Yves here. Please welcome KLG, a member of our Covid brain trust who is trying his hand at publishing articles on poor or questionable medical and bioscience practices, particularly the corruption of science. We are excited at how his contributions will extend our range of coverage and increase our expertise. Particularly in the US, medicine is an over-large share of the economy, and how it operates is of personal and societal importance.
KLG plans to post every other Wednesday. So keep an eye out!
By KLG, who has held research and academic positions in three US medical schools since 1995 and is currently Professor of Biochemistry and Associate Dean. He has performed and directed research on protein structure, function, and evolution; cell adhesion and motility; the mechanism of viral fusion proteins; and assembly of the vertebrate heart. He has served on national review panels of both public and private funding agencies, and his research and that of his students has been funded by the American Heart Association, American Cancer Society, and National Institutes of Health.
Review: The Illusion of Evidence-Based Medicine: Exposing the crisis of credibility in clinical research. Jon Jureidini and Leemon B. McHenry, Wakefield Press, 2020.
When we go to the doctor, we hope she bases her interaction with us on what has come to be called Evidence-Based Medicine (EBM), which is the “conscientious, explicit, and judicious use of current best evidence everyday practice.” This is certainly how medical students and resident physicians think they are taught to choose how to treat their patients.
But how does theory meet practice? Not so well according to The Illusion of Evidence-Based Medicine: Exposing the crisis of credibility in clinical research (IEBM) by Jon Jureidini (Professor of Psychiatry and Pediatrics at the University of Adelaide) and Leemon B. McHenry (Emeritus Lecturer in Philosophy at Cal State-Northridge), which was published in 2020. An accessible, short precis of their work was published in BMJ (formerly British Medical Journal) in March 2022.
The examples of clinical case studies gone awry by Drs. Jureidini and McHenry are well known if not well understood. They concentrate most of their attention (Chapter 2: The Corruption of Clinical Research) on two studies of selective serotonin reuptake inhibitors (SSRIs) that were used to show the SSRIs paroxetine (Paxil, SmithKlineBeecham and citalopram (Celexa, Forest Laboratories) are effective interventions to treat depression in adolescents and children. The evidence remains equivocal. Other examples include Rofecoxcib (Vioxx, Merck), a cyclooxygenase-2 inhibitor initially approved for treatment of osteoarthritis that also caused more than 100,000 cardiac “events” in the US, 40,000-60,000 of which were fatal. As to be expected, Naked Capitalism has covered Vioxx here and here.
Gabapentin (Neurontin, Parke-Davis/Pfizer) was initially approved for treatment of seizures but was later improperly promoted and prescribed for off-label treatment of pain and psychiatric conditions. Fenfluramine/Phentermine (Fen-Phen, American Home Products/Wyeth) was touted as a treatment for obesity after a public relations campaign that presented obesity as a dangerous health problem, which it most certainly can be. But those who are not skinny are not therefore by definition unhealthy, and in many cases just the opposite. And while Fen-Phen use did lead to weight loss in those who used it, this drug combination also caused heart valve damage and potentially fatal pulmonary hypertension. No reader of Naked Capitalism (here and here) needs to be reminded about Oxycodone (Oxycontin, Purdue Pharma) and the opioid epidemic that has caused more than 500,000 deaths).
The gory technical details are included in the book so there is no reason to repeat them here. My question is “How did ‘science’ go so far off the rails?”
Money is the short answer. Money is also the correct answer. Each of these drugs are/were blockbusters, with likely sales of more than a billion dollars a year, some of them many billions of dollars a year. How does this sound familiar, “Science and Money,” in the years 2020, 2021, and 2022? But I digress, for now.
As citizens and consumers[1], we are continuously told to “trust the science.” I have been a student of biology, scientific worker, and an academic scientist for my entire professional life starting at the age of 19, at research universities large and small. So, I am totally onboard with trusting the results of transparent, disinterested scientific research.
But as a committed and working scientist who cannot imagine having done anything else for a living, I must also ask: What science and whose science for what purpose? These questions are left hanging by our erstwhile scientific and political leaders, and we leave them hanging at our peril.
After explaining what has gone wrong, IEBM shows us how to tackle these questions, first by pointing out that clinical research conducted with commercial objectives cannot really be scientific research, both from a commonsense perspective (i.e., how likely is the answer to be “no” when billions depend on “Yes!”?) and by the formal definition of scientific research described by Karl Popper in The Logic of Scientific Discovery and The Open Society and Its Enemiesamong other works. These two books are often rightfully called magisterial, but I confess to never having developed a taste for Sir Karl’s philosophy of science, which seems more useful in physics than biology and the biomedical sciences (I also believe that T.S. Kuhn, who appears in IEBM with his paradigm shifts is a most overrated philosopher of science, but that is for another time).
Nevertheless, Popper’s concept of “falsifiability,” however counterintuitive and downright odd to me as a student, is exactly right as an explanation of how a scientist actually goes about her vocation. No scientist sets out to disprove his hypothesis, but no good scientist does her experiments without the proper controls. And these controls can and will indeed falsify a scientist’s hypothesis, as every good scientist well knows.
With these scientists, this negative result leads to a better hypothesis. The scientist who will not do the critical control experiment is not a scientist. The scientist who ignores the negative or inconclusive result is a marketer. The problem with science conducted with a commercial outcome is that disinterest in the outcome required of a genuine Popperian scientist is essentially impossible in practice. This is marketing, not science.
Clinical trials have been important in modern medicine since James Lind showed that citrus fruits prevent scurvy. Double blinding followed the development of the placebo, and shortly after World War II Bradford Hill showed in a clinical trial that streptomycin in association with para-aminosalicylic acid cures pulmonary tuberculosis (and at about the same time, using similar reasoning, Hill and Richard Doll also demonstrated that tobacco causes lung cancer). James Lind and Bradford Hill answered critical medical questions as scientists who went where their data and results sent them. According to Drs. Jureidini and McHenry, “the randomized, placebo-controlled clinical trial was perhaps the most important discovery of modern medicine.” One might use “development” instead of “discovery,” but the message is the same.
Unfortunately, “the validity of this new paradigm…depends on reliable data from clinical trials and because the data are largely, if not completely, manipulated, by the manufacturers of pharmaceuticals, evidence-based medicine is largely an illusion.” How do they do this, disguise marketing as science?
First, ghostwriting. Those who write the articles describing the results of a clinical trial are often not the authors listed at the top of the first page beneath the title. Honorary authorship has long been a thing in some research areas, and while the mechanism of ghostwriting includes getting “thought leaders” involved, the results are more significant than enhanced visibility for a junior author who attaches a senior scientist to his work in hopes of faster, better recognition (it should be noted that honorary authorship may be declining as legitimate scientific journals now require identification of the contributions of each author to the manuscript under consideration).
One of the first known cases of ghostwriting occurred when an obstetrician with five papers to his name published “Trial of thalidomide in insomnia associated with the third trimester” (paywalled) in the American Journal of Obstetrics and Gynecology. According to IEBM, this paper was actually written by a medical director of a company that wanted to market thalidomide in the US as it had been in 20 European countries and Canada. Only the work of Frances Oldham Kelsey at the FDA (those were the days) prevented that catastrophe from being much worse than it could have been in the United States.
A more recent case of what the authors identify as ghostwriting was a key exhibit in the case against GlaxoSmithKline (the successor of SmithKlineBeecham) that resulted in a $3B fine. Follow-up reports on this publication are here with the following conclusions:
The continuation phase did not offer support for longer-term efficacy of either paroxetine or imipramine. Relapse and adverse events on both active drugs open up the risks of a prescribing cascade. The previously largely unrecognised hazards of the taper phase have implications for prescribing practice and need further exploration.
And here, with the following conclusions:
Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs. Access to primary data from trials has important implications for both clinical practice and research, including that published conclusions about efficacy and safety should not be read as authoritative. The reanalysis of Study 329 illustrates the necessity of making primary trial data and protocols available to increase the rigour of the evidence base.
No legitimate scientist accepts that her work can be prepared for publication by a medical communications company. On the contrary, a legitimate scientist can only be dumbfounded to read that an outside firm “was hired to prepare eighty-five papers for publication to facilitate Pfizer’s promotion of sertraline” and that the authors assigned to papers already drafted were listed as ‘TBD” – to be determined” (p. 98).
These data are old and to be fair, as mentioned above, established journals now often require a statement of author contributions. But with the rise of internet-based “scientific journals” over the past 20+ years, the business of scientific publication has changed beyond recognition to those of us who predate the web (more on that, especially related to COVID-19, to come).
As an interested citizen, the publication records of scientists are freely and publicly available through the National Library of Medicine. This is a valuable resource when reading or reading about the biomedical literature. If a scientist has too few, or just as importantly too many, publications to his or her name, or the implied expertise seems spread out over a wide area, caveat emptor.
Finally, regarding the scientific literature about psychiatric drugs and those for chronic conditions such as hypertension, high cholesterol, hyperlipidemia, and prediabetes, it is good to remember that market expansion is the goal and “what is good for Pfizer is good for Wyeth.”
Where does Big Pharma get its scientists? Naturally from the same place that all scientists come from: The Academic-Corporate University. One can argue about when the academic-corporate university appeared, with MIT likely leading the way[2]shortly after Vannevar Bush published Science: The Endless Frontier, and many critics have addressed the question, perhaps none better than the former President of Harvard:
These growing demands [from government and business] allow universities to profit from their work in more ways than ever before. Ironically, however, the very same opportunities could easily end by harming the academic enterprise and sullying its contributions to the nation’s welfare…making money in the world of commerce often comes with a Faustian bargain in which universities have to compromise their basic values – and thereby risk their very souls – in order to enjoy the rewards of the marketplace…Thus far, however, university leaders have paid too little heed to the risks that profit-making activities often bring in their wake. Instead, they have eagerly embraced one commercial venture after another in the hope of gaining added revenue for their institution (Bok, 2003, 199-200)
As someone who was present at the creation, which I date to the Bayh-Dole Act of 1980, all I can say is, “Amen!” But this goes hand-in-hand with first the creeping and later the rampant neoliberalization of our world. This has led to the commodification of academic research and the education of our students, who are now clients and customers who must be satisfied.
Few university faculty members are appreciated more by their administration than those who bring in the industry dollars, lionized at their respective institutions and by their industrial patrons, who are most generous with honoraria and consulting contracts and offers to present “continuing medical education” lectures at international meetings, which are seldom held at state parks.
The result: Distorted Research Priorities. Which brings the us back to Karl Popper, who wrote (p.23), “My own misgivings concerning scientific advance and stagnation arise mainly from the changed spirit of science, and from the unchecked growth of Big Science (certainly including Big Pharma), which endangers great science.”
In the case of Big Pharma, this includes such “first-world problems” as “heartburn, obesity, toenail fungus, sexual performance, depression, allergies, high cholesterol and the like.” These are likely to be blockbuster drugs. In the era of COVID-19, we must include mRNA-based vaccines that may offer some benefit to those infected with SARS-CoV-2 but do not prevent transmission or infection or disease. These vaccines have provided Pfizer with more than $50B over the past two years, however.
The expressly stated ambition of Big Pharma to sell drugs to healthy people has been realized, as the following ordinary conditions have been medicalized: menopause, menstruation, shyness, anxiety, erectile dysfunction, female sexual dysfunction, with psychiatry the medical specialty/discipline most vulnerable to abuse. Psychiatric drugs include those for Social Anxiety Disorder, Pediatric Bipolar Disorder, Premenstrual Dysphoric Disorder, Hypoactive Sexual Desire Disorder, Disruptive Mood Disorder, and Seasonal Affective Disorder. Others in the pipeline include compulsive shopping, gambling addiction, smoking cessation, and writer’s block (Hmm…). These conditions can have serious consequences, but there can also be no doubt that disease mongering by Big Pharma has contributed to their prominence.
Perhaps my favorite study of this kind is Shyness: How Normal Behavior Became a Sickness, which I read when it was published in 2007. And for all those years I thought I was shy. I didn’t know I was also sick (those who know me laugh at my protestations of innate shyness). But as I have gotten older, I have learned that facultative shyness is an excellent tool in certain work and social situations.
The major ethical, social, and scientific problems associated with these distorted research priorities is that the opportunity costs are incalculable for serious medical problems, especially those that are not caused in the first place by Big Pharma disease mongering or an environment and “food system” that induces ill health and obesity in the so-called First World. Many conditions that could be cured outright, including serious viral, bacterial, and fungal infections and assorted parasitic diseases are left unaddressed, because no matter how costly the therapy, if it results in a cure, there goes another “customer.”
So, what is the solution to the fraudulence of so much EBM? In my view, this is where Drs. Jureidini and McHenry could have gone further. Their admirable list of proposals for reform includes:
….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.
They rightly note that failures of regulation have contributed to this impasse. While true, it is not clear that the regulatory capture of the FDA, which has become a client of Big Pharma, can be reversed under a neoliberalism ideology in which markets rule, and everything is part of the one, true “Market.” Whatever the motivation of individual scientist-regulators at the FDA, they are overwhelmed at every step by money and the power that comes with money. According to IEBM (p. 184), in 2018 there were 797 Big Pharma lobbyists at a cost of $133M, with Pharmaceutical Research and Manufacturers of America (PhRMA) accounting for $21M, followed by Pfizer at $9M and Amgen at $8M. These numbers have undoubtedly increased in the past four years, and given that Pfizer forecasts 2021-2022 vaccine revenues of $65B, their lobbying costs have a good return on investment.
So, can this be made to work? During my early days in a biomedical research laboratory, pre-Bayh-Dole Act of 1980, it was widely accepted that academic research built the foundation for the development of drugs and other biomedical and clinical interventions, while Big Pharma optimized synthesis, production, approval, and distribution, with marketing bringing up the rear. Although some will accuse me of romanticizing this past, during those days the system worked. Those who stayed in academic science were committed and content to do this essential research during sustained careers and those otherwise inclined moved to one of the then Big Five pharmaceutical firms (a combination of Upjohn, Merck, Ciba-Geigy, Hoffman-LaRoche, Pfizer, Eli Lilly, and Burroughs-Wellcome) to figure out how to best manufacture drugs, vaccines and the like.
As an example, Eli Lilly received approximately $320 million in the first year of the Salk vaccine against polio, adjusted for inflation, which is about 100-fold less than what Pfizer collected in the first year of their mRNA vaccine against SARS-CoV-2. Although soon supplanted by the Sabin vaccine, which I remember taking as a blue or purple spot on a sugar cube at my elementary school, the Salk vaccine worked by providing sterilizing immunity, not unlike the smallpox vaccine those of us of a certain age also took, frequently from a school nurse, one after another as the entire elementary school filed through her office.
The question remains: “What to do?” An answer is beyond the scope of this post and I hope to address this later, but it seems obvious that there can be very little legitimate, for-profit clinical research based on independent investigator-initiated fundamental research through FDA approval. After the research, yes, with for-profit competition in manufacturing, distribution, and marketing (to physicians and medical professionals instead of patients/consumers – this is not a matter of “free speech”). Unless and until we return to something fairer, better, and more functional than this Era of American Capitalism, when General Electric accounted for a full percentage point of the GDP of the United States and bragged in its annual report that it employed over 400,000 men and women in well-paying union jobs that did comprise a true middle class (which was also when Eli Lilly was large and profitable in the same manner), we must come up with another solution. This other solution is more likely, whatever form it will take.
Finally, I must point out that all is not amiss in the research community. Although basic biological and biomedical research is not exactly healthy under the neoliberal dispensation, especially in the United States, the problems there are not the same that afflict clinical research. There is room for hope. One problem, and one solution, at a time!
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[1]I have read in several places that “consumer” is neoliberal for “citizen.” Indeed, this is the truth and I thank others for pointing this out, and I apologize for not giving proper credit here.
[2]MIT pioneered the Big Business-University nexus beginning early in the 20thcentury, to its benefit and arguably for the benefit of society in the beginning.
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Even without the other problems, the effect in clinical psychology and therapy is baneful. Non-pharmaceutical talking/acting therapies lack the kind of massive financial support needed to conduct numerous studies on efficacy in the first place. Pharmaceutical solutions always do, because the company intending to provide and monopolize the solution has that kind of budget available as throwaway money.
It’s more cost-effective (i.e., profitable) to dispense pills than to pay therapists for an hour’s work — if you can even find and keep qualified staff anymore.
I’d also note the lack of studies about the effects of long-term use of some of these drugs. I was just thinking again yesterday about gabapentin, which KLG mentions above and which I suspect had the most to do with fairly rapid cognitive decline following a back injury in 2009. I was forced to sue for back wages, as my employer was operating under maritime and not workers comp laws, which meant that I had to use doctors approved by the lawyers, and I had to comply with all the treatment plans, including various cocktails of painkillers and antidepressants. The gabapentin actually worked for about two months, after which I became a sleepwalking zombie. I was thinking of this yesterday after a veterinarian recommended it for my cat. Yes, they’re now prescribing gabapentin and Prozac (fluoxetine) for cats! And of course there’s “no evidence it causes harm.” Who would fund that study?
I concur with the assessment of gabapentin; I was given an Rx for it to treat chronic pelvic pain and anxiety during and after treatment for cancer. I stopped it after 18 months but it did a number on my cognitive processes; 6 years on and I am only now pulling out of my zombie like situation.
People sometimes laugh at those who say “I did my own research”; well, I have the last laugh as I found conclusive evidence that the back pain was caused by unnecessary injections of leuprolide (hormone blocker) to treat prostate cancer. I’d already had external, narrow beam radiation which was quite effective in putting the cancer in remission. But out of date experiences touted by two medical practitioners had me on leuprolide injections for two years which were totally not needed. Not only did those bring on the back pain and extreme anxiety, they left me with a serious cardiovascular situation whereby I’m hanging on by a thread. And now I am taking medications to treat that situation.
I never thought I’d have to be my own oncologist, but here I am.
This is a good companion piece in the discussion of EBM, from someone whose books I have always enjoyed reading and learning from.
The writer mentions Ben Goldacre in UK so I’ll mention him again. As well as writing “Bad Science” and “Bad Pharma” books, he pioneered the website alltrials.net which advocates for:
!) all trials to be registered beforehand – including the hypotheses to be tested (no p-value shopping later);
2) all trials to be published afterwards – including anonymised raw data (no burial of sad results).
Website may not be very current as certificate has expired.
Are we there yet?
No we are not.
Thank you KLG,
I have have always read your comments with great interest and look forward to more in this longer format in the future.
I second that emotion. As someone who spent my career providing secondary back end support for the medical industry I’ve seen this distortion of goals and perspective as a fly on the wall.
I’d nominate this as the best post of the week, so far.
Thanks KLG
Excellent summary with many valuable references and links. All this has been known for many years, especially by some of those of us who are, or have a loved one who is, dependent on the tender mercies of “Evidence Based Medicine.” The development of patent law in this tragic neo-liberal takeover of the practice of medicine and corruption of science should also not be overlooked. Insulin is the poster child here.
“First think we do, we kill all the lawyers…” (yes, I know it means something else taken in context, but too tempting to pass up). Also, the MBAs… and the rest of the slavish, sycophantic bean counters.
Thanks, looking forward to more in this series. Its very useful to have facts at your fingertips when this subject comes up – in plenty of circles even to question EBM immediately gets you labeled a quack or an anti-vaxxer.
I would just add (I’m sure KLG will get to this eventually), that there are many more sources of bias than just money or prestige. Some forms of bias are so baked into academia that they are rarely acknowledged. As all NCers will know, the appalling intellectual failure over droplet dogma is one that will become quoted in the future as a classic of the kind, but its by no means the only example of where a lot of very smart and very highly qualified people have made fools of themselves by not rigorously questioning long held beliefs.
Much appreciated article, excellent analysis of the problem and a rarer clear identification of the fundamental source of the problem. Really look forward to more and to the ensuing discussion of this frightening problem afflicting us all.
“a lot of very smart and very highly qualified people have made fools of themselves by not rigorously questioning long held beliefs.”
I agree with PK re the fact that this is compoounded by the extremely common feature of medical/clinical practise/research, viz the frequent failure to re-examine the underpinnings of current medical beliefs ( hardening into dogma all too often). Having had to look very deeply into such dogma in several medical specialties I have seen this at work. The mechanism often appears to be traceable if you look at how current dogma arose in the early postwar period when ideas about for example thyroid disease, heart disease, diabetes began to be formed often based on shaky or no evidence, certainly no rigorous studies. Opposing belief camps were formed and whichever theory won (not usually because any sort of proof had been supplied) slowly became accepted as fact. In some fields this was the point at which Pharma entered the fray and designed pills to deal with the clinical fall-out from these flawed theories, at which point any possibility of questioning the evidence was lost. The worst example is the so-called lipid hypothesis of heart disease and the scandal of Statin marketing. Diabetology and thyroidology are similarly affected although the thyroid situation is exclusively attributalbe to PK`s point (nothing to do with drug sales) – institutional schlerotic thinking, where no-one dares question the convictions of the big cheeses of the discipline concerned. The topic is too complex for a post so I`m sorry I can`t back up these points with references etc
All this is to say nothing of what the pandemic has finally revealed about what modern medecine is really now about!
All this is a source of incalculable, unnecessary, often extreme human suffering and it continues to break my heart..
Another problem with the tools of EBM is failure to recognise that patients interact with the experiment – they are not passive automatons. Rules dictate that they be told possible side effects of a new SSRI before they agree to enter the trial.
Mr Smith takes the unknown to him tablet and notices ED problems. He immediately knows he’s in the active group not the placebo group. Blinding is broken. He is more likely to report improvements in mood etc as he “knows” SSRIs “work”.
Mrs Jones experiences no side effects. Correctly deduces she is in placebo arm. Opposite problem ensues.
Result is artificially boosted efficacy rate. And don’t get me started on the fact the whole paradigm based on a normal distribution with large numbers is ok. The average of a house and a banana means nothing. Gabapentin (mentioned above) has nothing on its big brother pregabalin.
I have always wondered this. Especially in the case of a nasal spray or drink where a smell or taste should be obvious. Or in the case of vaccines where some kind of injection site pain and malaise are expected.
One way of dealing with “self unblinding” by patients is to use an active placebo – a drug which is different from the target medication which has a physiologic effect which the patient will notice.
This approach isn’t in common use yet, but has been tried in some trials.
Many thanks KLG and looking forward to reading your future contributions (and hope you got a chance to watch some of The Open this past weekend ;) )
The book looks interesting. I know I’ve linked this before here in the past couple of years but for another critical overview of the evidence based medicine doctrine, it is mentioned at the Philosophy of Medicine article (and one or two others) at plato.stanford
An xlnt case of “writing down the bones.” I, too, look ahead for such honest, perceptive writing.
I am assuming that KLG is not using their full name because they do not want to deal with the bull (family blog) academic blow-back from declaring that the emperor has no clothes.
That being the case, the mini-bio at the top of the article looks to provide enough information to identify them. (I have not run the google machine on this)
They might want to make it a bit less detailed, particularly the dates and the dean bit..
Maybe I am being excessively paranoid, but I do not think so.
I want to make a note here: Much of the skepticism about science is not because people think themselves smarter than the scientist, though some do, but because people think that the scientists are corrupt.
They are correct in this assumption.
Too sweeping by half. Sure some of them are knaves and my feeling is that at least as many are fools but those two combined would be a small fraction of the vast majority who are like everyone else simply doing their best to get by and keep putting food on the table.
They know, as we all do now, that any evidence of independent thinking in their metier which threatens the sugar daddies who fund them means ostracism and career suicide. In the past they could have relied on the good offices of government and/or media to support them. Not any more.
Thanks to KLG for this excellent piece and for the prospect of more informed comment from within the belly of the beast to add to IM Doc’s honesty and expertise.
While having food on the table is a motivator, especially among younger scientists, I’ve found having a seat at the table to be a bigger one.
I can’t count the number of times I’ve been presented with something that is generally solid but has obvious flaws or missed implications, only to find out that it was massaged so decision makers would even listen.
“Well of course we know that is how things are, and we originally presented it this way but they ignored us until we edited it out,” is the common refrain
This has been going on for a long time and has had profound effects, the biggest of which is collapse in public confidence. By treating the political/business elite as their audience rather than the general public, prominent scientists have squandered trust.
I’m not sure what your experience is but mine is very different.
I’ve met many many scientists across many fields and can count on less than one hand how many are “corrupt”
What I have found is scientists are cowardly. They will do the research, write up the results and then forcefully argue only what they can 100% prove while being exploited on what they cannot. In private they will say what they really think but are scared to say so in public. They lend their credibility to forces far larger than themselves and then complain about it.
The things I have seen and heard at the heart of corruption in the scientific industrial complex …none of them came from the scientists.
If they actually stand up they will be cut off and lose everything they hold dear.. namely to understand how the universe works. And they rationalize it that at least they are able to help humanity a little. So they keep quiet and feel the burden on their soul. To be a scientist is to live in tragedy.
So Yeats, basically.
Not sure if there’s a way around that which doesn’t destroy the scientific method in the process. Scientists need to doubt results or they stop working properly, while marketers are free to have all the confidence in the world in their nonsense assertions.
Yes, precisely.
I actually disagree with your assertion about the role of doubt in the scientific process and believe that perspective has been weaponized. One of these days hope to write a book about it with numerous real world examples, with interviews of key actors. In my view the primary issue is reductionism. Most blunders can be avoided simply by reflecting on results in context of the larger whole, both scientifically and otherwise. There is too much emphasis on knowledge and intelligence over wisdom.
Hmmm yes I can see what you’re getting at there.
I think I am being too loose with my language – when I think of scientific doubt, I’m mostly thinking in terms of attempting to build comprehensive controls and appropriate samples as far as practical. These mechanisms are conceived of through appropriate skeptical forethought and harnessed pessimism.
But I’m also only an amateur at this stage in my career.
Cowardice is its own form of corruption here. Corruption is acting in service of one’s self while pretending to act in the common good.
Whether out of malice or cowardice – it’s still corruption.
To say one thing in private and another in public is out of integrity, and again cowardice is an excuse.
What you describe is the fundamental problem: the system demands corruption. I left the so-called defense industry when I realized there was no way to continue my career there while actually promoting our defense. I was lucky to have savings, health, and no debt. If we want medicine that heals And a defense industry that defends and food that nourishes and so on, then we must not tolerate cowardice but strengthen ourselves and each other so We must stand up for what we believe in.
Thanks for this post and for mentioning Frances Oldham Kelsey.
One thing that makes the “illusion” of evidence based solutions part of the tragedy of the failure of our free market capitalist system is that the false replaces or precludes the true. In medicine it might be more like delusion – big pharma is pretty delusional; all ga-ga for money to say the least. So allowing pharma to do its own research is foolish government policy. If we want to evolve toward a good, effective, scientific civilization (which we really need to start doing) we can’t waste time developing anything, especially medicine, purely for profit. There could be protocols that require any medical research be done with two simultaneous but separate designs. (A blind study of the blind study?) Both of them could lead to the correct conclusion, but unless both are corrupt they will be different enough to lead science in the right direction with a certain amount of efficiency. Something like this is probably currently prevented by patent concerns and privacy/secrecy policies (mostly driven by the profit incentive). But it shouldn’t be.
The needed reform on the international level is, I believe, already formulated as de-linkage (and searchable under that term). Research financing de-linked from pill production financing. This was discussed seriously at WHO under the Obama administration, with China, India, etc onboard for paying part of the research cost in return for getting freedom to produce pills without the patents hindering them.
Naturally the US delegation rallied small dependable countries and procedural tricks and managed to defeat it. But I think it is worthwhile to know that work has been done in this direction and can be built upon.
One of the big drivers of industrial-academic complex is that proceeds from the intellectual property rights remain at the university level, rather than the government, even though the government is providing all the research funding. So, even though research funding is supplied by NIH, NSF, etc. university itself retains the IP rights (those that are not passed to researchers or industry).
To give an example, during my recent stint at Northwestern, university was entitled to 75% of any intellectual property we developed, even though all research, equipment and salaries were funded by NIH and university was collecting 35% of the grant money as an upfront facility fee. External research funding contributes almost $1 billion a year to Northwestern, in addition to large amount of money derived from IP rights.
This creates incentives both on the research side and the administration side to use questionable research practices, even without financial incentives of something like pharma research. It creates a selection process that favours less scrupulous researchers that are willing to play fast and loose, if not outright cheat.
It’s even more extensive than this. What you do as a PI is go to a major corporate in your field of research and get their buy in to invest in your external startup. Then you use the grant money to solve the hardest parts (taking advantage of the global community in the process) but do the commercialization research in the startup, so the IP is isolated. Then when the primary research is complete you license from the university, which is all too happy (especially now that most are controlled by MBAs who have industry ties) and the corporate buys the startup for full IP ownership.
Thus the bulk of the value doesn’t even go to the university because it was ringfenced in the startup.
That said, even in these situations the PI often gets little (comparatively speaking) and in my experience goes this route because it’s the only practical way to get their research into the world.
If there was strong government behavior to capture research value publicly and incorporate it into broader policy aims then our society would be vastly more prosperous.
for those who might be interested, people working in the cross-disciplinary sub field known variously as sociology of science, science and technology studies (sts), and science studies, have been pursuing relevant research and questions for 30+ years now – longer really.
it’s been a while since i’ve actively reviewed the lit, but biomedical research/science has always seemed particularly vexed; subject to uncertainties of greater intensity and extensivity than pretty much any other broad area of scientific research.
one upshot is the factors discussed in the post have especially pernicious effects across and through the research, production, and delivery system.
I eagerly await more posts in this series. I worked in biomedical research as a grad student, then post doc, then research faculty for just shy of 20 years. When I left, more colleagues were entering into agreements with companies for contract research. With NDAs of course. Most knew it was bad, but it was a matter of career survival. Also, the stories I heard form people coming back to academia from Pharma research. Ugh (A common question following the relaying of disappointing results to management: “Why are your experiments not working?”). I am very curious what the resident experts think about some of the questions around statins. I am just starting to look into this because my primary care physician was recommending statins if my LDL did not go down. I got it down through diet, but that class of drugs still looms. High LDL is of course one of the affluence afflictions mentioned in the post and a source of huge pharma revenues. I have read critiques of satins that sound similar: early studies have not revealed raw data, side effects minimized, original research leading to the nobel prize weaker than you would think and overhyped, suppression of negative studies (cherrypicking and the point of those NDLs) and most damning for me is that new statin research on new drugs in that class that is occurring under more rigorous oversight is not finding nearly the effect as earlier studies on LDL and cholesterol. This is still pretty fringe although some critiques were published in respected journals. Is it fringe because it is just CT stuff or is it fringe because powerful interests want it to be fringe.
Thanks for this comment. Pretty much my entire family including myself have been on statins for years. The last two years (Covid and also working for a specialist medical college) have made me something of a MedSci sceptic and I had a period off them a few months ago, but a recent visit to the doc with a blood test showed my LDL at ‘danger level’ so I went back to them (in addition to ZanExtra for BP). My wife has been reading up on statins and is urging me to get off them again. I am torn, especially as I have made dietary changes and exercise daily, to no obvious effect…
This article might be of interest — gel-forming dietary fibre (not many of those, basically oats and psyllium) increases viscosity of the chyme and retards cholesterol re-uptake at the distal end of the ileum. Reduced cholesterol reabsorption lowers serum levels.
https://pubmed.ncbi.nlm.nih.gov/22845031/
I think that it doesn’t replace statins, but it might allow one to get by on a reduced dose.
One of KLG’s pet peeves is statins. There is no, and I mean no, evidence that statins are beneficial except in cases of actual heart disease. There is not even good evidence that high cholesterol is harmful. Cholesterol is a backup repair mechanism. The cholesterol plaques that can form in heart arteries look to be an attempt to address damage. If cholesterol were “gunk” that clogged up veins and arteries, you’d expect to see cholesterol completely shutting down the smallest arteries and veins first, well before gunking up arteries near the heart.
In women, the total cholesterol level correlated with lowest all factor mortality is 270.
Some tidbits from KLG in my inbox:
And:
He has more in that vein.
There was a link in the last few weeks about about research into genetic modification to lower cholesterol;
Edits to a cholesterol gene could stop the biggest killer on earth
Didn’t have time to respond that day, but my first thoughts were: as it will not impact on the the ‘biggest killer’, why on earth would you want to pursue such a harmful endpoint?
One of the problems pointed out in my link above is that EBM lends itself to the talyorisation of medicine.
Which is not a good thing.
I remain convinced that my mother’s health was ruined as a consequence of the blanket use of statins.
For what it’s worth, I asked my doctor (GP) about cholesterol and whether I should get tested after a relative had a health issue. His reply was in line with KLG’s statements: not unless you have a heart problem that we are looking into, and you don’t, so no.
This is a sample of one, but I think it reflects current standard of care in Sweden.
And he meant to write “HMG-CoA reductase,” not carboxylase. Biochemistry dyslexia strikes again! And not even on an exam this time.
Thank you and I have bookmarked this page. I am definitely going to look up references related to the comments in KLG’s emails. Good stuff. I have come across enough to convince me to refuse statins (I have no heart disease), but I like to be armed with info and references. A lot of medical paper references that have been linked to in Naked Capitalism have gone into my Zotero library. My correspondence sometimes comes with bibliographies.
Thanks Samuel. Very interesting. I used to take psyllium daily years ago and just stopped for no particular reason. Dont recall high LDL back then, though I was younger. It has now been added again to the daily intake.
Def not an expert on statins, just a long-time med skeptic with an anecdote. 30-odd yrs ago Mr HotFlash’s doctor (cardiologist?) told him his cholesterol was too high, but “if you’d have come in last week you’d have been fine, they just changed the standard”. Doc went on to prescribe statins for him, but said that he’d have to come in every six months for a liver biopsy. And he would be taking them forever. That didn’t sound too reassuring and MrHF suggested that he simply change his diet. PCP says, “Nobody ever does that!”
He went home, did some research, talked to some knowledgeable friends, incl a naturopath, an MD or two and a recently graduated nurse (bang up to date but not yet affected by pharma salespeople) and decided not to statin. Never did find out who sets the standards.
Post script: Well, looky here! SwissCows informs me that cholesterol/LDLstandards/guidelines are determined by the American College of Cardiology and the American Heart Association.
And who funds these outfits? Could not find info for the ACC, but HuffPo had checked on the AHA in 2013 (previous update for LDLs) and reported The American Heart Association — Protecting Industry Not Patients.
Thank you KLG, also IMDoc, GM, and all the NC Brain Trust, the whole NC Commentariat (which is, as Lambert says, “The Best Commentariat”), and to Lambert, Jules, and the rest of the modding crew who keep the comments so clean. Most of all to the Lady Yves, who runs the best salon of all time. This place is truly a miracle.
Hunnerd percent! Thanks to all for the statins info and insights.
One hypothesis (which I favour) is that damage to the wall of a blood vessel leads to the release of compounds which initiate the clotting cascade, attracting platelets and fibrin to the damaged endothelium. Cholesterol just gets caught up in this glob as an innocent bystander.
Messing with cholesterol metabolism is a risky business. If you look at the structures of cholesterol and the steroid hormones (cortisol, for example) you’ll notice a common molecular skeleton with different structures on the periphery. Interfering with cholesterol pathways is likely to have an impact on one or more steroids.
Thanks KLG. It is valuable and convenient to have your thoughts here in an official post because it is much easier for me to find and remember a post compared to a comment. The occasional “hoisted from the comments” post is similarly valuable. On the topic of Covid-19, I have in the past found lots of insight from you, IM Doc, Ignacio, Kris Alman, GM, etc. I really like your comments (and GM’s comments in particular) because you integrate your scientific background with present and historical political views.
I study a very narrow area of neuroscience because I have rare sensory augmentation problems and this is linked with neuropathic pain. Unlike KLG, I didn’t have some lifelong dream to be a scientist. I had to study neuroscience because no doctors had an explanation for what I suffer. Thus, I spent three or four years reading the hundreds of medical papers on my desk. It also took me several years to figure out who among the authors are skilled and are unskilled. Considering how much effort it took me to sort through my area of interest, I am deeply impressed by KLG and the rest of the Covid brain trust’s ability to sort through medical information and misinformation. In addition, the papers I read are usually about reviews of basic science and are not randomized controlled trials, which are far more inclined to be corrupted by money.
Marcia Angell, by the way, has been excellent in writing about undue political and monetary influence of the pharmaceutical industry on medical practice. IM Doc has said similarly in his comments. (He also recommended Angell in his first post.)
Big thank you to KLG for this well-written, thought-provoking piece, and to Yves for creating the space for it.
I’m an Army veteran and get most of my healthcare through the VA, which requires providers to follow “evidence based” clinical practices — which I presume is a companion(?) to EBM — set forth in voluminous clinical practice guidelines. This is supposed to prevent the kinds of mistakes that occasionally get publicized, despite best attempts to circle the wagons and cover them up. Personally, I’ve been severely harmed by providers who claimed they were “going by the books,” when I knew — and said so — that I had enough experience and knew my body well enough to know that I was an exception to the rules (and surely not the only one). It’s that much worse, because I am an older woman, and we tend to be dismissed as bored housewives, neurotic, hypochondriac, reading too many women’s mags, etc.)
The guidelines for clinical psychology are particularly lacking, IMO — ironic, as the VA has done some valuable, groundbreaking mental health research, e.g. PTSD, eat disorders, substance abuse. However, from what I’ve seen, the results can take years to filter down to the clinical level, and by the time they go through multiple layers of review for the clinical practice guidelines, they’re stripped of all but the current “conventional wisdom.” It seems to me that this trend has accelerated over the past 15 years or so, as the VA increasingly brings on commercial partners. For all practical purposes, the VA has been privatized.
Among the main attractions of partnering with the VA is access to the vast database of veteran health records. There is no way for veterans to opt out of having their data used for research. That it’s all “aggregated” and stripped of personally identifying info, blahblah, is a moot point, given the capability of data brokers to disaggregate personal information, at lightning speed, and I consider it an invasion of privacy. And while we’re repeatedly told that this research is “to help other veterans,” many (most?) of us aren’t buying it anymore.
I understand your cynicism about the “to help other veterans” line. Although, some of the research has certainly helped us all. Well, potentially could help us all. Some of the VA Covid research, especially that coming out about reinfections, I have been sending on to all my close family members. My wife is a civilian physician who works part time at the local VA. She is very strict and conscientious about privacy concerns so I know no details, but she has a pretty negative view of the health of the US military for women. The VA is fine. She has had no personal problem in the environment there and patients like her. Just the standard bureaucratic frustrations with trying to improve things. A deceased relative that I was very close to was a Vietnam vet and really liked the VA. He used to say:”There is no VA without the VA!” No volunteer army (VA) without veterans health care.
Geoff Shullenberger on his Outsider Theory podcast did a good and very informative episode on EBM
Thanks to KLG for addressing this topic.
My experience with the pharmaceutical industry, specifically psychiatric drugs, is the modus operandi of the marketing people often turns what is called publicly “evidence-based medicine” into what could more accurately be called the spread of “religious belief.” What do I mean specifically?
How do you get the med schools in the United States to be “believers” in your crusade to sell XYZ antidepressant?
Well, despite the commonly held belief the average university medical center likes to be “cutting edge” in their research and policies, instead what typically happens in the real world is most centers are conservative because the legal department doesn’t want to get sued for doing anything which could be considered controversial.
So they won’t touch something new until it is publicly accepted by Harvard or one of the handful of big name credible medical centers first. It’s monkey see monkey do with all eyes on the “thought leaders” at the Ivy League hospital giving the thumb’s up.
The way you get the faculty and students to follow along with the “evidence-based research” findings on any new cutting edge treatment or med is to capture the heart and mind of the department head. Acceptance of drug XYZ by the Head of Psychiatry insures the medical personnel at the university medical center know they are supposed to accept the drug’s efficacy as well and prescribe the sheet out of it. And they do.
So in my opinion, what often happens is the marketing people convert Department Head at Ivy League University to a beliver in XYZ med, then the rest of the congregation becomes true believers as well, at the behest of the
Department HeadSSRI preacher.Thing is, >95% of the people involved will tell you this is an evidence-based process rather than a religious conversion experience. They simply cannot see it for what it is. Their paycheck and career prosepects actually demand they not be able see it…
Do SSRIs cure depression? Well, “conventional wisdom” says they have efficacy and safety, yet there’s no evidence to say they do any such thing. What we’ve done instead is covert docs to the antidepressant religion. What’s called “evidence-based” medicine in the case of antidepressants amounts to little more than the placebo effect reinforced by marketing hype.
Patients feel different, but do they feel happy? Nobody knows. There’s no such thing as a “chemical imbalance,” at least nothing anyone can prove outside the marketing department. There is no scientifically proven anything going on here with the “brain balancing act.”
This realization was made public knowledge by The Emperor’s New Drugs 20 years ago, yet these drugs continue to skyrocket in number of prescriptions and profits.
This is what I have seen of the process in a nutshell.
This is an excellent comment that reveals the complexity of the issue and how scientists play their part in perpetuating a corrupt process that is externally driven. One is often an actual conspiracy that also targets prominent physicians who have their patients’ best interests at heart and want to provide the best care.
The follow on is that often these converted believers then radically change their opinions, but are conveniently ignored.
In The Body Keeps the Score by Bessel van der Kolk, he talks about being one of the pioneers of SSRI treatment and how they truly believed it was a miracle drug. His group played a key role in driving adoption and yet he’s been a staunch opponent of broad medication for almost 30 years now.
He was the priest, yet his actual life’s work of non-pharmaceutical treatment of developmental PTSD has been almost completely ignored by the establishment.
That book is an amazing work, highly recommended! It was suggested to me by a private-practice therapist after my VA mental health “team” traumatized and nearly killed me, then left me on my own to go find help elsewhere. The irony wasn’t lost on me that van der Kolk’s earliest clinical experience was at the VA. In any case, you are right about his pioneering work being largely dismissed in the mainstream. I reckon it goes back to the profit model of the U.S. healthcare system: prescribing drugs is simply faster and cheaper. And with mental health patients, it’s not hard to gaslight them into thinking that if the drugs don’t work, it’s because of their own shortcomings.
I am glad that you have found a path to recovery after so much suffering. I pray one day that the world at large will embrace it instead of continuing to perpetuate the gaslighting.
Mikkel ~ Yes. I don’t think it is so much that scientists and science are corrupt. These people are for the most part sincerely interested in being objective and most believe their work is as close to objective as it can be given the parameters in which they work. However, if they wish to get research funding, their research is going to be used in a process of money generation fundamentally corrupted by marketing and the media.
For example, there is simply no evidence for this “chemical imbalance” model of depression. How do we know this?
We have normal ranges measurable for all sorts of biochemicals. Someone with diabetes pricks their finger to measure glucose levels, right? Insulin levels, testosterone and estrogen, thyroid hormones, etc. These chemicals all have normal ranges in humans, which we have defined. Therefore, we can make medications specific to adjusting these levels in a quantitatively sound way.
What are the normal ranges for serotonin in the brain? We don’t have any.
So how can we say this brain is “unbalanced” for serotonin levels if we don’t know what “balanced” looks like quantitatively? Right. We can’t. We can define a “balanced” range for the pH of your blood. it should be 7.4 last time I checked. Deviation of pH +/- 1 will get you dead. What is the range for serotonin supposed to be in a healthy non-mentally ill human being? How much deviation is allowed to occur before something goes wrong? Who knows? Not us.
Someone in the marketing department just made this model up as a way to sell SSRIs to both physicians and the public. The docs became convinced of this “chemical imbalance” model as if it were the creation story in Genesis because in practical terms, docs can use it to explain to their patients why they should take antidepressants in a way their patient can understand, which helps with compliance.
None of this model stands up to scrutiny of any rigor, as the pachyderm in the clinic shows here:
https://link.springer.com/article/10.1007/s12115-007-9047-3
The results showing no efficacy for SSRIs above placebo level never get published, while the sketchy evidence that does get published is taken as evidence-based medicine. Which then goes on to drive pretty commercials of people running across fields of flowers being mindlessly happy on the TV, so they can ask their doctor to prescribe the magic pills.
The result being, because the system is corrupted, the average person may not be able to point out exactly where the faults are because they don’t have much direct experience doing science in a lab or analyzing data from published literature. So we get weird conspiracies about nanobots being in the vaccines because justified people’s fear makes their beliefs come out sideways in response to the exploitation coupled with their own scientific illiteracy.
Yet everybody can smell what the pharmaceutical companies are cooking. They’re cooking dope, and everybody associated with the process smells like Walter White.
Where’s a scientist going to practice science as a profession that isn’t ultimately funded by these corporations? The FDA gets its money from pharmaceutical corporations, so the average government funded research grant is ultimately derived from pharma corp funds. Lobbyists pay your local congress critters to lubricate the rest. People get the big picture, which is this process does not have your best interests at heart. It serves the stockholders and nothing but the stockholders.
Please note, I am not telling anyone they should or should not go off their meds. What we are saying here is no one has proven antidepressant efficacy or anything about the veracity of this chemical imbalance hypothesis, yet there are billions of dollars made from the prescription of SSRIs to the public.
What a small world!
When I was in high school and my brother in pre-med at the University of Hawai‘i in the early 1960s, we would sometimes chat with a young Dutchman who, it turns out, is that very same Bessel van der Kolk, at refreshments hour / youth discussion group following Sunday services at St. Andrew’s Cathedral (Episcopalian) in Honolulu.
https://en.wikipedia.org/wiki/Bessel_van_der_Kolk#Early_life_and_education
Amazing coincidence — I do get the feeling the Universe is signalling me on several levels that I ought to buy and read Dr. van der Kolk’s book.
Here’s a review of the lack of evidence for the chemical imbalance model published yesterday in Nature:
https://www.nature.com/articles/s41380-022-01661-0
thalidomide in third trimester not semester
smithkline beecham not beechum
this rather of detracts from what otherwise is an interesting treatise on something that is exceptionally important. The critical problem at the heart of institutional science, but has been ignored for so long, what is science for what do we collectively want it to do? can it present real truth not convenient dogma and group think?
Eisenhower in his farewell address talked about science and how it was now owned by the government and by industry simply because it had become so expensive and complex.
“The prospect of domination of the nation’s scholars by Federal employment, project allocation, and the power of money is ever present and is gravely to be regarded.
Yet in holding scientific discovery in respect, as we should, we must also be alert to the equal and opposite danger that public policy could itself become the captive of a scientific-technological elite.”
Insert silicon valley and Davos for scientific-technological elite then Dwight in 1961 pretty much accurately describes the current situation.
Academics are now totally owned by the grant doling organizations, the questionable NIH the NIDA DARPA BARDA BARBI and a whole raft of self serving tax avoiding foundations.
Industry science have always been bought and paid for. But academia is now just as dirty.
leaving aside that the farewell address by Eisenhower appears to have been an attempt at attaining personal absolution for the sins of a president. his warning was prescient and ignored and now we reap what has been sown.
Fixed, thanks!
I look forward to further posts by KLG. I am not a researcher, but I harbor a long standing interest in protein structure and the relationships between structure and function. The future will be a time with much less stored fossil fuel energy available to power our present civilization. I believe that uses of the increased, though diffuse, heat energy of future climate regimes, combined with a greater understanding for how enzymes function might provide an answer of sorts. I am concerned that studies of protein structure have been hijacked to support augmenting the High Performance Computing [HPC] facilities [I believe this was a DoD initiative and funding line] at many universities and government research centers. It would be heartening to learn of advances in relating protein structures to their functions. I remain mystified that I have run across no studies attempting to explain what to me seems the very complex and costly structures life uses to construct enzymes. The contrasts become particularly stark when examining the structures of commercial enzymes with their counterparts in life produced enzymes — and not just their differences in efficiency. I feel some key factors in enzyme function have been missed or ignored. I worry that the Neoliberal monetization of research will obscure further understanding of the basic science of life. I strongly believe Humankind must transcend the billion years of solutions life has discovered through the processes of evolution if Humankind and some forms of life amenable and useful to Humankind are to survive the extremely rapid changes the planet is already experiencing as a consequence of Climate Chaos. Humankind must become a new force of Nature, or diminish into an existence like that Hobbes invented as the origin of the social contract [the social contract without food, shelter, or clothing — is no more viable than the further existence of Human Society.]
The present post leaves me very concerned about KLG’s apparent lack of exposure to the extensive writings of Phillip Mirowski analyzing the Neoliberalization of Science and Academia. Evidence based medicine is only one among many areas of science debased by the Neoliberal concepts of Market and the profound application of those concepts of Market to Education and Science, and the Neoliberal captures of both. We live in an era of the best science money can buy. I am most curious to see what remedies KLG might recommend … though to be honest I am very pessimistic about the future of Humankind, and Human Society. Hope of some kind would be most appreciated.
I have another concern, unrelated to concerns about the caustic impacts of Neoliberalism to the practice of Science, and Medical Science in particular. Much of evidence based science and medicine involves results from statistical analyses of data collected from studies, either scientific or profits influenced. I have a basic mistrust of statistical analyses and statistical data. I also have a fundamental concern that even the very best and most Scientific statistical results leading to the use of a remedy detract from studies to determine the mechanisms by which that remedy operates and the mechanisms of its side effects in various populations receiving that remedy. It is not enough to learn that remedy ‘X’ “works”. How and why does it work? What approaches to other remedies does this understanding of how and why suggest, and perhaps lead to? I do not see how the Market follows through to this understanding of the basic Science or its applications.
I am very pleased that Yves has asked KLG to join her team, and look forward to the posts and to agreeing with or arguing with those posts.
This probably isn’t the place to discuss it, and I’m not well enough informed to add much, but I have the sense that Thomas Kuhn has been hijacked for all sorts of causes that he himself wouldn’t have considered important . The kind of “paradigm shifts” he was interested in were along the lines of (say) the change from the theory of “humors” to one based on structure and physiology in the understanding of the human body. You can’t make sense of one from the perspective of the other. Calling every change in medical practice a “paradigm shift” and then praising (or blaming) Kuhn-like thinking for it is a misuse of his ideas.
As prelude, my wife was diagnosed with “mixed connective tissues disease” at 17. It’s a catch all autoimmune diagnosis that boils down to “all the autoimmune diseases some of the time”. Medicine is a hobby of mine and it has included interactions with some of the top doctors in the country at places like Mayo Clinic and the University of Michigan. (So mostly research doctors.) I’ve seen a lot of shrugs and “let’s try this” rather than EBM but that’s to be expected with an outlier case. There’s the strand of EBM saying that something works but nobody knows why. And then the strand that says something should work even though it doesn’t. Or the side strand that has to admit something works but nobody should take that much of it for so many years. So I’m fascinated by this series and where it will go.
Also, I don’t blame the doctors mostly. We’ve known a few bad ones and I’ve learned to call them out on the most egregious things. We’ve also had a few that changed our lives and miss them. I’ve noticed a lot of blinders in many top doctors. One time the wife was having digestive issues (like somehow not digesting food, thought to be maybe scleroderma in the intestinal lining) and three rheumatologists with probably 1,000 papers between them, including the head of the department were pondering this. When I said, “if she’s not digesting food, is she digesting all the drugs you prescribe?” all three looked at me like I had opened the arc of the covenant. Frankly, I was shocked that it wasn’t the first and most obvious question/concern.
This is a true community of equals. Thank you all for the comments and discussion and for pointing out the many ramifications of “Evidence-Based Medicine,” as opposed to disinterested Biomedical Science, writ large. It has indeed become difficult to do the latter, as both NIH and NSF have focused on topics they view as “high yield.” I began when good science meant coming up with an interesting problem straight out of natural history, from the level of proteins to the level of populations and everything in between. The problem is that Program Directors, despite what they say out loud, cannot really identify what is high yield, because biology is so multifarious. There is no way to know ahead of time what will work. hope to return to this soon.
For example, several years ago NIH funded an initiative in Structural Genomics that was supposed to pave the way to using genomics to accelerate the determination protein structures. Well, not so much. I haven’t paid attention to this lately but IIRC about five structures emerged from the ~$50M spent, and the institution involved got to keep the instrumentation and the expertise developed. Oh, well. It was a good idea, but the $50M would have supported 30-40 individual scientists and their students for 5 years each. Might something more important have emerged? Possibly. Probably. Studies have shown that as an individual scientist (Principal Investigator) gets more grant money, the law of diminishing returns kicks in pretty hard. But don’t tell the Administration! Overhead is manna from heaven.
I also look forward to further discussion with Jeremy Grimm, who is always stimulating. He can rest assured that I am quite familiar with the work of Philip Mirowski on the neoliberalization of basic science. While Professor Mirowski was describing it in view of Touchdown Jesus and the Golden Dome, I was living it. And to tell the truth, that I was aware of what was going on made the attempt to surmount it more bearable. Most scientists are proud of their political naivete, if not outright political ignorance, while some are the most insufferable members of the PMC imaginable. TDS, it can be particularly strong in them. Back in the day, I was fond of repeating Pericles to my colleagues: “Just because you do not take an interest in politics doesn’t mean politics won’t take an interest in you.” And as for the use, misuse, and abuse of conventional statistics, I highly recommend Bernoulli’s Fallacy: Statistical Illogic and the Crisis of Modern Science by Aubrey Clayton (2021). The general un-recognition that a statistically significant difference often specifies no actual meaningful difference, i.e., that the difference has nothing valid to say about the natural world, is indeed pernicious. And this may be a large component of the hysteria over the “reproducibility crisis” in research.
Thanks for this. I think regarding the first point, Russell Brand once said in a Tweet: “The problem with following the science is that the later follow the money.”
Yves,
The article has been copied verbatim ( including your intro) at
saigonusanews.net/world/the-illusion-of-evidence-based-medicine/53220/
I”ve truncated the https
I don’t have the bandwidth to go after site scrapers, and they pretty much can’t be stopped unless they are hosted in the US. In those cases, I can sent a DMCA takedown notice.
The inverted funnel plot is simplest most damning indictment of so much medical publishing (including EBM) ever produced. This first article was necessarily cautious but it’s been used really widely since.
Declaration of interest. Some authors were my colleagues and the first author on the major followup paper was my PhD internal examiner.
Just came across this in Wikipedia regarding the development of the life-saving cancer drug Dasanitib. $108 daily dose in India (but potentially $4 a day). $367 in US. ‘Nuff said.