You might have noticed that my posting has been a bit…light…this week. That’s because I had been thinking of (mostly) taking the last two weeks of the year off from the blog to refresh, recharge, and chill a bit. However, as has frequently happened before, I found myself not entirely able to do that, particularly when yesterday I saw a post by Dr. Vinay Prasad on his well-monetized Substack entitled The Tragedy of COVID-19. Dr. Prasad, regular readers will remember, is the UCSF oncologist with a large Twitter following who is a self-fancied meta-critic of the science supporting medical interventions. Before the pandemic, he actually did some halfway decent work discussing “medical reversals,” basically the abandonment of previously accepted medical interventions and practices based on better, more rigorous clinical studies, and how the accelerated approval pathway for new drugs is not serving patients well. When the pandemic arrived, however, he pivoted fairly quickly to COVID-19 misinformation, even once likening public health nonpharmaceutical interventions to incipient fascism. Seeing Dr. Prasad whine about all the “ad hominem” supposedly directed against him and his fellow COVID contrarians led me to do a quick pre-Christmas response, particularly in light of his previous history and another post with his entirely take based on methodolatry about bivalent COVID-19 boosters, Latest MMWR analysis of bivalent booster is irredeemably flawed.
Projection and methodolatry (plus tone policing). Methodolatry and projection (plus tone policing.) Thy name is Dr. Vinay Prasad!
Call the tone police
There are two things that I’ve noticed about Dr. Prasad that have been remarkably consistent at least since the pandemic. The first is his tendency to tone police his critics and anyone holding positions with which he strongly disagrees, trying to discredit them because they might on occasion become sarcastic, angry, or even insulting, rather than addressing their actual criticisms. Of course, going along with this is hypocrisy, because longtime readers might remember the utter disdain that before the pandemic Dr. Prasad regularly heaped on skeptics who took on topics like homeopathy and, yes, the antivaccine movement. Likening such pursuits to “dunking on a 7′ hoop” Dr. Prasad considered such endeavors to be a waste of his obviously awesome brain and of the less awesome brains of other doctors (even yours truly), who, conveniently enough, he thought should devote their less awesome brains to the same questions that he was devoting his incredibly awesome brain to. An example included this Tweet from late 2019, since deleted, that appears to have been directed at me:
Rather snarky, eh? At least it wasn’t likening public health to the rise of the Nazis in Germany the way he did last year, an indirect ad hominem that implies that if you support public health interventions you must support fascism, but whatever.
Methodolatry vs. scientific rigor?
The second constant about Dr. Prasad has been his utter devotion to methodolatry, a term that I first learned in 2009 as the H1N1 pandemic was bearing down on us that is defined, more or less, as the profane worship of the randomized controlled clinical trial (RCT) as the only valid means of clinical investigation. (More broadly, methodolatry is an obsession over research methods over the actual findings of research and how to incorporate various studies into what we know.) Of course, under the framework of evidence-based medicine (EBM) RCTs are generally considered the strongest study design to evaluate the efficacy and safety of medical interventions. However, as all clinical investigators know (or should know), it is often not feasible, practical, or even ethical to carry out an RCT for some questions. For example, methodolatry denigrates epidemiological studies, which are the main type of studies that have demonstrated conclusively that there is no link between vaccines and autism. Basically, methodolatry would demand an RCT of vaccines versus placebo in order to answer once and for all the question of whether the MMR vaccine, any vaccine, or the entire vaccine schedule increases the risk of autism. Oh, wait, that’s what antivaxxers used to routinely demand, a so-called “vaxxed/unvaxxed” trial.
The “tragedy” of COVID-19?
So first let’s see what Dr. Prasad views as the “tragedy” of COVID-19 (rather than the tragedy that I see, millions dead worldwide, doctors contributing to disinformation about the virus and vaccines from the beginning, an antivaccine movement energized beyond anything I’ve ever seen in the last quarter century and now aligned with powerful far right political movements. Here’s his tragedy:
John Mandrola at some point limited commenting about COVID19 policy (I don’t blame him), and I was one of the few indefatigable people, but only because of a stubborn personality and a strong professional position (with 2 books and 400 papers before the age of 39, I’m hard to slow). Of course, I too will stop commenting about COVID19, but only because of boredom.
What I view as the tragedy of COVID19 is that medicine had no way to have a dialog about any important issue without devolving to ad hominem. Even policing ad hominem was uni-directional. The same people who wrote articles about online bullying or how to use twitter as a scientist were happy to bully John Ioannidis. IFR was window dressing. They were just scared that he was opposed to lockdown and school closure.Note how, even in lamenting “ad hominem,” Dr. Prasad is unable to resist bragging about his publication record at his still relatively young age and how “indefatigable” he is. Let’s just say that I might respect his “indefatigability” if and when Dr. Prasad has reached a quarter century of enduring abuse for his public takes, you know, like a certain blogger who took a ‘nym based on a supercomputer from a 40 year old obscure British science fiction series.
“Ad hominem.” You keep using that word, Dr. Prasad. I do not think it means what you think it means. Also, let me make a prediction. You saw how Dr. Prasad said that he would “stop commenting about COVID-19” (but “only out of boredom,” given how much better he is than the rest of us), right? Here’s my prediction: He won’t stop commenting about COVID-19 any time soon. He can’t. Thanks to audience capture, it’s so much part of his brand that he’d risk losing too much of his audience (and those lucrative Substack subscriptions) if he ever totally stopped offering the contrarian takes infused with methodolatry that his followers so crave.
Also, whenever you see someone like Dr. Prasad complain about “bullying” of his friends, note that it’s almost always projection. Dr. John Ioannidis is arguably the most published living scientist. Before the pandemic, he was widely admired to the point of being damned near untouchable as far as criticism goes. Since the pandemic, Prof. Ioannidis started issuing COVID-19 contrarian takes, starting with a study very early in the pandemic that produced a very low infection fatality rate (IFR) for COVID-19 based on vastly overestimating the percentage of the population infected.
For me, though, Ioannidis’ lowest blow was when he weaponized a satirical publication index, the Kardashian index, against public health scientists who had opposed the Great Barrington Declaration (GBD), which he supported. The GBD, as you might remember, was published in October 2020 (before there were vaccines) and advocated a “let ‘er rip” strategy for COVID-19 among the “young and healthy” (and therefore presumably low risk for complications and death) in order to achieve “natural herd immunity” faster, while using “focused protection” (never more than vaguely defined) to protect the elderly and those with chronic health conditions that put them at higher risk. It was a profoundly eugenicist proposal that never would have worked, even more so since the rise of variants like Delta and Omicron, which can evade immunity due to infection with prior variants. Dr. Ioannidis took the Kardashian index, which was proposed satirically as a means of measuring a scientist’s social media reach compared to the impact of the scientist’s scientific publication record, and tried to claim that the signatories of the John Snow Memorandum, issued in response to the GBD and highly critical of it, were “science Kardashians.” Then, when criticized very politely and based strictly on the science—or, more accurately, the lack of science—in his paper, Prof. Ioannidis reacted…very badly. Personally, there were a number of calls for his paper to be retracted (something it richly deserved), but it’s still there, not because it isn’t awful but because it’s Prof. Ioannidis. Because of its author, I strongly suspect that the editor is just too cowardly to pull the trigger and actually retract the paper.
But Ioannidis is the victim of “bullying”!
Dr. Prasad was also very unhappy with a criticism of how Prof. Ioannidis’s contrarian takes on COVID-19 were lionized in the. media very early in the pandemic, a reaction to the claim that COVID-19 was basically like seasonal influenza in its mortality in which Carl Bergstrom added upper and lower bounds to Prof. Ioannidis’ estimates:
Leading to one of the authors (who, unsurprisingly, now contributes to Dr. Prasad’s “Sensible Medicine” Substack) to respond:
To Dr. Prasad, who had long used his Twitter account to savage those whose medical takes he found lacking and denigrate trying to counter medical misinformation as “dunking on a 7′ hoop,” this was just too much:
But the tenor was set. If anyone said anything that could be used to argue for less restrictive policies there would be no limits to what would be acceptable ways to discredit them. Ad hominem was fair game, but only if they were minimizing COVID. If they were exaggerating it, that was fine. If you even pointed out the errors to a maximizers idea, you were “bullying them.” It was a bizarre double standard.
In the years that followed, nearly every single person who expressed skepticism about prolonged lockdowns, school closure, masking 2 year olds, vaccinating children for COVID 19 (despite dubious clinical data & high seroprevalence), perpetual boosters, paxlovid’s efficacy in vaccinated people, and the COVID19 testing industry complex was at one time or another labeled a contrarian, a right wing operative, a grifter, a charlatan, a disgrace, a crook, an anti-vaxxer, anti-masker, or a MAGA republican, etc etc.
“Bizarre double standard,” indeed. Oddly enough, Dr. Prasad seems very…reticent…when it comes to the Brownstone Institute, the right wing think tank to which he contributes, which has likened public health to fascism and Communism. (It can’t make up its mind and apparently shifts to one or the other form of totalitarianism depending on how useful it is to its contributors at the moment to demonize masks, vaccines, or public health.) He also apparently either hasn’t seen, ignores, or doesn’t see anything wrong with the calls of his buddies Drs. Jay Bhattacharya and Martin Kulldorff to hold “lockdowners” and public health officials responsible for mask and vaccine mandates “accountable,” complete with an image of a guillotine and language reminiscent of the “Nuremberg 2.0” language of antivaxxers who want show trials for vaccine advocates. True, Brownstone includes “plausible deniability” in the form of questioning how useful such trials would be, but for the wrong reasons, mainly fear that their flacks and allies might one day also be held accountable. Meanwhile, Dr. Prasad dismisses “pundits” who don’t see things his way as “weather vanes” as basically clueless doctors and scientists who follow the latest trend on COVID-19 to tell the media what they want to hear, all while being incapable of independent thought and analysis of scientific studies (unlike, of course, Dr. Prasad, who is a brave maverick who can “think for himself”).
Back to methodolatry, but only for studies Dr. Prasad doesn’t like
Speaking of double standards, let’s look at Dr. Prasad’s methodolatry. Again, methodolatry basically means dismissing and demeaning more than is scientifically appropriate any sort of evidence that comes from studies that are not RCTs. Another example of the consequences of methodolatry that I like to mention, other than the “old school” antivax call for an RCT of the whole childhood vaccine schedule to test whether vaccines increase the risk of autism, is smoking and lung cancer. All the human evidence that we have to show that smoking causes lung cancer (and other cancers) is epidemiological. There can never be RCT evidence to show that smoking causes lung cancer because doing such an RCT, even if it were possible given that no blinding is possible, would be unethical in the extreme. The reason is simple. There would be no clinical equipoise, the necessary ethical precondition for any RCT that there be genuine scientific uncertainty over which group, control or experimental, will fair better. In the case of such a study, we know which group would fair worse, because of all the epidemiological evidence that we have that smoking is associated with a hugely increased risk of lung cancer and death. The same is true for the “vaxxed/unvaxxed” RCT that antivaxxers used to demand. The placebo group would be expected to suffer far more from vaccine-preventable diseases. Because for such a trial it would be known in advance who would be harmed (and that it would be not by a little), a vaxxed/unvaxxed RCT of the vaccination schedule could never be ethical.
Which brings us to what is perhaps the most clear statement of methodolatry that I’ve seen in a long time from Dr. Prasad:
My take on COVID19 boils down to a simple worldview: I think it is reasonable to implement policies in the heat of the moment when you are scared and uncertain, but they have to be time-limited, and you have to work hard to run randomized experiments to separate what works from what doesn’t (the NIAID and CDC did not do those studies). Drug and vaccines are neither all good or all bad — they often work in some situations, but not others — and you desperately need randomized studies to sort the difference. And no person is a saint — Fauci made many, catastrophic mistakes: none worse than pushing for prolonged school closure.
If you rely on observational data, you do so at your peril. A sizable fraction of observational studies are incorrect, and without randomized data, you cannot separate wishful thinking from a true signal. Many observational studies may merely be a fulfilling prophecy — analytic choices that ensure the answer the authors seek. My worldview is nothing new. It is evident in both my books Ending Medical Reversal with Sensible Medicine’s Adam Cifu, Malignant, and over 400 peer reviewed papers.
Notice how Dr. Prasad starts out sounding very reasonable. When there’s no time to do an RCT given that people are dying now, then it makes sense to use a lesser standard of evidence to decide what to do now, but eventually RCTs need to be done to nail down the answers. As far as it goes, that’s not methodolatry, and I even acknowledged that very same argument with respect to hydroxychloroquine, the repurposed drug that was touted as highly effective against COVID-19 but turned out, unsurprisingly, not to be effective, as I pointed out that we didn’t even have halfway decent observational evidence to justify the use of the drug given the negative effects on patients who needed it but couldn’t get it for their autoimmune diseases because people were buying it up for COVID-19.
Also notice how, instead of just sticking with a somewhat reasonable statement of how evidence should be used, Dr. Prasad immediately pivots to attack Anthony Fauci as an example. Amusingly, even as Dr. Prasad criticizes “weather vane” scientists for not having any skin in the game, I can’t think of anyone who did have more skin in the game than Dr. Fauci, who had to spend the first year of the pandemic dealing with a profoundly dishonest and stupid President who sought to marginalize public health in order to save his reelection bid and, through it all, has endured abuse and credible death threats. Let’s just say that Dr. Prasad has a very large bug up his nether regions about Dr. Fauci, and publishing anonymous rants about the honors he is receiving.
It’s Dr. Prasad’s methodolatry that led me to be able to predict his reaction to a recently published study on MMWR about the efficacy of the new bivalent booster for COVID-19 before I even saw his take on it. He even sounds a lot like an antivaxxer:
There is only one right way to know who benefits from a bivalent booster, and that is a randomized trial. Take people over the age of 65, who have already gotten 3 doses of the parent vaccine, and randomize them in 3 arms to a 4th dose of Wuhan vaccine, a bivalent booster, and placebo vax, and measure severe disease and hospitalization.
Pfizer and Moderna can afford this study. It can be completed rapidly. The US FDA has a societal obligation to demand it, and yet that did not happen. This raises the question if regulators work for the public or instead plan their lucrative future consulting careers for Pfizer and wish to give them an easy market share. Remember that Scott Gottlieb former FDA commish, is now on their board of directors.
Over the last year White House officials continue to work closely with Pfizer to push bivalent boosters through based on mouse data. This has no precedent in modern regulatory history and constitutes a multi-billion dollar give-away to the company. Now the CDC seeks to perform a study to justify that action. Enter the latest MMWR study
Pharma shill gambit, anyone? Also, whenever you see someone say that there is “only one right way” to answer a scientific question, be wary. Again, an RCT would be the most definitive way to answer this question, but, contrary to what methodolatry demands, an RCT is not the only valid method to investigate this question. Moreover, for a self-proclaimed expert on clinical trial design, Dr. Prasad seems rather oblivious to the actual practical difficulties in carrying out such a trial, not the least of which would be recruiting an adequate number of patients to answer the question. Remember that the original phase 3 clinical trials for the vaccines enrolled tens of thousands of subjects each, and it would likely require at least thousands, if not tens of thousands, of subjects for the sort of trial that Dr. Prasad demands, and that would take months.
Rather amusingly, even as he complains to high heaven about “ad hominem” attacks, instead of just launching into why he thinks this study is flawed Dr. Prasad instead chooses to preface his discussion with a rant about Pfizer, Moderna, the FDA, and Scott Gottlieb and how they supposedly are warping the science to produce papers like this instead of doing The One True Study (much like The One True Study of COVID-19 vaccines in children). Seriously, I’d take Dr. Prasad’s complaints about harsh criticism and “ad hominem” more seriously if he had at least waited until after his discussion of the flaws that he attributed to the study to bring up these issues.
Dr. Prasad even gets a bit deceptive:
They assess the VE of bivalent booster vs unvaccinated people or those who received >=2 doses of mRNA. Yet, this is a farce. Bivalent boosters are largely given to people who have already gotten 3 or 4 doses. The question is: if I have gotten all the recommended doses, do I derive additional benefit from the bivalent booster? It makes no sense to compare them to unvaccinated people nor people who got 2 doses only. The analysis does not provide these results separately for those whose only difference is the bivalent booster.
Yet, the report states clearly why this design was chosen under a discussion of the limitations of the study (VE=vaccine efficacy):
First, the sample size was not sufficient to estimate VE by the number of COVID-19 monovalent vaccine doses received before the bivalent booster dose or compared with patients whose most recent monovalent vaccine dose was received 2–5 months before illness onset. Second, because use of monovalent COVID-19 mRNA vaccines as a booster dose is no longer authorized in the United States,††† this analysis could not compare the effectiveness of a bivalent booster dose with a monovalent booster dose administered during the same period.
Basically, there were not enough patients in each group to break them down into into smaller groups for analysis based on number of doses of monovalent vaccine received. So the investigators lumped them together. There’s nothing nefarious about this. It’s a preliminary study and the authors state that more needs to be done. I’m sure that Dr. Prasad knows this. Similarly, the authors simply point out that the only currently authorized vaccine in the US for a booster is the bivalent one.
Dr. Prasad also rants:
“Control patients whose influenza test results were positive were excluded from the analysis because of potential correlation between COVID-19 and influenza vaccination behaviors”. This is absolutely horrific. There is no justification on planet earth for this, and it strongly makes one suspect that the original analysis, which included these people, was null or unimpressive. These patients SHOULD NOT BE EXCLUDED. This violates the very principle of test negative design.
Not everyone will appreciate that these analytic choices are deeply problematic. They are unjustified. The CDC needs to preregister their analyses because there is a deep concern that the entire purpose to return the answer that the White House overlords have asked for.
Except that the authors again explain why they did this, with a link to a modeling study that found that there is indeed a correlation between COVID-19 and influenza vaccination behaviors, specifically:
Where vaccination probabilities are positively correlated, COVID-19 and influenza VE test-negative studies with influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ARI controls, respectively, underestimate VE. For COVID-19 VE studies, mean bias was low for all scenarios where influenza represented ≤25% of controls. For influenza VE studies, mean bias was low for all scenarios where SARS-CoV-2 represented ≤10% of controls. Although bias was driven by the conditional probability of vaccination, low VE of the vaccine of interest and high VE of the confounding vaccine increase its magnitude.
With the conclusion:
Researchers should consider potential bias and its implications in their respective study settings to make informed methodological decisions in test-negative VE studies.
You can argue about whether this was appropriate or not on a strictly scientific basis, but Dr. Prasad then launches into, yes, an ad hominem attack on the investigators by accusing them of, in essence, scientific fraud (“makes one suspect that the original analysis, which included these people, was null or unimpressive”) and being toadies, sycophants, and lackeys for the White House. Sure, Dr. Prasad doesn’t name names, but the accusations of fraud and being in the pockets of Big Pharma and the White House are no less ad hominem. What this study shows are promising preliminary data that the bivalent boosters are protective. Not even its authors claim that it’s definitive.
With Dr. Prasad, though, it is “RCTs for thee but not for me.” What do I mean? Dr. Prasad’s methodolatry goes pretty much one way: Against studies whose results he doesn’t like. If you don’t believe me, just look at how he’s defended bad VAERS studies and epidemiological studies that found elevated risks of myocarditis, which he called a “bombshell”:
As I said at the time, Dr. Prasad might be well-known for demanding ever more rigorous data for various medical interventions, such as masking to slow the spread of COVID-19, but on the topic of myocarditis and COVID-19 vaccines, he’s long seemed quite happy with a low-quality study that misused the VAERS database. He also seemed quite happy doing a commentary about “obsessive criticism” of him and his buddy Prof. Ioannidis social media based on even lower quality analyses.
I AM A LIBERAL! (No, you’re not, at least not anymore.)
Finally, it’s clear that Dr. Prasad is…uncomfortable…with many of those who lionize him. After going on about how COVID contrarians are often called “MAGA” or right wing, he goes out of his way to deny that he’s a right wing loon
The truth didn’t matter. I am a far left democrat. I supported Bernie Sanders and Elizabeth Warren. Both of my books are about progressive regulatory solutions to improve the medical drug and device marketplace. I am an expert in clinical trial design. I know the limits of observational data — I have taught many classes pointing them out, and my podcast Plenary Session is often praised as a great place to learn these skills. And yet, I was labeled many of these things.
To this, I respond simply: If you don’t want people to conclude that you are a right winger, don’t associate yourself with right wing anti-public health and antivaccine activists and make exactly the same arguments and use exactly the same cherry picking and misrepresentations of science as they do. I’m referring, of course, to the hacks at the Brownstone Institute, which is basically a right-wing astroturf “think tank” founded by a neo-Confederate white nationalist and advocate for child labor. If you don’t want people to think you’re a right wing anti-public health ideologue defend Elon Musk’s takeover of Twitter and rail against a university public health department for leaving Twitter because (supposedly) it’s too “woke.” If you don’t want people to suspect your motivations or think that you might be affiliated with Koch brothers-funded entities, get some actual NIH funding instead of relying on grants from Arnold Ventures, a charitable fund set up by ex-Enron hedge fund billionaire John D. Arnold, for a three-year project to identify and reduce low-value healthcare as a way to cut medical costs. Stop working with Koch brothers-funded organizations and COVID contrarian doctors. Meanwhile, Dr. Prasad has appeared on Dr. Drew Pinsky’s podcast to fear monger about the risk of myocarditis from the mRNA COVID-19 vaccines.
I will conclude by pointing out two rather obvious things. First, Dr. Prasad’s tone policing is performative. It’s intended to try to portray his critics as irrational and therefore people to be ignored, not as any genuine complaint against a lack of civility. After all, dating back to long before the pandemic, Dr. Prasad was not shy about being aggressive in his attacks on science he considered insufficiently rigorous, both on Twitter and in person. These days, it bothers him not in the least that one of the scholars at Brownstone. where he writes, is Paul Alexander, a Trump administration science adviser who used to advocate for mass infection and, in a throwback to “Nuremberg 2.0,” has also called for the hanging of politicians and public health officials who instituted any kind of public health mandate, such as masking, “lockdowns,” and vaccination:
Finally, his methodolatry is also performative—and selective. He demands ever more rigorous RCTs when less rigorous studies come to results that he doesn’t like, but then accepts crappy dumpster diving studies of VAERS done by his buddies and cronies as definitive evidence.
His cries of being a “progressive” who voted for Elizabeth Warren and Bernie Sanders now ring quite hollow. Perhaps that’s what he was. These days he’s a right wing propagandist for anti-public health measures. He should just own it now. Why not? It’s his brand.
Note: Orac will likely not return before December 27 and plans an even lighter-than-usual posting schedule between Christmas and January 3; that is, unless something comes up during the holidays that he just can’t resist commenting on which is entirely possible. In the meantime, Merry Christmas, Happy Hanukkah, and Happy New Years!