I last asked this question in January, but I’ll ask it again now: Why is Peter Doshi still an editor at The BMJ?
Why, you might wonder, am I asking this question again four months later? Simple. Last night, I was, as is my habit when I’m looking for blog fodder, perusing the websites of various antivaccine activists and quacks. I came, as I nearly always do, to Children’s Health Defense, the website of longtime antivaccine activist Robert F. Kennedy, Jr., and its newsletter The Defender. There, I read this article:
At the end of the article, there was this:
Interesting, I thought. Apparently RFK Jr. is doing the same thing with Peter Doshi as he did with Dr. Hooman Noorchashm and republishing his work on his antivaccine website, as there is also a notice:
Originally published by The BMJ May 18, 2021, written by Peter Doshi, reproduced here under the terms of the CC BY NC licence.
This refers to this Creative Commons license. I looked at the article and didn’t see the usual Creative Commons attribution giving permission to republish the post in whole or in part anywhere on the page, but apparently The BMJ allows this for most of its articles, thus facilitating an antivaccine organization simply republishing its content instead of forcing the organization to link to it and only quote parts of it. Be that as it may, as was the case for Dr. Noorchashm, RFK Jr. has an “author page” for Peter Doshi in order to give the appearance that Peter Doshi is an author for Children’s Health Defense:
The banner about CHD calling on the FDA to take COVID-19 vaccines off the market is actually rather appropriate, because CHD’s petition uses arguments very similar to those of Peter Doshi in his article. I also can’t help but use this image to laugh yet again at RFK Jr.’s claim that he is “fiercely pro-vaccine.” Sure, he’s “fiercely pro-vaccine,” so much so that his organization is trying to get life-saving COVID-19 vaccines off the market, so that the pandemic can barrel out of control again.
RFK Jr.’s shenanigans to try to make it seem as though Peter Doshi is writing for him aside, the original article was published in The BMJ and entitled Covid-19 vaccines: In the rush for regulatory approval, do we need more data? Betteridge’s Law of Headlines should (sort of) apply here, but, Peter Doshi being Peter Doshi, I was easily able predict Doshi’s answer to the question. Those of you familiar with him can also predict the answer: Yes. But it’s a “yes” that casts as much doubt as possible on the safety of the vaccines as Doshi can manage.
At this point, let me just recap briefly my my opinion of Peter Doshi based on his history. I first encountered him in 2009, when I noted that, as the H1N1 pandemic of 2009-2010 was bearing down on us, he had been scheduled to speak at an antivaccine conference hosted by the antivaccine group National Vaccine Information Center (NVIC). He knew NVIC was antivaccine too, as he had been contacted about the nature of the conference and replied with a lame, “my speaking there does not imply endorsement” gambit. Since then, he’s been nothing if not consistent. While all the while claiming he’s “not antivaccine, he’s parroted more than a few antivaccine talking points himself while trying to portray himself as an authority on influenza and the flu vaccine. Through it all, he’s played the “victim” card that people who are borderline antivaccine or antivaccine love to play, claiming that they are “just asking questions” and that anyone who “questions” vaccines is labeled, in a knee-jerk fashion, “antivaccine.” In fact, Doshi’s borderline antivaccine stylings go back further than 2009, when a senior pseudonymous epidemiologist whose blog I used to read religiously back then chastised him for an “unhelpful” commentary in which he had claimed without basis that estimates for yearly influenza deaths were “grossly inflated.” The year was 2006.
Since then, Peter Doshi has somehow managed to insinuate himself as an associate editor of The BMJ, one of the premiere medical journals in the world. No, not just an associate editor any more. He is now a senior editor, as listed in this article. How this happened, I have no idea, but periodically he publishes posts for The BMJ that are—to put it kindly—far below the standards that a medical journal with the history of The BMJ should ever associate itself with. The very fact that RFK Jr. would republish his work and try to give the illusion that Doshi writes for him should tell you all you need to know about the article.
Finally, before I get to the points Doshi makes in his article, I can’t help but point to its competing interests statement:
Competing interests PD gave a public statement at the October and December FDA advisory committee meetings mentioned in this article (transcripts here: https://faculty.rx.umaryland.edu/pdoshi/#publications), and may continue to engage in public input towards regulatory decision making around covid-19 vaccines. PD is also employed by a university that has mandated covid-19 vaccines for all faculty, staff, and students. The views and opinions expressed here are those of the author and do not necessarily reflect official policy or position of the University of Maryland.
I am amused that Doshi felt it important to mention that he works at a university that has mandated COVID-19 vaccines for all its faculty, staff, and students. One wonders if he’ll accept the “experimental” vaccine. More importantly, though, there is one conflict of interest that is noticeably lacking from Doshi’s statement. Specifically, he served as an expert witness for a lawsuit by Children’s Health Defense challenging the University of California’s influenza vaccine mandate. Whether he was paid or not for his services, personally, I consider it quite pertinent that he provided a statement for Children’s Health Defense against the mandate, and most conflict of interest statements do generally require the mention of any expert witness work related to the topic at hand. After all, if Doshi thinks it important to mention that he works for a university that now mandates vaccination against COVID-19, as though that would inoculate him against charges of antivaccine bias, he really should also mention his work for a bona fide antivaccine group.
As for Doshi’s publications, in virtually all of them he does his best to cast doubt on the safety of COVID-19 vaccines and to portray the regulatory approval process as rushed and insufficiently rigorous. That’s where he comes from. That’s where he’s always come from, and I wouldn’t even consider that viewpoint a bad thing were it not for Doshi’s long history of using dubious and disingenuous arguments to argue his point and his past expert witness work for an actual antivaccine group. Think of it this way. You can perhaps argue against influenza vaccine mandates, for instance, on the basis of “freedom” without being antivaccine yourself. However, if you do so in concert with one of the largest and most influential antivaccine activists in the US, you shouldn’t be surprised when scientists look askance at your other arguments and strongly suspect that you yourself are antivaccine.
No biodistribution data?
I’ll deal with one complaint Doshi makes first, and then delve into his main point, because I’ve seen a lot of antivaxxers quoting one part of the article, namely the box:
No, it’s not true that we “know nothing” about the vaccine’s pharmacokinetics, pharmacodynamics, and biodistribution. Even if that were true, as Doshi himself notes, such data are not required for most vaccines. The reason is simple. Most vaccines are injected intramuscularly, where they (mostly) stay. They’re not designed to distribute through the rest of the body like a drug, and what is required are data on the immune response to the vaccine. The full quote from the European Medicines Agency document states:
Pharmacokinetic studies are usually not required for vaccines. However, such studies might be applicable when new delivery systems are employed or when the vaccine contains novel adjuvants or excipients. The need for pharmacokinetic studies and their design should be considered on a case by case basis and it is recommended that applicants should obtain scientific advice from EU Competent Authorities.
In relation to vaccines, pharmacodynamic studies are essentially comprised of the immunogenicity studies that characterise the immune response to the vaccine. Therefore, this section will focus on considerations for an appropriate range of immunogenicity studies that may be conducted throughout the clinical development programme.
Which is, of course, appropriate for vaccines. Moreover, one of the documents cited by Doshi, a submission by Pfizer/BioNTech to Japanese regulatory authorities, specifically used lipid nanoparticles containing an mRNA encoding a marker gene (Luciferase, which can be localized using bioluminescence and is commonly used to label which cells have taken up a plasmid or viral vector) to do pharmacokinetic studies in mice. In some of the experiments, the lipid nanoparticles were labeled with 3H (tritium) as well. Basically, Doshi is complaining that pharmacokinetics studies weren’t done using the lipid nanoparticles containing the mRNA for the spike protein used for the vaccine weren’t included. This is disingenuous, because anyone with a knowledge of molecular biology knows that it’s unlikely that a different mRNA is going to distribute significantly differently than an mRNA for Luciferase. Doshi should know better than to point to a lack of a “perfect” biodistribution study as a reason to fear the vaccine. Basically, he’s implying that there are no valid biodistribution studies while ignoring that biodistribution studies of the sort that he demands are usually not required for vaccines.
But why the rush?
The complaints in the BMJ editorial about the supposed lack of the exact biodistribution studies demanded are just a sideshow, though. Now that I’ve dispensed with them, let’s get to the main event.
Doshi begins by noting that, after having announced the efficacy and safety results at the six month mark after their clinical trials for their COVID-19 vaccines, Moderna and Pfizer also announced plans to submit a Biologics License Application to the US FDA [Food and Drug Administration]. As antivaxxers love to point out, currently the Pfizer/BioNTech and Moderna vaccines are not fully licensed by the FDA. They are currently being distributed under an emergency use approval (EUA). Under an EUA, the FDA “may allow the use of unapproved medical products, or unapproved uses of approved medical products in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions when certain statutory criteria have been met, including that there are no adequate, approved, and available alternatives.” In the middle of a deadly pandemic, EUA was an entirely appropriate mechanism to use distribute the new COVID-19 vaccines.
Concerns about the EUA lead Doshi to opine:
Because lest we forget, all covid-19 vaccines currently in use in the US are available under emergency access only.
(The situation is similar in Europe, where four covid-19 vaccines have been granted “conditional marketing authorisations,” a fast track mechanism that can be used in emergencies. These can be converted into standard “marketing authorisations” pending positive data after authorisation, but this has not yet happened for any covid-19 vaccine being administered.)
As hundreds of millions of people around the world get vaccinated, it may seem like wordsmithing to highlight the fact that none of the covid-19 vaccines in use are actually “approved.” Through an emergency access mechanism known as Emergency Use Authorisation (EUA), the products being rolled out still technically remain “investigational.”3 Factsheets distributed to vaccinees are clear: “There is no FDA approved vaccine to prevent covid-19.”4
It doesn’t just “seem like wordsmithing.” It is wordsmithing of the sort that antivaxxers love, namely to emphasize legal definitions over scientific definitions. Yes, it is true that from a legal and regulatory perspective, existing COVID-19 vaccines are still considered “investigational,” and from such a perspective it is appropriate not to call them “approved” yet. However, after a number of large phase 3 clinical trials, plus the administration of hundreds of millions of doses of the vaccines, it’s difficult, from a scientific perspective, to consider these vaccines “experimental” or “investigational” any more.
One difference between a BLA and an EUA is the amount of followup required after the clinical trials. Last fall, the FDA announced that it would require two months of followup data before considering an application for an EUA. At the time, it was not entirely clear how long a followup period the FDA would require before it would consider an application for a BLA for a COVID-19 vaccine. At the meeting that considered Pfizer’s application for an EUA for its vaccine, the FDA suggested that six months followup for a “substantial proportion” of the phase 3 clinical trial participants would be a bare minimum. Doshi writes:
Six months also seems substantially shorter than previously conceptualised expectations. A World Health Organization expert group on covid-19 vaccines (which included FDA regulators) in August 2020 called for follow-up “until at least month 12, or until an effective vaccine is deployed locally.”10 Another group, composed of industry and academic authors, similarly wrote in October 2020: “we recommend longer term follow-up of all participants … for at least a year after randomisation.”11
On paper, the phase III studies by Pfizer, Moderna, and Janssen are all of two years’ duration. But the FDA’s official position on minimum follow-up before licensure is unclear at best.
In its formal guidance last June, the agency said that for licensure applications, it wanted participants followed for covid-19 outcomes for “as long as feasible, ideally at least one to two years”12 after the first injection. But the same document states that safety assessments for “serious and other medically attended adverse events” should be studied “for at least six months after completion of all study vaccinations. Longer safety monitoring may be warranted for certain vaccine platforms.”
Basically, scientists and regulatory bodies have been flying blind and trying to balance the urgency to protect people against a disease that has killed millions so far (around 600K in the US alone) versus safety and not approving a potentially harmful product prematurely. Obviously, when millions are being sickened and dying from a disease like COVID-19, the “need for speed” becomes much more imperative than it is during normal times. Thus, debates such as this about the minimum safest followup time for which safety and efficacy data should be required before an application for full FDA licensure (or licensure in other countries by their FDA equivalents) can be considered for approval.
Setting up his argument this way, Peter Doshi then delves into a question that has come up since the EUAs for the COVID-19 vaccines were approved. He takes advantage of an ethical dilemma that’s come up since then, a question that I wrote about three weeks ago, whether or not to unblind the participants in the original phase 3 clinical trials of the Pfizer/BioNTech and Moderna COVID-19 vaccines.
Doshi frames the issue this way:
“Very often, it’s the fact that we have that placebo controlled follow-up over time, that gives us the ability to say that the vaccine didn’t cause something at a longer period of time after vaccination,” the FDA’s Philip Krause explained last December.13
Yet there is a gap—currently of unknown size but growing—between any expectation of blinded placebo controlled data, and the reality that within weeks of the vaccines receiving an EUA the unblinding of trials commenced as placebo recipients were offered the chance to get vaccinated.
Steven Goodman, associate dean of clinical and translational research at Stanford University, told the FDA in an invited presentation last December, “Once a vaccine is made widely available and encouraged, maintaining a double blinded control group for more than a nominal period is no longer in the investigator’s (or regulator’s) control and undue pressure to do so may undermine the entire vaccine testing enterprise.”14
Steven Goodman featured prominently in my last post about the ethics and science of unblinding the vaccine clinical trials. I also can’t help but note how much like Joe Mercola Peter Doshi is sounding right now, just more subtle. Mercola portrayed the rush to unblind the clinical trials not as a response to an ethical dilemma, namely the questions:
- Is it ethical to require that vaccine clinical trial subjects assigned to the placebo group remain unvaccinated for the full one or two years (or however long the clinical trial was designed to run) during a deadly pandemic? (A related question that flows from this very important ethical question is whether it’s any longer feasible—or even possible—to require this of subjects assigned to a placebo group. After all, since COVID-19 vaccines became widely available under EUAs, anyone in the placebo arm of a phase 3 trial who suspects they got the placebo and wants to be vaccinated against COVID-19 can just get one of the vaccines. The only things preventing them from doing so are the availability of the vaccines where they live and their dedication to the trial.)
- How can we best balance the ethical imperative to minimize the chance of harm to vaccine clinical trial subjects versus maintaining the scientific rigor of the clinical trial?
Instead, Mercola portrayed the plan to unblind the clinical trial participants as a nefarious plot to undermine science in the name of ethics, all to prevent “late” adverse events from ever being identified as having been caused by the vaccines. Why? Profit and control, of course! The question is a lot more difficult than that, though.
Let me just repeat a thought exercise I did in my last post on unblinding. Try to imagine that you are a clinical trial participant in one of the major vaccine trials, be it for the Moderna, Pfizer/BioNTech, AstraZeneca, Johnson & Johnson, or the Novavax vaccines. The initial clinical trial results have been announced and demonstrate that the vaccine is highly effective in preventing COVID-19 with no major safety concerns. As a result, the vaccine has been issued an emergency use authorization (EUA) and is now being deployed widely, first being administered to high-risk individuals and now being administered to almost any adult who wants it. Thus far, hundreds of millions of people have received a dose. Now imagine that you strongly suspect that you were in the placebo control arm. Wouldn’t you really want to know which group you were in and, if you were in the placebo group, be given the opportunity to receive the real vaccine? Imagine, now, that you are the scientist in charge of this clinical trial and ask yourself: Is it ethical to keep the tens of thousands of people in the placebo arm of your clinical trial in the dark and leave them susceptible to COVID-19, as millions of people are receiving the vaccine from the clinical trial that they had agreed to participate in?
Just think about this dilemma for a minute. An intellectually honest person will quickly realize that the answer is not simple or obvious. It involves the balancing of the ethical imperative to minimize harm to the individuals in the clinical trial versus the scientific imperative to complete the trial to make the science as rigorous as possible. Not unblinding and allowing the control group participants to “cross over” to the vaccine arm leaves them susceptible to a potentially deadly disease against which millions are being vaccinated (as millions have died and thousands are dying of it each day) against using the very same vaccine in the clinical trial these people agreed to participate in. On the other hand, unblinding them and allowing them to receive the vaccine could make data on any longer term effects of the vaccines much harder to interpret. Imagine you’re in charge of this massive clinical trial. What do you do? Again, it’s not an easy or straightforward question. Consider, also, that the unblinding doesn’t just have the potential to miss late adverse events due to the vaccine; at least equally likely, it could lead to the misattribution of adverse events to the vaccine when they are not caused by the vaccine.
In fairness, Peter Doshi doesn’t attribute the unblinding of the studies to the same nefarious intent to control and profit that Mercola did, at least not exactly. Instead, first he starts with a seemingly reasonable concern, namely how the law does not so easily allow compensation for vaccine injuries that occur from a vaccine distributed under an EUA
The BMJ asked the manufacturers why they were seeking a BLA. Moderna did not respond and Janssen only confirmed it intended to apply for a BLA “later in 2021.” Pfizer likewise did not answer but instead quoted an FDA webpage on medical devices, which stated: “Sponsors of EUA products are encouraged to follow up the EUA with a pre-market submission so that it can remain on the market once the EUA is no longer in effect.”16 But EUAs have no built-in expiry date—in fact, 14 EUAs for Zika diagnostic tests remain active despite the public health emergency expiring in 2017.17
Cody Meissner told The BMJ he saw some distinct advantages of a BLA over EUA. An approved vaccine, for one, would provide “an element of assurance,” increasing public trust in the vaccines, particularly for those currently sitting on the fence. It would also pave the way for claims of vaccine injury to be routed through a more established compensation programme, and for adding the vaccine to government funded schemes to reach children in financial need.18
Personally, I find this one point compelling. One serious disadvantage of having these vaccines only covered by an EUA thus far is that injuries due to these vaccines are not covered under the Vaccine Injury Compensation Program, as mandated under the National Childhood Vaccine Injury Act of 1986. Rather, as Dorit Reiss has described, because COVID-19 vaccines are still considered “investigational” from a legal perspective, they are covered under the much less generous and more onerous Public Readiness and Emergency Preparedness Act (PREP), which allows the secretary to issue a statement limiting liability for a product during an emergency:
The statement completely isolates “manufacturers, distributors, program planners, and qualified persons, and their officials, agents, and employees, and the United States” from liability for harms or deaths from COVID-19 vaccines until October 1, 2024. In other words, you cannot sue these manufacturers at all.
The only exception is “willful misconduct,” which means (42 U.S. Code § 247d–6d (c)(1)(A))…
Attached to the act is a government compensation program, the Countermeasures Injury Compensation Program (CICP). This program is much less generous than NVICP.
First, to be compensated, a serious injury or death needs to be shown to have been caused by the vaccine (or other covered product) by “compelling, reliable, valid, medical and scientific evidence.” That is a very, very high bar, too, and for a new product, simply won’t always be achievable.
Second, the request needs to be filed within a year from the administration of the product – not a year from symptoms. This is a shorter statute of limitations and does not cover delayed injuries at all. I will add that to my knowledge, we have never had an injury from a vaccine that occurred a long time after the vaccine – issues usually arise within a few weeks at most – but the theoretical possibility exists.
The program does not cover legal fees. It also serves as the payer of last resort – so if you have another source of funding, like health insurance, workers compensation, etc., the program may not cover your cost even if you are eligible.
To reiterate, I find getting any potential injuries from COVID-19 vaccines covered under the standard procedures adjudicated by the Vaccine Court, just like all other FDA-approved vaccines, to be a compelling reason to get these vaccines fully approved as quickly as possible, if this can be accomplished with sufficiently rigorous science (which it can). Oddly enough, antivaxxers love to point out that currently COVID-19 vaccines are not covered by the Vaccine Court but rather the much more restrictive PREP, but don’t seem too anxious to see them attain full FDA approval, so that any real vaccine injuries can be covered under the Vaccine Court, whose rules are much more liberal in compensating people for vaccine injury. (Unlike regular courts, the Vaccine Court also covers reasonable legal and court costs for complainants to bring their cases before it, win or lose.) Of course, as I’ve written many times before, antivaxxers hate the Vaccine Court because it doesn’t recognize autism or all the other medical conditions that antivaxxers falsely attribute to vaccines as “vaccine injuries,” and lawyers hate the Vaccine Court even more because, apparently, they’d prefer to play the lottery for a huge payout (and huge contingency fees) over the guarantee of receiving their boring but still lucrative usual hourly rates for bringing cases before the Vaccine Court.
The plot to mandate COVID-19 vaccines
We now come to the point where Doshi starts to echo antivaxxers the most strongly. It is likely the main reason why RFK Jr. liked his article enough to republish it on The Defender:
Finally, it may affect the potential for vaccine mandates: “It is unlikely these vaccines will be mandated while an EUA is in place. Remember that currently these vaccines are still considered experimental.”
While still under EUA, an increasing number of educational and other institutions have already mandated vaccines, but debates over the legality of these actions has hinged on the distinction between authorisation and approval.19
But approving a vaccine in order to legally support mandates or convince people of its safety arguably puts the cart before the horse. Meissner responded that a BLA would not be issued until the FDA is convinced of the short and long term safety of these vaccines.
That’s right. Doshi is implying that the real reason that the vaccine clinical trials are being unblinded is to facilitate the ability of governments to mandate the vaccines fully, to remove the legal gray area of their being available only under an EUA and, from a legal perspective, still being considered “investigational.” It’s true, too, that FDA approval would eliminate the legal requirement to refer to these vaccines as “investigational.” It would also likely improve public confidence in the vaccines. However, what Doshi neglects to acknowledge is that, if the FDA really did rush these vaccines to be fully approved and a major safety concern were to be discovered later, it would backfire massively in terms of public trust of the FDA and the vaccines, which would likely immediately be severely undermined immediately.
Don’t think that the FDA isn’t aware of this risk. It most certainly is. Its regulators know the stakes, particularly the penalty for insufficient rigor in terms of public trust. Why else, as I asked, would the FDA have issued a pause on the Johnson & Johnson vaccine after detecting rare, literally (at the time) one-in-a-million serious adverse events, as I discussed?
Am I being unfair to Peter Doshi? Given his long history, I don’t think so. Also, look at who loves his BMJ article: RFK Jr. who reposted it; commenters on The Defender, who are ranting about its contents and the supposedly nefarious intent of the FDA; and antivaxxers and antivax organizations that include John Stone, Informed Choice WA, and others, who posted approving Rapid Responses to Doshi’s article.
I will conclude, as I did last time, by wondering why The BMJ has kept Peter Doshi as an editor. I’ll further question why The BMJ has also apparently promoted him to the position of senior editor. Does The BMJ like seeing Doshi’s articles reposted verbatim on antivaccine websites or seeing him listed on one such site as though he were a regular contributor there? Why doesn’t The BMJ and/or Peter Doshi at least insist that RFK Jr. remove the page whose purpose is clearly to imply that Doshi is a contributor to The Defender? Inquiring minds want to know why The BMJ tolerates Doshi’s continual game of footsie with antivaxxers and his antivaccine-adjacent articles.