Clinical Trials

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NIH Director Francis Collins doesn’t understand the problem with CAM

As the sole cancer surgeon among our stable of Science-Based Medicine (SBM) bloggers, I’m probably the most irritated at the infiltration of pseudoscience into academia (or, as we sometimes like to call it, quackademic medicine) in the realm of cancer. Part of the reason, of course, is that cancer is so common and that the consequences of adding pseudoscience to cancer therapy are among the most devastating. Witness, for instance, the use of Gonzalez therapy to treat pancreatic cancer, a form of quackery that harms patients and resulted in incredibly unethical and disastrous clinical trial of Gonzalez quackery versus chemotherapy whose results were entirely predictable, given the lack of prior plausibility of the treatment: Gonzalez protocol patients did worse, with no evidence that the therapy impacted the natural history of the disease and the Gonzalez patients scoring lower on quality of life measures. Or look at what happens when patients with breast cancer choose quackery over science-based therapy.

I realize that “complementary and alternative medicine” (CAM) or, what quackademics like to call it now, “integrative medicine” (IM) is meant to refer to “integrating” alternative therapies into SBM or “complementing” SBM with a touch of the ol’ woo, but I could never manage to understand how “integrating” quackery with SBM would do anything but weaken the scientific foundation of medicine. Moreover, weakening those foundations would have more consequences than just “humanizing” medicine; weaker scientific standards would allow not just ancient quackery like traditional Chinese medicine (TCM) into academia, but it would also provide an opening for drug and device companies to promote their wares under less rigorous requirements for evidence. There’s also perhaps a touch of personal embarrassment involved. After all, oncology and cancer surgery tend to be specialties that are the most steeped in science. If I had to rank specialties for how science-based they are, I’d certainly put oncology near the top, which is why I tend to come down so hard on “integrative oncology” and, even worse, “naturopathic oncology.”

Consequently, I was doubly disturbed several months ago when I learned that the director of the National Institutes of Health, Francis Collins, had agreed to be the keynote speaker at the Eight International Society for Integrative Oncology Conference in Cleveland, OH. I say “doubly” disturbed because it disturbed me that Francis Collins would agree to speak at such a function and, perhaps even more, because the host institution was Case Western Reserve University, the institution where I both completed my surgery residency and my PhD in Physiology and Biophysics. Sadly, it now appears that my old stomping grounds at University Hospitals has been thoroughly infiltrated with quackademic medicine, as evidenced by this clinical trial of reiki for psoriasis that’s making the rounds of news services and the offering of acupuncture, reiki, and even reflexology at various UH facilities through the University Hospitals Connor Integrative Medicine Network. Let me tell you, there was none of this pseudoscience going on when I finished my residency there in 1996. Seeing it there now provokes a reaction in me not unlike Sylvester Junior’s reaction when his father Sylvester embarrasses him, particularly when I noted that the director of the CWRU Comprehensive Cancer Center, Dr. Stanton L. Gerson, was to give one of the keynote talks, entitled, “The Future of Integrative Oncology.” (Hint for those of you not familiar with classic Looney Tunes cartoons: A paper bag is involved.) I guess that by expressing my extreme disappointment and embarrassment that the institution where I learned to become a surgeon has during the last 15 years gone woo, I’ve probably just killed any opportunity I might have to work at the Case Comprehensive Cancer Center ever again. Oh, well, add it to the list, along with Beth Israel and my alma mater the University of Michigan.)

Back when I first learned about it, I thought about blogging the meeting, but without much concrete to go on, given the copious other SBM-related topics to blog about, all I could do was to write a critical open letter to Dr. Collins about his decision to accept the offer to be the keynote speaker at the Society for Integrative Oncology (SIO). Then yesterday I saw popping up in my e-mail a notice from the American Society of Clinical Oncology (ASCO), along with a link to a story in its publication The ASCO Post entitled NIH Director Calls for Rigorous Evaluation of Integrative Medicine to Provide Evidence of Efficacy.

Et tu, Dr. Collins?
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Posted in: Basic Science, Cancer, Clinical Trials, Politics and Regulation

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The New England Journal of Medicine Sinks a Bit Lower

I suppose it was bound to happen, but it still rankles. Here is the back cover of last week’s issue of the decreasingly prestigious New England Journal of Medicine:

 


Here’s the front cover:

It’s the 200th Anniversary issue, no less. Some might protest that ‘probiotics’—live bacteria of ‘good’ varieties, as far as the gut is concerned—aren’t all that implausible, and that there is some trial evidence that they help for some conditions. That’s true, but as is typically the case even for the somewhat plausible end of the “CAM” spectrum, the hype greatly surpasses the evidence. The abstract of the most recent systematic review that I could find for probiotic treatment of irritable bowel syndrome (IBS: symptoms and signs that best match the claims in the advertisement above) concluded:

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Posted in: Clinical Trials, Herbs & Supplements, History, Legal, Medical Ethics, Pharmaceuticals, Politics and Regulation, Science and Medicine, Science and the Media

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Tonsillectomy Indications and Complications

Tonsillectomy remains a common surgical procedure with over half a million cases in the US per year, the most common surgical procedure in children. The indications and effects of tonsillectomy remain a matter of research and debate, as is appropriate. It is also a subject of popular misinformation and alarmism.

A recent article by Seth Roberts raises many of the issues with tonsillectomy, but also reveals the pitfalls of non-experts trying to understand the clinical literature and the effects of bias on evaluating a complex medical question. Throughout the article Roberts displays a persistent bias toward downplaying the benefits and exaggerating the risks of tonsillectomy, while accusing the medical establishment of doing the exact opposite.  The purpose of this post is not to defend the practice of tonsillectomy but to review some of the relevant issues and explore how bias can affect an assessment of the evidence.

Indications for Tonsillectomy

Roberts tells the story of Rachael who was offered tonsillectomy for her son and so did some research on her own. She looked on Pubmed (a good place to start) and found a Cochrane review from 2009.

The Cochrane Review that Rachael found (“Tonsillectomy or adeno-tonsillectomy versus non-surgical treatment for chronic/recurrent acute tonsillitis”) was published in 2009. It describes four experiments that compared tonsillectomy to the care a sick child would otherwise receive. All four involved children like Rachael’s son, and all four had similar results: Tonsillectomies had only a small benefit. (Contrary to what Rachael was told.) During the year after random assignment to treatment — the point at which some children had their tonsils removed, other children did not — children whose tonsils were removed had one less sore throat than children who were not operated on (two instead of three for children like Rachael’s son).

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Posted in: Clinical Trials, Surgical Procedures

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The rebranding of CAM as “harnessing the power of placebo”

If there’s one thing I’ve learned over the past seven years or so that I’ve been blogging, first at my other “super secret” (or, more accurately, super “not-so-secret”) blogging location, and then the four years I’ve been blogging here at Science-Based Medicine (SBM), it’s that the vast majority of “alternative medicine,” “complementary and alternative medicine” (CAM), and “integrative medicine” (IM) treatments (or whatever you want to call them) are nothing more than placebo medicine. True, there are exceptions, such as herbal treatments, mainly because they can contain chemicals in them that are active drugs, but any critical look at things like homeopathy (which is water), reiki (which is faith healing substituting Eastern mystical beliefs for Christianity), acupuncture (whose effects, when tested rigorously, are found to be nonspecific), or “energy healing” must conclude that any effects these modalities have are placebo effects or responses. Given writings on this topic by Steve Novella, Mark Crislip, Harriet Hall, Peter Lipson, myself, and others, this should be abundantly clear to readers of this blog, but, even so, it bears repeating. In fact, it probably can’t be repeated enough.

There was a time not so long ago when proponents of unscientific medicine tried very, very hard to argue that their nostrums have real effects on symptoms and disease above and beyond placebo effects. They would usually base such arguments on small, less rigorously designed clinical trials, mainly because, if there’s another thing I knew before from my medical education but that has been particularly reinforced in me since I started blogging, it’s that small clinical trials are very prone to false positives. Often they’d come up with some handwaving physiological or biological explanation, which, in the case of something like homeopathy, often violated the laws of chemistry and physics. Be that as it may, the larger and more rigorously designed the clinical trial, the less apparent effects become until, in the case of CAM therapies that do nothing (like homeopathy), they collapse into no effect detectable above that of placebo. Even so, there are often enough apparently “positive” clinical trials of water (homeopathy) that homeopaths can still cling to them as evidence that homeopathy works. Personally, I think that Kimball Atwood put it better when he cited a homeopath who said bluntly, “Either homeopathy works, or clinical trials don’t!” and concluded that, for highly implausible treatments like homeopathy, clinical trials as currently constituted under the paradigm of evidence-based, as opposed to science-based, medicine don’t work very well. Indeed, contrasting SBM with EBM has been a major theme of this blog over the last four years. In any case, for a long time, CAM enthusiasts argued that CAM really, really works, that it does better than placebo, just like real medicine.

Over the last few years, however, some CAM practitioners and quackademics have started to recognize that, no, when tested in rigorous clinical trials their nostrums really don’t have any detectable effects above and beyond that of placebo. A real scientist, when faced with such resoundingly negative results, would abandon such therapies as, by definition, a placebo therapy is a therapy that doesn’t do anything for the disease or condition being treated. CAM “scientists,” on the other hand, do not abandon therapies that have been demonstrated not to work. Instead, some of them have found a way to keep using such therapies. The way they justify that is to argue that placebo medicine is not just useful medicine but “powerful” medicine. Indeed, an article by Henry K. Beecher from 1955 referred to the “powerful placebo.” This construct allows them then to “rebrand” CAM unashamedly as “harnessing the power of placebo” as a way of defending its usefulness and relevance. In doing so, they like to ascribe magical powers to placebos, implying that placebos can do more than just decrease the perception of pain or other subjective symptoms but in fact can lead to objective improvements in a whole host of diseases and conditions. Some even go so far as to claim that there can be placebo effects without deception, citing a paper in which the investigators — you guessed it! — used deception to convince their patients that their placebos would relieve their symptoms. Increasingly, placebos are invoked as a means of “harnessing the power of the mind” over the body in order to relieve symptoms and cure disease in what at times seems like a magical mystery tour of the brain.

Part of what allows CAM practitioners to get away with this is that placebo effects are poorly understood even by most physicians and, not surprisingly, even more poorly understood by the public. Moreover, we all like to think that we have more control than we do over our bodies and, in particular, illnesses and symptoms, which is why the selling of placebo effects as a means of harnessing some innate hidden power we have to control our own bodies through the power of mind is so attractive to so many, including some scientists and physicians. Exhibit A is Ted Kaptchuk, the researcher from Harvard University responsible for spinning an interesting study of placebo effects in asthma into the invocation of the power of placebo. Kimball Atwood has written extensively about Kaptchuk recently, revealing his rather dubious background and arguments. More recently, however, Kaptchuk seems to be everywhere, appearing in articles and interviews, promoting just the argument I’m talking about, that CAM is a way of harnessing placebo effects, so much so that I felt it was time to take a look at this argument.

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Posted in: Basic Science, Clinical Trials, Medical Ethics, Science and Medicine

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Why Do We Really Need Clinical Trials?

A point I make over and over again when talking about new or alternative therapies that are not supported by good clinical trial evidence is that lower-level evidence, such as theoretical justifications, anecdotes, and pre-clinical research like in vitro studies and animal model testing, can only be suggestive, never reliable proof of safety or efficacy. It is necessary to begin evaluating a new therapy that does not yet have clinical evidence to support it by showing a plausible theory for why it might work and then moving on to demonstrate that it actually could work through pre-clinical research, which includes biochemistry, cell culture, and animal models. These sorts of supporting preclinical evidence are what we refer to when we refer to the “prior plausibility” of a clinical study. But this kind of evidence alone is not sufficient to support using the therapy in real patients except under experimental conditions, or when the urgency to intervene is great enough to balance the significant uncertainty about the effects of the intervention.

In support of this conclusion, we can consider the inherent unreliability of individual human judgments and all the many ways in which inadequately controlled research can mislead us. And we can reflect on how promising results in early trials often melt away when better, larger, more rigorous studies are done that better control for bias (the so-called Decline Effect). And it is not at all difficult to compile a large list of examples of the harm inadequately studied medical interventions can cause.

But what I’d like to do here is focus on a particularly good specific example of why thorough clinical trial evaluation of promising ideas is not just a nice extra to confirm what we already believe is true, it is the only way to genuinely know whether our treatments to more good than harm.

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Posted in: Cancer, Clinical Trials, Herbs & Supplements, Science and Medicine

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On the “individualization” of treatments in “alternative medicine,” revisited

As I contemplated what I’d like to write about for the first post of 2012, I happened to come across a post by former regular and now occasional SBM contributor Peter Lipson entitled Another crack at medical cranks. In it, Dr. Lipson discusses one characteristic that allows medical cranks and quacks to attract patients, namely the ability to make patients feel wanted, cared for, and, often, happy. As I (and several of us at SBM) have said before, it’s not necessary to invoke magic, quackery, or pseudoscience in order to show empathy to patients and provide them with the “human touch” that forges a strong therapeutic relationship between physician and patient and maximizes placebo effects without deception. In the old days, this used to be called “bedside manner,” but in these days of capitation and crappy third party payor reimbursement it’s very difficult for physicians to take the time necessary to listen to patients and thereby build the bonds of trust and mutual respect that can augment the treatments that are prescribed. Unfortunately, because of this the quacks have been all too eager to leap into the breach.

One aspect of this tendency of medical cranks is to claim that they somehow “individualize” their treatment to the patient, as Peter points out:

There are a number of so-called holistic doctors in town who claim to practice “individualized” medicine. What this really means isn’t clear. My colleagues and I certainly individualize the treatment plans for all of our patients, using data gleaned from decades of scientific studies of large groups of patients. What “individualized” care seems to mean in this other context is “stuff I made up to make that patient feel more unique and special.”

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Dr. Stanislaw Burzynski’s “personalized gene-targeted cancer therapy”: Can he do what he claims for cancer?

Last week, I wrote a magnum opus of a movie review of a movie about a physician and “researcher” named Stanislaw Burzynski, MD, PhD, founder of the Burzynski Clinic and Burzynski Research Institute in Houston. I refer you to my original post for details, but in brief Dr. Burzynski claimed in the 1970s to have made a major breakthrough in cancer therapy through his discovery of anticancer substances in the urine that he dubbed “antineoplastons,” which turned out to be mainly modified amino acids and peptides. Since the late 1970s, when he founded his clinic, Dr. Burzynski has been using antineoplastons to treat cancer. Over the last 25 years or so, he has opened a large number of phase I and phase II clinical trials with little or nothing to show for it in terms of convincing evidence of efficacy. Worse, as has been noted in a number of places, high doses of antineoplastons as sodium salts are required, doses so high that severe hypernatremia is a concern.

Although antineoplastons are the dubious cancer therapy upon which Dr. Burzynski built his fame, they aren’t the only thing he does. Despite the promotion of the Burzynski Clinic as using “nontoxic” therapies that “aren’t chemotherapy” by “natural medicine” cranks such as Joe Mercola and Mike Adams, Dr. Burzynski’s dirty little secrets, at least as far as the “alternative medicine” crowd goes, are that (1) despite all of the attempts of Dr. Burzynski and supporters to portray them otherwise antineoplastons are chemotherapy and (2) Dr. Burzynski uses a lot of conventional chemotherapy. In fact, from my perspective, it appears to me as though over the last few years Dr. Burzynski has pivoted. No longer are antineoplastons the center of attention at his clinic. Rather, these days, he appears to be selling something that he calls “personalized gene-targeted cancer therapy.” In fact, it’s right there in the first bullet point on his clinic’s webpage, underlined, even! Antineoplastons aren’t even listed until the third bullet point.

But what is “personalized gene-targeted cancer therapy,” according to Dr. Burzynski? Here is how it is described:
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Posted in: Basic Science, Cancer, Clinical Trials, Pharmaceuticals

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Stanislaw Burzynski: Bad medicine, a bad movie, and bad P.R.

And the Lord spake, saying, “First shalt thou take out the Holy Pin. Then shalt thou count to three, no more, no less. Three shall be the number thou shalt count, and the number of the counting shall be three. Four shalt thou not count, neither count thou two, excepting that thou then proceed to three. Five is right out. Once the number three, being the third number, be reached, then lobbest thou thy Holy Hand Grenade of Antioch towards thy foe, who, being naughty in my sight, shall snuff it.

Cleric from Monty Python and the Holy Grail

I’ve always wondered about the power of the number three. When it comes to quackery propaganda movies, certainly three seems to be the magic number. For example, The Greater Good, an anti-vaccine propaganda film, features three anecdotes, three children allegedly suffering from vaccine injury, and it interspersed its interviews with experts, both real (such as Dr. Paul Offit) and phony (such as Barbara Loe Fisher) with vignettes from these children’s stories interspersed between them in a highly biased manner. I have to wonder whether these cliches are taught in film school, given that they seem to be so common. Such were the thoughts running through my brain as I watched the latest medical propaganda film by writer/producer Eric Merola that’s floating around the blogosphere and the film circuit, Burzynski The Movie: Cancer Is Serious Business. In this movie, there are three testimonials, and, if anything, they are far more manipulative than even the testimonials featured in The Greater Good, because each of them are of the type that portrays doctors as sending a patient home to die; that is, until a “brave maverick doctor,” one Stanislaw R. Burzynski, MD, PhD, comes to the rescue with his unconventional and unproven therapy. The only difference is that this film counts testimonials up to the number three in the beginning as “proof” that Burzynski can cure cancer before lobbing the Holy Hand Grenade of Burzynski towards its foes in the hopes that, being naughty in the filmmaker’s sight, the FDA and Texas Medical Board will snuff it. Or, as a caption says right at very the beginning of the movie:

This is the story of a medical doctor and PhD biochemist who has discovered the genetic mechanism that can cure most human cancers. The opening 30 minutes of this film is designed to thoroughly establish this fact — so the viewer can fully appreciate the events that follow it.

It turns out that the grenade is a dud.
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Posted in: Basic Science, Cancer, Clinical Trials, Medical Ethics, Politics and Regulation, Science and the Media

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Weight Loss Customers Are Being Hoodia-Winked

I first wrote about Hoodia in my “SkepDoc” column in Skeptic magazine (Vol. 13, No. 1, 2007).  The following is adapted from that column with an update from new research revealing that it doesn’t work and that it causes worrisome side effects.

I first heard of Hoodia in 2006, when a radio ad informed me that it was the new miracle weight loss pill. Shortly after that, I started seeing ads for Hoodia everywhere. Anna Nicole Smith took it. It was featured on Oprah.  Lesley Stahl went to Africa to taste the plant on 60 Minutes. There are nearly 40 competing brands of pills, a patch version, and even a Hoodia lollipop. It seems to have taken the world by storm; but it’s not new.

Hoodia gordonii is a cactus that grows in the deserts of southern Africa, and the San people have traditionally used it as an appetite suppressant, thirst quencher and to treat severe abdominal cramps, hemorrhoids, tuberculosis, indigestion, hypertension and diabetes. The claim is that it banishes hunger and thirst. What is the evidence? At this point it’s strictly anecdotal. Skinny Bushmen report it relieves hunger pangs in starvation conditions on long hunts; we don’t know what happens if it’s used by lazy fat people with access to food. Before the new study, there hadn’t been a single published study in humans. (more…)

Posted in: Clinical Trials, Herbs & Supplements

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More Breast Cancer Awareness Month pseudoscience from (who else?) Joe Mercola

I have mixed emotions regarding Breast Cancer Awareness Month. On the one hand, I look forward to it because it provides us with a pretext to get out science-based messages about breast cancer and to highlight a lot of the cool science that we do at our cancer center. On the other hand, the quacks see an opportunity in Breast Cancer Awareness Month to spread their message too. That message, not surprisingly, generally involves attacking science-based modalities for the detection and treatment of breast cancer and promoting their “alternative” methods. For example, last year, Christiane Northrup promoted thermography as somehow being better than mammography for the early detection of breast cancer. It’s not. Yet there she is this year again, still promoting the same nonsense. In years past, I’ve seen people like Dennis Byrne promoting a link between abortion and breast cancer, a link that is not supported by science. I’ve seen the likes of Mike Adams claiming that Breast Cancer Awareness Month is nothing more than a conspiracy by the male-dominated “cancer industry” to keep women down and misinformation about “myths” of breast cancer while likening the “cancer industry” to Nazi extermination camp commanders and chemotherapy to Zyklon-B. I kid you not about that last part. Indeed, during October, I frequently get to look forward to images like this one (click for a larger image):

Or this one:
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Posted in: Basic Science, Cancer, Clinical Trials

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