One of the advantages of having been a blogger for over 17 years is that you start to get a sense of history and perspective. You see the same things (or similar things) pop up over and over again. Indeed, that’s one reason why I frequently say about antivaccine conspiracy theories in the age of COVID-19 that “everything old is new again” and “there is nothing new under the sun in antivaxland” (e.g., misusing and misrepresenting VAERS); none of the conspiracy theories that have popped up since COVID-19 hit and shocked and surprised my colleagues are new. I don’t want to dwell on that, because the current topic is more general (although certainly COVID-19 cranks are involved). I’m referring to attacks on evidence-based medicine (EBM) as an “illusion” or somehow hopelessly compromised, for whatever reason (most commonly, corruption by big pharma).
These articles seem to pop up every few years. Sometimes these articles make good points, sometimes not (more often it’s a mixture of both good and bad points and a failure to deal reasonably with the messiness of evidence-based medicine), but regardless of the quality of the article, such articles are always embraced by enemies of evidence-based medicine, which is how I became aware of an article published earlier this month in The BMJ by Jon Jureidini and Leemon B. McHenry entitled The illusion of evidence-based medicine. Where did I find out about it? In the comments of my blog and in an article by Dr. Robert “inventor of mRNA vaccines” Malone on antivax leader Robert F. Kennedy, Jr.’s website entitled How Politics Corrupted Evidence-Based Medicine — And How to Fix It, which turned out to be a reprint of the same article on his Substack under the title The illusion of evidence-based medicine, with the subtitle How the government stopped worrying and learned to love propaganda.
Interestingly, RFK Jr. didn’t include the tagline, which was an obvious nod to one of my favorite movies of all time Stanley Kubrick’s classic 1964 Cold War dark comedy Dr. Strangelove, or: How I Learned to Stop Worrying and Love the Bomb. Lest you fail to make the connection, Dr. Malone even included a photo of Peter Sellers as the eponymous Dr. Strangelove, the wheelchair-bound former Nazi scientist who in the film was the President’s scientific advisor pontificating about the Soviet doomsday device. (He also slipped up and the President as “Mein Führer!” with a Nazi salute.) Of course, I love to invoke Dr. Strangelove for other reasons, mainly the obsession of one of its other characters, Gen. Jack D. Ripper, with “purity of essence.”
Whenever I see articles like this one in The BMJ, I like to start with what the crank says about the article and then look at the article itself. Often—but not always—there is a disconnect. Often, the article is fairly reasonable, but the crank uses it to condemn all of evidence-based medicine and, by doing so, claim that their pseudoscience and conspiracy theories must be correct. Also, before I begin, far be it from me to dismiss criticism of evidence-based medicine. The problems with evidence-based medicine were the reason that Steve Novella and others came up with the concept of science-based medicine; to “fill in the holes,” so to speak, in evidence-based medicine, in particular its reliance on methodolatry and randomized controlled clinical trials über alles—sorry, given the Dr. Strangelove reference, I couldn’t resist—and its dismissal of incredibly low to zero prior plausibility based on basic science for modalities like homeopathy.
So let’s start with how Dr. Malone views this paper:
In 1990, a paradigm shift occurred in the development of new medicines and treatments. An idea so big, that it was supposed to encompass the whole of medicine. It was to start initially at the level of pre-clinical and clinical trials and work all the way through the system to the care and management of individual patients. This new concept for how medicine would be developed and conducted is called evidence-based medicine (EBM). Evidence-based medicine was to provide a more rigorous foundation for medicine, one based on science and the scientific method. Truly, this was to be a revolution in medicine – a non-biased way of conducting medical research and treating patients.Evidence-based medicine Evidence-based medicine is “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.” The aim of EBM is to integrate the experience of the clinician, the values of the patient, and the best available scientific information to guide decision-making about clinical management.So, what the hell happened?
First of all, evidence-based medicine was not a “new concept” three decades ago (which, ironically, was around about the time that—if you believe his account—Dr. Malone was supposedly busily inventing mRNA vaccines). The evidence-based medicine movement did, however, most definitely popularize it, as can be seen by the exponential increase in usage of the term in publications during the 1990s. The way I look at it is that “EBM” was a new term coined to describe and codify a concept that had been discussed since at least the 1960s, if not earlier. It worked, too. Evidence-based medicine is the gold standard of how we as physicians seek to practice medicine and surgery.
That observation aside, I bet that you can guess what, according to Dr. Malone, “happened”:
There is a big flaw in the logic of evidence-based medicine as the basis for the practice of medicine as we know it, a practice based on science; one that determines care down to the level of the individual patient. This flaw is nestled in the heart and soul of evidence-based medicine, which (as we have seen over the last two years) is not free of politics. It is naive to think that data and the process of licensure of new drugs is free from bias and conflicts of interest. In fact, this couldn’t be any farther from the truth. The COVID-19 crisis of 2020 to 2022 has exposed for all to see how evidence based medicine has been corrupted by the governments, hospitalists, academia, big pharma, tech and social media. They have leveraged the processes and rationale of evidence-based medicine to corrupt the entire medical enterprise.
This brings us back to the BMJ editorial, which Dr. Malone likes so much because it accuses the pharmaceutical industry of corrupting evidence-based medicine:
The advent of evidence based medicine was a paradigm shift intended to provide a solid scientific foundation for medicine. The validity of this new paradigm, however, depends on reliable data from clinical trials, most of which are conducted by the pharmaceutical industry and reported in the names of senior academics. The release into the public domain of previously confidential pharmaceutical industry documents has given the medical community valuable insight into the degree to which industry sponsored clinical trials are misrepresented.1234 Until this problem is corrected, evidence based medicine will remain an illusion.
The first four references are to articles about the promotion of gabapentin by Pfizer, cardiovascular risks from COX-2 inhibitors (e.g., Vioxx, a favorite among those attacking science- and evidence-based medicine), the H1N1 influenza vaccine Pandemrix (which was linked—although not definitively—with narcolepsy in Scandinavian countries), and study 329 of paroxetine in adolescents. I’m fairly familiar with the Pandemrix story and wasn’t particularly impressed that the article cited by Jureidini and McHenry was by Peter Doshi, a man who, as I’ve described, is at the very least antivaccine-adjacent if not outright antivaccine, and who can always be counted on to exaggerate harms and minimize benefits of any vaccine, going at least as far back as influenza vaccines in the mid-2000s. (He’s even spoken at at least one antivaccine conference and, more recently, has appeared on a panel with outright COVID-19 conspiracy theorists.) In the article cited, Doshi basically regurgitates the plaintiff’s side of a lawsuit over Pandemrix. As I’ve discussed before, though, the true situation is more complex, and it’s not even totally clear that Pandemrix can be causally linked to the narcolepsy cases. In any event, blog buddy Skeptical Raptor deconstructed Doshi’s article right after it was published, so that I don’t have to do it now. Similarly, the case of Vioxx and other COX-2 inhibitors was actually an example of the system working, albeit imperfectly. As Steve Novella once put it:
It does appear that the company dragged their heels on some of the data with Vioxx, and if this is found to be the case legally they should pay the price. But let’s review what happened. After Vioxx was on the market scientists continued to study its effects. The company supported this research, even though there was no requirement for them to do so. Eventually the data became clear that there was an increase in heart attacks among Vioxx users who were at high risk, and the company withdrew Vioxx from the market. If there were some big Pharma/FDA conspiracy, why would that have happened at all? Wouldn’t they have just kept the whole thing hushed up?
As for the other two, the article about the promotion of gabapentin consisted almost entirely of exhibits filed by plaintiffs in a lawsuit against Pfizer for using educational venues to promote off-label use of gabapentin. This actually doesn’t show that evidence-based medicine is somehow broken or corrupted; rather, it suggests that pharmaceutical companies do promote off-label use of drugs, which are often evidence-based. Remember, off-label use is not synonymous with unproven; rather, off-label use happens in medicine all the time because clinical trials can show that FDA-approved drugs have efficacy for other indications not included in the FDA approval. Drug companies aren’t allowed to promote off-label uses for the obvious reason that, if they were, they would have no incentive to submit new data to the FDA to seek formal approval for new indications for their drug. One could imagine a case where a pharmaceutical company won approval for a drug for one indication and then started marketing it for all sorts of indications, whether evidence-based or not. Finally, the article about study 329 demonstrated how a study by GlaxoSmithKline of paroxetine in adolescents claimed that “paroxetine is generally well tolerated and effective for major depression in adolescents,” a claim contradicted by internal company documents were examined.
Whenever I discuss pharmaceutical company chicanery in a way that doesn’t conclude that all pharmaceutical companies are pure evil, inevitably the charge of “pharma shill” will be aimed a me. My usual response is to point out that, if I were a pharma shill, I’d be the worst one ever, given that I’ve only ever had one small grant from a pharmaceutical company (which never really went anywhere) and have been studying repurposing a drug for amyotrophic lateral sclerosis (ALS) to use to treat breast cancer without big pharma support. In any event, we who promote science- and evidence-based medicine are far from oblivious to the misdeeds of pharmaceutical companies. We also often note the disconnect between how often quacks promote pharmaceutical products like ivermectin or hydroxychloroquine without evidence (off-label uses that pharmaceutical companies could have promoted to make lots of money), while damning pharmaceutical drugs that actually work.
But let’s see what Jureidini and McHenry have to say further:
The philosophy of critical rationalism, advanced by the philosopher Karl Popper, famously advocated for the integrity of science and its role in an open, democratic society. A science of real integrity would be one in which practitioners are careful not to cling to cherished hypotheses and take seriously the outcome of the most stringent experiments.5 This ideal is, however, threatened by corporations, in which financial interests trump the common good. Medicine is largely dominated by a small number of very large pharmaceutical companies that compete for market share, but are effectively united in their efforts to expanding that market. The short term stimulus to biomedical research because of privatisation has been celebrated by free market champions, but the unintended, long term consequences for medicine have been severe. Scientific progress is thwarted by the ownership of data and knowledge because industry suppresses negative trial results, fails to report adverse events, and does not share raw data with the academic research community. Patients die because of the adverse impact of commercial interests on the research agenda, universities, and regulators.
Whenever someone invokes the name of Karl Popper while attacking evidence-based medicine, my skeptical antennae start twitching fiercely. It’s not that they will necessarily be mistaken but that they almost always go on a rant right after doing that, and this passage is no exception. I also can’t help but note that The BMJ seems a bit lax in its peer review. Jureidini and McHenry make a number of factual claims here, but nowhere do they back up those claims with references. I will say right here that they aren’t wrong about free market champions promoting privatization and laxer standards of evidence. I myself have bemoaned that very tendency among libertarians who falsely claim that the FDA is “killing people” by being too stringent in its requirements for evidence and too slow to approve new medicines. Their solution? Loosen standards and let the “free market” work its magic, of course! Of course, the factual claims made by Jureidini and McHenry are likely at least partially true, but some references would have been nice.
But what does any of this have to do with evidence-based medicine? Obviously, evidence-based medicine is based on randomized controlled clinical trials (preferably placebo-controlled and blinded, at least when it’s ethical to do so). Also, the people who produce evidence-based medicine guidelines are generally academics based in medical schools and academic medical centers. So:
The pharmaceutical industry’s responsibility to its shareholders means that priority must be given to their hierarchical power structures, product loyalty, and public relations propaganda over scientific integrity. Although universities have always been elite institutions prone to influence through endowments, they have long laid claim to being guardians of truth and the moral conscience of society. But in the face of inadequate government funding, they have adopted a neo-liberal market approach, actively seeking pharmaceutical funding on commercial terms. As a result, university departments become instruments of industry: through company control of the research agenda and ghostwriting of medical journal articles and continuing medical education, academics become agents for the promotion of commercial products.6 When scandals involving industry-academe partnership are exposed in the mainstream media, trust in academic institutions is weakened and the vision of an open society is betrayed.
That reference, by the way, is a book from 2003. One thing I’ve noticed about this paper is that a lot of the references seem to be quite old. Again, I’m not saying that there aren’t problems related to business influence in academia. It’s a problem that goes beyond just medicine and biomedical research. You’d think, though, that someone arguing that evidence-based medicine is hopelessly corrupted by pharma influence could actually cite a clear and compelling example of how a single evidence-based set of guidelines was actually corrupted by—you know—big pharma influence, preferably more recently than two decades ago. None of the first four citations did that, because none of the examples were actually of pharmaceutical companies successfully corrupting evidence-based guidelines. Moreover, although it is true that the FDA often doesn’t see the raw data from clinical trials, it absolutely has the power to demand to see it when deemed appropriate.
I will, however, agree with Jureidini and McHenry’s decrying of “key opinion leaders” (KOLs). These are often physicians who have received funding (often a lot of funding) from pharmaceutical companies, either to support their research or to be part of a company’s speaker bureau.
So what are the proposed solutions? The authors argue:
Our proposals for reforms include: liberation of regulators from drug company funding; taxation imposed on pharmaceutical companies to allow public funding of independent trials; and, perhaps most importantly, anonymised individual patient level trial data posted, along with study protocols, on suitably accessible websites so that third parties, self-nominated or commissioned by health technology agencies, could rigorously evaluate the methodology and trial results. With the necessary changes to trial consent forms, participants could require trialists to make the data freely available. The open and transparent publication of data are in keeping with our moral obligation to trial participants—real people who have been involved in risky treatment and have a right to expect that the results of their participation will be used in keeping with principles of scientific rigour. Industry concerns about privacy and intellectual property rights should not hold sway.
First, I actually agree that public funding of independent clinical trials of new pharmaceutical candidates would be optimal, but I also realize that politically it’s a nonstarter, both due to expense and due to the current political climate. Again, when there are free market libertarians arguing that the current process for accelerated approval of new drugs should be accelerated still more, or even that FDA should be in essence neutered—or at least reduced in authority to its pre-Kefauver-Harris Amendments power to require safety data but not efficacy data before approving drugs—proposing a huge increase in the FDA budget or the creation of a government entity to run clinical trials just isn’t happening, at least not in the US. That’s not to say that there’s not more that can be done; for instance, actual enforcement of the law requiring that all clinical trial results be published expeditiously after completion of the trial would be a good start.
Also, although in concept sharing anonymized raw data sounds good (I can even get behind it to some extent), in practice there are a lot of problems. It’s not as though this sort of thing hasn’t been considered and discussed a long time, and, contrary to Jureidini and McHenry’s blithe claim that it would be “easy” to anonymize the data and place it in a publicly accessible repository, open sharing of clinical trials data that way is anything but easy, based on how difficult it is to maintain even non-public usable data repositories:
The key challenge is that preparing and maintaining usable data repositories require a great deal of effort and resources, especially the time of researchers who collected the data and need to describe it in meaningful ways to make the data legible to prospective users while ensuring simultaneous compliance with the open data mandates and any confidentiality, privacy, and internal policies that may apply. This is a time- and labour-intensive process, especially in organisations implementing controlled access to data. Receiving and processing applications for data release, developing agreements and contracts, producing and transferring data, and responding to subsequent requests for clarification involve a broad range of people across the data-sharing organisation . In this sense, open data more resembles new data products than readily available outputs from previous experiments. Research organisations typically have limited resources to handle these requests, which can result in conflict with other demands on staff time, such as ongoing research. In the absence of support from research funders to prepare the datasets, some research units may require applicants to provide funding to cover the necessary staff time, which in effect means spending research money on curation.50 In the absence of funding specifically to curate and release data as open data, researchers continue to share their data with others in different ways.
One of the risks raised by researchers as an impediment to data sharing is the possibility of data misuse or even wilful misinterpretation of the data. In the situation where there is a lack of agreement on what constitutes data reuse and reusability, these concerns are justified. In the absence of robust data descriptors, the data may be analysed incorrectly, and incorrect conclusions may be drawn. Another concern is that the purpose for which data is later reused may be incompatible with the original purpose for which the data was collected. Such purposes may include causes with which the original data creator disagrees or does not wish to be aligned. Researchers also raised concerns that future data users may not give proper credit to the original creators. A further concern is that data may be used to harm future business activities of research organisations, such as allowing others to commercially exploit the data.
This brings me back to Dr. Malone, who, ironically, uses the desire to misuse data to argue for data transparency, although obviously he would not admit that that’s what he’s doing:
US government employees also control the narrative. Take for example the use of the media, CDC and the FDA to control the narrative about early treatment for COVID-19. By now we should all know about the corruption of the early clinical trials of hydroxychloroquine. On the basis of these faked studies, one of the safest drugs in the world was recommended to not be used in an out patient setting – most likely, in order to increase vaccine acceptance. Or how our government used propaganda to control the use of ivermectin by such tactics as calling it unfit for human use and labelling it as a “horse wormer.” All indications are that these efforts by the US government were to dissuade early treatment to stop vaccine hesitancy.
I bet you can guess which “early clinical trial” of hydroxychloroquine to which Dr. Malone is referring. Yes, it’s the Surgisphere trial, which reported serious adverse events associated with hydroxychloroquine but was later found to have been likely impossible based on what was claimed. It was indeed a debacle, but the retraction of that study did not, contrary to what Dr. Malone seems to be implying, mean that hydroxychloroquine actually worked against COVID-19. It doesn’t. Similarly, ivermectin is the new hydroxychloroquine that clinical trials still hasn’t seemed able to kill. It’s actually an interesting example, given that greater data transparency would likely have undercover the incompetently poor design of some studies and the apparent outright fraud of the “positive” randomized trials for the drug. Amusingly, Dr. Malone might not like greater data transparency when it comes to his favored COVID-19 quackery.
That part about misuse or willful misinterpretation of data is also very pertinent. One risk of truly open access to clinical trial data is that cranks will willfully misinterpret it or cherry pick certain parts. If you don’t believe me, just look at how they’ve done exactly this with an actual truly open database, the Vaccine Adverse Events Reporting System (VAERS) database. Jureidini and McHenry’s claim that it would be “easy” to guarantee privacy of clinical trial subjects is a bit clueless too, given the history of antivaxxers doing their damnedest to violate that privacy when they can by combining databases to try to extract personally identifiable information. I’m not saying that what Jureidini and McHenry propose can’t be done. I’m simply saying that they seem oblivious to just how difficult it would be and how easily conspiracy theorists could weaponize the data.
While Jureidini and McHenry make some reasonable points about data transparency, they overreach when they imply that evidence-based medicine is an “illusion” because big pharma has so corrupted it. After all, pharma doesn’t do the only clinical trials of drugs, which often go into further trials after approval by other entities to compare their efficacy and safety to existing treatments.
It’s also no surprise that someone like Dr. Malone would be all over Jureidini and McHenry’s op-ed as slam-dunk evidence that he and the other COVID-19 cranks, contrarians, and antivaxxers were right all along. That is why I conclude by responding to Dr. Malone as I always respond to claims that evidence-based medicine is so hopelessly corrupted as to be wrong:
I also caution Jureidini and McHenry. While it’s true that one can’t control how one’s work is used once it’s published and “out in the wild,” so to speak, be willing to subject it to reevaluation when you see cranks and conspiracy theorists pointing to it enthusiastically as supporting their pseudoscience, quackery, and conspiracy theories, for example:
Let’s just say that, when conspiracy theorists and grifters like the Frontline COVID-19 Critical Care Alliance love you, even if your message was accurate, you might not have delivered it in the most effective manner and very well might have overstated your case by just a bit. Of course, there’s also this statement of Conflicts of Interest:
McHenry and Jureidini are joint authors of The Illusion of Evidence-Based Medicine: Exposing the Crisis of Credibility in Clinical Research (Adelaide: Wakefield Press, 2020). Both authors have been remunerated by Los Angeles law firm, Baum, Hedlund, Aristei and Goldman for a fraction of the work they have done in analysing and critiquing GlaxoSmithKline’s paroxetine Study 329 and Forest Laboratories citalopram Study CIT-MD-18.
So they’ve written a book and served as expert witnesses for plaintiffs suing drug companies. Why am I not surprised. No wonder they’ve written an article that someone like Dr. Malone can so easily use as a reason to invoke Dr. Strangelove about clinical trial science. That doesn’t mean that they don’t make some good points. After all, years ago Ben Goldacre wrote a book called Bad Pharma that argued many of the same things. It just suggests why someone like Dr. Malone would choose to cite their work instead of Dr. Goldacre’s.