhibitors were likely to “solve cancer,” in the words of Jim Watson (of Watson & Crick) when he famously announced “Judah Folkman has solved cancer.” (paraphrase) Angiogenesis inhibitors are very useful in a variety of disease states, including macular degeneration, but they are not magic. Incidentally, thalidomide is now used successfully
So what’s the bottom line? My fat ass will get the vaccine! Fortunately, while I am highish risk (age over 60, overweight, due to asthma, and having been hospitalized in the ICU with pneumonia twice) I don’t expect the call any time soon. This buys ‘me’ time to wait and see. Ditto my wife although she is very healthy and turns 65 this coming year. Why does this matter? Simple; it’s because data is going to be generated in a big way in the coming months and the math nerds will be all over it, and because of the Internet, it’s unlikely to be suppressed for long. The point being this; there are more than one vaccine in the pipeline and by the time my number is up, e.g. it’s my turn, I may have some say so in which vaccine I throw the dice. Thank you Susan for starting this whole thread. I feel indebted to you.
I lack your confidence that “the Internet” will not be controlled and manipulated to suppress honest scientific skepticism about the vaccine(s), and/or evidence of bad side effects.
Twitter is already censoring content related to the vaccine that doesn’t toe the line. FB is probably not far behind. Of course there will be “alt” media but beware labelling. This site already ran into a vicious smear campaign a few years ago where it was labelled as Russian propaganda.
Your point on multiple vaccines is fair and I have a similar stance – I am hoping the more traditional weakened-live virus or single-shot vaccines that come out in the future will be offered as an alternative.
“I am hoping the more traditional weakened-live virus or single-shot vaccines that come out in the future will be offered as an alternative.”
that’s where i’m at as well
as is every healthcare person i’ve asked about it …some of whom i’ve known for decades.
so far, i think i’d prefer the chinese vax…but i’d likely settle for the oxford.
that said, further study is warranted.
Yes! mRNA vaccines may be the future, but there is no reason to gamble on a first-in-history mRNA vaccine. No reason.
So I’ve been following the only one of the 6 Warped Speed vaccines made with traditional technology – the GSK-Sanofi product – protein subunit DNA recombinant, same as current Hep B vaccine.
However – this product hit a snag last week where the efficacy for >60 was not as good as it should be, so they now have a 6-9 month delay. The sinovac product from China is traditional inactivated vaccine, was purchased by the UAE and according to what has been published (no data) it blocks infection 100% and disease 85%. Blocking infection, or sterilizing immunity, is the holy grail here. Otherwise we have an endemic disease with no public health benefit. Actually we have the perfect neoliberal vaccine: I’m protected, and fuck you.
“Yes! mRNA vaccines may be the future, but there is no reason to gamble on a first-in-history mRNA vaccine”
!!!!yes!!!
this method could absolutely revolutionise medicine.
i’ve been excited about it for a year and a half.(found it while researching what our oncologist calls “clinical trials”
but there’s all manner of questions that must be answered before we turn it loose in the general population.
this is NOT mature tech, at all.
i feel gaslighted.
and i don’t trust any of these people at all.
An article in Dissident Voice raises some questions about all the vaccines:
“it should be noted that the US Food and Drug Administration (FDA) has never before approved human use of a vaccine for any previous strain of coronavirus due largely to severe inflammatory autoimmune side-effects in animal trials. At the same time, neither mRNA vaccines, nor DNA plasmid vaccines, nor genetically engineered adenovirus vaccines have ever before been approved for human use in the United States. Obviously, this begs the question: how is it that these experimental vaccines, which have never been approved by the FDA, are suddenly becoming safe and effective for the first time in history under less rigorous conditions when standard testing protocols are being shortcut at emergency “warp speed”?”
This is all true. We do have one adenovirus vector vaccine, but it is for rabies and is given to dogs. They are not known to complain much. Good dog.
I’ve been yelling about this since May – why do we have not one option for a vaccine made with traditional technology? By definition, when a drug or treatment gets a EUA, that means it is experimental. We are undergoing a huge experiment. God help us.
We seem to be doing everything wrong. After enough “car crashes” maybe we learn the hard way that all those rules and caveats are there for a reason, and shortcuts have a price.
Maybe each Pfizer vaccine vial should simply be stamped with the motto: ‘May the odds be ever in your favor.’
It’ll truly be the hunger games when you’re required to get your mRNA vaccine before you can get your SNAP/food stamp benefits.
“Your EBT card has been deactivated pending proof of vaccination. Please contact your county assistance office for details.”
****—-staggers over o the seedbank…opens it…shines a light down on all the jars and envelopes and packets in there(box my great uncle Carl made.)
we’re good.
not so certain about the rest of y’all.
The vaccine is now in my town and the local hospital system’s Covid spokesdoctor was the first to get the shot. Says he in this morning’s paper
Obviously people are sincerely desperate for this epidemic to be over and urgings re the vaccine shouldn’t be assumed to be sinister as many on the web rightwing are doing. But it does seem remarkable the extent that the “precautionary priniciple” which we’ve all been living by is being tossed when it comes to this likely to be profitable vaccine from Pfizer. It’s telling that some of the biggest skeptics of this and for that matter everything that has been going on are doctors themselves. Thanks for the above and the article from the other day. As one of our politicians once said: trust, but verify.
I will note for the record the comparison with Boeing execs promising that the new, revamped MAX will be “the safest plane evah!”
The Shakespeare quote about “the lady doth protest too much” applies to such hyperbolic statements.
As IMDoc pointed out the other day, pharma’s modern track record is a lot worse than Boeing’s. The difference is coverage may stem from pharma’s heavy advertising presence on TV in particular
+1000
And the Titanic was unsinkable. You think people would be more wary of anyone spouting hyperbole.
Pharma companies and commercial aircraft manufacturers have a common issue: both invest huge amounts of money and time in the development of highly complex products which, when they fail, can kill large numbers of people. That’s “when,” not “if,” because some failures are inevitable. Disciplined science and engineering practices can reduce the risks, but they cannot be completely eliminated. Henry Petroski has written on this topic – as a society, we accept some level of risk in order to realize the benefits of the technology, and learn from the failures to make it better next time.
This should be considered in light of the classic balancing act between quality, schedule, and cost, often stated as: “good, fast, or cheap, pick any two.” It is obvious that “Operation Warp Speed” is optimized for schedule. The tradeoffs that affect quality must be explained and the decision-making process fully transparent if people are going to trust their lives to the results.
Of course the decision-makers must be held accountable, but any lack of transparency here was most likely due to rushed and sloppy execution. Hanlon’s razor applies.
In today’s Links, there is an Alex Berenson tweet which reads numbers of covid cases recorded in a vaccine study and the fact that the vaccinated number was less, but not dramatically so, when compared to the placebo group.
Anyone, is this accurate? Are other trials having numbers similar to this? And what of the 95% number that gets tossed around in all the PR writeups? Does 95% represent the percentage of vaccine takers who will be protected from infection or is it the confidence that the vaccine shows any type of effective protection against covid (perhaps only 25%)?
Berenson is quoting directly from the FDA, as you can see from the link. On a commonsense reading, it looks really bad, but Berenson wasn’t willing to go there for the obvious reasons. You can apparently work out why the 43,000 ish subjects mentioned virtually at the top of the Pfizer article were somehow only 37,000 ish (and different 37,000ish) in the Safety and other breakdowns. Those people who maybe did, maybe didn’t get Covid and weren’t tested to ascertain their status may have been part of the reason the #s are disparate, but if so, that doesn’t seem to be a good reason for their exclusion. Point is I need to run this down and haven’t.
My understanding is that the 95% number is the risk reduction for infection resulting in disease symptoms.
As I understand it, they didn’t systematically test for the possibility of asymptomatic infection (which could, in principle, lead to vaccinated asymptomatic spreaders) in either arm of the trial, so it is not known to what degree, if any, the vaccine will influence the “reproduction number” in populations that have significant numbers of vaccinated people.
I hope that vaccinated people do not abandon their prior protective measures. I believe that Francis Collins has appealed for continued compliance for some period of time with the baseline public health recommendations even after one has received a shot.
I earnestly hope that these vaccines are able to induce “sterilizing immunity”. That would greatly ease concerns about the possibility that receiving the vaccine might predispose one to more severe disease symptoms if subsequently infected with live virus.
The extract from FDA is NOT about asymptomatic patients. It says there were nearly 1600 suspected cases in the vaccine group and over 1800 in the control group. WTF? Why wasn’t this run down?
It’s insane. They had a negative PCR on a test that is somewhere between 75-90 percent sensitive and somehow that’s enough to leave them out if the analysis?
If this…is…what it seems to be clearly stating it is, it is beyond what I expect both from fudging numbers, and from…wide scale societal impunity to fudged numbers. And my expectations are not high. Since reading bthat link this morning I’ve been confused all day by what seems to be the in-plain-sight badness of this.
Re “Does 95% represent the percentage of vaccine takers who will be protected from infection or is it the confidence that the vaccine shows any type of effective protection against covid (perhaps only 25%)”, you are asking what is efficacy. Efficacy has a simpler meaning than what most people think it is. Often people interpret efficacy to mean a personal measure of probability or risk. It is definitely not a measurement of probability. In the clinical trials, under favorable conditions, there are 2 populations: the vaccinated and the unvaccinated. Over time, people in both populations will become infected. Efficacy measures how much smaller is the infected, vaccinated population compared to the infected, unvaccinated population. Nothing personally can be extracted from efficacy as it relates to population data.
I’ve been reading this site since inception leading up to the 2008 real estate/mortgage financial collapse. The well documented articles of rampant corruption of mortgage market and financial institutions with moderated knowledgeable comments (and Yves book “Econned”) helped us avoid financial devastation as a result of the real estate collapse.
I’m now forwarding NC’s articles and comments to friends who are analytical thinkers and concerned about the many vax issues.
Thank you Yves
Agree 100%
A lot of strong critical thinkers on this site — led by the authors.
Great work!
I think the lesson here is that drug companies should not be in charge of testing their drugs. It should be done by a neutral organization. For me, the most disturbing aspect of the Pfizer study was they didn’t test for asymptomatic cases.
Perhaps equally disturbing is that this distinction (symptomatic vs asymptomatic infection) is rarely, if ever, discussed in the media rollout blitz, even when docs and immunologists are interviewed. One wonders why they did not test for asymptomatic cases, as it seems logical and necessary that they would, and it would have been relatively easy to do.
The difference between sterilizing immunity and suppression of symptoms is huge. It seems unlikely that they did not do this at least on a smaller sample. Could still be done. No data on this? Am I missing something here?
IM Doc said notice had gone out from the teaching hospitals not to say negative things about the vaccine. Maybe a similar notice went to the press. Its just weird to me they didn’t test for asymptomatic cases. Were there logistical problems? Were they afraid of bad results?
Occam’s Razor hypothesis:
A process that normally takes 5-10 years or more has been compressed into well under a year. This has necessitated a lot of short cuts. While it has been done as responsibly as possible in the time available [citation needed] there is still a fair amount of residual risk and uncertainty. As we have seen already during the pandemic, science playing out in real time tends to be messy and full of ambiguity and rarely delivers clear answers. This naturally leads to a lot of misinterpretation and FUD in the media and community.
Two primary strategies are available for dealing with this:
1. Devote resources to explaining the situation to the public as clearly and simply as possible, with updates when anything changes, so that there can be an informed debate
2. Devote resources to a propaganda campaign, make sure your story is the one that spreads, and actively suppress any criticism.
The political class in the US are going with the strategy they know best and are most comfortable with, which is #2.
Oh, and on the asymptomatic cases question, I think I read in the OP comments that they didn’t test asymptomatic participants because they were were trying to maximize participation and were worried it would put people off (it would have meant regular testing for all study participants whether they got sick or not).
I agree. IIRC, the reason is portrayed to have been fear that this would deter participation in the study.
But it would have been possible, me thinks, to have tested for asymptomatic infection in a subsample in both arms. To avoid deterring participation, I think it would even have been justified (though methodologically grotesque) to have allowed these sub-samples to be “self-selected” — ie, solicit volunteers who are not deterred by the repeated testing required.
I think this self-selection would have prevented meaningful assessments of the relative risk of asymptomatic infection in a notional general population whose properties did not match the self-selected sub-group, but I think it still would be useful to have some data about the absolute frequency of asymptomatic infection in the vaccine arm, since that would tell us at least a little about the possibility of the vaccine conferring sterilizing immunity in at least some recipients.
As it is, we know nothing about the frequency of sterilizing immunity. That strikes me as a very large hole in our knowledge.
I have a hard time believing all those clever people in medical research couldn’t devise a system for testing for the asymptomatic cases.
two-day old news, which is a long time in a pandemic:
https://www.usnews.com/news/top-news/articles/2020-12-15/moderna-says-its-covid-19-vaccine-may-prevent-asymptomatic-infection
Moderna is reporting evidence of risk-reduction for asymptomatic infection.
So they did test for this, though Pfizer did not.
The relative risk looks to my untrained eye to be statistically significantly lower than unity, but there is probably a pretty wide confidence interval for the precise value.
Samuel Conner:Moderna is reporting evidence of risk-reduction for asymptomatic infection. So they did test for this, though Pfizer did not.
Eh. I find it implausible that Pfizer didn’t test at all for risk-reduction of asymptomatic infection.
Easier to believe that they tested and for whatever reason(s) chose not to report.
It might be as simple as inadequate data and Pfizer wanted to be out the gate ahead of Moderna. Still not good.
I haven’t read the Pfizer protocol, but if Pfizer did test for asymptomatic infection as part of the study plan but did not report this data
AND
scrubbed the parts of the protocol that would necessarily mention the collection of this data
that would be a very bad look.
But surely the study protocol was made public months ago.
Could there be an unpublished protocol within the protocol?
I think that the least complicated unsympathetic explanation might be that they preferred to not make the effort in the early trials. I believe it has been affirmed that “sterilizing immunity” will be assessed as an outcome in ongoing study.
That’s the way I’ve felt for a long time. An independent organization paid for from taxpayer funds (preferably an international one) needs to be in charge of testing and approval of all pharmaceuticals. Pharma may submit their drugs for approval to this organization.
We used to have such a thing. It was called the FDA.
Thanks very much to NC for your early and wide ranging links about the C19 virus. You’ve become my go-to reading site not only for the links in general but also for the informed comments from IMdoc and many others.
My Mother is actually being Pfizer vaccinated today, but according to my sister who is her carer the old girl is already slipping away due to her physical state & the Alzheimer’s. Sis isn’t getting much sleep as she has to increasingly give Mum a nudge when she hears her breathing stop. I guess it is only a question of short time now, of which the vacc will likely make no difference or perhaps tip her over the edge. I just hope that it doesn’t cause discomfort & to be honest I hope Sis misses a breathing lapse fairly soon for her own sake & Mum’s as the latter’s quality of life is very poor – easy for me to say of course as I won’t be the one to find her gone.
I would have stopped the vaccination but it’s not my call.
I’m sorry you are going through that, truly.
Ma’am or Sir,
FWIW – I don’t know your mom or your family.
But your situation is the exact reason why immunizations should be handled by a PCP who knows her and her story well. To degenerate them into every one line up in the parking lot and get them one by one is not the best idea. We are in a crisis and we may well have to do things not the best. I keep telling myself that.
I have been a provider in this pandemic from Day 1. I have seen nursing home and rehab patients many of whom have dementia enough to make them unable to understand their circumstances. All across the land they have been turned into literal prisoners. It has not been a good scene.
I would suggest to you that you step back and evaluate the risk and benefit to your mom in her current situation as I am with every single patient. She sounds like she has a limited life span – and a limited quality of life. If this vaccine allows her to not spend that time as a prisoner – I think that sounds like a win for everyone involved. If she has a vaccine complication that is life ending (profoundly unlikely) – in my opionion that would have been worth the risk. One thing is for sure – you should not stress once you make the decision.
Good luck and God be with you.
Thank you Cocoman but as I mentioned it is my sister doing the heavy lifting & I am reconciled to the fate of my Mother, although I am fully aware that when it becomes a reality I will be hit by the emotional equivalent of a ton of bricks.
IM Doc
Mum is where she wanted to be which is under the loving care of my sister within a prison of a kind caused by the Covid restrictions. Sis can’t drive anyhow & Mum is so lost that all she has to hang onto is my sister’s presence in all it’s forms of expression, which is largely oblivious to where she might be. The vaccination occurred earlier today & I shall ring in the morning GMT to see how it went.
Thanks for your concern & the information you have added to this site – Mum has had enough & believes that my late Father is waiting for her & I just hope that she will go gently into that good night.
Eustache, so sorry. I am in a similar position, my BFF is sliding down, I only hope it is into a good night. All we can do is look after each other as best we can, and hope that when it is our turn, someone will look after us.
To live in hearts we leave behind is not to die.
Away for 2 days – thank you HotFlash & I wish you all the very best of possible outcomes for you & yours.
I think that there are two general problems here. First, a general carelessness or ineptness of scientists and scientific publications in the way they present their materials, even to other specialists. “Not My Job, I’m a researcher, not a writer.”
But even more so, an indifference of the expert world, or a significant part of it, about the way their work is presented to the serious but non-expert general public.
In my case, as a non-expert I tried to find out what I could about “excess deaths”, which I think is the ultimate fact when discussing the seriousness of the pandemic. When I looked at official sources, I found myself in a maze; I knew that the information I wanted was there somewhere, but I never found it.
Much the same for a summary discussion of the significance of different kinds of tests. Between the full-dress maze of thorough scientific discussion, and the scattered chit-chat of day to day news, I could find no usable general discussion.
Late to the party…
In response to the good physician Patrick and others: Yes, the information necessary to interpret the results in the Pfizer vaccine paper is available now. The point is that the relevant data were not readily available upon publication. Whatever the explanation/motivation for that, regarding Big Pharma: as Maya Angelou put it, “When someone shows you who they are, believe them the first time.” As a physician, this list shouldn’t be obscure: thalidomide, Vioxx, atorvastatin (a can of creepy wiggle-worms beyond the scope of this discussion), fen-phen, Oxycontin…And the powers that be wail and gnash their teeth at deplorables who won’t “just trust the science.”
And yes, the paper (NEJM 383: 1544-1555, 2020) on the mRNA vaccine in nonhuman primates is published, and well done. Moreover, the Supplementary Appendices (1 and 2) for this article are exemplary, one click on the link to each and the data are presented in all their glory. The experimental population was 24 rhesus macaques, 12 males/12 females, 3-6 years old. The results are good in that they demonstrate measurable responses that are encouraging, considering such a small experimental population (which is unavoidable for this kind of research). Whether the results show much of an effect is a legitimate question, however. But this is also the nature of research using primates as an animal model (small numbers and the population variability inherent in that, inability to follow up on experimental results because of the small numbers and experiments legitimately justified and constrained by the applicable Institutional Animal Care and Use Committee (IACUC) protocol, limited normal and experimental tissue availability, expense). In my view this paper perfectly illustrates what is/was wrong with the vaccine paper under discussion. It is straightforward and transparent, supported by public and charitable private sources, including NIAID/NIH, HHS, and the Burroughs Wellcome Fund for support of a postdoctoral fellow (https://www.bwfund.org/about/).
The vaccine paper was “Supported by BioNTech and Pfizer.” The results of this paper are difficult to parse, and though the relevant supplementary material is now easily obtainable, the Supplementary Appendix 1 is unhelpful (compare with same in the rhesus monkey paper mentioned above). The segmented bar charts in Figure 2 are not a particularly good way to present data in which some of the segments are so small relative to the others, but they could be standard for this kind of paper? I honestly do not know, but they tend to hide as much as they reveal. The thin orange bars do not necessarily represent an insignificant number of events. Large tables are usually dreary beyond endurance, but in this case a complete table (with raw numbers and percentages) would have worked much better if the object is to tell the simple truth of your results. Supplementary Appendix 2 in the rhesus monkey paper includes such tables.
I do find this interesting, potentially revealing: “The proportion of participants reporting local reactions did not increase after the second dose (Figure 2A), and no participant reported a grade 4 local reaction.” p. 8, end of paragraph from previous page. Grade 4 events are defined by Case Western Reserve University School of Medicine as “life threatening or disabling adverse events (e.g., complicated by acute, life-threatening metabolic or cardiovascular complications such as circulatory failure, hemorrhage, sepsis; life–threatening physiologic consequences; need for intensive care or emergent invasive procedure; emergent interventional radiological procedure, therapeutic endoscopy or operation).” I can’t imagine what a grade 4 local reaction would be. Perhaps the physicians here can help. Severe and uncontrollable necrosis at the injection site? Permanent paralysis at the injection site? Immobility of the shoulder that does not resolve, assuming the injections are in the deltoid? The local reactions reported do seem to be what one might expect after a tetanus shot, which is not surprising. In any case, local reactions are not generally dangerous to the subject/patient, in comparison to systemic events, and this particular usage conditions the reader to remember “no participant reported a grade 4…reaction.”
The substantive dispute is whether this paper is candid. I did not see any explicit mention of “Grade 4 events” regarding systemic responses. A temperature of 104.9F is 40.5C, which any physician should/would consider a stage 4 event, hospital visit or not. And this did happen; a fever of 104.9F/40.5C is definitely a “life–threatening physiologic consequence,” of an inoculation in this case. The authors also defined Grade 4 as only “all events indicated an emergency department visit or hospitalization.” That is sloppy writing. All events? Or any events? Which is it?
Regarding safety and efficacy trials, the macaque study showed some efficacy using relevant measures in rhesus monkeys, but the numbers were too small to address safety. In monkeys. We are doing that now, with the human population at large. Maybe this is necessary. Maybe mRNA vaccines are the answer. If we had not dropped the ball after SARS declined and had continued that research, perhaps we would now have a solution, alas. Mike Davis has covered that in his recently released and updated The Monster Enters. A recent paper on an mRNA vaccine against Zika virus in three different mouse strains (Cell 168: 1114-1125, 2017) includes direct links to 6 human clinical trials and simple, transparent links to supplementary materials that would allow one to replicate the entire study. I note that Moderna provided some support for that paper, which is very good.
Still and all, mRNA vaccines make perfect biological sense. They were first considered theoretically in the “pre-modern age” of molecular biology and have been actively pursued for nearly 30 years. The point here is that many clinical interventions make perfect biological sense. The pioneering immunologist Paul Erlich (Nobel Prize in Physiology or Medicine, 1908) proposed a “magic bullet” for cancer 100 years ago. Last time I looked, we are still waiting for the anti-cancer cell antibody conjugated to a toxin molecule that safely and effectively kills cancer cells and only cancer cells. Not to get too far into the weeds, but integrin antagonists that prevent metastatic cells from doing their thing make perfect sense. Still mostly waiting for that, too. And when we stop waiting, it won’t be because we performed the experiment on the human population, under duress or not.
Finally, I am struck in this discussion by something I have emphasized to my colleagues about the preclinical medical school curriculum. I hear frequently that “we should just tell them (medical students) what they need to know.” To which my response is, “If we just tell them what they need to know, what is to stop Pfizer from telling them what they need to know, later?” No, I am not that “basic scientist” who thinks medical students should go down rabbit holes that we so enjoy. But if your physician is unable to cut through the bullshit because s/he was not taught to think while in medical school, you do need another doctor. Not to mention another healthcare system, but I digress. I have read in this discussion that the target market of NEJM is “physicians,” with the corollary that NEJM can “just tell them what they need to know.” I did not know that, but it is a good thing to know going forward. The English equivalent of NEJM (the Lancet) told us what we need to know once and loosed Andrew Wakefield upon the world.
Nor am I singling out Pfizer or any particular Big Pharma entity. There was a time when scientists such as Gertrude Elion and George Hitchins did basic research at Burroughs-Wellcome (RIP) that has changed our world for the better in ways they did not and could not imagine. That was before “Big Pharma” was a term IIRC. Pfizer et al., are now doing only what Mr. Market tells them to do (including Kelo: https://en.wikipedia.org/wiki/Kelo_v._City_of_New_London).
And therein lies the big problem. Cheers!
Thank you for your response.
Can you think of a single vaccine which later showed a significant adverse effect which was not detected in phase III trials? I would put a very low prior probability on such an effect existing. How long would you propose we extend the human trials to be sure, while thousands of people are dying every day?
The FDA defines a grade 4 local reaction in a vaccine trial here – as you intuited it’s any reaction requiring hospitalisation.
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/toxicity-grading-scale-healthy-adult-and-adolescent-volunteers-enrolled-preventive-vaccine-clinical
Your comments aside, the criticisms of the trials here are so vague (and so spectacularly uninformed, such as Yves’ unchallenged assertion that the vaccine was not tested in animals), that I’m having a lot of trouble parsing what anyone’s actual issue is.
What experiments do you think haven’t been done, or haven’t been adequately reported, for you to have the information you want? If the substance of the criticism is that the supplementary material might have been hard to find for a day or two and some of the tables aren’t helpfully formated, isn’t that all pretty insignificant?
It feels to me that most of what’s left is mood affilitation and (largely uninformed) cynicism – pharma is bad and they can’t ever be trusted. Skepticism is good, but cynicism is dreary and self-fulfilling. Sometimes good news is actually good news.
No, I am not a vaccine specialist, so I can’t think of such a “single vaccine,” but I do remember the swine flu vaccine of 1976, famously received by Gerald Ford on television in the White House while wearing his tie and vest with his sleeve rolled up, caused many unexpected cases of Guillain–Barré syndrome (~8 per million IIRC). These very significant adverse effects were not expected. I was so young at the time that it hurts to contemplate, while working at a large university where we were encouraged to get vaccinated. I did. Soon thereafter I came down a severe flu-like illness. Could have been a coincidence, but I seem to remember that the vaccine was based on a live, attenuated virus. So maybe the vaccine did cause it? Stuff happens and everyone knew 40+ years ago the finite but minor risks associated with live virus vaccines. I didn’t put much stock in that, and I have regularly received the current flu shot (no live virus AFAIK) every October for many years. This is encouraged in my current institution because, while I am not a clinician, I work with many who spend much of their time with patients in the hospital.
I did not intuit the meaning of a “Grade 4 local reaction.” I did note that a local reaction is likely to be transient and have no lasting ill effects, and that the authors of the NEJM Pfizer paper seemed to (intentionally?) conflate local and systemic reactions. The latter can and do injure and kill, a fever of nearly 105F/40.5C, for example. Perhaps that is worth the cost in this crisis.
But if it is, then that must be considered by all of us as citizens of the world and not as consumers of a “healthcare product.” I’m reminded here that the neoliberal definition of citizen is “consumer” (apologies to the author; I would give credit if I could remember who you are). Not being cynical, just paying attention.
I suppose “vague” is in the eye of the beholder, just like an “adverse event.” Yes, this vaccine was tested for an immune response in animals, 24 rhesus monkeys. As noted, those results are encouraging and that NEJM paper is as clear as the Pfizer paper is muddy. Safety was not addressed, and from a scientific perspective, 24 monkeys is much too small a sample for that, to this scientist. But the limitations of such studies are also obvious, especially for evaluation of safety. These limitations may be unavoidable, and if so, so be it but be upfront about it. As I have taught my research students: Once is an anecdote, twice is data, three times is a result. I am fully aware that it is usually straightforward, if sometimes difficult, to reach a result as a molecular biologist using cultured cells as an experimental model, but even considering the limitations of studies on nonhuman primates, that monkey work is barely past the anecdote stage.
As has been stipulated, the supplementary materials are now available. And as has been noted, they are a mess, especially compared to the COVID-19 monkey study and the previously referenced paper on the Zika virus mRNA vaccine. Sloppiness implies what? Obfuscation? Maybe, maybe not. But it is not reassuring.
Intuition and mood affiliation? Uninformed? Try harder (but I must note that intuition is something every good scientist and physician uses, to her benefit to that of her patients’). I have dealt with grant reviewers who wondered in so many words how I remember to breathe, but I have also had grant reviewers of similar proposals who were very enthusiastic. Win some, lose some. There’s one in every crowd, and there is all too frequently a Reviewer #3. Cynicism? No. Skepticism? Yes, always. It comes with the territory.
I was taught by accomplished, old school scientists who neither expected nor gave any quarter when it came to their work and yours. But if I said, “Based on my experience and intuition, I think this wild-ass guess is the answer,” they would accept that, too, as a provisional way forward.
This vaccine is perhaps the best provisional answer we have at the moment, but it is nothing more. If it works, good news is indeed good news. If it doesn’t work and/or turns out to be a fiasco and the people feel they were misled by scientists who turned out not to be? That question answers itself. And that is what concerns me most.
a few points
1) we have good examples of safety concerns that later were shown to have been in the raw data but did not emerge till well into mass distribution.
2) the actual raw data for these trials has to be best of my knowledge NOT been made available.
3) the specific contents of the vaccines is proprietary and not available.
4) both mRNA vaccines showed more bels palsy in the vaccine groups. One expert in bells palsyepi weighed in that it oocured at higher than background levels. Bells palsy and such a vaccine association is biologically plausible
5) the efficacy data for preventing symptomatic infection was excellent. It was however short and failed to address the issues of reduction in LT morbidity and mortality. THis is likely the result of short time frame and too fewer participants BUT we cant say that with any degree of certainty
6) we dont know if these vaccine prevent transmission of virus. They may, there is some suggestive tidbits but we dont know this. If they dont, this whole thing gets MUCH harder.
7) we dont know how long immunity will last.
8) we can not definitively answer questions about possible ADE.
9) the trials overall had quite low rates of infection. I suspect trial participant were less likely than the general public to be infected. this matters.
10) there were no deaths from COvid in either trial..
11) We were shown relative reductions in symptomatic infections on the order of 95%! Wonderful news. Truly. What about absolute reductions? Why were we not shown that?
Yes. This is typical of the pharmaceutical industry when they market their wares: 50% reduction in fractures with _______! Yes, but that is RR, the AR, based on the incidence of fracture in the population, turns out to be 2%
Thank you for pointing this out!!!
I am a physician — and the difference between RELATIVE risk/benefit and ABSOLUTE risk/benefit is part of the tricks that companies and academics use to over-inflate their research. Drug companies are notorious for promoting relative benefit and then listing absolute risk in the adverse effects section of their drug insert. So much “evidence-based medicine” is corrupted by the poor logic of relative benefit. There is a small subset of clinicians who really try to promote the idea of Number Needed to Treat and Number Needed to Harm to make absolute risk/benefit more apparent to the average person.
Today’s NYTimes included an article “Consent Is Hurdle to Inoculating Nursing Homes” that claimed “some nursing home employees are reluctant to get inoculated even though [both vaccines] have been found safe and effective…” On the next page is “Health Worker hospitalized after Vaccine,” a report of a case of anaphylactic shock, a focus of IM Doc’s. Here it was even worse, with the patient being put on an epinepherine drip, then being taken off only to have sxs return, requiring returning to the drip. In a rural area, that could be a challenge to control in time.
If there’s even a hint that someone has died of this vaccine, it’s going to screw up the entire thing. The fact that twitter already feels the need to turn the dials on their algorithm to adjust for vaccines means there’s a huge national discussion coming our way. People being hurt is easy to dismiss, someone dying is not.
Yes, agree. The patient had to be moved to the ICU after her symptoms returned. That would be extremely hard in many places. IM Doc should be listened to, IMHO.
The Pfizer CEO hasn’t gotten his COVID vaccine yet, “because he doesn’t want to cut in line.”
A long way from
“When Roman engineers built a bridge they had to stand under it while the first legion marched across.”
Moral hazard.
Heads they win, tails you lose.
Best government money can buy.
Same as Boeing executives and 737 Max.
The discussion here at NC on this topic the last few days has been illuminating and bracing. The pandemic and its impacts on daily life (doctors and doofers, alike) has made the curious more so. I appreciate the experience/expertise brought to NC by its Commentariat. I think I’m better informed by it. I know it keeps me off the street, for sure.
Regarding Bell’s Palsy as a possible side effect, I have suffered from that twice–once on each side of my face.
I recovered 100% from the first round, but perhaps only 90-95% from the second round, as cold weather sometimes still affects my mouth muscles on that side.
I would not wish it upon most people (with exception of maybe a select few politicians?).
Regardless, I’m in no hurry to get vaccinated.
My preference is to continue isolating. (I prefer to call it ‘hermitizing’ & enjoyed it when possible, long before the virus).
Probably until 2022.
Did I miss something? There were 2 cases in Alaska?
https://twitter.com/Laurie_Garrett/status/1339582370257616896
The @moderna_tx
#vaccine hearing is underway @US_FDA
. Dr. Doran Fink of FDA opens, describing 4 cases of anaphylactic reactions to the @pfizer
vax, 2 in UK & 2 in Alaska. Bears ongoing close review, and FDA is investigating.
This is, I think as a layperson, a useful article: https://www.medpagetoday.com/infectiousdisease/covid19/89998?utm_source=Sailthru&utm_medium=email&utm_campaign=Weekly%20Review%202020-12-06&utm_term=NL_DHE_Weekly_Active
My apologies if attention has already (I haven’t noticed it) been drawn to this item — Derek Lowe’s recent (12/15) post on auto-reactivity and Covid severity
https://blogs.sciencemag.org/pipeline/archives/2020/12/15/autoantibody-problems
It looks like a tangled problem. I get the sense that this might be (must be?) involved to some extent in the very wide range of ways that the disease presents in different individuals.
my pet peeve is that youtube, twitter, Facebook are chock full to now end with content re. homeopathy.
But now opaque persons at those companies have deemed themselves as the final arbiters of empirical truth re. vaccination.
I haven’t seen a calm discussion like this in media (say like NPR or 60 Minutes) and I wonder if (as an example) IMDoc’s initial comments would have survived Twitter’s “acceptable speech” algos.
Grrrr.
Those companies’ fact-checking expertise is…well… not anything I’d call accurate fact-checking. Greenwald and Taibbi have both weighed in on the self-interested, political nature of these Silicon Valley giants “fact-checking” accuracy. Greenwald’s substack article isn’t about C19 and c*nsorship, but about the motives behind the internet social media behemoths’ discovered “facts”.
From Greenwald:
https://greenwald.substack.com/p/instagram-is-using-false-fact-checking
As Greenwald quotes Taibbi:
‘As Matt Taibbi put it last week when warning of the dangers of YouTube’s decision to ban from its platform any questioning of the legitimacy of the 2020 election while still allowing similar questioning of the 2016 election: “There’s no such thing as a technocratic approach to truth. There are official truths, but those are political rather than scientific determinations, and therefore almost always wrong on some level.” ‘