Undermining the childhood vaccine schedule with EBM fundamentalism

When last we encountered evidence-based medicine (EBM) maven and critic of oncology clinical trials and FDA licensure of chemotherapeutic agents turned COVID-19 contrarian, antimasker, and anti-COVID vaccine advocate Dr. Vinay Prasad, he was defending longtime antivax activist Robert F. Kennedy, Jr., saying, in essence, that he agrees with most of of RFK Jr.‘s positions, especially about big pharma, regulatory capture, and and corruption other than his peskily embarrassing (to him) belief that childhood vaccines cause autism. (That, and he was also denying yet again that he was antivaccine.) As you might recall, what struck me about Dr. Prasad’s post was how much he bent over backwards to portray RFK Jr. as “reasonable” other than a couple of bizarre ideas—his pesky adherence to the the discredited idea that vaccines cause autism again!—even someone as someone who could be persuaded that, for instance, vaccines don’t cause autism and the birth dose of the hepatitis B vaccine is safe with some well-designed placebo-controlled clinical trials and an expanded vaccine safety monitoring system.

It was one of the most bizarre examples of what I like to refer to as “methodolatry” (defined as the obscene worship of the randomized controlled trial (RCT) as the only valid method of investigating clinical questions in medicine). Of course, in the evidence-based medicine (EBM) paradigm, the randomized controlled trial (preferably double-blind and placebo-controlled) is second from the top of the evidence pyramid, the only evidence higher being meta-analyses collectively analyzing the results of—yet guessed it!—RCTs. Regular readers know that I’ve long pointed out how methodolatry leads the EBM paradigm to be too open to alternative medicine. More recently, I’ve even argued that the fetishization of the RCT as the ultimate method of clinical investigation, coupled with the often concomitant denigration of any “lesser” form of study as so much less rigorous as to be ignored, has contributed to COVID-19 contrarianism among what I like to call EBM fundamentalists like Peter Gøtzsche, Thomas Jefferson, and, of course, Dr. Vinay Prasad.

Before I discuss his latest weaponization of methodolatry in the service of supporting antivaccine talking points, let me just recount a couple of quotes by Dr. Prasad about the childhood vaccine schedule and vaccine safety. I realize that I just quoted them ten days ago, but they’re worth citing again because they set the stage for his latest doubling down on methodolatry. First, he takes a grain of truth, that the current vaccine safety surveillance system can be improved, and then, either naïvely or disingenuously (I suspect the latter given his giving himself plausible deniability), uses that grain of truth to express solidarity with RFK Jr. and (most of) his antivax conspiracy theories:

In order to deal with RFK Jr’s more troublesome points of view, I think the only solution is to agree that the current surveillance system— and the current epidemiologic evidence is limited in many ways. We need to improve the current surveillance system on vaccine safety, so that we can adjudicate whether or not even some of his claims are true. I personally believe that most will not hold up, but I think one must acknowledge that the current surveillance system is flawed, and some may hold up. Why do I think this compromise is worth it.

Note his bit about how he “personally believes that most [of RFK Jr.’s claims] will not hold up” but concedes that “some may hold up.” (Hint: None of RFK Jr.’s claimed harms from childhood vaccines holds up to scrutiny. None of them.) There’s the plausible deniability, in which Dr. Prasad portrays himself as the oh-so-reasonable, scientific- and logical disinterested outsider who can see the merits in “both sides” and only wants to find out what is correct and if there’s anything to RFK Jr.’s claims. Also note that, whatever the flaws of the current vaccine safety system in the US, the system has long been more than adequate from a scientific and data standpoint to “adjudicate whether some or not even some” of RFK Jr.’s claims are true, and if the US system isn’t enough for you there are many other systems in other countries (e.g., the EU and Canadian systems) also support the conclusion that childhood vaccines do not cause autism, sudden infant death syndrome, autoimmune disease, or any of the other of the panoply of conditions attributed to vaccines by RFK Jr. and other antivaxxers.

Worse, Dr. Prasad then suggested:

Yet on hepatitis B vaccination, RFK Jr makes a fair point that we could target higher risk populations. At least that could be the central question of a randomized control trial. He’s also fair to ask if the particular timing of doses is optimized, or if it could be given it a later date. That could also be a randomized trial. I think this century will see the pediatric childhood immunization schedule the subject to a multi-arm, factorial RCT. It is better to launch that effort now before public distrust gets too out of control.

As I pointed out, this is a longstanding antivax trope to call for RCTs of the childhood vaccination schedule, despite the expense and the impracticality of such an effort. Dr. Prasad’s suggestion was nothing new, other than making the call into a “multi-arm, factorial RCT.” Indeed, at the time I challenged Dr. Prasad to design such a “multi-arm factorial RCT” of the childhood vaccination schedule that would be (1) feasible; (2) not require hundreds of thousands or millions of participants; and (3) ethical. Remember, any placebo-controlled RCT would require leaving one group unprotected against potentially deadly infectious diseases. I also pointed out how the antivax hatred of the birth dose of the hepatitis B vaccine is based more on moral outrage that leads them to rage that, because my baby or child isn’t at risk because my child doesn’t have premarital sex, share needles, or engage in what I consider morally dubious high risk behavior, my child shouldn’t need the birth dose of hepatitis B vaccines (or the vaccine at all). The subtext, of course, behind saying that the “high risk” groups should be targeted is that those “dirty vaccines” should be reserved for people who need them because they are dirty too, just as the call for only “high risk” people to be vaccinated against COVID-19 was based on the false believe that those who “lived right” and are “healthy” don’t need protection against the disease.

With that background of Dr. Prasad playing footsie with RFK Jr.’s bonkers antivax conspiracy theories about the childhood vaccination schedule, let’s look at his doubling down yesterday. The post appeared on his Substack and was entitled The only real solution to vaccine skepticism: We need more randomized trials and a new phase IV safety system. Its blurb even led me to facepalm: “The way to address concerns about vaccines and other medical products is to hear what people are saying.”

What does Dr. Prasad think that public health officials have been trying to do for literally decades with respect to the vaccine hesitant? I sense a bit of conflation of the vaccine hesitant (who are merely afraid of vaccines but potentially persuadable) with diehard antivax activists like RFK Jr., who are not persuadable with evidence, data, logic, or even emotional counternarratives.

It’s easy, though (conceptually at least) to win back trust of parents shattered by those clueless and/or evil public health officials and doctors who didn’t “listen” to people’s concerns. Dr. Prasad tells us so right at the beginning of his post:

Whether anyone likes it or not, covid-19 policy mistakes mean that more and more people are going to be critical of routine immunization for children. They are also going to be critical of serotonin re-uptake inhibitors for depression, cancer medications, cancer screening tests, and most public health advice.

In many of those cases, skepticism is warranted. Cancer drugs do tend to underperform in the real world as opposed to clinical trial settings. The US FDA has authorized many psychiatric medications on the basis of short-term studies, even though these medicines are taken for years or decades. (Discontinuation studies don’t address the question).

It is, of course, true that the COVID-19 pandemic has led to a large increase in vaccine hesitancy that has shown signs of spilling over to taint the childhood vaccination schedule, a spillover encouraged by antivaxxers, who rejoice over it because undermining confidence in the vaccination schedule is one of their most cherished goals. Tellingly, Dr. Prasad leaves out one very important element to the story here. He makes it sound as though it was just COVID-19 policy mistakes, of which there have definitely been many, is what is fueling vaccine hesitancy or, as he puts it, criticism “of routine immunization for children.” Also note the odd collection that he lumps together as medicine that the public is now “critical of.” The first is an antipsychiatry dog whistle worthy of Scientology, combined with his favorite hobby horses of cancer drugs and cancer screening, and then, of course, most public health advice. However, it isn’t just policy missteps that have led to increased suspicion of public health.

The elephant in the room ignored by Dr. Prasad (mainly because he is part of that elephant, likely one of its waste excretory organs that aren’t the kidneys) is the massive, politically motivated and systematic attack on any collective action against COVID-19 that has been attempted going back to before even the Great Barrington Declaration, the eugenicist declaration advocating a “let ‘er rip” approach to the pandemic in order to achieve “natural herd immunity” within six months. (How’d that work out?) That same political movement that opposed “lockdowns,” mask mandates, and vaccine mandates soon fused with (or, perhaps more appropriately, co-opted and swallowed as particularly motivated one-issue foot soldiers) the pre-existing antivaccine movement, completing the decade plus long drift of the antivaccine movement towards the far right, a movement that RFK Jr. has exhibited as well.

After repeating his frequent claim that the US vaccine safety surveillance system “missed myocarditis” from COVID-19 vaccines and “did not detect myocarditis in young men,” claims that are actually patently untrue, as I discussed in my previous post. Again, that apparently lack of concern about myocarditis must have been why two years ago the CDC Advisory Committee on Immunization Practices (ACIP) carefully considered early signals of myocarditis only seven months after the vaccines had rolled out (and three months before Dr. Prasad’s buddies dumpster-dived into the Vaccine Adverse Events Reporting System (VAERS) database to try to fear monger about myocarditis and COVID-19 vaccines in children). Basically, the CDC was only marginally slower at picking up myocarditis as a possible adverse event from the mRNA-based COVID-19 vaccines than a country like Israel, which is a much smaller country with universal health care and an integrated health system very different from that of the US that allows for much more complete and comprehensive records of its citizens’ health data. Again, Dr. Prasad cites (again) one article from April 2021 in which CDC Director Rochelle Walensky said that the CDC had not yet found a link but was actively investigating based on a report of 14 cases from the Department of Defense database. It was and remains a profoundly misleading claim to to characterize the CDC has having been incredibly slow to notice the safety signal for myocarditis.

To address the “distrust” of the CDC, public health, medicine, and vaccines that was totally not stoked by a politically active antivaccine movement funded by dark money and weaponizing legacy and social media against anything resembling collective public health action against the pandemic, Dr. Prasad proposes five changes that will, according to him, regain the trust in public health and medicine of those people who had lost it because they’ve been encountering massive quantities of antivax and antimask disinformation on Twitter, Facebook, and other social media platforms. Let’s take them on one by one.

Let’s start with #1:

We must recommit to only authorizing or approving medical products after randomized trials show benefits on hard outcomes (living longer or better) and in populations that look like America.

This is, of course, not objectionable on its face. Indeed, there could be common ground between Dr. Prasad and myself given that I’ve argued myself that the standard for FDA approval, rather than being too rigorous, are in fact arguably too lax. I might take Dr. Prasad more seriously were it not for the examples he chose, Paxlovid and yearly COVID-19 boosters, and one that he glaringly did not mention, namely the emergency use approval (EUA) for hydroxychloroquine to treat COVID-19 in March 2020, mere weeks after the World Health Organization had declared COVID-19 a pandemic. Say what you will about the standard for approving Paxlovid, the drug did go through RCTs and the FDA regulatory approval process.

As for vaccines, recommendations for vaccines in the vaccination schedule have long balanced science, feasibility, and public health priorities, but that does not mean that they were, as Dr. Prasad seems to think, pulled out of someone’s nether regions. Contrary to what antivaxxers have been claiming for years and years (and what Dr. Prasad is now insinuating, having gone all-in with stoking vaccine hesitancy and sucking up to RFK Jr.), childhood vaccine schedules are evidence-based.

Next up, #2:

We need a new safety system that is capable of detecting very rare vaccine adverse events. This system should be observational, but a component must also leverage real-world randomization, whenever possible. In other words, after the debut of the COVID vaccine, the roll out should have been as part of a 5 million person randomized trial, with careful monitoring (active and passive) for any safety signal.

Hmmm. This sounds familiar. If only we had such a system for childhood vaccines, or even all vaccines. If only…

Oh, wait! We do have large active and passive monitoring systems for vaccine safety signals. The passive system is the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD), among others. During the pandemic, we added V-Safe to the mix. VAERS, of course, is the favorite reporting system of antivaxxers because anyone can report any “adverse event” to it, whether it’s a true adverse event or not, whether it is related to the vaccine or not, which allows them to point to large numbers of adverse events and blame them on vaccines, whether they were due to vaccines or not. VAERS is designed as the “canary in the coal mine,” to detect potential safety signals, which can then be investigated further. Meanwhile, the VSD is an active surveillance system that looks for signs of vaccine injuries by comparing diagnoses that occur in vaccinated versus unvaccinated patients, as well as temporality (time after vaccination):

The VSD uses electronic health data from participating sites to monitor and assess the safety of vaccines. This includes information on vaccines: the kind of vaccine given to each patient, date of vaccination, and other vaccinations given on the same day. The VSD also uses information on medical illnesses that have been diagnosed at doctors’ offices, urgent care visits, emergency department visits, and hospital stays. The VSD conducts vaccine safety studies based on questions or concerns raised from the medical literature and reports to the Vaccine Adverse Event Reporting System (VAERS). When there are new vaccines that have been recommended for use in the United States or if there are changes in how a vaccine is recommended, the VSD will monitor the safety of these vaccines.

This sounds a lot like what Dr. Prasad is proposing, doesn’t it?

VSD is fast, too:

Rapid Cycle Analysis (RCA) allows VSD to detect adverse events following vaccination in near real time so the public can be informed quickly of possible risks.

Using VSD data that are updated each week, the rates of adverse events that occur in people who have received a particular vaccine are compared to the rate of adverse events that occurs in a similar group of people who have not received that vaccine. If the rate of adverse events among vaccinated people is higher than among the comparison group, the vaccine may be associated with an adverse event. VSD has used RCA to publish important safety information regarding many vaccines…

VSD is also big:

The Vaccine Safety Datalink (VSD) is a collaborative project between the Centers for Disease Control and Prevention (CDC) and 9 health care organizations. Established in 1990, VSD is a vital resource informing policy makers and the public about the safety of vaccines used in the United States. Large linked databases are used to identify and evaluate adverse events in over 9 million individuals annually. VSD generates rapid, important safety assessments for both routine vaccinations and emergency vaccination campaigns. VSD monitors safety of seasonal influenza vaccines in near-real time, and provided essential information on the safety of influenza A (H1N1) 2009 monovalent vaccine during the recent pandemic. VSD investigators have published important studies demonstrating that childhood vaccines are not associated with autism or other developmental disabilities. VSD prioritizes evaluation of new vaccines; searches for possible unusual health events after vaccination; monitors vaccine safety in pregnant women; and has pioneered development of biostatistical research methods.

Nine million individuals per year? That’s a bigger number than 5 million!

So what do VAERS and the VSD lack that Dr. Prasad thinks that they need? What did V-Safe lack when it was still in operation? Apparently some sort of…randomization.

WTF?

How would this even work? After a vaccine has been demonstrated to be safe and effective at preventing a disease, as the COVID-19 vaccines were for COVID-19, it would be unethical to actually randomize anyone to an unvaccinated or placebo control group, much less one-third to one-half of five million people! [Sidebar to Dr. Prasad: In the unlikely event that you actually read this post, could you please explain how this proposal would work in the real world? You don’t have to give me a detailed protocol, but basics of clinical trial design would be nice, such as inclusion and exclusion criteria, randomization procedures, primary and secondary outcomes, and the power calculation for relevant outcomes that led you to suggest that we need 5 million subjects for this trial. Also, an estimate for how much it would cost and suggestions for where the money would come from would be helpful. Ditto a brief discussion of the ethical justification for randomization in the middle of a pandemic. I’ll wait.]

Basically, Dr. Prasad seems utterly oblivious to the actual vaccine safety systems that exist now. Except for that widely impractical and unnecessary bit about some sort of “randomization” with active and passive reporting, what he describes resembles pretty strongly what we already have in terms of vaccine safety monitoring systems, at least in the US and other wealthy industrialized nations. Either Dr. Prasad doesn’t know that, in which case he is too ignorant and clueless about the vaccine safety monitoring system to be taken seriously or he knows but knows that his readers don’t know, so that his proposal sounds all science-y and super rigorous when in fact he doesn’t know what he is talking about.

Let’s move on to #3:

Older vaccines and medical products which are subject to growing public distrust— even those whose distrust is unjustified in the opinion of experts— should be re-examined for safety. It doesn’t matter why there is distrust. If there is distrust, information is valuable.

I’m getting bruises on my cheeks and forehead from all the facepalming. Seriously, does Dr. Prasad think that this isn’t done? The childhood vaccination—indeed, the entire vaccination schedule, adult and childhood—is continuously reevaluated and then discussed in an open format at the CDC’s Advisory Committee on Immunization Practices (ACIP). New vaccines are discussed, and safety issues brought up about existing vaccines are examined, tested, and discussed. How many studies looking at whether the MMR vaccine and/or mercury-containing vaccines cause autism were carried out for years—decades, even!—after experts had concluded that there was no correlation and that vaccines are not associated with an increased risk of autism. Did that information and those studies stop antivaccine misinformation? I think you know the answer to that one.

Dr. Prasad seems to think “information is valuable.” I agree, but it’s not so valuable that it has the magical powers that he ascribes to it, which seem to include being able to magically counter antivax disinformation and assuage the doubts of the vaccine-hesitant. One also can’t help but point out to Dr. Prasad the long history of the antivaccine movement trying to co-opt these committees and use them for their own propaganda purposes.

Be still my aching face, as I move on to #4:

Trials of vaccine should contain at least 2 control arms. One a placebo arm of salt water, and another placebo arm perhaps containing adjuvant/ preservative/ or a different vaccine. Each control arm has different strengths and weaknesses. One allows accurate assessment of safety; the other preserves blinding, and or downstream behavioral change (think about it for a while).

Here we go again. Dr. Prasad is echoing yet another antivaccine talking point, namely the “no true saline placebo control RCTs” trope about vaccines that I discussed the other day. First of all, ethics, how does that work? As I discussed the other day, while it is appropriate to insist on a placebo-controlled RCT for a new vaccine against a disease for which there is currently no safe and effective vaccine licensed and available, it is completely unethical to do such a trial for a new vaccine against a disease for which there already exist safe and effective vaccines that are the standard of care. You cannot ethically randomize subjects to an arm where they receive less than standard, accepted medical care, such as randomizing a child to an arm where, for example, he doesn’t receive MMR because you want to test a new combination measles vaccine. The ethical thing to do is to test a new next generation vaccine against the existing standard-of-care previous generation vaccine for the same disease.This is methodolatry on top of methodolatry in that, not only is the RCT the only acceptable method of clinical investigation to Dr. Prasad, but it has to be a specific kind of RCT with a specific kind of placebo, clinical trial ethics and Helsinki declaration be damned!

But Dr. Prasad should know this. He’s an oncologist, and oncology trials were the type of RCTs that I used as an example to illustrate why placebo controls are often not ethical. Ethical RCT design is why most new chemotherapy agents used in oncology are either tested in an add-on design (standard of care + new drug versus standard-of-care + placebo) or a design that uses an active comparator (new drug vs. standard-of-care), so as not to require the randomization of subjects to an arm in which they receive no treatment for their cancer. Again, I discussed this just the other day, but I guess I need to belabor the point.

Also, as I discussed in a lot more detail last time (and therefore will not belabor further here), saline placebo control is not the only appropriate placebo comparator. Adding it as a third arm in an RCT using a more appropriate comparator when that comparator has a long, well-established history of safety, with well-known and well-characterized potential adverse events, would do nothing but add expense and complexity to the clinical trial, as well as necessitate larger numbers of subjects in the phase 3 trials, all for no real benefit. Does Dr. Prasad honestly think that retesting existing vaccines in new RCTs in which there is a saline placebo control arm would reestablish “trust.” If he does, he doesn’t know the antivaccine movement, which would simply shift to another of its many talking points and/or find reasons to discount the new trials.

They’re even showing up in his comments saying things like:

Great plan, I agree. Except on one thing.

It is totally unethical to inject a healthy baby with something that can only bring him harm, and absolutely no benefit. 

So no trial with an arm with adjuvant/preservative only

I laughed when I read that comment, so predictable are antivaxxers.

Finally, here’s #5, which is the only one of Dr. Prasad’s ideas that has merit:

FDA officials must be legally banned from revolving door politics for 5 years after service. Recently, Ashish Jha finished his term at White house where he worked on indoor air rules. Now he wins a *rarely* given award sponsored by the companies that benefit from these rules. The appearance of corruption is strong. These types of awards or jobs must be banned.

I’m fine with this one. Unfortunately, the ignorance and cluelessness exhibited in the previous four don’t make up for one good idea.

I’ll conclude with a simple observation. You might remember a few months before the pandemic, almost four years ago, which seems like ancient history. Back then, Dr. Prasad took to Twitter to portrayed those of us who had dedicated a significant portion of our free time and, in some cases, careers to combatting medical misinformation, quackery, and, in particular the antivaccine movement as wasting our time. I wish I had preserved more of his Tweets than I did when I discussed how little good Dr. Prasad was doing even as I argued that skeptics and people like Dr. Prasad should have been natural allies. However, the key metaphor that he used to describe our activities was to compare them to “dunking on a 7′ hoop,” the idea being that debunking and combating medical misinformation is just so damned easy, like dunking on the proverbial short hoop, with supplements, homeopathy, antivax misinformation, and the like all being “soft targets”:

Dr. Prasad deleted most of his Tweets, whether out of an attack of conscience or just because he didn’t like the attention they were bringing, but then a year later he doubled down on his “dunking on a 7′ hoop” metaphor for an article in MedPage Today entitled Applying Skepticism to Medical Skepticism that I deconstructed once again, noting once again that dealing with medical misinformation is far more difficult than he seems to think, as the pandemic, which was in full swing back then with the vaccines only having just been granted EUA, and suggested that he either learn what we actually do by actually talking to us instead of lecturing us or, being too lazy or uninterested to do that, at least do us the favor of staying out of our way.

Unfortunately, as we have seen, Dr. Prasad chose a third course, which was to become a font of the very sort of medical misinformation and disinformation that we’ve been trying to counter since the pandemic hit, just as we tried to counter the promotion of, for example, homeopathy before the pandemic, the effort that provoked Dr. Prasad’s original contempt and ire. It didn’t have to be this way. Dr. Prasad could have chosen to engage with us, rather voice his contempt for us. He might have even learned from us things that he clearly does not know or understand, such how VAERS, the VSD, and other vaccine safety monitoring systems work, what they are capable of, and how the antivaccine movement tries to weaponize them to spread fear, uncertainty, and doubt about vaccines. He might have familiarized himself with various quack and antivaccine tropes. If he had, he might have realized that calling for unnecessary and unethical RCTs of the childhood vaccine schedule is a very old antivax talking point. He might even have learned how EBM fundamentalism and the belief that only RCTs reveal the “truth” about vaccine safety do not inoculate one against becoming antivax. Just look at Cochrane’s Tom Jefferson and Peter Gøtzsche (formerly of the Nordic Cochrane Centre) if you don’t believe me, as well as any number of physicians who turned antivax during the pandemic, like Dr. Pierre Kory. In fact, this EBM fundamentalist belief in RCTs über alles has led him farther and farther down the antivaccine path.

It would appear, unfortunately, that Dr. Prasad is too far gone down the rabbit hole of contrarianism, denial, and, yes, antivaccine talking points. Indeed, I predict that it won’t be too long before he starts rethinking his previous disagreement with RFK Jr. about vaccines and autism and whether the harms of the childhood vaccine schedule outweigh the benefits, thus following other “COVID-19 contrarians” and “provaccine” anti-COVID-19 vaccine antivaxxers until he becomes just plain antivaccine. He’s definitely well along that path. He even likes the same Godwins that antivaxxers do.

More’s the pity.