The latest event sponsored by “integrative medicine” proponents on my medical school campus featured the naturopath “Dr.” PB, a 2003 graduate and valedictorian from Bastyr University. Advertisements all over campus billed the lecture as “Stress, nutrition, and the GI tract,” which seemed innocuous enough. However, the lecture title as written on PB’s slide show was “Naturopathic apologetics for treating the gut.” He explained “treating the gut” to mean that for a wide variety of symptoms the naturopath’s diagnosis inevitibly focuses on the intestine and interventions nearly always involve dietary changes or supplements. Apparently some critics find this preoccupation to be excessive; hence “apologetics,” a word that connotes rational defense of articles of faith. This word choice was appropriate, as the lecturer wove snippets of basic physiology, but never any direct evidence, into a just-so story about how nearly all disease is caused by the modern lifestyle and can be ameliorate with dietary intervention.
Archive for Science and Medicine
Is it ethical to overstate the efficacy of a treatment option, if it might lead to a patient’s enhanced experience of that treatment? Your response to this question may reveal the degree to which you favor Complementary and Alternative Medicine (CAM). Let me explain.
As far as I can tell, no CAM treatment has been proven effective beyond placebo. (If you’re not convinced of this, I suggest you take a look at Barker Bausell’s book on the subject.) That means that treatments like acupuncture, homeopathy, Reiki, energy healing, Traditional Chinese Medicine (such as cupping), and others (like “liver flushes”) perform about as well as placebos (inert alternatives) in head-to-head studies. Therefore, the effects of these treatments cannot be explained by inherent mechanisms of action, but rather the mind’s perception of their value. In essence, the majority of CAM treatments are likely to be placebo therapies, with different levels of associated ritual.
For the sake of argument, let’s assume that CAM therapies are in fact placebos – the question then becomes, is it ethical to prescribe placebos to patients? It seems that many U.S. physicians believe that it is not appropriate to overstate potential therapeutic benefits to patients. In fact, the AMA strictly prohibits such a practice:
“Physicians may use [a] placebo for diagnosis or treatment only if the patient is informed of and agrees to its use.”
Moreover, a recent article in the New England Journal of Medicine concludes:
“Outside the setting of clinical trials, there is no justification for the use of placebos.”
However, there is some wavering on the absolute contraindication of placebos. A recent survey conducted by researchers at the Mayo Clinic asked physicians if it was permissible to give a dextrose tablet to a non-diabetic patient with fibromyalgia if that tablet was shown to be superior to no treatment in a clinical trial. In this case 62% of respondents said that it would be acceptable to give the pill.
The authors note:
“Before 1960, administration of inert substances to promote placebo effects or to satisfy patients’ expectations of receiving a prescribed treatment was commonplace in medical practice. With the development of effective pharmaceutical interventions and the increased emphasis on informed consent, the use of placebo treatments in clinical care has been widely criticized. Prescribing a placebo, it is claimed, involves deception and therefore violates patients’ autonomy and informed consent. Advocates of placebo treatments argue that promoting the placebo effect might be one of the most effective treatments available for many chronic conditions and can be accomplished without deception.”
How do you feel about placebos? Are they a legitimate option in some cases, or a violation of patient autonomy and informed consent?
The primary goal of science-based medicine (SBM) is to connect the practice of medicine to the best currently available science. This is similar to evidence-based medicine (EBM), although we quibble about the relative roles of evidence vs prior plausibility. In a recent survey 86% of Americans said they thought that science education was “absolutely essential” or “very important” to the healthcare system. So there seems to be general agreement that science is a good way to determine which treatments are safe and work and which ones are not safe or don’t work.
The need for SBM also stems from an understanding of human frailty – there are a host of psychological effects and intellectual pitfalls that tend to lead us to wrong conclusions. Even the smartest and best-meaning among us can be lead astray by the failure to recognize a subtle error in logic or perception. In fact, coming to a reliable conclusion is hard work, and is always a work in progress.
There are also huge pressures at work that value things other than just the most effective healthcare. Industry, for example, is often motivated by profit. Institutions and health care providers may be motivated by the desire for prestige in addition to profits. Insurance companies are motivated by cost savings. Everyone is motivated by a desire to have the best health possible – we all want treatments that work safely, often more so than the desire to be logical or consistent. And often personal or institutional ideology comes into play – we want health care to validate our belief systems.
Thankfully, I don’t receive all that much blog-related mail. But this weekend I received several communications about a piece in popular liberal blog. The piece is (ostensibly) about Lyme disease, which coincidentally happens to be one of the topics of my first post here at SBM. In fact, I’ve written about Lyme disease a number of times, and Dr. Novella has a very good summary of the controversy at one of his other blogs. Since we’ve discussed this so many times, I won’t be reviewing the entire controversy, but looking at this particular blog post to examine how our personal experiences and errors in reasoning can distort our view of reality.
The topic of Lyme disease has come up recently in the press, and as the weather improves, cases in the northeastern U.S. should start to increase soon. Just as a reminder, so-called “chronic” Lyme disease is not Lyme disease at all. Lyme disease can have early and late manifestations, none of which correspond to the vague, protean symptoms labeled as “chronic” by some. The disease is often diagnosed without resort to objective evidence, such as reliable, positive lab tests. But let’s look at the blog post in question and see what’s there.
The overriding them, the raison d’être if you will, of this blog is science-based medicine. However, it goes beyond that in that we here at SBM believe that science- and evidence-based medicine is the best medicine. It’s more than the best medicine, though; it’s the best strategy for medicine to improve therapy for our patients. We frequently contrast science-based medicine with various forms of “complementary and alternative medicine,” specifically pointing out that SBM changes its practices as new science and new evidence mandates it while CAM tends to rely on ancient, vitalistic, pre-scientific or pre-modern scientific beliefs about how disease occurs as the basis for its therapies. Although it may be painfully slow and frustrating at times and even though there may be major stumbles along the way, the overall course of SBM over the last century has in general been to produce ever more effective therapies and to discard therapies that are either ineffective or whose risk-benefit ratios are insufficiently favorable. The one single most important thing behind the advancement of medicine is good science.
That’s why I really, really hate scientific fraud, and I’m really, really upset, perhaps even more so than Dr. Atwood, over the discovery last week of what is arguably one of the most massive scientific frauds in medical history. It doesn’t matter that Dr. Atwood is an anaesthesiologist and I am not, meaning that the specific scientific fraud unearthed, which was perpetrated by an anesthesiologist studying multimodal anesthesia, as reported in Anesthesiology News, the Wall Street Journal, and the New York Times. I am a surgeon, and the relief of surgical pain in my patients is an important part of my practice. If the scientific basis of what my colleagues in anesthesiology do before, during, and after my operations is called into doubt, I have to wonder if I am giving my patients the best surgical care. Aside from that, there is the intellectual outrage I feel as a result of seeing science and patients betrayed in such a systematic and blatant manner.
Last week the story broke that Scott Reuben, an anesthesiologist and clinical researcher at Baystate Medical Center in Springfield, MA, had falsified data in at least 21 publications over a period of at least 12 years—making it one of the most enduring examples of scientific fraud in memory. Almost all of Reuben’s papers had reported innovative methods for providing post-operative pain relief (analgesia); many of them involved ‘multimodal’ regimens for painful orthopedic procedures such as spinal fusions and total knee replacements. Recent papers reported regimens that included celecoxib (Celebrex) and pregabalin (Lyrica), both made by Pfizer. Much of Reuben’s research had been funded by Pfizer, and Reuben has been a member of the Pfizer speaker’s bureau (that information is included because the reader would otherwise wonder, but there is no indication that Pfizer has been intentionally involved in Reuben’s fraud).
I will not discuss this case in detail; look for a more comprehensive piece on SBM next week. Rather, I present it now to offer a local example of how such a breach of trust affects those who rely on clinical research to inform their care of patients.
One of the consistent themes of SBM since its very inception has been that, when it comes to determining the efficacy (or lack thereof) of any particular medicince, therapy, or interventions, anecdotes are inherently unreliable. Steve Novella explained why quite well early in the history of this blog, and I myself described why otherwise intelligent people can be so prone to being misled by personal experience and anecdotal evidence. Unfortunately, as I have also demonstrated, it’s not just patients who can allow themselves to be misled by anecdotes, but certain physicians who do not understand the scientific method but in their hubris think that their “personal clinical experience” trumps science, clinical trials, and epidemiology.
None of this is to say that there aren’t frequent instances when applying data from population-based studies to individual patients is problematic. It can indeed be. However, it often goes beyond that, and, indeed, if there is one defining characteristic of a quack that I’ve never failed to find when looking at individual cases, it’s a belief that he is able to identify when a treatment works based on his own personal experience and anecdotes. Unfortunately, it’s not just quacks who sometimes fall prey to this, because humans are cognitively wired to infer causation from correlation. This tendency, which was no doubt adaptive early in our evolution, simply doesn’t work well when it is applied to medicine and science. Without a doubt, it is the key driver, for example, behind the widely believed myth that vaccines somehow cause autism and that chelation therapy and other biomedical quackery can “cure” autism, a view popularized most recently by the very popular but very ignorant Jenny McCarthy in the U.S. and before that by the outright dishonest Andrew Wakefield in the U.K.
One of the other reasons why testimonials for quackery seem convincing is because most people simply do not know enough about disease, be it my specialty (cancer) or any other disease, how it is treated, and what its natural course can be expected to be. That is why, when I came across an example of just such a testimonial, specifically a breast cancer testimonial, I saw what is known as a “teachable moment. This teachable moment occurred on the very popular science blog Pharyngula, written by the ever sarcastic biology professor from Minnesota, P.Z. Myers. It actually surprised me in that the usual topics on Pharyngula include evolution, biology, the pseudoscience known as “intelligent design” creationism, politics, and atheism. P.Z. doesn’t usually dabble much in the realm of medical quackery, but my guess is that he was attracted to this particular piece of pseudoscience because of the religious angle.
Specifically, the quackery under consideration is known as God’s Answer to Cancer (GAC). Basically, it looks a lot like any number of quack electronic devices that promise to cure cancer; examples include Bill Nelson’s Electro Physiological Feedback Xrroid (EPFX) machine (1, 2, 3), Hulda Clark’s parasite zapper, or Alan Back’s Advanced Bio-photon Analyzer. All of these devices promise, in essence, to use low level electrical energy to “boost the immune system” and “replenish your life energy” plus or minus an additional promise to “zap parasites” (Hulda Clark’s unique spin on these devices, in which she claims that all cancer, AIDS, and most other diseases are due to a liver fluke, which her device supposedly “zaps.” Like these devices, the maker of GAC promises vague “immune system boosts,” but with the added twist that he claims that all disease is due to original sin (along, apparently, with the conventional alt-med “toxins,” diminished qi, and uncharacterized immune dysfunction). Amusingly, the Monsignor who created this device also disses Hulda Clark and advocates the use of laetrile and Linus Pauling’s orthomolecular medicine. The main difference is that he claims to have received the design for the device from God through a dream.
Let me begin with a story. An assistant professor submits a reasonable application to NCCAM to investigate the potential metabolic and pharmacodynamic interactions of St. Johns wort with conventional chemotherapy. This was the year or year-and-a-half before SJW was known to have significant CYP3A4 inductive activity due primarily to its component, hyperforin. Said investigator used this preliminary data, not explicitly required for theNIH funding mechanism (called an R21), to question whether St. John’s wort used by depressed cancer patients might interfere with chemotherapy. The original proposal earned a priority score of 228 (as with golf, the lower the better: the best is 100, the worst is 500.)
The major reviewer critique was that the assistant professor, Your Humble Pharmacologist, lacked, at the time, significant natural products chemistry expertise. YHP was then doing his sabbatical in the NC Research Triangle area and wisely sought the support and expertise of the now-late Dr. Monroe Wall and surviving Dr. Manuskh Wani. These gentlemen discovered and solved the structures of taxol from Taxus brevifolia and camptothecin from Camptotheca acuminata. Taxol itself became a blockbuster drug for Bristol-Myers Squibb while camptothecin required water-soluble modifications to foster topotecan (Hycamptin) and irinotecan (Camptosar) that collectively saved or prolonged the lives of thousands of men and women subjected to breast, ovarian, lung, and gastrointestinal tumors. In 2003, they received the designation of an American Chemical Society National Historic Chemical Landmark for their three decades of work in this area. (Sadly, they received none of the profits from these drugs as their discoveries pre-dated the Bayh-Dole Act that allowed NIH funded researchers to share in the revenues of intellectual property emerging from their work.).
Being a savvy young investigator, I sought and enlisted the assistance and support of Dr. Wall and colleagues to provide my team with world-class, natural products expertise. Stunningly, the subsequent application was awared a score of 345 (*much worse than the original) with the criticism from reviewers that all Dr. Wall did was to lend a drug development aspect to an otherwise “herbal” applicaton.
To this day, I cannot fathom who better I could have sought for natural products expertise on this grant application.
Since then, three of my colleagues and I have submitted 13 applications to NCCAM, including an application for a comprehensive Botanical Research Center grant. All 13 received unfundable scores. Among these was a 279-page application for a NCCAM Botanical Research Center – reviewed but not discussed by the evaluation panel.
Nonetheless, I have taken the approach that if NCCAM were to continue its existence, I would try to be part of the solution. I have accepted several invitations to review research and training grants for NCCAM and I am pleased to say that one or two projects that I ranked highly ended up being very productive, specifically in the area of natural products and traditional herbal medicines. I also have some friends and valued colleagues who contribute to the scientific integrity of NCCAM. However, my collective experiences lead me to believe that they are voices quenched by the vast wilderness of the promotion and advocacy of “integrative medicine” and CAM.
My colleagues and I will be holding a Science-Based Medicine conference on Thursday, July 9th. This is an all-day conference covering topics of science and medicine. The conference is designed for both a professional and general audience.
The conference will be at the Southpoint Casino and Hotel in Las Vegas, Nevada. It is also part of The Amazing Meeting 7 (TAM7) which is run by the James Randi Educational Foundation (JREF). You can register for the conference either separately or packaged with TAM7. You can register for both here.
Physicians can earn 6 hours of category 1 CME credits for attending the conference.
Below is the list of speakers and the titles of their talks, and below that is the bio for each speaker.
Last week, two events took place in Washington that ought to inspire trepidation in the minds of all who value ethical, rational, science-based medicine and ethical, rational, biomedical research. One was the Senate Panel titled Integrative Care: A Pathway to a Healthier Nation, previously discussed by my fellow bloggers David Gorski, Peter Lipson, and Steve Novella, and also by the indefatigable Orac (here and here); the other was the “Summit on Integrative Medicine and the Health of the Public” convened by the Institute of Medicine (IOM) and paid for by the Bravewell Collaborative, previewed six weeks ago by fellow blogger Wally Sampson. This post will make a few additional comments about those meetings.
Senator Harkin and the Scientific Method
Thanks to Dr. Lipson, I didn’t have to listen to the Senate Panel video to find out that Senator Tom Harkin (D-Iowa) made this statement of disappointment regarding his own creation, the National Center for Complementary and Alternative Medicine (NCCAM):
One of the purposes of this center was to investigate and validate alternative approaches. Quite frankly, I must say publicly that it has fallen short. It think quite frankly that in this center and in the office previously before it, most of its focus has been on disproving things rather than seeking out and approving. (from last week’s hearings, time marker approx. 17:20)
Are scientists at the NIH really too afraid of Harkin to explain to him how science works? Apparently so. Otherwise Harkin might learn that his statement is more wrong-headed than it would be for one of us to complain that the Supreme Court ought to assume that a defendant is guilty until proven innocent, rather than the other way around. In scientific inquiry, for those who don’t know, good experimental design is always directed at disproving a hypothesis, even one that pleases its investigator. The rest of Harkin’s sentiment—“seeking out and approving”—is incoherent.
The Selling of ‘Integrative Medicine': Snyderman Trumps Weil
Spin doctors shilling for ‘integrative medicine,’ which the NCCAM defines as “combining treatments from conventional medicine and CAM,” appear to have now decided that subtler language is more likely to sell the product. We’ve previously seen an example offered by ‘integrative’ Mad Man Andrew Weil: