Over the years that this blog has been in existence, beginning very early on, there has been one overarching theme. That theme is that the best medicine is science-based medicine. Sure, we could quibble about how that was originally defined, and I used to be more of a booster of evidence-based medicine until its blind spot with respect to “complementary and alternative medicine” (CAM) and “integrative medicine” (IM). That blind spot, as I’ve explained time and time again, both here and elsewhere at my not-so-super-secret other blogging location under my real name, that blind spot is prior plausibility. Once I learned about John Ioannidis, Bayesian statistics, and how doing clinical trials with a low prior plausibility is far more likely to produce false positive results than true positive results, I realized that testing modalities with incredibly low prior plausibilities is so unlikely to be fruitful that it’s only something that should be considered when money is no object, and that’s even leaving aside the dubious ethics of doing clinical trials of treatments like that.
And, of course, money is always an object, arguably now more than ever.
The normal sequence of development of a drug or treatment is a progression from preclinical research (basic and translational science that can involve any combination of biochemical studies, cell cultures studies, and animal studies) to early stage pilot clinical trials. If the drug or treatment shows promise in these early studies, then–and only then–are large phase III clinical trials warranted. In an ideal world, basic science considerations determine plausibility, translational preclinical studies solidify the plausibility of a treatment, and then clinical trials confirm whether that plausibility translates into a working therapy that is both efficacious and safe. Similarly, in an ideal world, the first steps of this process are informed by clinical observations that lead to laboratory investigations that progress through the various steps to clinical trials. The paradigm of bedside to bench and back to bedside often works. Indeed, the entire ethics of our current clinical trial system assumes that there is a certain degree of prior plausibility based on preclinical evidence before subjecting human subjects to the potential risks of a clinical trial.
The problem with CAM is that it bypasses that process. With the exception of some herbal medicines (which, of course, could well contain active ingredients that can function as drugs) the vast majority of what passes for CAM lacks prior plausibility. I realize I beat on this example a lot, but homeopathy is the paradigm here. For homeopathy to “work,” huge swaths of physics, biochemistry, and biology would have to be not just wrong, but spectacularly wrong. The same is true for “energy healing.” Acupuncture relies on “meridians” that have no anatomic structure associated with them that anyone has yet been able to find. Chiropractic relies on “subluxations” that, similarly, no one other than chiropractors have been able to find. In other words, their prior plausibility, particularly that of “energy medicine” and homeopathy, is about as close to zero as it is possible to be and not actually be zero. For all practical intents and purposes, homeopathy and energy medicine are impossible.
And the National Center for Complementary and Alternative Medicine (NCCAM) spends about $125 million a year to study CAM, which my good bud Kimball Atwood has quite accurately described thusly as:
A spectrum of implausible beliefs and claims about health and disease. These range from the untestable and absurd to the possible but not very intriguing. In all cases the enthusiasm of advocates vastly exceeds the scientific promise.
As much as I have lamented the infiltration of quackademic medicine into medical academia, it’s not all bad news. Even though an awful lot of woo has found its way into even once-respectable medical journals, every so often there’s something good there by someone who “gets it” with respect to CAM. This very thing happened in yesterday’s issue of the Journal of the American Medical Society (JAMA). I have no idea why, but the editors actually published a commentary by Dr. Paul Offit. While that means that antivaccinationists will automatically dismiss this article as the spawn of Satan, for the rest of us Dr. Offit provides a strong argument that studying much of CAM is a waste of scarce resources in the form of an article entitled Studying Complementary and Alternative Therapies.
After giving a brief history of NCCAM, from its very humble beginnings as the Office of Alternative Medicine back in 1992, a brain child (if you can call it that) of Senator Tom Harkin and Representative Berkley Bedell, to the $125 million a year juggernaut of woo it became, Dr. Offit describes the rationale used by CAM apologists to defend NCCAM:
In support of NCCAM’s mission, proponents argue that one century’s folk medicine can be the next century’s mainstream medicine. For example, Hippocrates used leaves from the willow plant to treat headaches and muscle pains. By the early 1800s, scientists had isolated the active ingredient: aspirin. In the 1600s, a Spanish physician found that bark from the cinchona tree treated malaria. Later, cinchona bark was found to contain quinine, an antimalarial drug. In the late 1700s, William Withering used foxglove to treat heart failure. Later, foxglove was found to contain digitalis, a drug that increases heart contractility. More recently, Artemisia, an herb used by Chinese healers for more than a thousand years, was found to contain artemisinin, another antimalarial drug. Indeed, most drugs on today’s hospital formularies were originally derived from plants.
All of which is true but irrelevant to much of the research that NCCAM funds. It also confuses CAM with pharmacognosy, the latter of which is the study of natural products as potential drugs. Pharmacognosy is an important and respectable branch of pharmacology because, as Dr. Offit mentions, many, if not most, drugs in use today were originally derived from natural products, some of them modified for better pharmacological properties. I’ve asked time and time again why pharmacognosy is in any way “alternative.” it’s a rhetorical question, of course, because pharmacognosy is not “alternative.” But CAM has co-opted pharmacognosy as “alternative” much as it has also co-opted diet, exercise, and lifestyle when the study of such interventions is every bit as much the purview of science-based medicine as the latest drug developed by big pharma. As for the rest, the problem boils down to prior plausibility:
However, unlike studies of drugs derived from plants, many studies funded by NCCAM lack a sound biological underpinning, which should be an important requirement for funding. For example, NCCAM officials have spent $374 000 to find that inhaling lemon and lavender scents does not promote wound healing; $750 000 to find that prayer does not cure AIDS or hasten recovery from breast-reconstruction surgery; $390 000 to find that ancient Indian remedies do not control type 2 diabetes; $700 000 to find that magnets do not treat arthritis, carpal tunnel syndrome, or migraine headaches; and $406 000 to find that coffee enemas do not cure pancreatic cancer. Additionally, NCCAM has funded studies of acupuncture and therapeutic touch. Using rigorously controlled studies, none of these therapies have been shown to work better than placebo.4â Some complementary and alternative practitioners argue reasonably that although their therapies might not work better than placebos, placebos may still work for some conditions.
I get the feeling here that Dr. Offit is bending over a little too far backwards to be “fair.” While he points out all these highly implausible treatment modalities that NCCAM has wasted money funding, he seems to be buying into the selling of placebo effects as being anything more than subjective improvement without the correction of underlying physiological derangements responsible for disease. CAM is in essence placebo medicine, sometimes to a ridiculous degree. A really ridiculous degree, even, to the degree that it’s not for nothing that I’ve referred to CAM as the new paternalism.
Another point that Dr. Offit makes is that the marketing of CAM, including the supplement industry, is completely divorced from reality and science. Some have argued that NCCAM has done good in funding studies of various CAM modalities that turned out to be negative. In a world where the marketing of CAM treatments is based on solid scientific evidence, that would indeed be a valuable service. We do not live in such a world, and Dr. Offit describes that well:
Several studies have shown that garlic does not lower low-density lipoprotein cholesterol, St John’s wort does not treat depression, ginkgo does not improve memory, chondroitin sulfate and glucosamine do not treat arthritis, saw palmetto does not treat prostatic hypertrophy, milk thistle does not treat hepatitis, and echinacea and megavitamins do not treat colds. Moreover, some studies have found that megavitamins increase the risk of cancer and heart disease. Because the vitamin and supplement industry is not regulated by the US Food and Drug Administration (FDA), negative studies have not precipitated FDA warnings or FDA-mandated changes on labeling; as a consequence, few consumers are aware that many supplements have not delivered on their claims. In 2010, the vitamin and supplement industry grossed $28 billion, up 4.4% from the year before.8â “The thing to do with [these studies] is just ride them out,” said Joseph Fortunato, chief executive of GNC Corp. “We see no impact on our business.”
It’s not just supplements, either. The evidence that homeopathy is nothing more than water is enormous and indisputable; yet that doesn’t keep Boiron from raking it in hand over fist selling homeopathic flu remedies or, sadly, a number of academic medical centers from setting up “integrative medicine” centers that feature all manner of what used to be considered (and should still be considered quackery), such as energy healing. Given that, I agree with Steve Novella and Paul Offit that it is entirely reasonable to ask why taxpayer dollars should be used to fund studies with such a low prior plausibility that the likelihood that they will result in useful information or that they will validate the therapy being tested is incredibly slim and none. Let’s just put it this way, using my favorite example of homeopathy again: When faced with a therapy that violates the currently known laws of physics, which are supported by a few hundred years worth of experimental observations, veritable mountains of evidence, and a messy, bias-prone clinical trial that shows a barely statistically significant apparent effect, which are you going to believe. I know what I will believe. It takes a lot more than an equivocal clinical trial to overthrow hundreds of years of physics and chemistry. To show that homeopathy “works” would require evidence of approximately the same quality and quantity as the evidence that says that homeopathy can’t work. In other words, it takes a lot to prove the impossible to be possible.
That is why I’d quibble a little bit with Dr. Offit when he characterizes CAM therapies as “bordering on mysticism.” Reiki, homeopathy, acupuncture, and “energy healing” don’t border on mysticism. They are mysticism. He is, however, correct when he suggests that NCCAM should stop funding studies of such incredibly implausible modalities. I’m not so sure, however, that I agree with Dr. Offit when he suggests as an alternative that NCCAM might redefine its mission to understanding placebo responses. To some extent, this is already happening, and the results have not been pretty. My vote goes for the third alternative: Dissolve NCCAM and distribute its components to other Institutes and Centers at the NIH. There’s nothing that NCCAM does that can’t be done–and done better–in the rest of the NIH. Keeping the actual plausible modalities claimed by CAM, such as pharmacognosy and nutrition studies, in NCCAM in essence ghettoizes them, and there’s no reason to study the impossible, such as homeopathy.
This is especially true when promising research with a reasonable amount of biological plausibility is going unfunded. NIH paylines right now are abysmal (in the 7th percentile range) and threatening to get worse. My senior colleagues tell me that the NIH funding situation is the worst it’s been in at least 20 years, possibly considerably longer. I remember the early 1990s, and this is at least as bad. Worse, it shows no sign of getting better any time soon. In an environment like this, it’s inexcusable to waste $125 million a year that could go to useful science and useful research.
When it comes to NCCAM I suggest nuking the entire center from orbit. It’s the only way to be sure.
NOTE: For those of you who are humor-challenged (or not fans of the first two Alien movies, I am not seriously suggesting that NCCAM be nuked from orbit. Really. I’m not. It’s a metaphor. Defunding NCCAM and distributing its budget to the rest of the NIH would be just fine.