Thunder god vine may not be a useful herbal medicine but the compounds isolated from it are fascinating – if not as medicines, then most certainly as laboratory tools. Nature Chemical Biology recently published an article where a research team from Johns Hopkins, the University of Colorado at Boulder, and Drew University in New Jersey, has determined the molecular mechanism of action of triptolide, an unusual triepoxide compound from the plant.

Tripterygium wilfordii Hook F, or thunder god vine, is known as lei gong teng in Chinese traditional medicine and has a history of use as an anti-inflammatory herb. As with many traditional medicines, usage patterns do not necessarily indicate scientific validity. In fact, a Cochrane review published just last month on herbal therapies for rheumatoid arthritis indicated that the efficacy of thunder god vine was mixed. More concerning is that the herb had significant adverse effects in some trials, from hair loss to one case of aplastic anemia.

Nevertheless, the herb’s components have been studied since the 1970s for since they also appears to kill tumor cells in culture with nanomolar potency and have immunosuppresant activity in animal models. The group of the late natural products chemist at the University of Virginia, S. Morris Kupchan, first identified the unusual structures of triptolide and tripdiolide from Tripterygium wilfordii as described in this 1972 paper from the Journal of the American Chemical Society. Cytotoxic activity toward tumor cells in culture was used to guide the chemical fractionation of extracts. The unusual presence of three consecutive epoxides in the structures of both compounds led Kupchan to hypothesize later in Science that they target leukemia cells by covalent binding to cellular targets involved in cellular growth.

As an aside: Epoxides are chemically reactive groups composed of an oxygen atom bonded to two carbons; the constraints of this triangular structure and the electrons on the oxygen favor the opening of this ring and attack of other atoms such as sulfur, often present in regulatory regions of enzymes. The Wikipedia entry gives a pretty nice primer. The reactivity of epoxides also makes these compounds highly useful intermediates in industry, particularly in the manufacture of ethylene glycol antifreeze and industrial paints and adhesives (e.g. epoxy resins).

Conventional wisdom would drive most scientists to take one look at triptolide and say that this stuff is a royal mess – so chemically reactive that it couldn’t possible have a specific cellular target. It’s probably too “dirty” – so promiscuous in its binding that it probably attacks all manner of sulfhydryl-containing enzymes and blows the cells to smithereens.

However, several groups have shown over the last 10 or 15 years that some epoxide-containing natural products have very specific cellular targets. Epoxides are not so wildly reactive that they bind everything in their midst. Instead, the environment in which the epoxide exists seems to provide some binding specificity. For example, the group of Jun O. Liu, then at MIT, showed in 1998 that another epoxide-containing natural product, fumagillin, exerted its antiangiogenic activity by binding to a protein called methionine aminopeptidase 2 (MetAP2). Similarly, Brent Stockwell at Columbia University and the Howard Hughes Medical Institute recently published a tour de force in another Nature Chemical Biology paper showing that a reactive 2-chloromethylketone compound specifically targets protein disulfide isomerase, preventing neuronal cell death from misfolded proteins with potential use in Alzheimer’s or Huntington’s diseases.

Jun Liu was again at the helm in the current thunder god vine study in Nature Chemical Biology. The group started with a simple approach to narrow down the target of triptolide from thunder god vine: they treated the venerable HeLa cervical carcinoma cell line with the drug and examined the incorporation of the building blocks of DNA, RNA, or protein. Triptolide was several orders of magnitude more potent in rapidly inhibiting RNA synthesis.

In an elegant series of experiments, the researchers progressively dissected the modulation of RNA synthesis – first identifying the multiprotein complex of RNA polymerase II (RNAPII) as the target but acting via a mechanism different from known RNAPII inhibitors such as the mushroom toxin, ?-amanitin.

Further experiments revealed that triptolide bound to a transcription factor component of the RNAPII complex called TFIIH. Then, finally, the investigators demonstrated that triptolide specifically attacked a component of TFIIH called XPB. XPB is a type of DNA unwinding enzyme called a helicase and is involved in DNA repair. The group then made semi-synthetic chemical analogs of triptolide to determine how inhibition of the ATP hydrolyzing activity of XPB correlated with potency in killing HeLa cells. While the rank order of potency of the compounds correlated, the drugs were less potent in attacking the enzyme activity of the XPB protein than in killing HeLa cells. So, it’s unclear as to exactly how binding to XPB is leading to cell killing. The investigators do note that triptolide may have other cellular targets that are less abundant than XPB that contribute to its activity.

Of course, we can’t tell right now if triptolide selectively kills tumor cells relative to normal cells. Again, conventional wisdom would argue that a drug that hits such a crucial target as a transcription factor is unlikely to have selective activity. After all, the classic RNAPII inhibitor ?-amanitin is well-known as a lethal toxin responsible for legendary poisonings by the death cap mushroom, Amanita phalloides. However, low concentrations of such a compound might indeed have some selectivity when given together with a DNA-damaging anticancer drug. But that’s a very fine tightrope to walk.

In the end, triptolide may end up “just” being a useful laboratory tool for understanding the basics of gene transcription and DNA repair. But if normally disregarded epoxides do indeed have some specificity in their action on cellular targets, perhaps analogs can be made with selective action against tumor cells. Many triptolide analogs have been synthesized over the years and should certainly be revisited in the context of cancer treatment. But this finding should also serve to warn us that the indiscriminate use of the herb as an anti-inflammatory should be revisited, particularly if the dose of the herb gives variable concentrations of compounds with a very low margin of safety.

Titov, D., Gilman, B., He, Q., Bhat, S., Low, W., Dang, Y., Smeaton, M., Demain, A., Miller, P., Kugel, J., Goodrich, J., & Liu, J. (2011). XPB, a subunit of TFIIH, is a target of the natural product triptolide Nature Chemical Biology, 7 (3), 182-188 DOI: 10.1038/nchembio.522

I’ve really come to detest Dr. Mehmet Oz.

You remember Dr. Mehmet Oz, don’t you? How can you escape him? He is, after all, Oprah Winfrey’s protege, and of late he’s really been living up (or down) to the example set by his television mentor, who of late apparently thinks nothing of promoting faith healing quack John of God on her show. Following in the footsteps of his much more famous and well-known mentor, this season on his television show, The Dr. Oz Show, Dr. Oz has in some ways imitated Oprah and in some ways gone her one better (one worse, really) in promoting the Oprah-fication of medicine. And this season has been a particularly bad one for science-based medicine on The Dr. Oz Show. Apparently Dr. Oz felt that he had to surpass what he did last season, which included inviting a man whom I consider to be one of the foremost sellers of quackery on the Internet, Dr. Joseph Mercola. Prior to that, Dr. Oz had done an episode touting the glories of that form of faith healing known as reiki. In between, he made appearances at various panels of woo-friendly physicians trying to coopt President Obama’s health insurance reform initiative to cover more “holistic” care (i.e., “integrative medicine”).

In the next season, in particular over the last couple of months, Dr. Oz showed me just how wrong I had been when I had previously been saying that Dr. Oz seemed to be mostly science-based but with a soft spot for certain kinds of pseudoscience. This season, Dr. Oz has thrown down the gauntlet to science-based medicine (SBM) and, as I like to put it, crossed the Woo-bicon. First, he not only invited Joe Mercola back on his show, but he did it defiantly, defending Mercola against what I consider to be much-deserved charges of being a seller of quackery and lauding him as a “pioneer of holistic treatments.” A couple of weeks later, Dr. Oz pulled the classic “bait and switch” of alternative medicine, featuring a yoga instructor on his show who also advocated all sorts of Ayruvedic quackery. Then, a mere few days later Dr. Oz, apparently not satisfied at his transformation from nominally science-based to being based solely on whatever would bring him higher ratings, completed his journey to the Dark Side of quackery by credulously featuring a faith healer on his show and hosting what has to be the lamest faith healing that I’ve ever seen in my entire life. After that, I didn’t think Dr. Oz could go much lower, although he tried, two examples of which were his anti-vaccine-sympathetic episode on autism in which he featured Dr. Robert Sears and his utterly reversing a previous scientifically correct stance of his and promoting a dubious and potentially dangerous diet.

So where could Dr. Oz go after these episodes? After his credulous featuring of a faith healer on his show, I didn’t think that even Dr. Oz could or would go any lower. Man, was I wrong. Wrong, wrong, wrong, wrong, wrong! I admit it freely and incredulously. As I found out from all of you, Dr. Oz’s guest on his show on Tuesday this week was psychic scammer John Edward, whose show Crossing Over with John Edward ghoulishly featured Edward convincing bereaved guests that he could speak with their departed loved ones. But it was even worse than it sounds just from my description thus far. How low can a physician go to feature someone like Edward, who claims to be able to talk to the dead but in reality is nothing more than a so-so cold reader? He can entitle his segment featuring Edward, Are Psychics the New Therapists (part 2 and part 3). Dr. Oz even helpfully features a segment in which Edward gives his audience advice on how to harness their psychic powers and a chapter from John Edward’s latest book. As I watched, I couldn’t believe my eyes. I guess that means I just haven’t become cynical enough yet, because Dr. Oz’s trajectory has been so obviously leading to something like this for several months now. After all, once you’ve had a faith healer on your show, there really aren’t any boundaries left with regards to your respect for science to justify barring someone like Edward from your show, are there? Certainly, I can’t think of any, but then I am not Dr. Oz. Come to think of it, Dr. Oz obviously couldn’t think of any, either, which is why John Edward was on his show.

Perhaps the most telling part of the episode came right at the beginning of the John Edward segment, telling about Dr. Oz’s audience, that is. Dr. Oz introduces the segment by saying:

We’ve had more requests to join this show than any other we’ve ever done before, more than weight loss, more than cancer, more than heart disease. The topic? Do you believe we can talk to the dead?

Yes, apparently Dr. Oz’s fans were clamoring to be in the audience for this episode above all others, and throughout the show the audience was completely enthusiastic and fawning, just like the show’s host, who asks the question: Is talking to the dead a new kind of therapy? I kid you not. I wish I were kidding. I really do. Then, Dr. Oz even goes one step beyond by answering his own question with a comment to the effect that “psychic medium John Edward believes it can be,” after which he asks another question: “Could it help you someday?” What follows is a taped segment about grief from “devastating loss” and how some people even resort to trying to talk to the dead, for which, we are told, they need a person like John Edward. Edward then describes grief as an “energetic form of cancer” that will, if not treated, “metastasize to other parts of your life.” This is actually not a bad analogy, but the devastating effect of grief doesn’t mean that one has to lie to the patient. Edward apparently disagrees, as he even assures us that speaking to a psychic medium can be very therapeutic if you’re suffering from grief due to the death of a loved one. Even if that were true, would it justify the lying and deceit inherent in claiming to “speak to the dead”?

After that, Dr. Oz comes back on and finishes the introduction by saying:

Now as a heart surgeon I have seen things about life and death that I just cannot explain and that science can’t study.

So, let’s see. Just because the great and powerful Dr. Oz can’t explain it, he assumes that talking to the dead must be real and that science can’t study it. It’s a massive argument from ignorance combined with special pleading, in which it is assumed that the methods of science are inadequate for studying the phenomenon of people like Edward who claim to be psychic mediums. Dr. Oz lives that attitude as well, as he shows not even the slightest whiff of skepticism, nor does he offer anything more than the most perfunctory of challenges to what Edward is doing. Actually, he doesn’t even do that. Other than a brief question near the beginning about whether people who have limited resources should spend money on a medium or use it to find a good counselor, there are no challenges. Throughout the entire segment, Dr. Oz’s tone is more than just respectful. It’s downright fawning and deferential.

Consistent with that, Oz doesn’t even include a “skeptic” in the audience as he has with previous woo-filled episodes. The closest he comes to it is having Katherine Nordal, PhD of the American Psychological Association, who not really introduced on the show but is described on the APA website as “the executive director for professional practice of the American Psychological Association.” Her job is described as overseeing “the promotion of the professional practice of psychology” and ensuring “psychological services’ accessibility and availability through legislative and judicial advocacy, public education and marketplace initiatives.” I’m not sure what purpose Nordal served because she didn’t really question whether Edward could speak to the dead, which makes her a pretty lousy candidate to play the role of token skeptic that is common on these shows. Then, when Dr. Oz asks her whether finding a medium might be a form of therapy, rather than stating unequivocally that it is not, or at least not a good form of therapy because it involves deceiving the patient in a major way and is thus unethical, she says that it can be a form of therapy, just answering the question in the title of the segment with in the affirmative and giving the imprimatur of the APA to psychic mediums. At the very best, Dr. Nordal was naive and credulous, which led her to be taken advantage of by the producers of the show; at the worst, her behavior was profoundly cynical. What she should have said is that, although some people might find imagining conversations with their deceased loved ones to be comforting, mediums are not professionals; most have no medical or psychological training; and there is no evidence that they can speak with the dead. Given these facts, it is far better to use the services of a qualified psychologist trained in grief counseling.

At this point, Edward goes into his routine. If you ever caught his television show back when it was still on the air, nothing Edward does in his segment on Dr. Oz will come as a surprise. It’s nothing more than the old psychic medium trick of cold reading. This time around, he was actually a lot better at it than I remember him. His “hits” were more common and his “misses” fewer than I remember from the handful of episodes of his old show. In fact, there was one part that turned out so conveniently that I have to wonder if Edward’s people had managed to stage it somehow. At one point, Edward insists that someone in the room has experienced the death of a loved one associated in some way with St. Patrick’s Day or occurring in March. Of course, in an group of people the size of Dr. Oz’s studio audience, the odds are quite high that at least one person there has a relative or friend who died in March within reasonable proximity to St. Patrick’s Day. After badgering the audience, finally a young woman says that a friend of a friend had died in a car crash on St. Patrick’s Day. Predictably, Dr. Oz was awestruck. In fact, if you want to know just how lacking in skepticism Dr. Oz is, just check out this TV Guide article released before the show in which Dr. Oz Says Psychic John Edward “Changed My Life”:

I walked out of that studio thinking, “There’s something here. It’s bizarre. I don’t know what exactly is happening. But it’s definitely something.” I’m a heart surgeon. I can explain a lot of weird things. I’ve seen people who should have died who didn’t. Over the years I’ve had some pretty deep conversations with people who died and say they saw “the light” and came back with stories. I’ve heard many things that are not easy to reconcile with the western scientific mind, so you try to think of a reason for what’s going on. Could it be synapses short-circuiting in the brain that make people think they’re having an out-of-body experience? That’s what a doctor does. He tries to find a rational explanation. But I can’t make up an explanation for what John Edward does. And, again, what was most eerie was his level of detail, the concreteness of it all.

Or, one could say that there are times when Dr. Oz’s knowledge isn’t equal with that of skeptics who actually pay attention to these things. Otherwise he wouldn’t be so amazed by Edward’s transparent schtick. But he is, and once again he uses the argument from incredulity. Worse, he uses his position as a physician to create a false argument from authority. Just because he can’t imagine a scientific explanation for what John Edward does, Oz assumes that there isn’t one, and most of his audience accepts his authority as a surgeon as being reason enough to accept his assertion that science can’t explain Edward:

But I can’t make up an explanation for what John Edward does. And, again, what was most eerie was his level of detail, the concreteness of it all.

Which is, of course, what psychic mediums do. It’s what they do and have done for hundreds of years, if not longer. It’s not for nothing that John Rennie characterized Oz as the “great and gullible.” Dr. Oz was gullible when it came to faith healing and quackery, and he surpasses himself in gullibility in his treatment of John Edward and psychic mediums. What they do and how they do it are not mysteries to, for example, James Randi or Joe Nickell, who quite properly described Edward as “hustling the bereaved.” Both describe how Edward uses the technique of cold reading, and Nickell even describes how Edward has been caught in the past using “hot reading,” or using information gleaned from his minions having chatted up the audience before the taping of his show and then presenting that information as having been received from the dead. When he can’t guess right, Edward’s technique is to do this:

What separates John from other cold readers, is that John works with a sizable audience (the Gallery) and when his readings go like the above, as happens far too often, he will just say that he’s picking up the “energies” of two different or distinct families which is suppose to explain away wrong guesses. Enough wrong guesses or if the guest isn’t cooperating, he will just claim the “energy” is pulling back and then move on to someone else he hopes this time will be more volunteering of information.

This is what Edward appeared ready to do with the “St. Patrick’s Day” connection; that is, until the young woman in the audience finally came forward. She later explained her delay in doing so to fear of standing up and being on the show, after which Edward praised her for being honest.

After watching a sad spectacle like this, that of a once respected surgeon debasing himself with faith healers and psychic mediums, I asked myself what could possibly be going on here. My first thought was that reiki must be a powerful gateway woo, leading to the really hard stuff, like faith healing and psychic mediums. After all, Dr. Oz’s wife is a reiki master, and he got his start in the CAM world by (in)famously allowing reiki masters into his operating room to work their magic (and I do mean the word “magic” literally) on his cardiac patients as he was operating. Ten or fifteen years on, that little incursion into woo seems very quaint.

In actuality, what’s going on here, I think, is more likely to be pure hubris. I submit to you that Dr. Oz has become so enamored with himself and his image as “America’s doctor” an the iconoclast who bucks the medical system, sees beyond “Western medicine,” and is just so much more damned smart than other doctors, that it likely never occurred to him that he could be fooled by a psychic scammer like John Edward just as easily as anyone else. Add to that his need to fill the insatiable maw of his daily TV show with new topics and new guests, coupled with the demands of his audience, who are clearly very much into this sort of thing, and it becomes easy for him to justify having a guest like John Edward as both evidence of his intelligence and open-mindedness and giving the people what they want.

Bread and circuses. That’s apparently what they want. I can only wonder what’s next for The Dr. Oz Show after this? I predict alien abductions. Or maybe the “conspiracy” to keep the One True Cure for Cancer from the people. One of those will be the next topic Dr. Oz tackles. Either that, or David Icke will be involved. It’s coming. I know it.

I often receive e-mail from SBM readers (or SGU listeners) who have had the experience of their doctor, nurse, dentist, physical therapist, or other health care provider recommending to them a treatment option that seems dubious, if not outright pseudoscientific. They want advice on what to do.  There are common themes to the e-mails – the writer often feels very uncomfortable in the situation. They do not feel comfortable confronting their provider directly, yet they do not want to acquiesce to the advice either. They are also often asking my opinion about the advice – is it really as wacky as it seems. This uncertainty saps them of their resolve, leaving them feeling a bit helpless.

Here is one such e-mail:

Ten days ago, my wife and I welcomed our first child into the world. She was born a couple weeks early, which left her mouth a bit too small and week to breastfeed effectively. To prevent her from losing too much weight, we were referred to a lactation consultant (who works out of the pediatrics department at the hospital where our daughter was born). This consultant (who is also an RN) suggested a regimen of supplementing nursing with pumped breast milk.

This was working great until my wife’s milk production dropped the day before our follow-up appointment. When we asked what to do about this, the nurse recommended that my wife take fenugreek, an herbal supplement. I was a bit skeptical of this advice, so I asked what it was about fenugreek that helped with milk production. The lactation nurse’s answer was vague — she said things like, Herbs can be helpful for lots of health issues, and, a lot of women I see seem to think it helps (oh, the logical fallacies). When we pushed her on this a little more, she handed us a flyer, printed by the hospital about fenugreek. The flyer seemed to support the use of the supplement, but mentioned that there was no scientific research demonstrating that fenugreek increases milk supply. When we asked why it hadn’t been researched, the nurse responded that there wasn’t a lot of money in lactation and that scientists generally aren’t interested in the kind of things she does (basically, that she was doing the good work that cold-hearted scientists refused to do).

She also mentioned that there was a prescription drug that boosts milk supply, but it carries with it the risk of a pretty serious side effect (depression), so she prefers her patients to try the supplement first. I asked how we could be sure the supplement didn’t also carry the risk of negative side effects if it hadn’t been studied, she simply said that it worked out fine for the patients she’s seen.

My wife and I decided to let it go for the time being and decide later whether or not to go the supplement route (it’s hard to argue with a nurse when you’re under-slept, one of you is topless, and the baby is screaming for food). Fortunately, her milk supply picked up a bit on its own, so we didn’t have to resort to using an untested therapy (yet).

First, let’s address the recommendation – fenugreek to increase breast milk production. Substances that increase milk production are called galactogogues. There are a number of drugs that have been shown to increase milk production, although the levels of evidence varies. For many there are only case series. Oxytocin is supported by double-blind placebo controlled trials, and is both safe and effective. Other commonly used drugs, like metoclopramide, are supported by unblinded case series only.

Fenugreek is a common spice and medicinal herb used in India. Among its putative effects is increased lactation, however, there are no clinical trials to support its use. Recommendations are based upon anecdotes only. This 2010 review article reports:

The side effects most commonly reported are a maple-like smell of the urine, breast milk, and perspiration, diarrhea, as well as the worsening of symptoms in individuals with asthma or hypoglycemia. The potential for transfer to milk or side effects in the infant are unknown. As is the case for most herbal products, the dose necessary to obtain a galactogogic effect has not been defined. Only one study on the effect of fenugreek on lactation has been reported. Swafford asked 10 mothers to maintain a diary of the quantity of milk produced with a pump for a period of two weeks. In the first week, baseline milk production was evaluated; in the second week, mothers took fenugreek, 3 cups, three times daily. In the first week average quantities were 207 ml/day, whereas, milk production in the second week averaged 464 ml/day (p = 0.004). Unfortunately, the report excluded any information regarding the characteristics of the mothers enrolled in the study or the postpartum period during which the study was done. Nevertheless, the daily milk quantities reported during treatment do not seem to be particularly high (reference: Swafford S, Berens P. Effect of fenugreek on breast milk production. Abstract 5th International Meeting of the Academy of Breastfeeding Medicine September 11-13, 2000, Tucson, Ariz Academy of Breastfeeding Medicine News and Views 2000;6(3).)

So – there are side effects, even potentially serious side effects like exacerbating asthma and hypoglycemia. The dosing is unknown, and the one small efficacy study that was done was unimpressive.

There is nothing implausible about the claim that an herb can be an effective galactogogue – herbs can be drugs with pharmacological activity. What is disturbing about the nurse’s recommendation is the double standard. She seems to believe that herbs are inherently safer than drugs, which is a false dichotomy based on the naturalistic fallacy, but not logic or evidence. She essentially recommended an untested drug with uncertain dosing, side effect, or efficacy over drugs with better evidence for both safety and efficacy.

It should also be noted that the e-mailer’s mild production spontaneously increased after the consultation. If she had taken fenugreek, that would have been one more anecdotal report apparently supporting its efficacy.

But onto the real question of the e-mail – how to respond in this situation. My advice is to first not be intimidated. Feel free to express your concerns or uncertainty about the recommendations being made. I commend this e-mailer for asking for published evidence, but don’t take an evasive answer as adequate. Ask for published evidence or authoritative reviews. If they do not have any handy, they can certainly prepare this material for the next visit or simply e-mail it to you.

If you feel up to the task, you can research the question yourself and then ask your health care provider to comment on the material you find (but don’t overwhelm them with mounds of material).

Depending on how egregious the pseudoscientific advice was, you should also consider simply leaving that provider for someone with whom you feel more comfortable and confident. I do recommend, whether or not you stay with the provider, to give them feedback. Express your exact concerns about their advice. How they respond will also tell you a great deal about their approach and dedication to evidence-based practice.

In short, I think patients should feel empowered to push back against practitioners who stray from science and reason as a basis for health care recommendations and practice. Those pushing for anti-science in medicine are certainly vocal, and their agenda will advance if others simply do nothing. In fact – if a practitioner recommended an outright anti-scientific treatment (like homeopathy, say) I would go beyond giving them individual feedback. I would write to the head of their clinic, hospital, or department and express your concerns. You are a consumer as well as a patient, and administrators listen to their consumers.

The above situation is becoming distressingly common, and it is not easy to deal with. It is one more type of harm that is caused by the infiltration of anti-science into medicine. I had a similar experience myself. My wife and I were referred to a practitioner to address a problem with one of our children (I am being deliberately vague on details). At the first visit the practitioner made a comment (as an aside, not directly related to the visit) about vaccines and autism. I, of course, politely challenged her on that statement, and she backpeddled – I think just to end the confrontation. My wife thought that I was inappropriate to challenge her – she was concerned about my accepting the role as patient rather than physician.

At the next visit, however – the visit when the practitioner was giving us her actual recommendations, my wife had a change of heart. The practitioner’s recommendations were entirely limited to “natural” interventions like diet and herbs, and she shied away from any medications. Her recommendations were ideology-based, not evidence-based, and in the end the consultation was entirely useless. My concerns at the first visit – that perhaps this practitioner does not have a firm grasp on the concepts of science-based medicine, were entirely vindicated.

This is an important point – if a practitioner recommends something that is blatantly against the science and evidence, how can you have confidence in any of their recommendations? I am not talking about not being up on one bit of latest evidence – no one can know everything. A serious lapse, however, can reveal a systematic bias in a practitioner’s approach to evidence and practice.

Unfortunately, patients cannot take for granted that a licensed professional is necessarily science-based.

Lest some of our readers imagine that the authors of this blog are mere armchair opinion-spouters and keyboard-tappers for one little blog, I’d like to point out some of the other things we do to spread the word about science and reason. Steven Novella’s new course about medical myths for “The Great Courses” of The Teaching Company is a prime example: more about that later.

First, some examples of the kinds of things we have been doing:

• Personal blogs.
• Podcasts, both as hosts and as interviewees.
• Magazine articles and columns.
• Teaching doctors and laymen in medical schools, hospitals, and workshops.
• Radio show interviews.
• Public speaking: informal talks to local groups and formal presentations at regional conferences, national conferences, even international conferences.
• Guest columns and letters to the editor in newspapers.
• Interviews by journalists who quote us in the media.
• Founding fellows and board members of the new Institute for Science in Medicine.
• Invited to write commentary to accompany published articles in major journals.
• Peer reviewing journal articles prior to acceptance for publication.
• Special Science-Based Medicine conference, workshops and panels at the annual Amaz!ng Meetings of the James Randi Educational Foundation (JREF) (more to come at TAM 9  July 14-17, 2011 in Las Vegas).
• Participation in online forums and discussion lists.
• Books: articles included in anthologies and even used as a chapter in a book.
• Links, reprints and translations of our articles have spread around the world (one of mine was even translated into Turkish!).
• Working with lawyers as medical experts on lawsuits about bogus health products and false claims.
• Co-authoring a new edition of a textbook.
• Advising organizations that deal with health information.
• Answering personal inquiries.
• Haranguing our friends and families.

I have done almost everything on this list myself (the only exceptions are that I don’t have a personal blog or host a podcast, although I have appeared on several). My colleagues have done a lot more that I haven’t heard about: if all their accomplishments were included, the list would undoubtedly be much longer. I am retired and at leisure; but my colleagues manage to practice medicine, do research, teach, constantly scour the Internet and the medical literature, raise young children, and still get so much else done that I find it hard to believe they ever sleep (particularly supermen Steven Novella and David Gorski). And contrary to the imaginative accusations of some of our detractors, none of us are in this for profit: most of our efforts to spread the word about science-based medicine are pro bono, without any pay. When we do get paid, it’s usually a pittance, often in the form of a small honorarium or reimbursement of travel expenses for a talk. If a Big Pharma teat exists, we certainly haven’t managed to latch onto it.

Steven Novella is our founding editor and has arguably done more to support science and reason than any of us. His latest triumph is one of the “Great Courses” for The Teaching Company entitled “Medical Myths, Lies, and Half-Truths: What We Think We Know May Be Hurting Us.” It consists of 24 half-hour lectures that cover:

1. Medical Knowledge versus Misinformation
2. Myths about Water and Hydration
3. Vitamin and Nutrition Myths
4. Dieting—Separating Myths from Facts
5. The  Fallacy That Natural Is Always Better
6. Probiotics and Our Bacterial Friends
7. Sugar and Hyperactivity
8. Antioxidants—Hype versus Reality
9. The Common Cold
10. Vaccination Benefits—How Well Vaccines Work
11. Vaccination Risks—Real and Imagined
12. Antibiotics, Germs, and Hygiene
13. Vague Symptoms and Fuzzy Diagnoses
14. Herbalism and Herbal Medicines
15. Homeopathy—One Giant Myth
16. Facts about Toxins and Myths about Detox
17. Myths about Acupuncture’s Past and Benefits
18. Myths about Magnets, Microwaves,  Cell Phones
19. All about Hypnosis
20. Myths about Coma and Consciousness
21. What Placebos Can and Cannot Do
22. Myths about Pregnancy
23. Medical Myths from around the World
24. Roundup—Decluttering Our Mental Closet.

The concept and presentation are pure genius. The “myth” format will attract people who might not want to listen to something labeled “Science-based Medicine” or “Alternative Medicine.” He manages to cover almost all the topics we discuss on this blog, and he does it in a way that is palatable, easy to understand, and non-offensive. He is not dogmatic about anything: he points out areas of uncertainty and even tells students not to treat him as a definitive authority, but to think for themselves. He comes across as serious, professorial, fair, balanced, calm, cool, collected, organized, thoughtful, and very credible.

The course is available at a sale price of $69.95 on DVD, $49.95 on audio CD, or $34.95 for audio download. It comes with a booklet that provides a 2 to 4 page summary of the information in each lecture, each with suggested reading and questions to consider; and a glossary and bibliography. The introduction includes a whole paragraph about the Science-Based Medicine blog, and he cites several SBM articles in the bibliography section.

Dr. Novella deserves a lot of credit for creating this course. It is a worthwhile source of medical information and teaches critical thinking about science. It will reach a lot of people that we wouldn’t be able to reach otherwise. Thank you, Steven!

We may not be as sexy or popular as the purveyors of medical misinformation, but I think we are making a dent. At least we are getting reliable information about SBM out there where people can find it.  And I know our readers and commenters have done a thing or two themselves to help spread the word. I’d like to hear more about their activities and their accomplishments.

Sometimes standing up for science-based medicine can feel like a losing battle. Achievements like Dr. Novella’s course make me pause from weeping about our bêtes noires and break out a smile. Quality efforts like his do much to spread the word. They encourage my optimism that science will prevail in the long run. We may have to keep running constantly just to stay in one place, but it’s well worth the effort. The consequences of letting pseudoscience and woo-woo overtake us are unthinkable.

I graduated from the University of Michigan Medical School in the late 1980s. If there’s one thing I remember about the four years I was there, it’s that U. of M. was really hardcore about science back then. In fact, one of the things I remember is that U. of M. was viewed as being rather old-fashioned. No new (at the time) organ system approach for us! Every four weeks, like clockwork, we’d have what was called a concurrent examination, which basically meant that we were tested (with multiple choice tests, of course) on every subject on the same morning. The medical curriculum for the first two years had been fairly constant for quite some time, with a heaping helpin’ of anatomy, histology, biochemistry, and physiology in the first year and the second year packed full of pharmacology, pathology, and neurosciences. Nowhere to be found was anything resembling “energy medicine” or anything that wasn’t science-based!

Of course, back in the 1980s, the infiltration of quackademic medicine into medical schools and academic medical centers hadn’t really begun in earnest yet, although the rumblings of what is now called “complementary and alternative medicine” (CAM) and, more frequently these days, “integrative medicine” (IM) were starting to be heard in East Coast and West Coast schools. Even there, though, the incipient CAM movement was viewed as fringe, not worthy of the attention of serious academic physicians. Indeed, in the late 1980s, even at what are now havens of quackademic medicine if someone had suggested that diluting substances until there is nothing left, as in homeopathy, or waving your hands over a patient in order to channel the “universal source” of energy into a patient in order to heal a patient, as in reiki, had any place in scientific medicine, he’d have been laughed out of medical school–and rightly so.

Not so today, unfortunately. Although the problem of infiltration of quackademic medicine into academic medical centers goes way beyond this example, I can point out that faith healing based on Eastern mystical beliefs instead of Christianity is alive and well and ensconced in academic medical centers such as the University of Maryland School of Medicine Center for Integrative Medicine, where reiki masters are roaming the halls of the University of Maryland R. Adam Cowley Shock Trauma Center and Bonnie Tarantino, a Melchizedek practitioner, holographic sound healer, and an Usui and Karuna Reiki Master holds sway. Meanwhile, all manner of woo, such as acupuncture, homeopathy, craniosacral therapy, reiki, and reflexology are offered. Truly, you know that when an academic medical center has gone so far as to offer homeopathy, reflexology, and reiki, it’s all over as far as academic credibility is concerned, and it has become a center of quackademic medicine. Sadly, even a hospital where I trained, MetroHealth Medical Center, has succumbed to the temptation to add the quackery that is reiki to its armamentarium. That aside, I had never expected that my old, hardcore University of Michigan would go woo in such a big way.

I was wrong.

Over the last decade, the University of Michigan Medical School has gotten into alternative medicine, adding IM to its curriculum and even having a fellowship in IM. At the time I first learned of this a few years ago, as disturbed as I was, I reassured myself that at least U. of M. seemed to be sticking to the milder woo, like acupuncture and massage. Then, while browsing the blogs last month, I came across reports by P.Z. Myers and Tufted Titmouse, both of which contained a link to the University of Michigan Integrative Medicine (UMIM) resource page. And what to my wondering eyes did appear? (Actually, I should rephrase that as, “What to my despairing eyes should appear?”) The answer: Anthroposophic Medicine. Yes, it’s anthroposophy, Rudolf Steiner’s mystical, magical system that is the bottom of a lot of quackery and anti-vaccine beliefs. Indeed, outbreaks of vaccine-preventable disease have been distressingly common at Waldorf schools, where the educational philosophy is based on the teachings of Rudolf Steiner, which is why they are sometimes called Steiner schools or Steiner-Waldorf schools. Although the European Council for Steiner-Waldorf Education, which represents approximately 700 of the 1000 Waldorf schools world wide, has stated unequivocally that opposition to immunization forms no part of the goals of Waldorf education, Waldorf schools are magnets for parents opposed to vaccination. One example occurred in California in 2008, when there was a measles outbreak at the East Bay Waldorf School in El Sobrante. Given that the UMIM program, although interdisciplinary, boasts heavy involvement of family medicine faculty, I can’t imagine the cognitive dissonance that must be going on. After all, many family medicine doctors also take care of children and are responsible for making sure they are properly immunized just as much as any pediatrician.

But let’s look at what UMIM’s webpage on anthroposophy says about it:

Anthroposophic medicine views health as a matter of mind-body-spirit balance. It is centered on the idea that humans are not independent organisms but, instead, beings composed of the interactions of physical body, inner life body, soul (mind and emotions), and spiritual ego (self-awareness). Whereas conventional medicine focuses on “fixing” the part of the physical body that is “broken,” anthroposophic medicine prescribes treatment for the whole being through conventional methods in combination with holistic methods. As such, anthroposophic medicine integrates theories and practices of modern medicine with alternative, nature-based treatments and a spiritual-scientific understanding of the human being. The practice is based on Austrian philosopher Rudolf Steiner’s concept of anthroposophy, a scientific and philosophical world view that connects the spiritual within the human being to the spiritual in nature, the world and the cosmos.

This is consistent with what the Holistic Health Internet Community says about anthroposophic medicine:

Austrian scientist and philosopher Rudolf Steiner (1861-1925) refused to accept the contemporary scientific view of the body as a purely physical entity. From that conviction was born the doctrine of anthroposophy, a word he coined from the Greek words for “man” and “divine wisdom.” Steiner believed in the uniqueness of each human being, and contended that health and well-being deteriorated without that belief. Trained as a scientist and a mathematician, he was influenced by Hindu and Buddhist beliefs and founded a school in which his theories became practice.

Anthroposophical medicine determines the nature of illness based on Steiner’s principal of polarity. His system attempts to link and harmonize both the upper and lower poles of the body. Good health then depends on a harmonious relationship between the physical, etheric and astral bodies, and the ego. Practitioners are trained as medical doctors and may treat childhood infections, hay fever and asthma, anxiety, depression, cancer, musculoskeletal problems and fatigue.

If twenty years ago someone had told me that one day that not only would my medical alma mater be publishing dreck like this, but that it would have formed an interdisciplinary program devoted to it, I would have told that person he was delusional. If you had told me that anthroposophy would be part of a larger program of woo run by a physician who is described as having “studied herbalism and spiritual healing for 14 years with a Native American Healer” and as having research interests that include the “use of herbs, energy healing, environmental healing, and the therapeutic relationship” or that a physician trained in “functional medicine” would be a big part of a program in anthroposophic medicine there, I wouldn’t have believed it. All I can wonder is what Bill Kelley, the infamously hardcore scientific chair of the Department of Internal Medicine while I was at Michigan, would think or say if he were still at U. of M. In fact, having read the section on anthroposophy on U. of M.’s website, I wish I were delusional. But I’m not. The section is real, and the medical school from which I graduated has not only started to tolerate such nonsense, but begun to embrace it.

Anthroposophical medicine, it turns out, is rooted in prescientific vitalism. Rudolf Steiner, before he came up with the idea of anthroposophy, had led the German section of Theosophy. When he became enamored of his spiritual concept of anthroposophy, Steiner in essence caused a schism. Anthroposophy, it further turns out, is far more a religious and spiritual philosophy than a scientific or medical one. Based on his philosophy, Steiner created Waldorf schools, anthroposophic medicine, and biodynamic farming, the last of which would be a suitable topic for an amusing post on a non-medical blog. Suffice to say that some of the practices of biodynamic farming involve stuffing Yarrow blossoms (Achillea millefolium) into urinary bladders from Cervus elaphus, Red Deers, placing them in the sun during summer, burying them in earth during winter and retrieving them in the spring, all to strengthen the “life force” of the farm. There’s also a lot of use of cow horns, based on Steiner’s rationale, “The cow has horns in order to reflect inwards the astral and etheric formative forces, which then penetrate right into the metabolic system so that increased activity in the digestive organism arises by reason of this radiation from horns and hoofs.” Moreover, many of the concepts of homeopathy are combined with Steiner’s woo, such that many of the concoctions of biodynamic farming, which consist of various bits of dead animals plus or minus ground quartz crystals, are diluted into many tons of compost, to be spread over acres of farmland.

But let’s get back to anthroposophic medicine, which is based on the same sort of mystical philosophy that biodynamic farming is. Simon Singh and Edzard Ernst characterize this form of medicine thusly in their book Trick or Treatment?:

Applying his philosophical concepts to health, he [Rudolf Steiner] founded, together with Dr. Ita Wegman, an entirely new school of medicine. It assumes metaphysical relations between planets, metals, and human organs, which provide the basis for therapeutic strategies. Diseases are believed to be related to actions in previous lives; in order to redeem oneself, it may be best to live through them without conventional therapy. Instead, a range of other therapeutic modalities is employed in anthroposophic medicine: herbal extracts, art therapy, massage, exercise therapy, and other unconventional approaches.

Perhaps the most common example of anthroposophic medicine is the use of mistletoe extracts for the treatment of cancer. Perhaps you’ve heard of Iscador? While Iscador might actually have some activity against, for example, breast cancer, it is not without toxicity, and the evidence for its efficacy in cancer is at best conflicting. Even if Iscador turned out to be an effective treatment for breast cancer, it would be an example of being right for a reason that is spectacularly wrong. That’s because Steiner argued that mistletoe is a parasitic plant that eventually kills its host. To him, this represented a striking parallel to malignant tumors, which, like mistletoe, are parasitic entities that eventually kill their hosts. Steiner’s conclusion? Because of this resemblance, mistletoe must be an effective treatment for cancer. Readers knowledgeable about homeopathy will immediately recognize that Steiner clearly must have believed in the homeopathic principle of “like cures like.” In fact, he even went beyond that to generalize that “a plant is a healing plant when it has a distortion or an abnormality in its physiology and morphology,” presumably related to human disease. Indeed, according to Dr. Peter Hindenberger this represents a “modern, scientific reformulation of what, in former times, existed in the ‘doctrine of signatures‘”; i.e., the belief that God has marked everything he created with a sign (signature) that is an indication of the purpose for which the item was created.

Although you can read more about anthroposophic medicine, either at a Steiner website or the Physician’s Association for Anthroposophic Medicine (to get it right from the horse’s mouth, so to speak) or over at The Skeptic’s Dictionary and Quackwatch, including a description of what being a student at a Waldorf school is like, because this is about UMIM’s apparent embrace of anthroposophical medicine, I think that I will close by discussing what UMIM says about it. But, before I do so, let me quote a passage from what PAAM says about it in a PDF booklet. After all, U. of M. includes a link to PAAM on its website, which leads me to assume that the UMIM program in anthroposophic medicine endorses PAAM. So does the fact that PAAM is based in Ann Arbor. But back to the PAAM pamphlet:

Medicine based purely on material science is limited to explaining an illness solely on the basis of the laws of physics and chemistry.

I’m sorry. I can’t help but interject here that PAAM says this as though it were a bad thing. Personally, though, I’m curious as to how we can explain illness not based on the laws of physics and chemistry. Unfortunately, PAAM is more than happy to tell us how anthroposophic medicine is “more ambitious” than us mere practitioners and proponents of science-based medicine. I suppose it is, casting off, as it does, all those inconvenient laws of physics and chemistry that took hundreds of years to discover and understand:

Anthroposophic medicine is more ambitious. It takes into account additional factors, both general and individual, that may affect the patient’s life, mind, and soul, and their physical manifestation: in growth, regeneration, microcirculation, fluid retention in the skin, muscle tone, biorhythms, head distribution, posture, uprightness, gait, mental focus, speech. When illness occurs, examination of the above may reveal deviations, imbalances, and extremes–additional diagnostic parameters that need to be considered when selecting a therapy. Anthroposophic medicine also has a different understanding of the role played by the patient in overcoming illness. The patient is not simply a passive recipient of medical skill, but an equal partner with the doctor. After all, nobody can know the patient better than the patient. During an illness, the patient has the opportunity to recognise the state of imbalance body and soul have reached, to understand this and rectify it. The illness can provide an opportunity to learn new modes of behaviour, to develop further insights, and acquire greater maturity.

And, yes, anthroposophic medicine embraces homeopathy:

In addition, other substances tailored to the patient’s unique characteristics are administered. These are frequently homeopathic substances designed to stimulate the organism and its powers of self-healing.

Science-based medicine, anthroposophy clearly is not. Of course, that’s quite obvious from what UMIM itself says about the anthroposophic view of health. According to UMIM, this consists of these tenets, with my comments in brackets after each item:

• Health involves a dynamic balance and high functioning of all aspects of a person’s life. [This is so vague as to be meaningless and all but impossible to argue with, but it's the sort of trope common in alt-med circles.]
• Illness is the result of disharmony and imbalance amongst the three systems of the body and their related forces and effects. [This sounds very much like attributing disease to imbalances in the four humors. Teach the controversy! about the Four-fold Man!]
• Illness is a tragedy, but also an opportunity for learning and transformation. [This sounds very much like the quackery that is the German New Medicine and Biologie Totale to me; that is, if you strip away Steiner's belief in reincarnation wherein illness isn't the working through of unrecognized emotional traumas in this life (as German New Medicine teaches) but is rather the working through of issues from previous lives.]
• The signs and symptoms of an illness are often the body’s attempts at healing and, in general, should not be suppressed, but rather, aided, observed and resolved. [More German New Medicine- and Biologie Totale-like gobbledygook. Again, odd how U. of M. leaves out Steiner's belief that these body's attempts at healing are related to past life experiences.]
• Many illnesses, especially benign ones, should not be artificially prevented, but should be allowed to occur and be treated and healed. The patient thereby gains strength and experience, both biologically and spiritually. [This would appear to be the basis for so many anti-vaccine beliefs that permeate every aspect of anthroposophic medicine and the education taught in Waldorf schools. After all, what is vaccination, but preventing illness? I guess your kids get so much stronger, spiritually and biologically, if you just let them, take their chances with measles, mumps, whooping cough, and Haemophilus influenzae type B. Because, you know, that worked out so well for children in terms of childhood mortality back in the days before vaccines could prevent these diseases. Oh, wait. No it didn't.]
• True prevention of illnesses involves a healthy lifestyle with positive habits, strengthening the biological, psychological and spiritual aspects of a person, and avoiding the detrimental and illness-producing effects of much of modern civilization. [Do I detect a reference to "toxins" here? I think I do.]

UMIM even goes on to link to a company that produces skin care products and medicines based on Steiner’s biodynamic farming (including Iscador and homeopathic remedies), as well as to point out that many anthroposophical remedies can only be administered as an inpatient at a facility like the Rudolf Steiner Health Center in Ann Arbor, Michigan. There, you can find a video about anthroposophic medicine:

Check out the part around 24:25, where a chemist describes how anthroposophic medicines are made, including the part about how he “potentizes” many of them in decimal fractions, just as homeopaths do with their remedies. His goal is, as he puts it, to “strengthen the vital forces within the living organism while at the same time respecting its natural rhythm.” He also heads out to the French border at 4 AM during the summer so that he can harvest Arnica plants at dawn, thus allowing the “morning strength” to be maintained in them. I kid you not. Then, get a load of this description of anthroposophic medicines, right off the U. of M. website:

Many anthroposophic remedies are specially prepared using homeopathic or modern alchemical pharmaceutical processes to naturally stimulate healing processes in the ill person.

Yes, it would appear that alchemy is alive and well at U. of M.!

Fortunately, the Rudolf Steiner Health Center does not appear to be affiliated with the University of Michigan, at least as far as I can tell. Unfortunately, it’s still very disturbing that UMIM would recommend such an institution and even more disturbing that “anthroposophic physicians at the University of Michigan” appear to be partnering with the Rudolf Steiner Health Center to research anthroposophic medicine as supportive care for cancer patients.

Personally, I think that Robert Carroll gets it exactly right when he characterizes anthroposophic medicine as being “even more out of touch with modern, science-based medicine than homeopathy.” Think about it. Homeopathy is based on just two magical ideas: The Law of Similars and the Law of Infinitesimals, which together can be viewed as an expression of the ancient principles of sympathetic magic. In marked contrast, anthroposophic medicine is based on many ideas with no basis in science that can best be described as pure magical thinking. Indeed, to me at least, anthroposophic medicine resembles more than anything else naturopathy in that there doesn’t appear to be a form of unscientific, prescientific, vitalism-based woo that it doesn’t embrace. In fact, anthroposophic medicine appears to go far beyond naturopathy in that respect. It also brings into play a veritable cornucopia of mystical concepts, including the etheric body, the astral body, and the ego. It postulates that the soul, the senses, and the consciousness are beings that have an independent existence outside of the body and further asserts that herbs, essential oils, and movement therapy known as eurythmy can bring these things into harmony and balance with each other and the physical body. Reading about anthroposophy and anthroposophic medicine, I had some serious acid flashbacks to my youth, when I used to be an avid Dungeons & Dragons player. My personal oddities during my high school and college years aside, anthroposophic medicine openly denigrates science-based medicine for only being able to diagnose and treat disease according to its understanding of the laws of physics and chemistry, to which I respond: Upon what else would a physician base his understanding of disease? As Carroll put it:

Steiner approached medicine the same way he approached everything else from astrology to Atlantis to education to farming to metaphysics: He dictated his visions. Why anyone considers him a scientist is a great mystery. His notion of science as involving the explanation of how immaterial entities affect material entities is the very opposite of science.

Indeed, and the medical school from which I graduated over 20 years ago now has a program dedicated to teaching physicians and medical students as fact the medical philosophy of this very man, whose philosophy is not only far more religion and mysticism than science but is indeed antiscience at its very core despite its superficial declaration of allegiance to science. Indeed anthroposophic medicine’s assertion of relationships between the various bodies (physical, etheric, etc.) and astronomical bodies is far more akin to astrology than science. Would that it were only homeopathy U. of M. were teaching and practicing!

I used to be very proud to have graduated from the University of Michigan Medical School. When I was there, it was one of the top public medical schools in the country and compared quite well with any private medical school in the U.S. you could name. In many ways, it still does. Unfortunately, like those other top medical schools, including Harvard, Yale, Stanford, and Columbia, U. of M. appears to have embraced quackademic medicine. I only wish it had, instead of imitating such schools, resisted the siren call of unscientific, prescientific, and pseudoscientific medicine. Unfortunately, as its embrace of anthroposophy demonstrates, it has not. As a result, the pride I have as a U. of M. alumnus is now tarnished with the knowledge that, even though the vast majority of what happens at the medical school and its affiliated hospitals is still solidly science-based and U. of M. boasts some of the best medical research programs anywhere, there now exists section within it that teaches pseudoscientific nonsense as if it were science. It makes me very sad and depressed to contemplate.

No doubt the U. of M. faculty and leadership responsible for this travesty will say that they pick and choose only the bits from anthroposophic medicine that are evidence-based and ignore all the woo. Quite frankly, to me anthroposophic medicine is pretty much all woo as far as I can tell. Or perhaps they would argue that the anthroposophic medicine program is a tiny part of a vast enterprise of science-based medicine. This is almost certainly true. It’s also probably true that relatively few U. of M. faculty even know about the existence of a Steiner-inspired program at their school. To me, however, there is zero place for such religious- and mysticism-inspired nonsense in any reputable medical school, other than as a footnote in courses in the history of medicine. Certainly there is no place for it being taught or practiced as though it had any validity whatsoever anywhere near medical students, residents, or fellows–and especially nowhere near patients.

Finally, knowing that U. of M. is teaching and practicing anthroposophic medicine makes me very irritated whenever I get mail soliciting donations for its medical school. From here on out, I think that, whenever a U. of M. Medical School solicitation arrives in the mail, I’ll send it back with a link to this post as the reason why I must decline.

There is germaphobia, the fear of germs. Or Germans.  One of the two. Oddly, I do not fear most germs, despite my daily reminders as to how destructive these wee beasties can be.   I recognize their limits and my immunologic strengths and know I have more to fear from cars or unsaturated fats than E. coli or influenza.

There is also a fear of vaccines, the too many too soon that is said to be at the heart, or maybe the left atrial appendage, of one of the imaginary problems with vaccines.  There are, by my counting, 5 live attenuated viruses and 21 different antigens in the vaccine schedule by age 6, for a total of 26 or twice thirteen.  Some fear those antigens and viruses, making it a  triskaidekaphobia times two (1).

From my perspective the paltry quantity of antigens children receive with the vaccine schedule are, when compared to the enormity of antigens in the environment, a rounding error.  We are awash in bacteria, fungi, viruses and an enormous number of environmental organisms.  I think of each of us like Pig-Pen, but instead of dirt, we are in a cloud of micro-organisms.

Our immune systems, contrary to the opinions of the unimaginative who direct scorn and derision at Dr. Offit, can cope.  As discussed, we have a ability to stave off the phenomenal number of organisms that would just as soon use us as the ultimate supersized meal.  Of course, it is not all the immune system that keeps the wee beasties away.  Being warmer than ambient temperature helps.  Understanding disease epidemiology, hygiene and the prn malum q 24 h also keeps the doctor away.Hygiene is an interesting two edged sword, and the rule in medicine is that no good deed goes unpunished. We are cleaner, at least in the urban industrialized wWest, than  most people through most of history.  Exposure to a large assortment of environmental filth and germs, with the exception of my 13 year old’s bedroom, is rare.  Cleanliness has helped to decrease the spread of contagion both in the community and in the hospital, at least for those who believe in good hand hygiene (2) and sterile technique.

However, lack of exposure to the background microbiology has had a potentially interesting downside.  Several epidemiologic studies have demonstrated an association between, to put it crudely, increased cleanliness and an increase in asthma and atopy (3).   The NEJM had a recent article with a similar result,  Exposure to Environmental Microorganisms and Childhood Asthma. From my perspective, this link between cleanliness and allergic disease  is interesting, but not what I want to focus on.  An interesting suggestion of this study is that, while you cannot boost the immune system, evidently the immune system needs a good microbial work out as it develops to ensure proper functioning as an adult.  Not only is the infants immune system able to process and react to a mind boggling number of antigens, apparently it needs to be exposed to these antigens in childhood for optimal function.  The motto ‘Use it or lose it’ applies to B cells as well as biceps.

In the NEJM study they surveyed the bedding and dust for microorganisms in the environment of children who live on farms and those that live in an urban environment.  They did both microbiology counts and molecular methods to evaluate the number of organisms in the environment.

Kids on farms live in a haze of bacteria and fungi at levels far higher than their urban counterparts and to their benefit. Organisms isolated included

“Listeria monocytogenes, Bacillus licheniformis and other bacillus species, corynebacterium species, methylobacterium species, xanthomonas species, enterobacter species, pantoea species, and others. …Staphylococcus sciuri and other staphylococcus species, salinicoccus species, macrococcus species, bacillus species, jeotgalicocus species, and others. …eurotium and penicillium species”

I no longer feel  as bad about the time my son was playing in the dirt, flipped a rock over and, before I could react, ate the slug he found underneath.  He was just exercising his young immune system. The NEJM study only evaluated the microbiology of the inside environment; there was no measurement of the larger outside environmental community.  I would imagine the number of organisms outside the home dwarfed what they could find inside.

As the accompanying editorial notes

“… that newborns begin to be colonized by microbes at birth, coincident with a period of rapid development of the immune system and lungs. These symbiotic organisms can be beneficial (e.g., gut bacteria that synthesize vitamin K) or pathogenic, or they may have no effect on the host (commensals). The authors propose that microbes found on farms adeptly stimulate innate immune receptors in early life and thereby favor the generation of regulatory T cells that promote immunologic tolerance.”

and the results are limited by

” microbial diagnostics provid(ing) only a low-resolution picture of microbial identity and diversity.”

There are far more wee beasties in and on us that we can currently identify. Farms, I would wager, are filled with far fewer bacteria than the environment in which pre-industrialized humans evolved.  Too many too soon runs counter, as does much of what is understood by antivaxers, to reality. When you are young, you can’t get enough.  The early immune system is the Johnny Rocco of the body (4).

The world is a crowded place at the level of the microorganism and we have evolved to respond to that crowding from birth.  Not just respond, but we need to be exposed to these antigens.

“Nothing is unnatural – just untried.” ~Rita Mae Brown

It may be argued that vaccines are not natural, whatever natural is.  I am the result of natural selection, so is not everything I do natural?  Infection with a needle is not how bacteria, fungi and virus get into the body.  I suppose this is a group of people who never had a percutaneous injury with a splinter or a cut from a thorn or a child who did not skin their knee on the dirt.  Percutaneous inoculation is a common way to be exposed to environmental antigens, just not as safe a way when sterile technique is avoided.

One would wonder if vaccines, in our ever so clean modern environment, could not only protect against the plagues of the past, but be a surrogate for our former environmental exposure to microbial squalor?

“adolescents having been vaccinated (n = 694) had a significant lower risk to suffer from asthma or atopic diseases than non-vaccinated adolescents did (n = 24) [odds ratio (OR) = 0.30; 95% CI: 0.10, 0.92]. The relationship did not depend on the disease against which the vaccine was used as prophylaxis, the observance of the vaccination schedule or the number of inoculations. A higher protection was observed in the case of live attenuated vaccines (oral poliomyelitis and bacilli Camille-Guerin; OR = 0.26; 95% CI: 0.08, 0.83). These results, in agreement with previous ecological data, support the hypothesis that early vaccines could promote Th1 proliferation in response to the infectious agent contained in it, which inhibits the enhancement of atopic manifestations. Further studies are needed to confirm the phenomenon.”

None of the above is  rock solid information when applied to vaccines, but an intriguing curiosity and, perhaps, hints about into disease etiology, but interesting when considering the potential responses of children to vaccines.  Too many too soon?  Doubt it.  Just enough, just in time?  Maybe.  Consider that receipt of MMR on schedule has been associated with decrease in autism.  I, of course, do not know what causes autism.  I had thought that the MMR results could be explained by lack of protection to neurotropic virus in the unvaccinated, but now I wonder.  There are articles on autoimmunty as a factor in autism, way beyond my current knowledge base . I will defer to others on the validity of these studies, I note them with interest but no deep understanding.

I think all human disease has, at its core, an association with infections. Most of the microbial studies on autism have concerned the use of antibiotics to treat the disease.  Autism rates have increased along with the expanded vaccine schedule, increasing cleanliness, global warming and the decline in pirates. The Amish do not get autism and they don’t live in a (relatively) sterile urban environments, and use a horse and buggy for transportation.    There must be a association in there somewhere that is actually causal. I know, probably not, but play along at home.

Let us  speculate: It would be ironic if  someday it was determined that part of the etiology of autism is, like asthma,  partly due to our microbial free environment and subsequent immune dysregulation and that vaccines, by supplying a surrogate immune stimulation, are protective.  Those who fought vaccines as a cause of autism turn out to be partly responsible for autism’s spread.  Truly worthy of  Medical Hypothesis, I admit, but it is amusing to speculate.  Someday science will sort it out.

It is fun to think about possible ramifications of the current literature.  I would certainly not use the speculation as a basis for my practice or to develop a therapeutic or preventative intervention with an exclamation mark. Hmm.  Or should I? I need to patent  a neonatal and infant probiotic  autism prevention supplement (NIPAPS!) containing the correct proportion of live and killed naturally occurring environmental bacteria and fungi.   There is a fortune to be made if I can just get rid of my ethics and morals.

Rationalization.

(1)  Not certain what ancient Greek for ’26′ would be.

(2)  Stay away from the Atlanta VA ICU. http://www.medscape.com/viewarticle/737884

(3)  Sorry.  Just epidemiology.  No gold standard, randomized, placebo controlled, blind trials utilizing the hypothetical/deductive technique, so ignore everything that follows. I am a snot.

(4) Johnny Rocco: Well, I want uh …
Frank McCloud: He wants more antigens, don’t you, Rocco?
Johnny Rocco: Yeah. That’s it. More. That’s right! I want more antigens!
James Temple: Will you ever get enough?
Frank McCloud: Will you, Rocco?
Johnny Rocco: Well, I never have. No, I guess I won’t.
~ Key Largo

During my continuing education about so-called “complementary and alternative” medicine one question presents itself in my mind over and over: Isn’t that fraud?   Well, is it?

And by “CAM,” I mean …

The book Snake Oil Science, by R. Barker Bausell, defines “Complementary and Alternative” therapies as “physical, mental, chemical, or psychic interventions … practiced in the absence of both 

• scientific evidence proving their effectiveness and 
• a plausible biological explanation for why they should be effective, 

and their practice continues unabated even after 

• …there is scientific evidence that they are ineffective and 
• …their biological basis is discredited.”  

(Emphasis added.)

Science Based Medicine has given us an abundance of examples supporting Dr. Bausell’s definition: homeopathy, subluxation-based chiropractic , energy healing , acupuncture , and so on. 

Fraudulent Misrepresentation

Unfortunately for ‘CAM” products and practitioners, there is no equivalent of “alternative medicine” in the law.   “Conventional law” will have to do for our analysis.  In “conventional law,” fraud can be a crime, a breach of contract or a tort.  Here we will confine our analysis to fraud as a tort, that is, a private or civil wrong, independent of contract, and more particularly the tort of fraudulent misrepresentation.

Tort law varies from state to state, and a discussion of the law of fraudulent misrepresentation in all 50 states (plus assorted other U.S. jurisdictions) is beyond the scope of this post.  However, the Restatement of Law 2d, Torts,¹ [hereinafter, the Restatement] is widely regarded as the best compilation of current law on the subject.   “The Restatements … are famous as an effort to bring analytical coherence into nonstatutory fields of law otherwise marked by a flood of discrete instances and judicial rationalizations of divergent results.”²  Where the law is in flux, they offer recommendations based on policy grounds. The Restatements of various areas of the law (Torts, Contracts, Agency, and so on) are highly respected and often cited in court opinions.    

According to the Restatement, Sec.  525, if A 

1. fraudulently makes a misrepresentation of fact, opinion, intention or law to B 
2. for the purpose of inducing B to act (or refrain from acting), 
3. A is liable to B for  B’s monetary loss 
4. caused by B’s justifiable reliance on the misrepresentation.  

“Monetary loss” includes loss caused by physical harm in cases where there is a duty to disclose a fact.  Restatement, Sec. 557A.  “Misrepresentation,” as you might guess, means that the representation is “untrue,” “not in accordance with the facts.”³ Actions for fraudulent misrepresentation (as distinct from malpractice) have been successfully maintained against health care providers, including M.D.s, dentists and chiropractors.⁴

Let’s consider more closely that first element: under what conditions is a misrepresentation considered fraudulent?  That is largely a question of intent (or “scienter”). But, contrary to what some may think, actual lying is not required to hold one accountable.  According to the Restatement, Sec. 526, 

A misrepresentation is fraudulent if the maker

1. knows or believes that the matter is not as he represents it to be,
2. does not have the confidence in the accuracy of his representation that he states or implies, or
3. knows that he does not have the basis for his representation that he states or implies.

Subsection (a.) describes what we colloquially call “lying.”  But subsection (b.) and (c.) do not require actual knowledge that one’s statement is false to impose liability. According to the Restatement’s comments to Sec. 526, which further explain its meaning, A cannot state to B that X is a fact when A merely believes it is a fact but recognizes there is a good chance it is not true.  This is sometimes referred to as making a statement “recklessly,” careless as to whether it is true or false.   Nor can A tell B that he knows X to be a fact based on his personal knowledge or investigation, or imply that this is the case, when A actually has no personal knowledge or has not made an investigation, even where A is honestly convinced of the truth of his representation.  

Misrepresenting Science

Lack of scientific evidence as misrepresentation

To understand “CAM” in the context of fraudulent misrepresentation, let us first consider the sale of goods and services outside the “CAM” area.  Will the lack of scientific evidence for a product’s or service’s claims support a cause of action for fraud? 

The tobacco cases provide an excellent example of how one industry misrepresented the scientific evidence and got burned for its efforts.    Here, we’ll look at just one of the many cases brought against a tobacco company for, among other things, fraudulent misrepresentation.

In Henley v. Philip Morris,⁵ the defendant tobacco company claimed on appeal that there was insufficient evidence to support the jury’s finding of liability on plaintiff’s claim of fraudulent misrepresentation.  The court thoroughly rejected that argument:

Our review of the record satisfies us that there was substantial evidence that [defendant] engaged in a conscious, deliberate scheme to deceive the public,  … about the health hazards and addictive effects of cigarette smoking. The jury could properly find that … defendant and other cigarette manufacturers acted both in concert and individually to issue innumerable false denials and assurances concerning the dangers of smoking, deliberately fostering a false impression by the public … that assertions of health risk were overblown … , that any real hazards had yet to be shown, and that the industry itself was acting and would act diligently to discover the scientific truth of the matter and promptly disclose its findings, good or bad. The jury could also find that plaintiff   … was falsely led to believe, as defendant intended, that there was a legitimate ‘controversy’ about whether cigarettes actually caused cancer or carried any other serious health risks.

Does this remind anyone of another fairly recent controversy regarding the safety of a certain “CAM” procedure, discussed here, here
and here?

In addition, defendant argued that its statements were “opinions,” not statements of fact, and were therefore not actionable.  That argument was equally unpersuasive to the court:

This argument relies on the general rule that statements of opinion will not support an action for fraud, while ignoring the exception … applicable to any statements of opinion: ‘[W]hen one of the parties possesses, or assumes to possess, superior knowledge or special information regarding the subject matter of the representation, and the other party is so situated that he may reasonably rely upon such supposed superior knowledge or special information, a representation … though it might be regarded as but the expression of an opinion if made by any other person, is not excused if it be false.  … Further, if a statement of opinion ‘misrepresents the facts upon which it is based or implies the existence of facts which are nonexistent, it constitutes an actionable misrepresentation.’ … The jury here was entitled to find that insofar as any of defendant’s statements constituted opinions, they implied the existence of superior knowledge as well as a state of facts that did not exist.

  In another example, a number of claims for fraud were brought against Amoco for false advertising arising out of Amoco’s assertions regarding its gasoline’s benefits.⁶  In one of these cases, plaintiff claimed that the following representations were “made without any competent and/or scientific substantiation”:

‘The clear color of Amoco Ultimate gasoline demonstrates the superior 
engine performance and environmental benefits Amoco Ultimate provides compared to other premium brands of gasolines that are not clear in color;

A single tankful of Amoco Silver or Ultimate gasoline will make dirty or clogged fuel injectors clean … ’

Do you notice a certain similarity between Amoco’s second claim and those made for colonic irrigation?

Thus, the answer is yes, as common sense would indicate, lack of scientific evidence, or distortion of the actual evidence, for a product or service will support a cause of action for fraudulent misrepresentation.  Even if the misstatement would otherwise qualify as an opinion, it is actionable fraud if the statements imply superior knowledge and are based on non-existent “facts.”

Implausibility as misrepresentation

It is difficult to find cases discussing the other element of Dr. Bausell’s “CAM” definition—lack of a plausible basis in science (as opposed to lack of scientific evidence for claims about the product or service).  Of course, outside of ‘CAM,” what sort of product or service would fit that description?    Levitation  lessons?  A perpetual motion machine?  Man-capturing  perfumes? In fact, yes, all of these have elicited the judicial equivalent of “you gotta be kidding!” 

In Hendel v. World Plan Executive Council and Maharishi International University,⁷ plaintiff sued for fraud arising out of defendants’ claims that, according to her complaint, courses in Transcendental Meditation would allow her to “attain certain extraordinary powers, such as clairvoyance, ability to levitate, ability to fly, invisibility, and superhuman strength.” In addition, she “would ultimately become a ‘Master of Creation’ with the ability to manipulate the physical world and the laws of nature.”  

The court did not reach the merits of her fraud claim, finding instead that her suit was barred by the statute of limitations.   However, in reaching that conclusion, the court did remark that defendants’ representations were such that “any reasonable person would recognize as being contrary to common human experience and, indeed, to the laws of physics.” This meant plaintiff should have been on notice earlier that she was being defrauded.  

Similarly, in Waterman v. Haumaier,⁸  the laws of physics prevented one party from claiming he could justifiably rely on representations in an agreement which “closely approach the concept of the perpetual motion machine … [S]uch machines  … are impossible in light of the First Law of Thermodynamics,” citing Handbook of Chemistry and Physics  (64^th ed. Weast 1983).   

Less specifically, but equally based on scientific implausibility,  in Gottlieb v. Schaffer,⁹  the court found that various perfumes the seller claimed would allow the wearer to “control men” (“Desire” perfume), to make a man “stay close to you” (“Nirvana”), “make men obey you” (“Command”), and so on, were so “patently absurd” that no proof of their falsity or intent to deceive was necessary due to “the universality of scientific belief that [such] advertising representations are wholly unsupportable.”   The Gottlieb case was decided in 1956, which makes me think the perfume seller was simply ahead of his time and could have marketed his product as a combination of aromatherapy and energy medicine in today’s market.
 
Thus, both the lack of a plausible basis in science and the lack of scientific evidence for claims made for products or services are well-recognized as “misrepresentations” which will  support a cause of action for fraud.   Now let’s apply the law of fraudulent misrepresentation to a few hypotheticals involving “CAM.”

B, the poor devil¹⁰

Acupuncture

Imagine that A is an M.D. practicing family medicine.  His patient, B, has long complained of back pain, but has not found relief in any of the remedies A has prescribed.  The doctor, being an “integrative” practitioner, suggests acupuncture, which he has learned to perform, might help B’s pain, adding that he has “seen it work” in other patients.  B justifiably takes all of this to mean that acupuncture is an effective treatment for back pain, and relies on that representation.  B undergoes a series of 12 treatments, which costs about $1,200. In fact, A is aware, from his undergraduate education in the sciences and his medical education and training, that the basic principles of acupuncture are highly implausible and, having reviewed the literature, knows there is no good evidence that it is effective. Thus, A knows that his express and implied representations of the effectiveness of acupuncture for back pain are “not as he represents [them] to be” within the meaning of Sec. 526(a). Therefore, all the elements of a cause of action for fraudulent misrepresentation under Sec. 525, are present.  

Naturopathy/Homeopathy

Next, let’s suppose that A is an N.D. licensed to practice naturopathy in her state.  B, her patient, has the flu, so A prescribes oscillococcinum, which she describes to B as a homeopathic flu remedy.  A, having taken classes in chemistry and physics, has her doubts about homeopathy, but she does not express them to B. B justifiably relies on A’s advice because A is a licensed health care provider.  B takes the homeopathic remedy, but continues to suffer because, as we know, homeopathic remedies cannot be, and have proven not to be, effective.  As a result, B is out the cost of the remedy plus additional monetary losses due to the physical harm caused by ineffective treatment, which delays her seeking medical care for the flu, which progresses into pneumonia.   A’s conduct has thus satisfied the definition of fraudulent misrepresentation under Sec. 526, subsection (b), as she knew when she prescribed  oscillococcinum that homeopathy is inconsistent with the laws of chemistry and physics and therefore could not be confident that it was, in fact, an effective remedy.  In other words, she did “not have the confidence in the accuracy of [her] representation that [she] states or implies.”  All the elements of a cause of action under Sec. 525 are present.  

Chiropractic
 
Assume A is a D.C.  B visits his office for the first time, complaining of headaches.  A explains to B that he is suffering from subluxation of a cervical vertebrae, the cause of his “cerviocogenic headache,” and that cervical manipulation will reduce the subluxation, thereby allowing the body’s self-healing ability to function properly.  B asks A about the safety and effectiveness of this treatment.  A responds that “the scientific evidence for the safety and effectiveness of chiropractic care is overwhelming.”  He adds that “over the past twenty years, many controlled clinical research studies have shown that chiropractic care is safe and effective for back pain, neck pain and headaches.”¹¹   B justifiably relies on these statements due to the chiropractor’s presumed superior knowledge on these subjects.   

In fact, A has not reviewed the recent literature on the scientific validity of the chiropractic subluxation, which does not support its existence. Nor has he reviewed the recent literature on the safety and effectiveness of cervical manipulation for headaches, which does not support his unequivocal statement.   He is simply repeating statements in a patient brochure he purchased in bulk for his office. Unfortunately, the cervical manipulation causes B to suffer a vertebral artery dissection and subsequent stroke, resulting in lifelong disability.  A’s conduct satisfies the definition of fraudulent misrepresentation as he did not actually investigate the literature and therefore “knows that he does not have the basis for his representation that he states or implies.”  This is so even though he “is honestly convinced of its truth from hearsay or other sources that he believes to be reliable.”  Restatement, Sec. 526(c), and comment (f).  All the elements of a cause of action for fraudulent misrepresentation under Sec. 525 of the Restatement are present.

Reiki

Finally, assume A, a licensed massage therapist in her state and a reiki practitioner, places an ad for her services in the newspaper, and is contacted by B, who asks for more information.   A tells B that reiki is based on the idea that there is a universal, or source, energy that supports the body’s innate healing abilities. Practitioners seek to access this energy, allowing it to flow to the body and facilitate healing.  A adds that people use reiki for relaxation, stress reduction, and symptom relief, in efforts to improve overall health and well-being and that reiki has been used by people with anxiety, chronic pain, HIV/AIDS, and other health conditions, as well as by people recovering from surgery or experiencing side effects from cancer treatments. A tells B that if it is inconvenient for her to come in, A can practice reiki from a distance, that is, when B is not physically present in the office. B tells A she suffers from chronic anxiety and pain and schedules an appointment.  A tells B after her first session that the standard for treatment is at least four sessions of 30 to 90 minutes each.¹²  B ultimately ends up attending 10 sessions, and having reiki performed without her presence twice, which costs her $1,000 total.

In a departure from the previous hypotheticals, it is not certain that B can satisfy all the elements of proof to succeed on a claim of fraudulent misrepresentation against A.  A’s description of reiki’s purported mechanism of action is clearly contrary to the laws of physics, so much so that one can argue the average person should be aware of its implausibility.  Even if B can prove that A knew, or should have known this, reiki’s very implausibility might keep B from being able to prove she justifiably relied on A’s statements, as was the case in Waterman.  Hendel, although decided on a different issue, points to the same result.  However, for the purposes of our discussion below, let’s assume the facts in this hypothetical satisfy all the elements of a cause of action for fraudulent misrepresentation under Sec. 525.

A license to defraud?

I’ve concluded that all the elements of a cause of action for fraudulent misrepresentation are present in each hypothetical.    However, that is not the same as concluding the plaintiff will succeed (assuming he or she can prove the allegations of the complaint) because in any suit the defendant can plead and prove an “affirmative defense” which defeats the plaintiff’s claim.  By way of example, one common affirmative defense is failure to bring an action within the time provided by the statute of limitations, as was the case in Hendel, above.   Ms. Hendel may have had a textbook claim of fraudulent misrepresentation against the defendants,   but because she waited too long to bring her suit, the defendants won on their affirmative defense that her claim was barred by the statute of limitations.  

So what affirmative defense might be raised to defeat claims of fraudulent misrepresentation brought by B against A?  

Again we turn to the …

Restatement:

“Sec. 890 Privileges

“One who otherwise would be liable for a tort is not liable if he acts in pursuance of and within the limits of a privilege …” 

Sec. 10 of the Restatement further describes the types of consent and how they are created.  Some privileges are based on the consent of another.  The most familiar of these to readers of SBM is likely consent to medical treatment, so that the person who cuts one open with a sharp object will not be liable for battery if that person is a surgeon and one has consented to the surgery.  We are not talking about that kind of privilege here even if consents to treatment were obtained as consent induced by fraud is invalid.  

Other privileges are nonconsensual, and they can be either conditional or absolute.  These privileges allow the A’s of the world to adversely affect the legally protected interests of the B’s of the world without their consent and to avoid liability for doing so.  Absolute privilege is not applicable here.  It is the conditional privilege which may form the basis of an affirmative defense in our hypotheticals. 

“A person ‘who otherwise would be liable for a tort is not liable if he acts in pursuance of and within the limits of a privilege.’ … The term ‘privilege’ denotes the existence of circumstances that justify, or excuse, conduct that would ordinarily subject the actor to liability… . Conduct that would otherwise be actionable is held to be privileged as a matter of law where, under the circumstances, it furthers an interest of social importance.”  Schultz v. Elm Beverage Shoppe,¹³  quoting, Restatment, Sec. 890.

However, a person is liable for any acts that are in excess of those permitted by the privilege.  Thus, if A acts in self-defense during an attack by B, the privilege of self-defense against attack by another would protect him from liability for injury to B.  But if A uses excessive force he has exceeded the scope of his privilege and the privilege will not protect him from liability for injuries caused by his use of unnecessary force.  Restatement, Sec. 890, comment e.

Privileges can be based on a constitutional or statutory provision protecting the alleged wrongdoer’s interests even where the creation of the privilege is not specifically mentioned.¹⁴  A familiar example is the privilege protecting the media from a claim of defamation where the defamatory statement was published without malice or reckless disregard of the truth (and a few other requirements).  This privilege is recognized by the courts to protect First Amendment freedoms, although obviously you don’t find actual language to that effect in the First Amendment.   
 
The defendants in our hypotheticals can raise the affirmative defense of conditional privilege. The M.D., N.D., D.C. and L.M.T. would all argue that because their practice acts incorporate a right to perform the procedures which the patients claim are fraudulent, the practice acts create a privilege.   In other words, the state legislatures, by incorporating implausible and evidence-free practices into the law, are protecting these practitioners from liability even if their patients can prove their representations are untrue and were made with the requisite intent to deceive.  

The D.C. and the N.D. appear to have the best case for defeating the patient’s claim of fraudulent misrepresentation, as their practice acts incorporate their science-and-evidence-free procedures. All state chiropractic acts either explicitly or implicitly allow chiropractors to detect and correct “subluxations.”¹⁵  However, any privilege afforded by the practice act obviously would not extend to statements regarding the safety of cervical manipulation as that subject is not specifically addressed in the act.  Likewise, because the naturopathy practice acts allow the use of homeopathy, the N.D. can plead privilege as an affirmative defense, although it could be argued that she exceeded the scope of her privilege by not disclosing her doubts about homeopathy.

The L.M.T’s claim of privilege would depend on whether her state included reiki in the definition of massage practice.  If it does, the court could find that the statute creates a privilege.  If not, there would no statutory basis for it, although she might argue that by virtue of the state’s allowing practices “taught in massage schools” (as some do) the practice act implicitly affords a privilege if her massage school training included reiki.

The M.D. is on shakier ground.   While some states have enacted statutes protecting physicians to a certain extent in using “CAM”¹⁶ it is unlikely those would protect an M.D. who believed in neither the plausibility nor effectiveness of the treatment but, at least impliedly, represented otherwise to the patient.   In addition, some of these statutes protect a physician solely from disciplinary action for using CAM and arguably create no privilege in a civil action. Thus, even though the M.D.’s scope of practice is broad, it does not insulate physicians from knowingly making false claims about a therapy. 

In response to claims of privilege, plaintiffs could argue that a nonconsensual privilege which defeats their right to recover damages for fraudulent misrepresentation should not be recognized unless it protects some important public interest. Restatement, Sec. 10, comment (d.); Sec. 890, comment (a.).  Certainly there is no important public interest served by allowing health care practitioners to make demonstrably false representations to patients.   
 

Conclusion

So, is ‘CAM’ fraud? According to the Snake Oil Science definition, it most certainly is misrepresentation.  Whether it is fraudulent misrepresentation depends on whether one of the three elements required for establishing fraudulent intent can be proved: knowing misrepresentation, reckless misrepresentation, or stating (or implying) a basis for the misrepresentation that one does not actually have.   As criticism of CAM for scientific implausibility grows and study after study fails to support claims of effectiveness, we may reach a point where it becomes impossible for the CAM practitioner to avoid knowing that CAM is based on misrepresentations, making it much harder to defeat claims of fraudulent misrepresentation.  Key to this will be the courts’ refusal to interpret the state practice acts as creating a privilege which allows CAM practitioners to avoid liability for defrauding their patients.

References

1. Restatement of the Law 2d, Torts, American Law Institute (1979) Return to text
2. U.S. Nat. Bank of Oregon v. Fought, 630 P.2d 337, 352 (Or. 1982) (Linde, J., concurring). Return to text
3. Black’s Law Dictionary (4th Ed. 1968) Return to text
4. Ohlsson GL, Malpractice Considerations in Complementary Medicine, in Louisell & Williams, Medical Malpractice, Sec. 17D.04 (Matthew Bender 2010) Return to text
5. 114 Cal. App. 4th 1429, 1465-66, 9 Cal. Rptr. 3d 29, 62 (Cal. App. 1st Dist. 2004), cert. den., 544 U.S. 92, 125 S. Ct. 1640 (2005) Return to text
6. Oliveira v. Amoco Oil Co., 776 N.E.2d 151, 156, n. 2 (Ill. 2002) Return to text
7. 705 A.2d 656 (D.C. App. 1997) Return to text
8. 222 B.R. 40, 1998 U.S. Dist. LEXIS 10124 (S.D.N.Y. 1998)141 F.Supp. 7 (S.D. N.Y. 1956) Return to text
9. Because B, through no fault of his own, is the second letter in the alphabet, he is constantly subjected to A’s actions, both devious and innocent, in the legal literature: A sells B real property A doesn’t own, rear ends B in traffic, shoots B in self-defense, fails to deliver goods B has purchased, and so on. Return to text
10. This is actually a direct quote taken from a video about the safety and effectiveness of chiropractic featuring Rick McMichael, D.C., described as the president of the American Chiropractic Association. The video appears on the Sharecare website. http://www.sharecare.com/question/chiropracticcareeffective According a Sharecare press release, the site was created by Dr. Mehmet Oz and Jeff Arnold. Return to text
11. http://static.sharecare.com/docs/SharecareLaunchRelease100710.pdf?v=47 Return to text
12. This description is taken almost verbatim from the NCCAM website. “Reiki: An Introduction,” http://nccam.nih.gov/health/reiki/introduction.htm. Return to text
13. 40 Ohio St. 3d 326; 533 N.E.2d 349, 351 (1988) Return to text
14. See, e.g., New York Times v. Sullivan, 376 U.S. 254, 84 S.Ct. 710 (1964) Return to text
15. Bellamy JJ, Legislative Alchemy: the state chiropractic practice acts, Focus Alt & Comp Ther; 15: 214-222 Return to text
16. Cal Bus & Prof Code Sec. 2234.1 (2010); Fla.Stat. Sec. 456.41 (2010) Return to text

“You are not going to change what we do, you’re not going to change our determination to make these patients better. I see these patients, I know these patients, I value these patients, I’ve looked after them for years. I’ve seen them after the procedure, the vast majority are improved.”

The above quote could be a reference to just about any fringe medical treatment. It is partly an expression of faith in anecdotal experience over scientific evidence. It is partly the fallacy of justifying a treatment because it is needed – whereas the real question is whether or not the treatment works. It is an attempt to justify specific claims with compassion, as if the person quoted cares more for the health of their patients than those who might be skeptical of their claims. And it is an expression of stubbornness – I know the truth, so don’t confuse me with evidence and logic.

Is this person talking about acupuncture? Perhaps they run a stem cell clinic in China, India or somewhere outside the reach of regulation. Or maybe they are defending hyperbaric oxygen therapy for unproven indications, like autism. It could be anything, because this sentiment is the standard mantra of the dubious practitioner, practicing outside the bounds of science-based medicine.

The quote is from Dr. Tom Gilhooly, a GP who runs Essential Health, a clinic in the UK that offers the liberation procedure for presumed CCSVI (chronic cerebrospinal venous insufficiency). Gilhooly is defending his practice to the BBC, after a healthy investigator, Sam Smith, presented to his clinic and paid to have a screening procedure performed – which diagnosed her with CCSVI.

I wrote about CCSVI last year – this is a controversial claim by vascular surgeon Dr. Paolo Zamboni, who believes that multiple sclerosis (MS) is caused by venous insufficiency in the brain. The liberation procedure uses balloons to open up the allegedly blocked veins, and in some cases stents are place to keep the veins open. Since my last reporting there have been several more attempts to replicate Zamboni’s research – all negative. This study compares MS patients to patients with other neurological disease and healthy controls, and found no significant difference in the prevalence of signs of venous insufficiency. Another study found that venous pressure is not different in MS patients vs normal controls Yet another study found a lack of association between CCSVI and HLA DRB1*1501 in MS patients, which is a genetic variant that carries an increased risk of developing MS.

The bottom line is that, so far, it is not looking good for CCSVI being a real disorder that is associated with, let alone a major cause of, MS.

Further – there is no clinical data (other than anecdotes) to demonstrate that the liberation procedure is a safe and effective treatment for any subtype of MS. But the claims for the treatment are dramatic, there is impressive-sounding anecdotal evidence of benefit (because there always is – no matter what the alleged treatment), and in many patients MS is a debilitating and progressive disease that does not always respond to treatment. In other words, there are desperate patients out there, and the combination of desperation and dramatic claims leads to people seeking treatment, despite the lack of scientific evidence.

These situations require thoughtful regulation in order to ensure that patients are not exploited (even by well-meaning practitioners, and we certainly cannot assume that everyone offering an expensive treatment is going to be well-meaning). The system needs to allow for some flexibility within the standard of care, and certainly for experimentation to advance the science of medicine. But this has to be balanced with the needs of informed consent and ethical practice and research.

This can be a difficult balance to strike. But as some countries are struggling to achieve the optimal balance of freedom and protection at the edge of scientific knowledge, medical tourism is undercutting such efforts.

The BBC reports, for example, that while the NHS does not cover the liberation procedure, thousands of patients have already gone overseas to have the procedure. There are reports of at least two deaths from the procedure, so it is not without its risks.

Clearly, use and demand for the liberation procedure has raced ahead of the evidence, which is mostly negative. More research is needed to put this claim to bed, or perhaps discover a more limited role for this syndrome and its treatments. But there is certainly an insufficient basis to offer the procedure outside of an ethically designed and executed clinical trial.

This is not an isolated example, nor is it even the worst example. Stem cell tourism appears to be a much greater problem, with patients (victims) spending tens or hundreds of thousands of dollars to fly around the world to get unknown cocktails (claimed stem cells) injected into them without any reasonable expectation of benefit, but with clear risks.

We are seeing the globalization of high-tech quackery. Current regulatory systems are not designed to address this problem All we can do is ask countries in which these clinics thrive to crack down, but there is a reason why such clinics are set up in these countries to begin with.

Meanwhile we can educate the public, and potential victims, about the evidence and the dangers. But information is often impotent against the power of desperation.

After giving birth, most mammals eat the afterbirth, the placenta. Most humans don’t. Several hypotheses have been suggested as to why placentophagy might have had evolutionary survival value, but are there any actual benefits for modern women? Placentophagy has been recommended for various reasons, from nutritional benefit to preventing postpartum depression to “honoring the placenta.” In other cultures, various rituals surround the placenta including burial and treating it as sacred or as another child with its own spirit. Eating the placenta is promoted by some modern New Age, holistic, and “natural-is-good” cultural beliefs.

Some women eat it raw, but many women have a yuck-factor objection to eating raw bloody tissue. It can be cooked: recipes are available for preparing it in various ways. For those who don’t like the idea of eating the tissue, placenta encapsulation services are available, putting placenta into a capsule that is more esthetically acceptable and that can even be frozen and saved for later use in menopause.

Does placentophagia benefit health? Does it constitute cannibalism? It it just a way to recycle nutrients? How can science inform our thinking about this practice?

Is It Cannibalism?

As I researched this, I found the assertion that the placenta is part of the woman’s body. Actually, this is inaccurate. While there is a maternal component, placental tissue is mainly derived from the fertilized egg and carries the fetus’s genome. So technically, wouldn’t eating the placenta fit the definition of cannibalism: eating the flesh of another individual of your own species? Some people have categorical philosophical or ethical objections to cannibalism, but there is no evidence (and no reason to think) that eating “long pig” would be harmful to health as long as the tissue is healthy and unable to transmit diseases (such as the infamous kuru).

My mind wandered into other hypothetical scenarios. What about swallowing semen: would that fit the definition of cannibalism? If eating human tissue is sometimes acceptable as in placentophagia, when does it become not acceptable and why? Would it be acceptable to eat surgical specimens of healthy tissue? For instance, a healthy uterus that had been removed only because of prolapse, or breast tissue from breast reduction surgery? Circumcised foreskins? Unused tissue from a phallus removed during sex-change surgery? Not that anyone has suggested eating those things, but it’s interesting to think about where reasoning might lead us once we have accepted a principle. Socrates was famous for that: he would get his interlocutors to agree to a statement and then would make them explore the logical consequences that would necessarily ensue.

Some vegetarians make an exception for placentas. One writer on Yahoo! Answers justified placentophagia by rationalizing that she eats eggs and placenta is basically human egg white!

My personal preference? I didn’t eat my placentas because I saw no reason to do so, but I don’t object on principle. Even if placentophagia qualifies as cannibalism, I don’t see any rational objection to cannibalism per se, as long as it doesn’t involve unethical practices like murder. I have an aversion to raw meat, but I wouldn’t have any objection to eating placenta if it were cooked and seasoned. With the high blood content, I imagine it would taste somewhat similar to the fried (bovine) blood I enjoyed eating when I lived in Spain. Fried blood tastes something like liver and is delicious when prepared with garlic and olive oil.

Forgive the digression and the weird speculations.

Is It Recycling?

The placenta contains a lot of nutrients and could help replace the nutrients depleted during pregnancy, especially iron. This might be important for some animals; but for humans who have adequate access to food, these nutrients are easily replaced through more conventionally accepted means. It seems a shame for good nutrients to be thrown away. On the other hand, recycling placental nutrients would have only a very small impact. Most of us don’t feel an obligation to recycle everything. We throw away other nutrients by discarding the outer leaves of cabbages and the fat trimmings from cuts of meat. A fanatical recycler might accept recycling as a compelling reason for placentophagia, but I suspect that most people wouldn’t be persuaded by that argument alone.

What Health Benefits Are Claimed?

According to Placentabenefits.info, health claims include:

• Increase general energy
• Allow a quicker return to health after birth
• Increase production of breast milk
• Decrease likelihood of baby blues and post natal depression
• Decrease likelihood of insomnia or sleep disorders
• Other benefits are also likely but too numerous to mention.
• “Definitely worth considering as part of a holistic postpartum recovery for every expectant woman.”

Dried human placenta is also used in traditional Chinese medicine (TCM) to treat wasting diseases, infertility, impotence, and other conditions.

Is there scientific support for those claims?

The Placentabenefits website offers the following scientific research to support those claims:

1. A 1954 article from Czechoslovakia showed that taking a supplement derived from placenta increased milk production, but after 57 years this study has still not been replicated. This same study is mentioned by the authors of the second reference only to question it, characterizing it as “a somewhat unrigorous study”
2. “Placentophagia: A Biobehavioral Enigma” discusses animals and human cultures that practice placentophagia and ponders why. It provides no data directly relevant to the claims for human health.
3. A study of opioid levels in rats after placenta ingestion, showing that placenta enhances y- and n-opioid antinociception, but suppresses A-opioid antinociception — in rats. No apparent relevance to their claims for human benefits.
4. A 1980 study showing that placentophagy alters hormone levels in rats. It didn’t even look at what clinical effects might result from those altered levels.
5. They cite an article without giving sufficient clues for me to be able to locate it. By their description, the article apparently cites research by Chrousos suggesting that lower levels of human corticotrophin releasing hormone (CRH) after delivery might be a possible etiology for postpartum depression; but it says nothing about treatment or the effects of eating the placenta.
6. An article showing that iron deficiency anemia affects postpartum emotions and cognition, with no discussion or evaluation of whether eating placenta elevates serum iron levels significantly or improves emotions or cognition.
7. An article about predicting postpartum depression by assessing postpartum fatigue. Nothing about eating placenta.
8. Unexplained fatigue may benefit from iron supplementation. Nothing about eating placenta.
9. A discussion of why postpartum iron deficiency should not be overlooked. No mention of placentas.

My own search of PubMed didn’t uncover any relevant studies on humans. If these 9 articles are their best effort, they’re grasping at straws. All they’ve got is rats and speculation. The best they can do is to mention the need for adequate iron and speculate that placenta-eating might be a useful source of iron. To counter that, we know enough about iron metabolism to make us think it is highly implausible that a one-time ingestion of placenta would contribute very much to effectively replenishing the body’s iron stores.

Conclusion

Science does not offer sufficient evidence to either support or reject placentophagia as a health practice. Nonscientific considerations will continue to determine women’s choices in this matter.

Science-based medicine depends upon human experimentation. Scientists can do the most fantastic translational research in the world, starting with elegant hypotheses, tested through in vitro and biochemical experiments, after which they are tested in animals. They can understand disease mechanisms to the individual amino acid level in a protein or nucleotide in a DNA molecule. However, without human testing, they will never know if the end results of all that elegant science will actually do what it is intended to do and to make real human patients better. They will never know if the fruits of all that labor will actually cure disease. However, it is in human experimentation where the ethics of science most tend to clash with the mechanisms of science. We refer to “science-based medicine” (SBM) as “based” in science, but not science, largely because medicine can never be pure science. Science has resulted in amazing medical advances over the last century, but if there is one thing that we have learned it’s that, because clinical trials involve living, breathing, fellow human beings, what is the most scientifically rigorous trial design might not be the most ethical.

About a week ago, the AP reported that experiments and clinical trials that resemble the infamous Tuskegee syphilis study and the less well known, but recently revealed Guatemala syphilis experiment were far more common than we might like to admit. As I sat through talks about clinical trial results at the Society of Surgical Oncology meeting in San Antonio over the weekend, the revelations of the last week reminded me that the intersection between science and ethics in medicine can frequently be a very tough question indeed. In fact, in many of the discussions, questions of what could or could not be done based on ethics were frequently mentioned, such as whether it is ethically acceptable or possible to do certain followup trials to famous breast cancer clinical trials. Unfortunately, it was not so long ago that such questions were answered in ways that bring shame on the medical profession.

More than Tuskegee and Guatemala

The most notorious of highly unethical human experiments outside of Nazi Germany and the Japanese empire during World War II is the infamous Tuskegee syphilis study. This study, conducted by our very own Public Health Service (PHS) was conducted between 1932 and 1972 and examined the natural progression of untreated syphilis in poor black men who received free health care from the government. In 1932, when this study was conceived it was not inherently unethical. At the time there were precious few treatments for syphilis, and none of them worked very well. Consequently, observing the progression of syphilis, using the treatments available at the time, and following the subjects prospectively constituted a reasonable trial design. However, in the late 1930s and early 1940s, penicillin became available, and by 1947 was the standard of care for treating syphilis. When campaigns to eradicate syphilis came to the county in which most of the subjects, study researchers prevented their subjects from participating. In essence, even after an effective treatment for syphilis had become widely available, study still researchers denied it to their subjects. By the end of the study in 1972, of the original 399 men in the study, 28 had died of syphilis; 100 were dead of related complications; 40 wives had been infected with syphilis; and 19 children had been born with congenital syphilis. The rationale for not providing effective treatment for these men and even discouraging them from undergoing such treatment? This:

Such individuals seemed to offer an unusual opportunity to study the untreated syphilitic patients from the beginning of the disease to the death of the infected person. An opportunity was also offered to compare the syphilitc process uninfluenced by modern treatment, with the results attained when treatment had been given.

Worse, there was no informed consent, and considerable inducements were offered to the men to join the study.

The Tuskegee syphilis study, unfortunately, is not the only abuse committed by the PHS. About six months ago, it was revealed that these sorts of experiments had been more widespread than commonly believed. Indeed, in the 1940s in Guatemala, the PHS had gone one better in that they had deliberately infected prison inmates in Guatemala with syphilis. As I described in a lot more detail when the revelations first hit the press, prostitutes who had tested positive for syphilis were recruited to visit the men in prison. The hypothesis to be tested was whether prophylactic penicillin treatment could prevent infection, and the other purpose was to define the response of syphilis to penicillin treatment. Again, there was no real informed consent. Worse, subjects were intentionally infected with a potentially fatal disease. True, they were treated, but treatment is not 100% effective, and one has to wonder if the prisoners, a vulnerable population, understood the nature of the risks they were being induced to take.

On Sunday, AP medical writer Michael Stobbe published a long article detailing the sordid history of medical research in the U.S. before the 1970s. His timing was not coincidental, because on Tuesday in Washington, DC, there was a meeting of a presidential bioethics committee, the Commission for the Study of Bioethical Issues, triggered by the revelations last fall about the Guatemala syphilis experiment 65 years ago. Those revelations led the AP to do an exhaustive review of reports from medical journals and press clippings, and the AP found at least 40 studies similar to the Guatemala syphilis study in that patients were put at risk for serious disease or, even worse, healthy people were intentionally made ill to study disease. Some of these abuses are well known, others much less so.

Here are some examples from the AP article:

The AP review of past research found:

• A federally funded study begun in 1942 injected experimental flu vaccine in male patients at a state insane asylum in Ypsilanti, Mich., then exposed them to flu several months later. It was co-authored by Dr. Jonas Salk, who a decade later would become famous as inventor of the polio vaccine.

Some of the men weren’t able to describe their symptoms, raising serious questions about how well they understood what was being done to them. One newspaper account mentioned the test subjects were “senile and debilitated.” Then it quickly moved on to the promising results.

• In federally funded studies in the 1940s, noted researcher Dr. W. Paul Havens Jr. exposed men to hepatitis in a series of experiments, including one using patients from mental institutions in Middletown and Norwich, Conn. Havens, a World Health Organization expert on viral diseases, was one of the first scientists to differentiate types of hepatitis and their causes.

A search of various news archives found no mention of the mental patients study, which made eight healthy men ill but broke no new ground in understanding the disease.

• Researchers in the mid-1940s studied the transmission of a deadly stomach bug by having young men swallow unfiltered stool suspension. The study was conducted at the New York State Vocational Institution, a reformatory prison in West Coxsackie. The point was to see how well the disease spread that way as compared to spraying the germs and having test subjects breathe it. Swallowing it was a more effective way to spread the disease, the researchers concluded. The study doesn’t explain if the men were rewarded for this awful task.
• A University of Minnesota study in the late 1940s injected 11 public service employee volunteers with malaria, then starved them for five days. Some were also subjected to hard labor, and those men lost an average of 14 pounds. They were treated for malarial fevers with quinine sulfate. One of the authors was Ancel Keys, a noted dietary scientist who developed K-rations for the military and the Mediterranean diet for the public. But a search of various news archives found no mention of the study.
• For a study in 1957, when the Asian flu pandemic was spreading, federal researchers sprayed the virus in the noses of 23 inmates at Patuxent prison in Jessup, Md., to compare their reactions to those of 32 virus-exposed inmates who had been given a new vaccine.
• Government researchers in the 1950s tried to infect about two dozen volunteering prison inmates with gonorrhea using two different methods in an experiment at a federal penitentiary in Atlanta. The bacteria was pumped directly into the urinary tract through the penis, according to their paper.

The men quickly developed the disease, but the researchers noted this method wasn’t comparable to how men normally got infected — by having sex with an infected partner. The men were later treated with antibiotics. The study was published in the Journal of the American Medical Association, but there was no mention of it in various news archives.

Stobbe goes on to point out the “Holy Trinity” of news stories in the 1960s and early 1970s that brought to light the sorts of activities that we now consider abuses in medical research. The last of these was, of course, the Tuskegee syphilis study. The first of these occurred in 1963, when it came to light that researchers had injected cancer cells into elderly debilitated patients at the Jewish Chronic Disease Hospital in Brooklyn to discover whether their bodies would reject them. With our knowledge of tumor immunology now, we can look back on this experiment and know that the odds of any harm were quite small because tumors, with very, very rare exceptions, are not transplantable in humans. Our bodies recognize cells from another person to be foreign, whether they are cancer or not, and quickly destroy them. However, at the time, based on what was known, undoubtedly the scientists thought that there was at least a chance that these tumor cells would form cancers in the patients into whom they were injected, the denial of the hospital director who deemed the cells “harmless,” notwithstanding. (Indeed, the hospital director strikes me as either lying or deluded.) Otherwise, why seek to answer the question? Just as bad, there was no informed consent, the justification being that the cells were thought to be “harmless.” More details can be found here. The outcome was that the Board of Regents censured the researchers and suspended the licenses of two of the doctors involved. Later, however, they stayed the suspensions and instead put the doctors on probation for one year. There were no repercussions for the hospital or for Memorial Sloan-Kettering Cancer Center, where one of the investigators was on faculty.

The third of the “Holy Trinity” was an infamous experiment in Staten Island at the Willowbrook State School, which was a school for children with mental retardation. During the mid-1960s, children there were intentionally infected with hepatitis in order to determine whether gamma globulin could cure it. Besides the targeting of a vulnerable population (children and teens with profound mental retardation), this study demonstrated a number of problematic issues as well. First, the investigators rationalized infecting these children by rationalizing that hepatitis was so endemic in the facility due to the fact that most of the children there were incapable of being toilet trained that over 70% of new residents became infected within a year. This, of course, leads to the obvious question, namely: If that were the case then why not study the effect of gamma globulin on children who were infected normally? More disturbing, again investigators played fast and loose with informed consent, the form being worded in a vague and ambiguous manner that played down the fact that the children were going to be intentionally infected with hepatitis and implying that the serum they would be given would be an experimental vaccine. Finally, as is the case in many such studies, there was an element of coercion. Willowbrook at the time was very crowded, with long waiting lists for children to be admitted. At times, there was only room in the experimental wing. For parents who could not afford to take care of their children, this situation could bring considerable pressure to bear to “persuade” them to “do the right thing.”

Changing ethics

In studying the history of medicine and clinical trials, what never ceases to amaze me is the different attitudes that physicians and scientists had towards their human subjects not all that long ago. Remember, it was primarily in the 1960s and 1970s when attitudes began to change. Before the 1970s, for instance, researchers thought little of using prisoners for experiments, even though prisoners are correctly considered a population that is vulnerable and for whom true informed consent without coercion is difficult to obtain without special attention to making it happen. Indeed, in his news story Stobbe recounts an anecdote of a man at Holmesburg Prison in Philadelphia who agreed in exchange for cigarette money to have the skin peeled off of his back and searing chemicals painted on the open wounds in order to test a drug. Similarly, as the Willowbrook story shows us, it was not really all that long ago when scientists apparently felt justified in infecting profoundly mentally retarded children with hepatitis on the basis of at best dubious ethical justification.

Arguably, this willingness to experiment on children who were not normal and who were never going to be able to contribute to society was a holdover from the eugenics movement earlier in the 20th century. It’s important to remember that, however much eugenics was discredited by the Nazis, prior to the Holocaust Hitler was actually quite the admirer of American eugenics policies, drawing inspiration from them. Another factor that is frequently invoked as an explanation for the willingness of American scientists to flout ethical considerations is war, particularly World War II and then the Cold War, the resulting idea that it was “us against them,” and that for us to win would require shared sacrifice in the name of the nation. After all, the scientific primacy of the U.S. was viewed as one of the most critical sources of our economic and military strength. Moreover, the concept of the Cold War could be generalized to other “wars,” such as the “war on disease” or the current “war on cancer” that I’ve written about twice in the last month. As Stobbe put it:

Attitudes about medical research were different then. Infectious diseases killed many more people years ago, and doctors worked urgently to invent and test cures. Many prominent researchers felt it was legitimate to experiment on people who did not have full rights in society — people like prisoners, mental patients, poor blacks. It was an attitude in some ways similar to that of Nazi doctors experimenting on Jews.

“There was definitely a sense — that we don’t have today — that sacrifice for the nation was important,” said Laura Stark, a Wesleyan University assistant professor of science in society, who is writing a book about past federal medical experiments.

There was clearly also more than a little hubris at play as well:

It was at about this time that prosecution of Nazi doctors in 1947 led to the “Nuremberg Code,” a set of international rules to protect human test subjects. Many U.S. doctors essentially ignored them, arguing that they applied to Nazi atrocities — not to American medicine.

Finally, with the rise of large pharmaceutical companies in the 1940s and 1950s, increasingly there was more of a profit motive than a purely scientific one. Drugs needed to be tested, and prisoners provided a convenient source of young, healthy men upon which to test new products. Hubris, profit, and a wartime attitude that sacrificing for the good of the nation all swirled together into a mixture toxic to medical ethics during World War II and well into the postwar period. In having defeated the Nazis, we failed to learn a lesson from what had happened in Germany, where one of the most technologically and medically advanced societies then on the face of the earth did horrible things in the name of its ideology.

Yes, it is true that American scientists did not intentionally expose prisoners to freezing water in experiments designed to find better ways of rewarming pilots shot down over frigid waters or sailors who survived the sinking of their ship, as Nazi doctors did. It is also true that American scientists did not intentionally irradiate men’s testicles and women’s ovaries in order to develop a means of rapid sterilization, causing horrific bowel and bladder complications, especially in women, as Nazi scientists did, although American scientists did subject many to various radioactive substances in the name of research. Nor did American scientists inject dyes into the eyes of children in order to try to turn them blue, as Dr. Mengele did. On the other hand, American scientists did, as we have seen, intentionally infect prisoners and mentally retarded children (the same sort of children that the Nazis would have called “life unworthy of life”) with diseases and then treat them, just as Nazi physicians intentionally infected concentration camp inmates with various diseases in order to determine the efficacy of different treatments or as Japanese physicians did when they intentionally broke the limbs of prisoners and contaminated them with bacteria-laden dirt. American offenses were different in scale and horror, but not significantly different in kind. Unfortunately, it was not until the 1970s, years after the international Helsinki Declaration was first published, until the Belmont Report was adopted and then not until the 1990s when The Common Rule became the basis of all federal regulations protecting human research subjects, as I have described before.

Could it happen again?

Fortunately, as one who now participates in clinical trials and clinical trial development, given the current level of regulation on human subjects research by the federal government, I have a hard time imagining how abuses such as the one’s I’ve described could happen again now. The amount of paperwork, regulation, and oversight of clinical trials has become so burdensome and complex that sometimes I wonder why I or anyone else would want to continue doing clinical research. Unfortunately, Stobbe doesn’t sound too optimistic. Actually, it’s not so much Stobbe, but rather the presidential Commission for the Study of Bioethical Issues, as Stobbe documents in a followup story:

Speakers noted that over the last several decades, as many as 1,000 rules, regulations and guidelines have been enacted worldwide to ensure the ethical conduct of medical research. In the United States, there are rules to protect people in every study done by federal scientists, funded by federal agencies or those testing a product requiring federal approval to be sold.

But that oversight is inconsistent — ethical rules can vary among federal agencies. What’s more, if federal funding or review is not involved, an unethical study could be done and no one in authority would ever know about it.
“We have a leaky system,” said Eric Meslin, director of the Indiana University Center for Bioethics.

Dr. Robert Califf, Duke University’s vice chancellor for clinical research, agreed there are weaknesses.

“It’s night and day and what you could do in the ‘good old days’ with no one knowing about it. But there’s no 100 percent guarantee. There still will be bad things that will happen,” he said.

In terms of pharmaceutical companies, there are clearly loopholes when it comes to overseas studies. Indeed, pharmaceutical companies have been doing more and more studies overseas. Although federal law states that such studies, if they are funded by the federal government or if they are to be used as part of an application for FDA approval of a drug, that is not always enough of a guarantee of oversight:

Last year, the U.S. Department of Health and Human Services’ inspector general reported that between 40 and 65 percent of clinical studies of federally regulated medical products were done in other countries in 2008, and that proportion probably has grown. The report also noted that U.S. regulators inspected fewer than 1 percent of foreign clinical trial sites.

Clearly, this is an unacceptable level of oversight, particularly outside of developed countries, such as those in Europe, where clinical trial oversight is comparable to that in the U.S.

Ironically, two examples come to mind of clinical trials that show the holes in our regulatory system for human subjects protection, both of which I have written about right here on SBM before. The first trial was a trial of homeopathic remedies for infants with infectious diarrhea in Honduras, as I wrote about here and Wally Sampson wrote about here. At the time I couldn’t figure out how the investigators at the University of Washington managed to get this study through their IRB, but somehow they did, demonstrating that an IRB is not a guarantee against the approval of totally unethical and scientifically worthless experiments. Fortunately, as far as I can tell, no infant was injured, but the potential was definitely there. Then, let’s not forget the Gonzalez trial, a trial of a regimen of what can best be described as pure quackery consisting of up to 150 supplement pills a day, various nutritional pseudoscience, and daily (or more) coffee enemas. The results were devastating, in that subjects on the standard-of-care chemotherapy arm lived three times longer than those on the Gonzalez protocol arm. Such is the effect of the National Center for Complementary and Alternative Medicine (NCCAM) on research ethics.

The more disturbing example is Mark and David Geier, the father-son tag team of anti-vaccine activists who fervently believe that mercury in vaccines causes autism and somehow came up with an idea that can only be described as dangerously wacky, namely that by suppressing testosterone with a powerful drug (Lupron) they could make the quackery known as chelation therapy “work better” at chelating mercury from the brains of autistic children. The reason? Because “testosterone sheets” bind mercury and keep it from being chelated! In pursuing this research, the Geiers have created an IRB stocked with their cronies and fellow anti-vaccinationists to “oversee” the research, as Kathleen Seidel has so thoroughly documented. In the process, autistic children were subjected to a powerful drug that depresses their sex hormone levels, which is why its use is often referred to as “chemical castration.” Predictably, Anne Dachel, Media Editor over at the anti-vaccine crank blog Age of Autism, has leapt all over this story as “evidence” that vaccines must be dangerous and that unethical scientists have been lying all along about the science showing tthat there is no evidence that vaccines cause autism:

Either Stobbe is a naïve and trusting soul and can’t consider that the same government that allowed horrific medical experiments in the past also allowed our children to become vaccine guinea pigs, or he’s afraid of an issue that’s just too controversial to talk about here and now. It’s much safer to attack what went on in the last century.

Maybe 70 years from now, some enterprising reporter will bring up the ethics of injecting known neurotoxins in pregnant women, babies, and small children.

Maybe around 2080, they’ll ask why no one ever demanded independent studies on the cumulative effect of so many vaccines, so soon, on the health of a baby. Or why there was never a simple vax-nonvax comparison study looking at autism rates.

Or maybe in 2050, Dachel will understand that this is the sort of work that’s been replicated so many times and done in so many different countries that even if you were to throw out all the U.S. data it wouldn’t change the conclusion that vaccines do not cause autism. She also overlooks the fact that the vast majority of the studies that have failed to find a link between vaccines and autism were performed after the adoption of the Common Rule and much-increased federal oversight over clinical trials. Of course, stories like Stobbe’s make it easier for cranks to attack the entire U.S. clinical research enterprise as corrupt and unethical. However, that is not the reason why we need to close the loopholes in our current clinical trial regulations. We need to do it because it is the right thing to do.

We at SBM argue that medicine should be based on science, rather than be a science, because we realize that medicine can never be completely scientific. There are too many human variables, not the least of which are patient values, individual patient situations, and resources. Another reason is the clinical trial process itself. Sometimes the most scientifically rigorous clinical trial design is not the most ethical design; indeed, sometimes it might be downright unethical. One example is, as I have pointed out, the aforementioned study of vaccinated versus unvaccinated children that seems to be every anti-vaccine activist’s most fervent dream. The most scientifically rigorous design for such a study would be a randomized, double-blind, placebo-controlled trial. However, such a trial would leave half of its participants completely unprotected against potentially deadly childhood infectious diseases, making it totally unethical to perform, even if it could be scientifically and fiscally justified based on existing preliminary data, which it really cannot.

Perhaps a better example is how placebo-controlled trials have almost gone the way of the dodo in cancer chemotherapy trials. Most oncology trials are now designed to test a new drug against the current standard of care or the new drug plus the standard of care versus standard of care alone. This is because our ethical considerations have evolved such that we now no longer consider giving placebos to cancer patients to be ethical unless there truly is no existing effective treatment for their cancer or if we truly do not know if the proposed treatment is better than observation alone and observation alone is currently the standard of care. As I have described before, in clinical trials, there must be clinical equipoise; i.e., based on the scientific evidence as it is known at the time the trial begins, a reasonable scientific assessment of the risks and benefits must conclude that the risks to the experimental group are either minimal or outweighed by the potential benefits. Here’s another thought to chew on. Experiments in which people were intentionally exposed to infectious agents and then subjected to various treatments to cure the disease thus caused are potentially the most scientifically rigorous way of all to test such treatments in humans because they allow control of the start of the infection, the amount of bacteria injected, and many other variables that can’t be so easily controlled in “wild” cases of infectious disease. However, because such experiments violate the precept of, “First, do no harm,” they are utterly unethical and now properly condemned by any physician with a shred of ethics. That we should require laws, rules, and regulations to prevent such unethical experiments by scientists is unfortunately, but scientists are no different than any other person. Not all of them are ethical; some are completely unethical. Some can be corrupted.

There will always be unethical scientists, at least as long as there are unethical people. That’s why we need laws to protect human subjects. However, we must also remember that the protection of human subjects is a balancing act. Go too far in the direction of lax regulation, and incidents such as those described in Stobbe’s article will start to happen again. Go too far in the other direction, and the pace of discovery will grind to a halt. Key to finding the balance is to respect patient autonomy and to provide true informed consent that accurately balances risks versus benefits and to protect patients from any form of coercion. Doing so without making the clinical trial process so onerous that researchers flee the field while at the same time protecting patients from foreseeable harms will be the challenge.

I have a mental basket of drugs that I suspect may be placebos. In that basket were the topical versions of non-steroidal anti-inflammatory drugs (NSAIDs). When the first products were commercially marketed over a decade ago, I found the clinical evidence unconvincing, and I suspected that the modestly positive effects were probably due to simply rubbing the affected area, or possibly due to the effects of the cream or vehicle itself. Frankly, I didn’t think these products worked. So when I recently noticed a topical NSAID appear for sale as an over-the-counter treatment for muscle aches and pains (seemingly only in Canada, for now), I was confident it would make a good case study in bad science.

It’s not that I’m partial to the oral NSAIDs. Yes, they’re among the most versatile, and probably most well-loved drugs in our modern medicine cabinet. They offer good pain control, reduce inflammation and can eliminate fever. We start using it in our sick and feverish infants, through childhood and adulthood for the aches and pains of modern life, and into our later years for the treatment of degenerative disease like osteoarthritis, which affects pretty much everyone as we age. An astonishing 17 million Americans use NSAIDs on a daily basis, and this number is expected to grow as the population ages. In the running groups I frequent, ibuprofen has the affectionate nickname “Vitamin I”, where it’s perceived as an essential ingredient for dealing with the consequences of training.

But NSAIDs have a long list of side effects. Not only do they cause stomach ulcers and bleeding by damaging the gastrointestinal mucosa, there are heart risks, too. It was the arrival (and departure) of the drugs Bextra and Vioxx that led to documentation of the potential for cardiovascular toxicity. And now there’s data to suggest that these effects are not limited to the “COX-2″ drugs – almost all NSAIDs, including the old standbys we have used for years, seem capable of raising the risks of heart attacks and strokes.

So despite my initial skepticism, I took another look at the topical NSAIDs. The data were not what I expected.

The use of NSAIDs

ASA (acetylsalicylic acid, Aspirin) the prototypical NSAID, traces its origin back to willow bark, a natural source of salicylate. All NSAIDs work the same way, interrupting the production of inflammatory and pain-related hormones called prostaglandins. Since ASA’s introduction in 1897, more than two dozen chemically related drugs have come to market. They’re now among the commonly used drugs used worldwide, playing a crucial role in pain management. Given the ubiquity of acute pain conditions, as well as chronic conditions like osteoarthritis, it’s estimated that 1 in 20 physician visits are related to prescriptions for NSAIDs. In general, all NSAIDS have equivalent efficacy at the population level, though individual response, and side effects, can vary between drugs. The discovery of different forms of cyclooxygenase enzymes led to new drugs that targeted COX-2 (at sites of inflammation) rather than COX-1 (which is involved with the stomach mucosa. Inhibit COX-2 rather than COX-1, the thinking went, and you could get the antinflammatory action of a traditional NSAID without the gastrointestinal toxicity. However, as the COX-2 saga demonstrated, effects can include the creation of a significant prothrombic effect – with devastating consequences.

The Risks of NSAIDs

Prescription drugs can and do cause significant morbidity, leading to frequent hospital admissions. While we may think nothing of popping a few ibuprofen now and then, NSAIDs have been linked to about 30% of drug-related hospital admissions, and it’s estimated that 12,000-16,000 Americans die annually as a result of gastrointestinal bleeding caused by NSAIDs.

Stomach bleeding and ulcers are a consequence of an NSAID’s mechanism of action – their effect on prostaglandins. The lining of the gut is weakened, and stomach and duodenal ulcers result. Even very low doses of ASA have been documented to have measurable effects on the mucosal lining of the gastrointestinal tract. The risks of gastrointestinal toxicity are significantly increased in the elderly, in those on high doses of NSAIDs, and when combined with other drugs (e.g., steroids) that suppress normal stomach protection.

The cardiovascular risks of NSAIDs became well documented following the worldwide withdrawal of rofecoxib (Vioxx) and international examinations of the cardiovascular risks of the entire category of drugs. Data have now emerged to convincingly establish that most NSAIDs (except ASA) are associated with an increased risk of cardiovascular events. Chronic (routine) consumption of most drugs is linked to small but real increases in heart attacks and stroke. These effects may be a consequence of interference with the beneficial effects of ASA (Aspirin), direct negative cardiovascular effects, and exacerbations of fluid balance, leading to heart failure.

When it comes to cardiovascular risks, not all NSAIDs are the same. A recently published network meta-analysis summarizes the differences, and the overall risks. Both traditional NSAIDs, like naproxen, ibuprofen, and diclofenac, as well as the COX-2 selective NSAIDs, like celecoxib (Celebrex) and rofecoxib (Vioxx) were studied. Happily for those that use over-the-counter anti-inflammatories only occasionally: naproxen seems to be the safest among the NSAIDs, with little to no increase in risk, and ibuprofen’s elevated risk seems limited to regular doses of 1200mg per day or more. So for the individual consumer, when do the risks outweigh the benefits of NSAIDs? Ultimately this comes down to an individual consideration of reasons for use, risk factors, and expected benefits.

To be clear, the absolute cardiovascular risks of NSAIDs, on an individual level, are low, compared to the other side effects of NSAIDs. They seem to cause three or more excessive events like heart attacks and stroke events, per 1000 patients, per year. Compare this to the 20-40 per 1000 per year that may have a (sometimes fatal) stomach bleed, a risk that’s 4x that of non-users. Still, their risk profile suggests that a consideration of their risk and benefits is warranted, particularly when they’re being contemplated in people with preexisting cardiovascular disease. On balance, when treating short-term conditions, the incremental risk in patients without cardiovascular disease is probably very low. Still, it seems prudent to use safer alternatives first (when possible) and if using NSAIDs, considering the lowest possible dose for the shortest possible duration.

Topical NSAIDs: The evidence

Over the past two decades, evidence has emerged to demonstrate that topical versions of NSAIDs are well absorbed through the skin and reach therapeutic levels in synovial fluid; muscle, and fascia. With topical use, little drug actually circulates in the plasma, leading to levels that are a fraction of comparable oral doses. As adverse events from NSAIDs are largely dose-related, it’s expected (thought not as well documented) that serious side effects should be minimized.

For chronic conditions like osteoarthritis, the data are of fair quality and are persuasive. The National Institutes for Health and Clinical Excellence osteoarthritis guidelines provides a nice summary of the trials. Studies varied by site of osteoarthritis (knee, hand, hip, etc), the type of NSAID studied, the regimen, and trial design. On balance, there’s good evidence to show that topical NSAIDs are clinically- and cost-effective for short term (< 4 weeks) use, especially when pain is localized. Topical and oral versions seem to be similarly effective under these circumstances, and there there’s a significant reduction in non-serious adverse events with topical products. While there’s no conclusive evidence to demonstrate a reduction of serious adverse events, they’re expected to be better than oral products, given the blood levels are much lower. What impressed me is that topical NSAIDs are recommended as a preferred treatment before oral NSAIDs. And given many taking oral NSAIDs need to take stomach protecting drugs like omeprazole, the topical products, while more expensive than their oral versions, may actually be more cost-effective overall.

A Cochrane review from 2010 is equally positive about the treatment of acute pain conditions. Forty-seven trials were included in their analysis that considered topical NSAIDs for strains, sprains, and overuse-type injuries. Compared to placebo, topical NSAIDs were evaluated to be effective, with few side effects, with a number needed to treat (NNT) of 4.5. About 6 or 7 out of 10 users can expect to achieve pain control with a topical NSAID, compared to 4 with a placebo. Side effects are comparable to placebo. And given systemic absorption is lower, the serious toxicity we associate with NSAIDs should be lessened, too. Not bad.

Given there’s no long-term data with topical NSAIDs, the evidence doesn’t give us enough insight to understand the risk profile beyond a few weeks. Consequently it seems reasonable to try using topical products instead of oral products, particularly for intermittent, rather than chronic, pain conditions. While compounding pharmacies have made topical versions of NSAIDs for years, there’s little information on effectiveness and safety of these products. As commercial formulations are supported with pharmacokinetic and clinical studies demonstrating efficacy, they are the preparations of choice.

Conclusion

NSAIDs, which already had a bad side effect profile, cause more harm then we thought. Evidence has emerged to demonstrate that topical NSAIDs are effective for many conditions that might otherwise require oral therapies. There’s little evidence to demonstrate that topical NSAIDs are effective for some types of pain, like back pain, headache, or neuropathic pain. But based on what’s now known about the cardiovascular toxicity of NSAIDs, it’s likely that topical products provide a superior risk/benefit perspective for regular and occasional users. The Cochrane review points out that topical NSAIDs are widely accepted in some parts of the world, but not in others. The reasons why are not clear. But having read the evidence, I’ve changed my opinion. And when I’m recovering from my next marathon, I’ll think about reaching for a topical NSAID, instead of that comforting bottle of vitamin I.

References

Haroutiunian, S., Drennan, D., & Lipman, A. (2010). Topical NSAID Therapy for Musculoskeletal Pain Pain Medicine, 11 (4), 535-549 DOI: 10.1111/j.1526-4637.2010.00809.x

Massey T, Derry S, Moore RA, & McQuay HJ (2010). Topical NSAIDs for acute pain in adults. Cochrane database of systematic reviews (Online) (6) PMID: 20556778

Solomon DH. Up-to-Date: Nonselective NSAIDs: Overview of adverse effects; Nonselective NSAIDs: Overview of adverse effects. From Up-To-Date (Database on the Internet).

Trelle, S., Reichenbach, S., Wandel, S., Hildebrand, P., Tschannen, B., Villiger, P., Egger, M., & Juni, P. (2011). Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis BMJ, 342 (jan11 1) DOI: 10.1136/bmj.c7086

OK, I admit that I pulled a fast one. I never finished the last post as promised, so here it is.

Cochrane Continued

In the last post I alluded to the 2006 Cochrane Laetrile review, the conclusion of which was:

This systematic review has clearly identified the need for randomised or controlled clinical trials assessing the effectiveness of Laetrile or amygdalin for cancer treatment.

I’d previously asserted that this conclusion “stand[s] the rationale for RCTs on its head,” because a rigorous, disconfirming case series had long ago put the matter to rest. Later I reported that Edzard Ernst, one of the Cochrane authors, had changed his mind, writing, “Would I argue for more Laetrile studies? NO.” That in itself is a reason for optimism, but Dr. Ernst is such an exception among “CAM” researchers that it almost seemed not to count.

Until recently, however, I’d only seen the abstract of the Cochrane Laetrile review. Now I’ve read the entire review, and there’s a very pleasant surprise in it (Professor Simon, take notice). In a section labeled “Feedback” is this letter from another Cochrane reviewer, which was apparently added in August of 2006, well before I voiced my own objections:

The authors’ state that they: “[have] clearly identified the need for randomised or controlled clinical trials assessing the effectiveness of Laetrile or amygdalin for cancer treatment.” This is to fail completely to understand the nature of oncology research in which agents are tested in randomized trials (“Phase III”) only after they have been successful in Phase I and II study. There was a large Phase II study of laetrile (N Engl J Med. 1982 Jan 28;306(4):201-6) which the authors of the review do not cite, they merely exclude as being non-randomized. But the results of the paper are quite clear: there was no evidence that laetrile had any effect on cancer (all patients had progression of disease within a few months); moreover, toxicity was reported. To expose patients to a toxic agent that did not show promising results in a single arm study is clinical, scientific and ethical nonsense.

I would like to make a serious recommendation to the Cochrane Cancer group that no reviews on cancer are published unless at least one of the authors either has a clinical practice that focuses on cancer or actively conducts primary research on cancer. My recollection when the Cochrane collaboration was established was that the combination of “methodologic” and “content” expertise was essential.

Wow! That letter makes several of the same arguments that we’ve made here: that for both scientific and ethical reasons, scientific promise (including success in earlier trials) ought to be a necessary pre-requisite for a large RCT; that the 1982 Moertel case series was sufficient to disqualify Laetrile; and that EBM, at least in this Cochrane review, suffers from “methodolatry.” It also brings to mind Steven Goodman’s words:

An important problem exists in the interpretation of modern medical research data: Biological understanding and previous research play little formal role in the interpretation of quantitative results. This phenomenon is manifest in the discussion sections of research articles and ultimately can affect the reliability of conclusions. The standard statistical approach has created this situation by promoting the illusion that conclusions can be produced with certain “error rates,” without consideration of information from outside the experiment.

…

This method thus facilitated a subtle change in the balance of medical authority from those with knowledge of the biological basis of medicine toward those with knowledge of quantitative methods, or toward the quantitative results alone, as though the numbers somehow spoke for themselves.

Perhaps most surprising about the ‘Feedback’ letter is the identity of its author: Andrew Vickers, a biostatistician who wrote the Center for Evidence-Based Medicine’s “Introduction to evidence-based complementary medicine.” I’ve complained about that treatise before in this long series, observing that

There is not a mention of established knowledge in it, although there are references to several claims, including homeopathy, that are refuted by things that we already know.

Well, Dr. Vickers may not have considered plausibility when he wrote his Intro to EBCM, but he certainly seems to have done so when he wrote his objection to the Cochrane Laetrile review. Which is an appropriate segue to a topic that Dr. Vickers hints at (“content expertise”), perhaps unintentionally, in the letter quoted above: Bayesian inference.

Bayes Revisited

A few years ago I posted three essays about Bayesian inference: they are linked below (nos. 2-4). The salient points are these:

1. Bayes’s Theorem is the solution to the problem of inductive inference, which is how medical research (and most science) proceeds: we want to know the probability of our hypothesis being true given the data generated by the experiment in question.
2. Frequentist inference, which is typically used for medical research, applies to deductive reasoning: it tells us the probability of a set of data given the truth of a hypothesis. To use it to judge the probability of the truth of that hypothesis given a set of data is illogical: the fallacy of the transposed conditional.
3. Frequentist inference, furthermore, is based on assumptions that defy reality: that there have been an infinite number of identically designed, randomized experiments (or other sort of random sampling), without error or bias.
4. Bayes’s Theorem formally incorporates, in its “prior probability” term, information other than the results of the experiment. This is the sticking point for many in the EBM crowd: they consider prior probability estimates, which are at least partially subjective, to be arbitrary, capricious, untrustworthy, and—paradoxically, because it is science that is ignored in the breach—unscientific.
5. Nevertheless, prior probability matters whether we like it or not, and whether we can estimate it with any certainty or not. If the prior probability is high, even modest experimental evidence supporting a new hypothesis deserves to be taken seriously; if it is low, the experimental evidence must be correspondingly robust to warrant taking the hypothesis seriously. If the prior probability is infinitesimal, the experimental evidence must approach infinity to warrant taking the hypothesis seriously. 
6. Frequentist methods lack a formal measure of prior probability, which contributes to the seductive but erroneous belief that “conclusions can be produced…without consideration of information from outside the experiment.”
7. The Bayes Factor is a term in the theorem that is based entirely on data, and is thus an objective measure of experimental evidence. Bayes factors, in the words of Dr. Goodman, “show that P values greatly overstate the evidence against the null hypothesis.”

I bring up Bayes again to respond to Prof. Simon’s statements, recently echoed by several readers, that people may differ strongly in what they consider plausible, and that it is not clear how prior probability estimates might be incorporated into formal reviews. I’ve discussed these issues previously (here and here, and in recent comments here and here), but it is worth adding a point or two.

First, it doesn’t really matter that people may differ strongly in what they consider plausible. What matters is that they commit to some range of plausibility—in public and with justifications, in the cases of authors and reviewers, so that readers will know where they stand—and that everyone understands that this matters when it comes to judging the experimental evidence for or against a hypothesis.

An example will explain these points. Wayne Jonas was the Director of the US Office of Alternative Medicine from 1995 until its metamorphosis into the NCCAM in 1999. He is the co-author, along with Jennifer Jacobs, of Healing with Homeopathy: the Doctors’ Guide (©1996), which unambiguously asserts that ultra-dilute homeopathic preparations have specific effects. Yet Jonas is also the co-author (with Klaus Linde) of a 2005 letter to the Lancet that includes this statement, prefacing his argument that homeopathy, already subjected to hundreds of clinical trials, has not been disproved and deserves further trials:

We agree that homoeopathy is highly implausible and that the evidence from placebo-controlled trials is not robust.

Bayes’s theorem shows that Jonas can’t have it both ways. Either he doesn’t really agree that homeopathy is highly implausible (which seems likely, unless he changed his mind between 1996 and 2005—oops, he didn’t); or, if he does, he needs to recognize that his statement quoted above is equivalent to arguing that the homeopathy ‘hypothesis’ has been disproved, at least to an extent sufficient to discourage further trials. 

Next, does it matter that we can’t translate qualitative statements of plausibility to precise quantitative measures? Does this mean that prior probability, in the Bayesian sense, is not applicable? I don’t think so, and neither do many scientists and statisticians. Even “neutral” or “non-informative” priors, when combined with Bayes factors, are more useful than P values (see #7 above). “Informative” priors—estimated priors or ranges of priors based on existing knowledge—are both useful and revealing: useful because they show how differing priors affect the extent to which we ought to revise our view of a hypothesis in the face of new experimental evidence (see #5 above); and revealing of where authors and others really stand, and of the information that those authors have used to make their estimates.

I believe that frequentist statistics has allowed Dr. Jonas and other “CAM” enthusiasts to project a posture of scientific skepticism, as illustrated by Jonas’s own words quoted above, without having to accept the consequences thereof. If convention had compelled him to offer a prior high enough to warrant further trials of homeopathy, Dr. Jonas would have revealed himself as credulous and foolish.

Finally, there is no reason that qualitative priors can’t be translated, if not precisely then at least usefully, to estimated quantitative priors. Sander Greenland, an epidemiologist and a Bayesian, explains this in regard to household wiring as a possible risk factor for childhood leukemia. First, he argues that there are often empirical bases for estimating priors:

…assuming (an) absence of prior information is empirically absurd. Prior information of zero implies that a relative risk of (say) 10¹⁰⁰ is as plausible as a value of 1 or 2. Suppose the relative risk was truly 10¹⁰⁰; then every child exposed >3 mG would have contracted leukaemia, making exposure a sufficient cause. The resulting epidemic would have come to everyone’s attention long before the above study was done because the leukaemia rate would have reached the prevalence of high exposure, or ~5/100 annually in the US, as opposed to the actual value of 4 per 100,000 annually; the same could be said of any relative risk >100. Thus there are ample background data to rule out such extreme relative risks.

The same could be said for many “CAM” methods that, while not strictly subjects of epidemiology per se, have generated ample experimental data (see homeopathy) or have been in use by enough people for enough time to have been noticed for substantial deviations from typical outcomes of universal diseases, should such deviations exist (see “Traditional [insert ethnic group here] Medicine”).

Next, Greenland has no problem with non-empirically generated priors, because these are revealing as well:

Many authors have expressed extreme scepticism over the existence of an actual magnetic-field effect, so much so that they have misinterpreted positive findings as null because they were not ‘statistically significant’ (e.g. UKCCS, 1999). The Bayesian framework allows this sort of prejudice to be displayed explicitly in the prior, rather than forcing it into misinterpretation of the data.

By “misinterpretation,” Greenland is arguing not that the “positive findings” of epidemiologic studies have proven the existence of a magnetic field effect, but that the objections of extreme skeptics must be made explicit: it is their presumed, if unstated, prior probability estimates that justify their conclusions about whether or not there is an actual magnetic field effect associated with childhood leukemia; it is not the data collection itself. Prior probability estimates put people’s cards on the table.

I recommend the rest of Greenland’s article, which is full of interesting stuff. For example, he doesn’t agree that “objective” Bayesian methods, using non-informative priors (see my point #7 above) are more useful than frequentist methods, since they are really doing the same thing:

…frequentist results are what one gets from the Bayesian calculation when the prior information is made negligibly small relative to the data information. In this sense, frequentist results are just extreme Bayesian results, ones in which the prior information is zero, asserting that absolutely nothing is known about the [question] outside of the study. Some promote such priors as ‘letting the data speak for themselves’. In reality, the data say nothing by themselves: The frequentist results are computed using probability models that assume complete absence of bias and so filter the data through false assumptions.

All for now. In the next post I’ll discuss another Cochrane review that has some pleasant surprises.

…

*The Prior Probability, Bayesian vs. Frequentist Inference, and EBM Series:

1. Homeopathy and Evidence-Based Medicine: Back to the Future Part V

2. Prior Probability: The Dirty Little Secret of “Evidence-Based Alternative Medicine”

3. Prior Probability: the Dirty Little Secret of “Evidence-Based Alternative Medicine”—Continued

4. Prior Probability: the Dirty Little Secret of “Evidence-Based Alternative Medicine”—Continued Again

5. Yes, Jacqueline: EBM ought to be Synonymous with SBM

6. The 2nd Yale Research Symposium on Complementary and Integrative Medicine. Part II

7. H. Pylori, Plausibility, and Greek Tragedy: the Quirky Case of Dr. John Lykoudis

8. Evidence-Based Medicine, Human Studies Ethics, and the ‘Gonzalez Regimen’: a Disappointing Editorial in the Journal of Clinical Oncology Part 1

9. Evidence-Based Medicine, Human Studies Ethics, and the ‘Gonzalez Regimen’: a Disappointing Editorial in the Journal of Clinical Oncology Part 2

10. Of SBM and EBM Redux. Part I: Does EBM Undervalue Basic Science and Overvalue RCTs?

11. Of SBM and EBM Redux. Part II: Is it a Good Idea to test Highly Implausible Health Claims?

12. Of SBM and EBM Redux. Part III: Parapsychology is the Role Model for “CAM” Research

13. Of SBM and EBM Redux. Part IV: More Cochrane and a little Bayes

14. Of SBM and EBM Redux. Part IV, Continued: More Cochrane and a little Bayes

It has long been recognized that there are substantial multifactorial placebo effects that create real and illusory improvements in response to even an inactive treatment. There is a tendency, however (especially in popular discussion), to oversimplify placebo effects – to treat them as one mind-over-matter effect for all outcomes. Meanwhile researchers are elucidating the many mechanisms that go into measured placebo effects, and the differing magnitude of placebo effects for different outcomes.

For example, placebo effects for pain appear to be maximal, while placebo effects for outcomes like cancer survival appear to be minimal.

A recent study sheds additional light on the expectation placebo effect for pain. The effect is, not surprisingly, substantial. However it does not extrapolate to placebo effects for outcomes other than pain, and the results of this very study give some indication why. From the abstract:

The effect of a fixed concentration of the ?-opioid agonist remifentanil on constant heat pain was assessed under three experimental conditions using a within-subject design: with no expectation of analgesia, with expectancy of a positive analgesic effect, and with negative expectancy of analgesia (that is, expectation of hyperalgesia or exacerbation of pain).

What they found was that the positive expectation group reported twice the analgesic effect as the no expectation group, and the negative expectation group reported no analgesic effect. This is a dramatic effect, but not surprising.

There are systems in the brain that specifically alter the perception of pain. Mood, expectation, and attention all affect the perception of pain. This makes evolutionary sense, since pain is meant to be a warning system for tissue damage or disease, and so needs to have an acute grip on our attention. At the same time, there are circumstances when we may need to function despite our pain, or when it would be adaptive to habituate to chronic pain. There are therefore mechanisms in the brain that function to enhance and draw our emotional attention to pain, and others that  function to inhibit pain.

It also needs to be noted that, broadly speaking, there are two components to pain. There is the origin and transmission of the pain signal, which is perceived as any tactile sensation. But then there is a specific emotional component to pain which occurs in the brain – that processing which makes pain hurt, that makes it into an emotionally negative experience. These two components can be separated. Narcotics, for example, are especially good at blocking the emotional component of pain, so that at times patients on opiates may report that they feel the pain but it does not bother them. Additionally, while withdrawing from narcotics the emotional component of pain in enhanced – patients may have what appears to be an exaggerated emotional response to even minor pain.

Therefore – since there is a built in system for modulating pain in response to both the physical and emotional environment, it makes sense that this system can be manipulated with physical and emotional inputs. If you make a patient feel better emotionally or decrease their stress or anxiety, their perception of pain will decrease, or at least it will not bother them as much (or, more precisely, their reporting of pain will decrease). This is why multi-disciplinary pain clinics often include psychological therapy as part of the overall approach.

This study demonstrates that expectation itself can have a dramatic effect on pain perception. They further elucidate, with fMRI analysis, the neuroanatomy that underlies this effect.

These subjective effects were substantiated by significant changes in the neural activity in brain regions involved with the coding of pain intensity. The positive expectancy effects were associated with activity in the endogenous pain modulatory system, and the negative expectancy effects with activity in the hippocampus.

This finding support prior research:

Further PET studies with dopamine D2/D3 receptor-labeling radiotracer demonstrate that basal ganglia including NAC are related to placebo analgesic responses. NAC dopamine release induced by placebo analgesia is related to expectation of analgesia. These data indicate that the aforementioned brain regions and neurotransmitters such as endogenous opioid and dopamine systems contribute to placebo analgesia.

The fMRI shows us where the effect is, and the PET scanning additionally shows us that dopamine is the important neurotransmitter involved in this effect.

What I would have loved to have seen in this study (perhaps this will be part of a follow up) is the same three treatment arms with a placebo treatment. This would enable us to directly compare the relative size of the expectation effect to the opiate effect. There are other questions as well. How much variation is there in the magnitude of this effect from person to person? Does the expectation effect habituate over time? Is the magnitude the same for different kinds of pain?

Conclusion

This study reinforces prior research indicating that there are built-in neurological mechanisms that modulate the perception and emotional content of pain. The study gives us further information about the exact brain structures involved in this effect. The authors conclude:

We propose that it may be necessary to integrate patients’ beliefs and expectations into drug treatment regimes alongside traditional considerations in order to optimize treatment outcomes.

They should have added “for pain.” This study says nothing about other treatment effects for which there does not exist a target system for symptom modulation. This error is distressingly common, especially in the translation of such research to the public. Pain is uniquely amenable to manipulation through mood and expectation. This does not predict that any other symptom or disease state can be so manipulated.

This situation is analogous to stress and heart disease. The heart is specifically susceptible to the physiological effects of emotional stress. Stress reduction, therefore, decreases, for example, the risk of heart attack. This does not mean, however, that stress reduction will therefore decrease the risks of any disease or adverse outcome.

All too often, however, people speak of “the placebo effect” as if it is one effect, equal for all outcomes. This notion is then supported with hand-waving explanations about self-healing. But the research is actually quite clear. There are many placebo effects. Expectation is only one effect among many,  and many of these effects are illusory – they create the false appearance of improvement where none exists (like regression to the mean or observational bias). Further, when speaking of the expectation effect we must be careful not to falsely extrapolate this effect from one outcome (like pain) to others.

This and other studies show that the brain is hardwired to modulate pain based upon expectation. There is no reason to think that this effect translates to other subjective symptoms, let alone objective outcomes like survival.

But I do agree with the authors to the extent that this and other studies do suggest that practitioners should seek to ethically maximize the benefits of positive expectation when treating pain. This should not, of course, violate the principles of honesty or informed consent. But putting a positive spin on the potential of a pain intervention is therapeutic. This does not justify, in my opinion, using a known placebo intervention (unless the patient was informed that it was a placebo or a treatment without any biological activity), because otherwise this would involve unethical deception (and could also create and reinforce unscientific beliefs in patients that could result in harm downstream). Further, as this study shows, you can get a sizable placebo effect from physiologically effective treatments.

A new article in the Journal of Women’s Health by Westhoff, Jones, and Guiahi asks “Do New Guidelines and Technology Make the Routine Pelvic Examination Obsolete?”

The pelvic exam consists of two main components: the insertion of a speculum to visualize the cervix and the bimanual exam where the practitioner inserts two fingers into the vagina and puts the other hand on the abdomen to palpate the uterus and ovaries. The rationales for a pelvic exam in asymptomatic women boil down to these:

• Screening for Chlamydia and gonorrhea
• Evaluation before prescribing hormonal contraceptives
• Screening for cervical cancer
• Early detection of ovarian cancer

None of these are supported by the evidence. Eliminating bimanual exams and limiting speculum exams in asymptomatic patients would reduce costs without reducing health benefits, allowing for better use of resources for services of proven benefit. Pelvic exams are necessary only for symptomatic patients and for follow-up of known abnormalities.

Screening for Chlamydia and Gonorrhea

Screening for Chlamydia in young women is evidence-based: it reduces the rate of pelvic inflammatory disease. New tests are available (on urine and self-administered vaginal swabs) that do not require a pelvic exam by a doctor. They are sensitive and cost-effective. Supporting references are listed in the article.

Hormonal Contraception

Doctors used to require pelvic exams before they would dispense prescriptions for oral contraceptives. This was never shown to be necessary; no findings from these exams influenced the decision to issue a prescription. One concern, the possibility of a pre-existing pregnancy, can’t be entirely ruled out by a pelvic exam; but the risk can be minimized by starting the pills after a normal menstrual period. Now all the major guidelines (from the FDA, WHO, ACOG, Planned Parenthood, etc.), specify that a pelvic exam is not required for hormonal contraception.

Cervical Cancer Screening

Pap smears have been proven effective in reducing morbidity and mortality from cervical cancer. Speculum exams are necessary to obtain specimens for Pap smears, but Pap smears need not be done annually and speculum exams need not be accompanied by bimanual exams. Current recommendations are to begin screening at age 21 and to re-screen at intervals of 2-3 years. New technology currently in development may eventually allow for equivalent screening without a pelvic exam.

Ovarian Cancer

The evidence shows that bimanual exams are useless for detecting ovarian cancer, and they are no longer recommended for this purpose.

Other Benefits/Risks of Pelvic Exams

While other conditions such as fibroids, ovarian cysts, and yeast infections can be detected by examining asymptomatic women, there is no evidence that early diagnosis improves outcomes. Over-screening for cervical cancer has been shown to lead to harm. Findings on pelvic exams can be false positives and can lead to unnecessary interventions.

“U.S. rates of ovarian cystectomy and hysterectomy are more than twice as high as rates in European countries, where the use of the pelvic examination is limited to symptomatic women.”

Is It Time to Abandon the Annual Pelvic Exam?

Yes, I think so. The existing evidence indicates that omitting it in asymptomatic women would not affect health outcomes. This article is representative of a growing consensus in the medical community, especially in other countries; but many US doctors are still doing annual pelvic exams. I suspect (just my opinion) that they are afraid of looking stupid or getting sued if they miss something, or are clinging to what they were taught to do out of inertia.  Meanwhile, science-based doctors are leaning away from annual physical exams in general. As this website says,

The annual physical exam is beloved by many people and their doctors. But studies show that the actual exam isn’t very helpful in discovering problems. Leading doctors and medical groups have called the annual physical exam “not necessary” in generally healthy people.

Even in patients being followed for diagnosed diseases, the physical exam sometimes degenerates into a token ritual. I’ve noticed that although I have no heart or lung symptoms, my own doctors like to check my lungs at every visit by putting the stethoscope on four spots (right, left, front and back) for one breath each, and to check my heart by applying the stethoscope briefly to one spot. I tolerate it because I know it makes them feel better, but I consider it totally useless.
Admittedly, there is a human element involved: hands-on interactions and the perception of “doing something” can be reassuring and can enhance the doctor/patient relationship. But can’t a caring clinician attain those same benefits within the realm of science-based medicine? A doctor’s time is better spent on proven health screening measures and in educating and counseling patients than in carrying out nonproductive rituals.

Last Friday, Mark Crislip posted an excellent deconstruction of a very disappointing article that appeared in the most recent issue of Skeptical Inquirer, the flagship publication of the Committee for Skeptical Inquiry (CSI). I say “disappointing,” because I was disappointed to see SI (Skeptical Inquirer, not Sports Illustrated) publish such a biased, poorly thought out article, apparently for the sake of controversy. I’m a subscriber myself, and in general enjoy reading the magazine, although of late I must admit that I don’t always read each issue cover to cover the way I used to do. Between work, grant writing, blogging, and other activities, my outside reading, even of publications I like, has declined. Perhaps SI will soon find itself off my reading list. Be that as it may, I couldn’t miss the article that so irritated Mark, because it irritated me as well. There it was, emblazoned prominently on the cover of the March/April 2011 issue: Seven Deadly Medical Hypotheses. I flipped through the issue to the article to find out that this little gem was written by someone named Reynold Spector, MD. A tinge of familiarity going through my brain, I tried to think where I had heard that name before.

And then I remembered.

Dr. Spector, it turns out, first got on my nerves about a year ago, when he wrote an article for the January/February 2010 issue of SI entitled The War on Cancer A Progress Report for Skeptics. I remember at that time being irritated by the article and wanting to pen a discussion of the points raised but don’t recall why I never actually did. It was probably a combination of the fact that SI doesn’t publish its articles online until some months have passed after the paper version has been released and perhaps my laziness about having to manually transcribe with my own fingers any passages of text that I might want to cite. By the time the article was available online, I forgot about it and never came back to it–until now. I should therefore, right here, right now, publicly thank Mark (and, of course, Dr. Spector) for providing me the opportunity to revisit that article in the context of piling on, so to speak, Dr. Spector’s most recent article. After all, Deadly Hypothesis Seven (as Dr. Spector so cheesily put it) is:

From a cancer patient population and public health perspective, cancer chemotherapy (chemo) has been a major medical advance.

Dr. Spector then takes this opportunity to cite copiously from his 2010 article, sprinkling “(Spector, 2010)” throughout the text like powdered sugar on a cupcake. There’s the opening I needed to justify revisiting an article that’s more than a year old! And what fantastic timing, too, hot on the heals of my post from a couple of weeks ago entitled Why haven’t we cured cancer yet?

Back to the future, before visiting the past

Before I leap back more than a year, first let me just point out that I agree with Mark 100% when he castigated Dr. Spector for his opening volley. Although thought had never occurred to me at the time, in retrospect I even agree with Crislip’s likening Dr. Spector’s tirade to a Mike Adams screed, at least in dogmatic certainty and tone. Sadly, for entertainment value at least, Dr. Spector lacks the looney hyperbole of Mike Adams. Also, unlike Adams, Dr. Spector is a real scientist, but damn if, references omitted, this first sentence couldn’t have come right out of a Mike Adams special:

A chronic scandal plagues the medical and nutritional literature (Spector and Vessell, 2006; Spector, 2009): much of what is published is erroneous, pseudoscientific, or worse.

Like Mark, I’m a John Ioannidis convert, and I accept that there is a lot of medical literature that is erroneous. (Just search for Dr. Ioannidis’ last name on this blog, and you’ll find copious posts praising him and discussing his work.) In fact, as I’ve pointed out, most medical researchers instinctively know that most new scientific findings will not hold up to scrutiny, which is why we rarely accept the results of a single study, except in unusual circumstances, as being enough to change practice. I also have pointed out many times that this is not necessarily a bad thing. Replication is key to verification of scientific findings, and more often than not provocative scientific findings are not replicated. Does that mean they shouldn’t be published?

As for pseudoscience, I’m half tempted to agree with Dr. Spector, but just not in the way he thinks. Unfortunately, over the last 20 years or so, there has been an increasing amount of pseudoscience in the medical literature in the form of “complementary and alternative medicine” (CAM) studies of highly improbable remedies or even virtually impossible ones (i.e., homeopathy). However, that does not appear to be what Dr. Spector is talking about, which is why I looked up his references. The second reference is to an SI article from 2009 entitled Science and Pseudoscience in Adult Nutrition Research and Practice. There, and only there, did I find out just what it is that Dr. Spector apparently means by “pseudoscience”:

By pseudoscience, I mean the use of inappropriate methods that frequently yield wrong or misleading answers for the type of question asked. In nutrition research, such methods also often misuse statistical evaluations.

Ah, now I get it! Dr. Spector doesn’t really know the difference between inadequately rigorous science and pseudoscience! Now, don’t get me wrong. I know that it’s not always easy to distinguish science from pseudoscience, especially at the fringes, but in general bad science has to go a lot further than Dr. Spector thinks to merit the the term “pseudoscience.” It is clear (to me, at least) from his articles that Dr. Spector throws around the term “pseudoscience” around rather more loosely than he should, using it as a pejorative for any clinical science less rigorous than a randomized, double-blind, placebo-controlled trial that meets FDA standards for approval of a drug (his pharma background coming to the fore, no doubt). Pseudoscience, Dr. Spector. You keep using that word. I do not think it means what you think it means. Indeed, I almost get the impression from his articles that Dr. Spector views any study that doesn’t reach FDA-level standards for drug approval to be pseudoscience. He also piles on nutritional science (that is, after all, his area of specialty), and there is no doubt that here is a lot of pseudoscience there; however the vast majority of it is not in the scientific literature. Rather, it’s snake oil salesmen selling diets and supplements based on less rigorous science, the willful twisting and misinterpretation of acceptable science, and making up claims out of whole cloth.

Here’s the deal. Medical science, when it works well, tends to progress from basic science, to small pilot studies, to larger randomized studies, and then–only then–to those big, rigorous, insanely expensive randomized, double-blind, placebo-controlled trials. Dr. Spector mentions hierarchies of evidence, but he seems to fall into a false dichotomy, namely that if it’s not Level I evidence, it’s crap. The problem is, as Mark pointed out, in medicine we often don’t have Level I evidence for many questions. Indeed, for some questions, we will never have Level I evidence. Clinical medicine involves making decisions in the midst of uncertainty, sometimes extreme uncertainty. One example is hormone replacement therapy for menopause before the results of the Women’s Health Initiative study were reported. Indeed, Dr. Spector makes much hay out of the widespread use of hormone replacement therapy (HRT) back in the 1980s and 1990s, as an example of what happens when we don’t adhere to proper clinical trial design, labeling Deadly Hypothesis Two as:

The hypothesis was that if women replace these hormones postmenopausally with HRT, they will remain “youthful” and not suffer from heart disease, dementia, vaginal dryness, hot flashes, and fractured bones.

Dr. Spector then proceeds to paint a picture of reckless physicians proceeding on crappy studies to pump women full of hormones. Actually, it was more than a bit more complicated on than that. That was the time when I was in my medical training, and I remember the discussions we had regarding the strength (or lack thereof) of the epidemiological data and the lack of good RCTs looking at HRT. I also remember that nothing works as well to relieve menopausal symptoms as HRT, an observation we have been reminded of again since 2003, which is the year when the first big study came out implicating HRT in increasing the risk of breast cancer (more later). It’s also hard not to point out that, these days, it’s not physicians promoting HRT. Rather, it’s women like Suzanne Somers promoting “bioidentical hormones” and telling postmenopausal women that they should strive for the estrogen levels that they had when they were 25. Be that as it may, I found a rather fascinating editorial in the New England Journal of Medicine from more than 20 years ago that discussed the state of the evidence back then with regard to estrogen and breast cancer:

Evidence that estrogen increases the risk of breast cancer has been surprisingly difficult to obtain. Clinical and epidemiologic studies and studies in animals strongly suggest that endogenous estrogen plays a part in causing breast cancer. If so, exogenous estrogen should be a potent promoter of breast cancer. Although more than 20 case–control and prospective studies of the relation of breast cancer and noncontraceptive estrogen use have failed to demonstrate the expected association, relatively few women in these studies used estrogen for extended periods. Studies of the use of diethylstilbestrol and oral contraceptives suggest that a long exposure or latency may be necessary to show any association between hormone use and breast cancer. In the Swedish study, only six years of follow-up was needed to demonstrate an increased risk of breast cancer with the postmenopausal use of estradiol. It should be noted, however, that half the women in the subgroup that provided detailed data on the duration of hormone use had taken estrogen for many years before their base-line prescription status was defined. The duration of estrogen exposure in these women before the diagnosis of breast cancer was probably seriously underestimated; a short latency cannot be attributed to estradiol on the basis of these data. Other recent studies of the use of noncontraceptive estrogen suggest a slightly increased risk of breast cancer after 15 to 20 years’ use.

One notes that, even now, the evidence is conflicting regarding HRT and breast cancer, with the preponderance of evidence suggesting that mixed HRT (estrogen and progestin) significantly increases the risk of breast cancer, while estrogen-alone HRT very well might not increase the risk of breast cancer at all or (more likely) only very little. Indeed, I was just at a conference all day Saturday where data demonstrating this very point were discussed by one of the speakers. None of this stops Dr. Spector from categorically labeling estrogen as a “carcinogen that causes breast cancers that kill women.” Maybe. Maybe not. It’s actually not that clear. The problem, of course, is that, consistent with the first primary reports of WHI results, the preponderance of evidence finding health risks due to HRT have indicted the combined progestin/estrogen combinations as unsafe. Even at this late time, we do not truly know whether estrogen-alone HRT carries significant risks (there are even some studies, a subgroup of the WHI included, that hint at a slightly protective effect of estrogen against breast cancer), but we do have a pretty good idea that estrogen-alone HRT is almost certainly safer than estrogen-progestin HRT, at least with respect to breast cancer. Unfortunately, there is good evidence that estrogen-only HRT increases the risk of uterine cancer. Either way, Dr. Spector’s dogmatic and unnuanced discussion of the issue suggests an axe to grind more than an interest in providing an accurate picture. Indeed, he even goes so far as to slip this sentence in there: “In legal challenges the U.S. Supreme Court has upheld the notion that HRT causes breast cancer.”

What? Who cares what the Supreme Court says about medical causation? That’s a legal standard, not a scientific standard! There’s no reason to throw such a sentence into a serious medical article.

The rest of the “Seven Deadly Medical Hypotheses” remain just as questionable, particularly the way Dr. Spector castigates the idea that screening populations for breast and prostate cancer saves lives. In all fairness, Dr. Spector’s skepticism towards screening is actually the least unreasonable part of his most recent article, given recent evidence. He even concludes that mammography has a small benefit. Therein lies a contradiction. If mammography, for instance, is beneficial, even if only slightly, then how can it be part of a “deadly medical hypothesis”? Calling screening a “deadly” medical hypothesis is, as is the case with much of this article, way over the top. A “disappointing” medical hypothesis would be a far better description. In any case, for a far more nuanced discussion of cancer screening, I will blow my own horn and suggest that you go to read these posts:

Posts by yours truly:

1. The early detection of cancer and improved survival: More complicated than most people think
2. Early detection of cancer, part 2: Breast cancer and MRI
3. Do over one in five breast cancers detected by mammography alone really spontaneously regress?
4. Are one in three breast cancers really overdiagnosed and overtreated?
5. The cancer screening kerfuffle erupts again: “Rethinking” screening for breast and prostate cancer
6. The USPSTF recommendations for breast cancer screening: Not the final word
7. The mammography wars heat up again
8. Molecular breast imaging (MBI): A promising technology oversold in a TED Talk?

Posts by Harriet Hall:

1. Screening Tests – Cumulative Incidence of False Positives
2. Overdiagnosis

By Val Jones:

• The Mammogram Post-Mortem

Read them now, or read them later. They are far more informative and nuanced than anything Dr. Spector has written on these topics for SI. For example, you won’t find the word “deadly” in there anywhere. In the meantime, let’s move on to the article that irritated me so over a year ago. Oddly enough, it was a bit more balanced and less dogmatic than the current article.

“We’re losing the war on cancer”?

The beginning of The War on Cancer A Progress Report for Skeptics, while not as over-the-top as the beginning of Seven Deadly Medical Hypotheses, is still pretty negative:

In 1971, President Nixon and Congress declared war on cancer. Since then, the federal government has spent well over $105 billion on the effort (Kolata 2009b). What have we gained from that huge investment? David Nathan, a well-known professor and administrator, maintains in his book The Cancer Treatment Revolution (2007) that we have made substantial progress. However, he greatly overestimates the potential of the newer so-called “smart drugs.” Re searchers Psyrri and De Vita (2008) also claim important progress. However, they cherry-pick the cancers with which there has been some progress and do not discuss the failures. Moreover, they only discuss the last decade rather than a more balanced view of 1950 or 1975 to the present.

On the other hand, Gina Kolata pointed out in The New York Times that the cancer death rate, adjusted for the size and age of the population, has decreased by only 5 percent since 1950 (Kolata 2009a). She argues that there has been very little overall progress in the war on cancer.

I find it rather amusing how Dr. Spector accuses investigators like Dr. Vincent DeVita (who is a coauthor of one of the widely used textbooks of oncology there is, a copy of which sits on my shelf in my office) of “cherry picking” cancers for for which progress has been made and focusing primarily on the last decade while at the same time stating that he is going to focus on adult solid cancers, where less progress has been made. One might argue that this is a correct way to do it, and far be it from me to claim that the war on cancer has been an overwhelming success. As I pointed out a couple of weeks ago, however, there is a reason (many reasons, actually) why progress has been so elusive. There is also at least one other reason. However, it’s quite obvious in both articles that Dr. Spector has himself concentrated on data that he can use to make the situation look as dismal as possible; i.e., to support his apparently preconceived conclusions that the war on cancer has been a miserable failure and that chemotherapy doesn’t work (that is, except when it does work very well). Indeed, in his most recent article, Dr. Spector uses terminology that is even more negative about chemotherapy than in his previous article. For example in the current article, Dr. Spector writes:

The hypothesis behind current chemotherapy is deeply flawed. How can we expect these drugs, most of which are nonspecific cellular poisons, to kill only wiley cancer cells and not normal cells? In fact, cacner chemotherapy routinely kills bone marro and the cell lining of the gastrointestinal tract, with very distressing (indeed sometimes fatal) side effects.

It rather shocks me that a pharmacologist like Dr. Spector would write something like this without mentioning that the reason chemotherapy can work in some tumors is because it is more toxic to the cancer cell than it is to (most of) the surrounding normal tissue. The same thing is true of radiation. This is not a trivial point. Dr. Spector makes it sound as though chemotherapy poisons everything equally and that it’s a miracle that it ever works at all. He then writes:

However, it cannot be denied that there are a few populations for which chemotherapy is marvelously effective, as noted above, and must be used.

No kidding! For example, many leukemias and lymphomas, testicular cancer, and anal cancer (which is treated primarily with the Nigro protocol, which consists of chemotherapy and radiation), among others!

Dr. Spector correctly points out that smoking tobacco products is a major cause of lung cancer, which causes most cancer deaths these days in both men and women. He even shows several very nice graphs that demonstrate that lung cancer death rates began to skyrocket about twenty years after cigarette consumption began to skyrocket (Figure 3) and that lung cancer death rates have been declining (in men at least; they appear to be peaking in women, Figures 4 and 5), approximately 25 years after cigarette consumption began to decline. All of these results are very much in accord with what we know about cigarette smoke as a carcinogen. One thing is clear: If we could eliminate cigarette smoking completely, approximately 20 years later, declines in lung cancer deaths would drive major declines in overall cancer deaths. There’s little doubt of that. However, such an observation is very much a “Well, duh!” conclusion. It’s not as though public health authorities in the U.S are unaware of such statistics or that dramatic gains or haven’t been working to try to discourage smoking. Changing behavior is very, very hard. In fact, I would argue that decreasing cancer mortality by 5% since 1950 is actually pretty darned good, given that lung cancer mortality tripled among men between 1950 and 1990 and more than doubled among women from 1970 to 2000. If you don’t believe me, take a look at these graphs from the SEER Database of cancer death rates from the various major forms of cancer, in particular Figure 4 and Figure 5. Then there is this graph in Figure 2:

This demonstrates that, although cancer incidence rates are leveling off, cancer death rates are decreasing. Sure, it’s not as good as we need to do, but notice that the curves are separating. Indeed, if you look at Figure 7, you’ll see an estimate of how high cancer mortality would be if cancer mortality rates had remained the same over the last 20 years:

The American Cancer Society attributes the decreases in cancer mortality to this:

The decrease in lung cancer death rates among men is due to a reduction in tobacco use over the past 50 years, whereas the decrease in death rates for female breast, colorectal, and prostate cancer largely reflects improvements in early detection and/or treatment. Between 1990–1991 and 2006, death rates increased for liver cancer in both men and women, esophageal cancer and melanoma in men, and lung and pancreatic cancer in women. Figure 7 shows the total number of cancer deaths avoided since death rates began to decrease in 1991 in men and in 1992 in women. Approximately 767,000 cancer deaths (561,400 in men and 205,700 in women) were averted between 1991–1992 and 2006.

Death rates from all cancer are a rather crude measure of how the war on cancer is going, anyway, being an aggregate number that is only likely to be affected very late as a result of improvements in cancer therapy. Our population is aging, which means that more people are living long enough to develop cancer, particularly given that we’ve made such dramatic progress in decreasing death rates from cardiovascular disease. People who live longer because they don’t die of cardiovascular disease have to die of something, and cancer, being number two (although not for long), is the next most likely cause. In any case, let me provide an example of what I find wrong with Dr. Spector’s thesis. In his “war on cancer” article a year ago, Dr. Spector wrote:

The FDA has approved bevacizumab for the cancers listed in table 5 (Physicians Desk Reference [PDR] 2009; Health Agencies Update 2009). Since the median survival of colorectal cancer is eighteen months, bevacizumab therapy would cost about $144,000 (in such a patient) for four months prolongation of survival (Keim 2008). In the other cancers in table 4, there is no prolongation of survival. Moreover, bevacizumab can have terrible side effects, including gastrointestinal perforations, serious bleeding, severe hypertension, clot formation, and delayed wound healing (PDR 2009). By the criteria in table 4, bevacizumab is at best a marginal drug. It only slightly prolongs life, demonstrable only in colorectal cancer, has serious side effects, and is very expensive.

Here’s a more provocative and somewhat more optimistic assessment of the progress we’ve made in treating metastatic colorectal cancer in graph form (click to make bigger):

Untreated metastatic colorectal cancer has about a four to six month median survival. Our old chemotherapy regimens increased the medical survival in metastatic colorectal cancer to around 12 months. Newer regimens boosted that to around 16 or 17 months. Adding bevacizumab then increased the survival to around 21 months. All of this has occurred since the mid-1990s. Is it enough? Of course not! But as a clinician I would argue that quadrupling the life expectance of someone with metastatic colorectal cancer is nothing to sneeze at. Indeed, I even have personal experience with this. The father of a good friend died last summer of metastatic colorectal cancer after having lasted over six years. A combination of surgeries, chemotherapy, and other treatments kept him going. He played golf until a week before his health declined precipitously and unexpectedly, and he died. Yes, he was certainly an outlier, but if the median survival of a group of cancer patients is pushed longer and longer, there will be more and more outliers like my friend’s father. True, we would much prefer a cure (or at least a reasonable chance of a cure), but ask the cancer patient what that extra year or several months means to him or her. Also true, as a society, we have to decide how much we are willing to pay for that additional survival, but that is a societal question more than anyone else. It’s also rather disappointing that Dr. Spector would describe bevacizumab as a “nonspecific toxin” that interferes with blood vessel growth throughout the body. That’s not quite true. Bevacizumab does interfere with angiogenesis, but it tends to be much more specific for tumor blood vessels and other abnormal blood vessels than for normal blood vessels. Indeed, the most recent concepts regarding bevacizumab is that it actually “normalizes” tumor blood vessels, allowing chemotherapy to get to the tumor better. This observation explains a paradoxical observation that I made in the 1990s that radiation and antiangiogenic therapy with anti-VEGF antibody produced greater than additive anti-tumor effects.

Be that as it may, suppose I’ll be accused of “cherry picking” this example, but I don’t care that much. I choose it because I want to point out that the situation is not always as grim as Dr. Spector claims and that we have made enormous progress in treating some cancers over the last 40 years. I would also point out that the $105 billion we have spent on the war on cancer since 1970 breaks down to only around $2.6 billion a year. In recent years, the yearly budget for the National Cancer Institute has hovered in the $4.7 to $5.2 billion range. This may sound like a lot of money, but in reality it is only 0.1% of the $3.8 trillion federal budget this year. Let’s just put it this way, the entire yearly budget for the NCI would fund the war in Afghanistan for approximately 16 or 17 days. That is not a lot of money in the grand scheme of things; certainly it isn’t enough money to pay for a real “war” on cancer.

Where do we go from here?

Let me just begin my conclusion by conceding that Dr. Spector does make a few good points, albeit in insufficient detail in some cases. For example, his discussion of lead time bias is superficial and doesn’t even use the proper term for the concept, and he leaves out the concept of length bias in screening altogether. More irritating, though, is that there’s clearly a relentless effort on his part in both articles to paint as grim a view of the situation as before. Yes, Dr. Spector is correct that, if we could only decrease smoking to nothing we could decrease the death rate from breast cancer dramatically over the next 20-30 years. He’s also correct that decreasing use of HRT will help decrease the death rate from breast cancer, but in reality we’ve already done that. HRT use has declined precipitously after 2002; there isn’t much room to decrease it further. He also recommends vaccines to prevent HPV infection and thereby decrease the risk of cervical cancer, but that is really a pretty small contribution to the overall cancer death rate. Even so, let’s say we do all these things that Dr. Spector suggests because they are good things to do and will have an effect. Ignore for the moment how difficult it is to get people to stop smoking to prevent lung cancer, to stop drinking to prevent head and neck, esophageal, and liver cancers, and to lose weight to decrease the incidence of obesity-related cancers. Let’s say we can do it. What then? We will still have lots of people who will develop cancer and die from it if we don’t come up with better therapies. How do we do that? On that score, Dr. Spector is profoundly self-contradictory. I’ll show you what I mean.

At one point, Dr. Spector opines:

In my view the principal problem is that we just do not understand the causes of most cancers. We don’t even know if the problem is genetic or epigenetic or something totally unknown. In theory, problems 2 through 6 in table 6 are all correctable with political and scientific will and more knowledge. Even though we know cancer of the lung is caused by cigarette smoking, we do not know the mechanism, and (except for surgery) we do not know how to meaningfully intervene (see table 2). The pharmaceutical industry cannot make real progress until we understand the mechanisms and molecular causes of cancer so that industrial, academic, and governmental scientists have rational targets for intervention. We will make no progress if there are five hundred or more genetic abnormalities in a single cancer cell. Where would one begin?

And:

Moreover, with better mechanistic understanding of cancer, we could make truly “smart” drugs, as has been done in recent years for atherosclerosis (heart attacks), hypertension (strokes), gastrointestinal diseases (ulcers), and AIDS—with truly remarkable results. Let us hope cancer is next.

I can’t argue with that. Indeed, I’m very much about trying to understand the biology of cancer much better, so that we can design treatments that will be much more effective, “truly smart drugs,” as Dr. Spector puts it. That’s the direction, in fact, that I’m trying to move my research effort, with the help of a very good systems biologist. Here’s the problem. In his most recent article, Dr. Spector dismisses as useless and deadly the very techniques that we will require in order to generate the hypotheses that could lead to that better understanding of cancer upon which Dr. Spector’s proposed next generation of “smart drugs” would be based. Yet Dr. Spector poo-poos genome-wide association studies (GWAS), using them as an example of Deadly Hypothesis One. He lambastes the concept of personalized medicine and the genetic studies that will be necessary to achieve it as Deadly Hypothesis Six. He praises the methods used by the FDA, but, as explained by Mark Crislip, the rigor demanded by the FDA is the final step in a long process that begins with basic science, progresses through epidemiology and pilot studies, and then finally concludes with large, phase III randomized trials. Moreover, the final studies leading to FDA approval really are the “safest” part of the process, based on scads of data from all those earlier studies.

In other words, Dr. Spector, while claiming we need new and innovative hypotheses and ways to understand biology is in reality advocating very safe science indeed.

Dr. Spector makes a point that we need a better understanding of cancer, but he clearly has little idea about how to bring that about from a basic science perspective. So boxed into his clinical trial and pharma perspective is he that he castigates the very means of developing new hypotheses to test that we need. While Dr. Spector is correct that GWAS and gene expression profiling studies have been disappointing thus far, one needs to remember that the technology to do these studies has been in existence only a relatively few years and that these studies generate huge masses of data that strain even the best computers to analyze. In other words, we are early into these processes, but, as the cancer genome anatomy project demonstrates, we are learning.

That’s why I conclude that the worst aspect of Dr. Spector’s most recent article and his whole attitude in general is how he labels as Deadly Hypothesis One the concept that either “the investigator does not need a specific hypothesis and/or can use an inadequate method to test the hypothesis.” Yes, failing to use a specific hypothesis is not a good idea later in the process of drug development, but if we are to understand the biology of cancer sufficiently to design the next generation of “smart drugs,” we need new hypotheses, and these come from pilot studies. We sometimes call these studies “fishing expeditions” or, less pejoratively, “hypothesis generating experiments.” Come to think of it, one wonders whether Dr. Spector approved of the Human Genome Project. After all, there was no hypothesis to test there; scientists were simply trying sequence the entire human genome, and they learned a lot. More importantly, the results of the HGP generated many new hypotheses to test, many of which are being tested now, along with a revolution in genomic technology. The problem with Dr. Spector’s point of view is that he strikes me as seeing everything through the lens of pharma and the FDA. Scientific rigor is a good thing before approving drugs and treatments; in fact, it’s absolutely essential. However, the discovery process often begins by looking around and seeing if there’s anything interesting to see. Without that discovery process, all those rigorous trials meeting FDA requirements would never come to fruition because there would be no basic science pipeline to supply the translational research pipeline that eventually results in new drugs. Many–the vast majority, actually–of these hypotheses will never pan out, but they are just as essential to science-based medicine as the studies Dr. Spector loves.

Can we do better in the “war on cancer”? Of course we can–and must. However, it must be remembered that the “war on cancer,” like most wars, is not World War II. There is not, nor will there be, a total victory, an atomic bomb-like magic bullet that destroys all cancer. There will, as with most wars, be equivocal results, wins and losses, and pyrrhic victories. But we won’t get even that far if we embrace scientific nihilism over healthy skepticism.

Now here’s something that can be used to counter the antivaccine musical stylings of Mike Adams and his song Don’t Inject Me: Play ZDoggMD’s Immunize!:

Sometimes, even on SBM, we need to lighten things up a bit. Take that, Mike Adams!

There are sources of information I inclined to accept with minimal questioning.  I do not have time to examine everything in excruciating detail, and like most people, use intellectual short cuts to get through the day.  If it comes from Clinical Infectious Diseases or the NEJM, I am inclined to accept the conclusions without a great deal of analysis, especially for non-infectious disease articles.  Infectious disease publications I have to read more closely; its part of passing as an expert.

Outside of medicine, I am predisposed to accepting at face value many of the articles in Skeptic and Skeptical Inquirer. They are trusted sources.  Some topics, like haunted house or Big Foot investigations, I barely skim. After all these years, I doubt there will be any new insights into the subject.  Other topics, depending on my interest, I may read more carefully.

I  often read longer articles  many times.  First a quick skim to see if it offers anything of interest.  If it does, then I may read it carefully.

This months Skeptical Inquirer had an article called  Seven Deadly Medical Hypotheses by Reynold Spector.  Just seeing the title and knowing the magazine, I was primed to accept the content at face value.  I enjoy a well reasoned, thoughtful rant. I relish a clever diatribe, even if I do not agree with the topic.   So I gave it a quick skim.  I was discomfited.  My first gut check was ick.  But I was uncertain why.  So I read it slowly and carefully, and still ick.  But why?There is a degree of self absorption in being a blogger.  I can write about what I want any way I want (I remain amazed at how much I can get away with).  The process of writing about a topic helps me clarify in my own mind issues with articles.

The author of 7, as I shall refer to the article,  has over 200 published articles, is a former executive vice president in charge of drug development at Merck and oversaw the development of 15 drugs and vaccines.  I am nobody from nowhere who just takes care of infected patients for a living.  He wins the argument from authority; I am the E. coli evaluating the human.  Oh well,  this is more an exercise for me to enlighten myself; you are the innocent bystander.

Overall the tone of 7 ? It reminded me of the Health Ranger at NaturalNews.com. Really.  Lots of dramatic statements, no qualifiers, no buts, no subtlety, no nuance.  To me, what marks good medical writing is an understanding that there is far more grey than black and white and that generally people are doing the best they can within numerous limitations  One of the many characteristics of the Health Ranger is hyperbole without nuance.  The Health Ranger has a belief system and sees the medical industrial complex through that lens; information is used to support a predetermined conclusion.  Health Ranger is a bombastic style that is both self assured and self referential.

Let us see what 7 has to say. It begins

A chronic scandal plagues the medical and nutritional literature: much of what is published is erroneous, pseudoscientific, or worse.

I’ll grant the first.  I am an Ioannidis convert.  The second seems hyperbole and exaggeration. Pseudoscientific?  Like homeopathy, psi and astrology?  Sorry The author is 17 words in and he has lost me.  I already question his veracity and judgement.  I read the literature. Hundreds of papers a month. I know the literature, and Sir, it is not pseudoscientific.  Suboptimal, often, but not pseudoscientific.  The third?  What could be worse than pseudoscientific?  Oh yeah.  Wakefields Lancet article.  But fraud  is a very rare exception in the over 20 million references on Pubmed.  The author’s opening salvo strikes me as someone more interested in polemic than truth. If done with verve and panache, and above all wit, I like a good polemic. Pomposity with hyperbole, not so much, and calling the medical literature erroneous, pseudoscientific, or worse leans towards the latter.

Two major factors account for a large proportion of this problem.  First, many medical and nutritional hypothesis are ill-conceived.

Are they?  Over 20 million references in Pubmed.  A few, perhaps, were ill conceived before they are tested. Say, measles vaccine induced gastroenteritis causing autism?  Not even that.  If approached honestly and competently, it would be a long shot, but you never knows unless you look.   That is what a great deal of medical research is about: looking around to see if an etiology or intervention or medication will be effective.  Most ideas, I would guess, go nowhere.

Second, the methods used are often epistemologically unsound.

Got me there.  What is epistemologically unsound?  Even after looking epistemologically up on the interwebs, I am uncertain what it means.   I expect the comments will school me on the meaning of epistemologically unsound. I guess that is why I am a lowly clinician.

Moreover, the same unsound methods are often repeated multiple times on the same tired hypotheses with the same incorrect results.

Isn’t that three major factors?  Or is that the unsound epistemological I cannot understand?  I shouldn’t quibble about counting, but I feel a rising tide of ridicule and scorn, and I am not one to hold it back.

I am not even done with the first paragraph, and the author has epistemologically lost me. Maybe there is good reason to be unsettled with the article.   And in the first five sentences, there are four references, all to works by the author, to justify the position.  I tend to prefer external references in my literature; the hyperbolic self-validation is what I expect from the Health Ranger and his ilk.  But again, who am I to question (1)?

… there is an epidemic of published studies that do not follow the principles of sound medical science- the principles demanded by the US Food and Drug Administration for the licensure and sale of medications.

Well, most studies are preliminary and exploratory.  The rigor demanded by the FDA is the final step in a long process starting with basic principles and, perhaps, epidemiology.  I can’t imagine we should jump to huge randomized, placebo controlled trials for every therapy and to answer every question.  Seems a wee bit excessive to me. Start small and build.  The downside is that there will be dead ends and false conclusions.  The upside is that in the end, a close approximation of Truth will be determined.

The resulting “findings” of such misleading or erroneous studies are often hyped by the news media on the day they are reported or published without any additional, careful analysis.

Hyped “findings”?  Nothing like that in the first two paragraphs of the this essay. Nope.  Nothing to see there but a well reasoned, careful, nuanced prologue for the body of the  essay.  “I” am always “mistrustful” of people who use “quotes” as a form of “sarcasm” when sarcasm is not used for good “effect” like “humor” because it otherwise comes across as “supercilious”.

Now I am starting to understand my discomfiture. Still, that’s just the first two paragraphs.  The body will better, right?

The author then proceeds to the background of how to do a good study: generate a plausible, testable hypothesis and test it.  He uses the Scandinavian Simvastatin Survival Study as an example of medicine done right (a Merck product if you care) and bemoans that not every study meets this high standard.

Too many published studies fail to adhere to these high scientific standards and lead to faulty, and even dangerous, conclusions.

Which is true and to my mind understandable, since there are not the resources to do perfect studies of every hypothesis.   Not every car is a Lexus, not every restaurant has a Michelin three star rating. You can’t always get what you want (2).  The issue to my mind is not that there are suboptimal studies; they are often used to find search for hypothesis that can be tested in better trials.  A large part of research is flailing about looking for something interesting to investigate in further detail.  Not everyone has the resources to test everything using the ‘hypothetical/deductive method” to answer all out questions, like the FDA demands.  Although this is not always the preferred method of generating ideas to test.  I don’t need quotes to cast aspersions on the validity of information or generate guilt by association.  I have learned a thing or two from reading the Health Ranger.

I wonder how many suboptimal studies it required to get to the point of the Scandinavian Simvastatin Survival Study?  The concepts to be tested did not appear from the void, fully formed.  The author does not, as will be seen, pay attention to the history and context of the evolution of medical ideas.

The author then proceeds to his 7 deadly hypotheses. Well, one deadly,  6 not so much.  But guilt by association is a game played by the author of 7 as well.

1) the investigator does not need a specific hypothesis and/or can use an inadequate method to test hypothesis.

He uses the example of epidemiology generated by case-control and cohort studies (the kind of studies that lead to the simvastatin study) and the effects of hormone replacement therapy.  He points out that these epidemiologic studies, for a variety of reasons, can lead to erroneous conclusions. Fine.  The other option?  With no preliminary studies jump straight to a huge trial?  And sometimes epidemiology can lead to important results: that a certain water pump is the epicenter of cholera or that chimney sweeps have more testicular cancer. Or that lowering cholesterol is associated with a decrease in vascular deaths.

Epidemiology is part of a continuum of understanding and evolution of medical knowledge.  But strawmen are easier to burn than recognizing the stuttering, somewhat chaotic progress of medical knowledge.  If proving a point is more important than understanding complexity, this is how you argue.

He then proceeds to genome-wide association studies (GWAS) that have been a disappointment for  elucidating genetic causes of heart disease and Alzheimer’s. The author considers GWAS a failure.  I suppose if you have a narrow perspective, yes it has been a failure. So far.  Huge amounts of information about the genome have been generated, and I am always a fan of knowledge for knowledge sake.  In the world of infectious diseases, there are single gene polymorphisms in the immune system that can increase or decrease a patients risk for a variety of infections.  Is it of clinical relevance yet? No.  Is it interesting? Oh, yes.  Will it lead to a new treatments and diagnostic interventions in the future? Who knows. But trying new ideas may fail but still  lead to insights that may lead to better interventions. I would wonder what secondary advances in technology and understanding were accomplished as a results of the GWAS studies.

It is like complaining that the Apollo program only put 12 people on the moon so the program is a bust since we are not going to the moon for vacation.  Here is a dirty little secret from a mere clinician.  I learn far more from failure than I ever have from success.  “The most exciting phrase to hear in science, the one that heralds new discoveries, is not ‘Eureka!’ (I’ve found it!), but ‘That’s funny…’ -Isaac Asimov.”  If you are a clinician, it is not ‘That’s funny,’ but ‘Oh shit’ that really drives change and knowledge.

2) If women replace these missing hormones post menopausally with HRT, they will remain “youthful” and not suffer from heart disease, dementia, vaginal dryness, hot flashes, and fractured bones.

I remember the late ’80′s,  a time that was the heyday of HRT, when I was in my internal residency training and discussing the issues at length not only in clinic, but with my mother.  I remember discussing the epidemiologic data and the worries of cancer.  The author states that

…based on these  (biased) studies, false claims were made the HRT protected against cardiovascular disease and dementia.

As if we knew it was false at the time. It was the best guess based on the data, and epidemiology can give insights that can be later confirmed  by better studies.  He also says

“the proponents…ignored the well-documented fact that estrogen is a carcinogen that causes breast cancer that can kill women” and that “HRT caused a 25% increase in breast cancer.”

I do not know where the author was practicing, but I remember talking with patients (I know, flawed memory) and my mother about the relative risks of cancer and fracture from HRT.  And 25%. Increase.  That’s bad.

What was the study?  On “16 608, patients, there were  more invasive breast cancers compared with placebo (385 cases [0.42% per year] vs 293 cases  [0.34% per year]…and the estrogen group had higher mortality (25 deaths [0.03% per year] vs 12 deaths [0.01% per year].”

That is bad.  Equally bad was the way the author presented the data, the same author who complains in the opening paragraphs about complex data being presented as looking “superficially adequate to the unsophisticated reader,” but I know when someone is presenting information in an manipulating manner designed to blow smoke out a usually inaccessible area.

In a section worthy of the Vaccine Council or Dr. Mercola, it sounds like people deliberately ignored cancer risk to push estrogen to kill women.  Someone mention hype?  I know it is important to make a point, but those who were investigating HRT and prescribing it, as I did once upon a time, were doing it carefully and with knowledge that there could be risks.

Information does not exist in a vacuum.  When talking with my patients and Mom in the late 1980′s, I basically said, based on the odds, how do you want to live your life?

Lifetime risk is a useful way to estimate and compare the risk of various conditions. Hip fractures, Colles’ fractures, and coronary heart disease, and breast and endometrial cancers are important conditions in postmenopausal women that might be influenced by the use of hormone replacement therapy. We used population-based data to estimate a woman’s lifetime risk of suffering a hip, Colles’, or vertebral fracture and her risk of dying of coronary heart disease. A 50-year-old white woman has a 16% risk of suffering a hip fracture, a 15% risk of suffering a Colles’ fracture, and a 32% risk of suffering a vertebral fracture during her remaining lifetime. These risks exceed her risk of developing breast or endometrial cancer. She has a 31% risk of dying of coronary heart disease, which is about 10 times greater than her risk of dying of hip fractures or breast cancer. These lifetime risks provide a useful description of the comparative risks of conditions that might be influenced by postmenopausal hormone therapy.

That was the kind of information and conversations about HRT I was having with patients in my clinic as I completed my residency, the years the author was at Merck developing drugs.  Many patients were far more worried about the disability and pain of fractures than they were of breast cancer.

In continued hyperbole that is totally disconnected from what I remember, he calls HRT a “flagrant example of the harm done by straying from the principles of hypothetical/deductive approach and sound clinical science.”

Really?  Did this guy ever take care of patients?  Has he ever had to make decisions based on incomplete information?  We are only into number two of seven and he last lost me with the hysteria.  I wonder how he would suggest exploring the effects of waning estrogen on the health of women?  Jump straight to a large trial?  Do no preliminary work?  Ignore any potential leads?  What is the alternative to the incremental, and sometimes erroneous, results of medical understanding?  How about fluoride and tooth decay?  So many insights start with a guess and a little epidemiology. Sometimes it pans out, sometimes it doesn’t.  But you do not know unless you try.

3)  if small dosages of vitamins are good for humans, very large doses would be better for everyone.

He then notes the studies that show the hypothesis was wrong.  But this was only known after the fact, after the studies,  and perhaps using vitamins like drugs would have beneficial effects.

Then the odd summary: ” megavitamin therapy tested in properly controlled trials either does nothing or is harmful (except in a few well defined exceptions).”

So it does nothing except when it does.  And how would we know the well defined exceptions unless we did the trials?

He goes from complaining about the science to complaining about the regulatory and commercial issues of megavitamins, changing arguments in midstream.  Is it the science or how the science is used?  Two different issues.

This is getting tedious, even for me.  I will soldier on, although the re re re reading 7 is increasingly painful. The closer I read it, the greater the errors and manipulations; a Mandelbrot set of manipulative medical writing.  Soon I will find the indefinite articles and pronouns suspect.  I try to skim the Health Ranger for a few chuckles; that is not why I read SI. And when is their swimsuit issue?  Oh. Wrong SI.

4) Screening tests beyond the standard medical examination are necessary for identifying disease and the risk of disease in apparently healthy, asymptomatic adults.

I will leave this issue to the more knowledgeable hands of Dr. Gorski.  His argument seems to be based on the 20:20 vision of hindsight, which is apparently the primary argument in all seven cases.  We thought screening would be effective,  studies showed it wasn’t, so the hypothesis was flawed and we should not have suggested screening or done the studies.

The author does not show in this, or other examples, why the ideas were wrong in the context of time the ideas were first offered. It is only viewed through the all powerful retrospectoscope that the author finds his deadly hypothesis. It is ever so easy to predict the past.

He also seems to argue that since our understanding of the ramifications of screening are not perfect, they are suspect, referencing himself for issues with PSA and mammograms (1).  The author argues in part that since our understanding is imperfect, it is a deadly hypothesis. I have always been comfortable with making decisions based on incomplete information, as that is the only kind of clinical information we ever have, save for the results of the occasional autopsy.  The perfect always being the enemy of the good.

He also complains about genetic screening. He notes that few people with high risk genes will develop disease and they can’t do anything about it, so why bother?  I wonder if the author has had much direct patient care.  What  most patients dislike is uncertainty about the why of their disease and most prefer as much understanding and certainty about their health as they can gather.  That is why they bother. And todays why bother may be tomorrows critical insight.  I have discussed how the show Connections made an impact on my view of the serendipity underlying advances. It may not be cost effective or useful currently,  the author does note that for some patients (breast cancer) it may have utility. Again, it is a deadly hypothesis except when it isn’t. So much sound and fury.

But how do you know until after you have done all the studies and see what works and what doesn’t?  His argument still seems to be since in some patients genetic testing has been shown to be of no utility, in the past they should not have done the work to show it is not useful. Except where it is.  Sort of like going back in time to kill Hitler as a child because he was found to be evil in the future, even though you could not tell that the babe in the crib was going to be the source of Goodwin’s law. And far worse.

Circular argument much?

I do not get the impression the author is one for thinking outside the box.  Usually new ideas lead nowhere, but again, you never know unless you try. Nothing ventured, nothing gained vrs nothing ventured, nothing lost.  It is often not the results of studies that are the issue, but how they are portrayed in the media, as noted by the author, and, probably not intentionally, his entire article is a superb example of just that concept.  Maybe 7 is really meta.

5) Manipulating one’s nutrition can prevent cancer.

As he says,  “In retrospect,  this hypothesis does not seem plausible.”

The whole crux of almost every one of his arguments. Repeat after me. In retrospect. In retrospect. In retrospect.  In retrospect everything is clear.  I have had MD after my name for 27 years, and I remember the uncertainty and interest in all his 7 mostly not so deadly hypotheses.  In the beginning, it was not so clear as he makes it out to be.  The past is easy to predict.

6)  Personalized medicine will greatly advance medical care.

His argument is the same: it hasn’t worked except where it has.

“Personalized medicine has only been shown to be cost effective in a few well defined situations.”

How did we find these well defined situations?  Doing a ton of studies that show benefit in some cases and none in others.

I think the solution to this problem is being able to see the future and know in advance which research ideas will bear fruit and which will be a bust.  Precognition is apparently the only solution. Miss Cleo may be available to help review research proposals, I understand that her readin’ is free.

7) cancer chemotherapy has been a major medical advance.

Of course, in some cases it has been extremely effective, but the war on cancer has not been what it was promised.  Again it seems his argument is the same hindsight argument:  when cancer therapy has been effective, it is great, and when it is not so good, we should not have done the work to show that wasn’t effective.   Again, I leave the details to Dr. Gorski should he choose to cover the topic.

And of course the author doesn’t have a dog in the fight (and there are those quotes, so commonly used by the dispassionate):

“When one dispassionately weighs the minimal prolongation of ‘good’ life in patients with metastatic cancer versus the very distressing side effects of chemotherapy with ‘targeted’ drugs, the case is close.”

I’m convinced,  He is dispassionate.  And Jenny isn’t anti-vax, just pro-safe vaccine. Here is my hypothesis to be tested.  Anyone who argues they are dispassionate isn’t. They are fooling themselves and trying to fool others with their alleged practice of arei’mnu.  Me? I am never dispassionate; although sometimes I do not care, but there is a difference.

Some of his conclusions are reasonable: we need to do our science as best as we can.

The author argues that all these errors and  expenditures of his 7 mostly no so deadly hypotheses could have “been avoided if the hypothetical/deductive method had been applied rigorously.”  I am not convinced, since most of his arguments are based after the fact.  I would be far more impressed if, by using only the hypothetical/deductive approach (no epidemiology, no early studies, no preliminary clinical data, no basic science) if he would predict 7 hypotheses that warrant jumping straight to large, randomized, placebo controlled clinical trials so beloved by the FDA. The Randi prize awaits.

We all need that god like perfection and prescience, unlike those

“guilty of perpetuating worthless practices include “scientists” who repeatedly employ flawed methods and then publish them, government agencies who fund such practices, editors of journals that publish pseudoscience, the USDA and NCI bodies that perpetuate unscientific regimens…”

My. God.  The Health Ranger was right.  The conspiracy has incorporated itself into every aspect of the Medical-Industrial  complex.  A different conspiracy than the one we get from the woo world, but  everyone is involved.

Putting scientists in quotes. A very Health Ranger thing to do.  I don’t suppose he is referring to the “scientists” at Merck who repeatedly employed flawed methods and then published them.

“Approximately 250 documents were relevant to our review. For the publication of clinical trials, documents were found describing Merck employees working either independently or in collaboration with medical publishing companies to prepare manuscripts and subsequently recruiting external, academically affiliated investigators to be authors. Recruited authors were frequently placed in the first and second positions of the authorship list. For the publication of scientific review papers, documents were found describing Merck marketing employees developing plans for manuscripts, contracting with medical publishing companies to ghostwrite manuscripts, and recruiting external, academically affiliated investigators to be authors. Recruited authors were commonly the sole author on the manuscript and offered honoraria for their participation…

This case-study review of industry documents demonstrates that clinical trial manuscripts related to rofecoxib were authored by sponsor employees but often attributed first authorship to academically affiliated investigators who did not always disclose industry financial support. Review manuscripts were often prepared by unacknowledged authors and subsequently attributed authorship to academically affiliated investigators who often did not disclose industry financial support.”

I see people doing the best they can with the tools at hand.  Mostly honest people (I say mostly not knowing what their IRS forms show), working within many limitations, to advance medical understanding.  They do not deserve quotes applied to their work or the title of pseudoscience.  Not everyone is able to achieve the peerless, perfect knowledge bestowed on  a Professor of Medicine and Merck Vice President.

We need “honest” corporations.  Ironic from a former Merck executive;  casting the first stone and all that. I do not need quotes to show my snotty superiority.  We need better regulation of “unsafe and unproven products.”  Like Merck’s Vioxx?.   Ohhh, snap. The Merck shots are cheap shots,  I know. But they made me laugh, and above all I like to make me laugh. It is all about me.

Like the Health Ranger, I see someone with a bee in their bonnet, selectively and histrionically arguing in circles, hoping that if the same cognitive errors and circular reasoning are repeated they will be believed as fact.  I am not enthusiastic about the conclusions and arguments used, being significantly more flawed than the research he rails against. It is not far in style and content from being in the Natural News.  Science, at least,  is ultimately self correcting.  This article, probably not so much.

Of course, I am nobody from nowhere. Not a professor or scientist or a vice president.  I am a clinician and citizen who has to trust his sources of information.  I was raised to judge a man by the company he keeps.  When the NEJM published garbage on acupuncture, my trust in the Journal fell a notch.  The Lancet has always had a reputation of being flaky, it is part of the British charm and I have never held it against them; I just factor it in when reading a paper.  The Annals of Internal Medicine has been untrustworthy for years. Clinical Infectious Diseases remains unsullied.  Now the Skeptical Enquirer (sic) has slipped a bit as well.  7 was primarily deadly for my confidence in its editors. Oh well, at least I can still trust the material published by DC.

Rationalizations

(1)  Crislip et. al.  I said it here before, so it must be right.

(2) And if you try sometime you find/You get what you need.

The Supreme Court of the United States made a ruling the other day that has profound implications for the health of millions of children. Since October 12, 2010, The Court has been quietly deliberating the case of Bruesewitz v. Wyeth, inc. The case centers on Russell and Robalee Bruesewitz’s allegation that their 18 year old daughter, Hannah, was irreversibly injured by a DTP vaccine she received when she was 6 months old. What is important about this case is not the allegation itself (I will discuss its merits, or lack thereof, in a moment), but the ramifications the ruling has for the future of childhood immunization in this country. The Supreme Court’s ruling against the Bruesewitz’s and in favor of the U.S. vaccination program was the right one, and safeguards our children from the irrationality of the anti-vaccine movement. Some important background is necessary here to understand why this is so.

Prior to the development of effective vaccines, diphtheria, tetanus, and pertussis were common diseases, terrifyingly familiar to all parents. Death records from Massachusetts during the latter half of the 1800’s indicate that diphtheria caused 3-10% of all deaths. In the first part of the 20^th century, these dreaded organisms still caused illness in hundreds of thousands of people each year in the United States. These are devastating diseases which, if not resulting in death, often produced severe and permanent damage to those afflicted. In the 1920’s, vaccines against each of these scourges were finally developed, and in the mid 1940’s the combined DTP vaccine was introduced. The vaccines were so effective that cases of these deadly infections were practically eliminated. Today, few parents know the terror once routinely wrought by these pathogens.

Despite the effectiveness of the original DTP vaccine, it did frequently produce reactions in the children who received it. Fever (and fever seizures in those genetically predisposed), irritability, and sometimes frightening hyporesponsive episodes were seen. The side effects of the DTP vaccine were attributable to its pertussis component. The vaccine was produced using the whole pertussis organism in an attenuated state so that it could not cause the disease itself. Utilizing the whole organism, however, exposed the child to a large number of proteins, some of which were responsible for the fever and other side effects the vaccine produced. These deleterious reactions certainly paled in comparison to the dangers of the diseases themselves. Nonetheless, as the diseases prevented by the vaccine disappeared, parents began to take more seriously these annoying and often frightening reactions. Because some of these reactions were so frightening, including febrile, or fever seizures, many people began to believe the vaccine was responsible for more serious side effects, including brain damage and even death. As outlined in an earlier SBM post, the side effects of the original “whole cell” DTP vaccine (DTwP) were not, however, life-threatening and produced no long-term problems in those receiving it. In 2006, a retrospective case-control cohort study of more than 2 million children concluded there was no increased risk of developing encephalopathy following administration of the original DTwP vaccine¹. But when encephalopathy or a new onset seizure disorder occurred in temporal association with the receipt of the DTwP vaccine, causation was often ascribed to it.

It was the escalating, yet unfounded fears surrounding the original DTwP vaccine that led to the emergence of the modern-day anti-vaccine movement in this country. In 1982, the shockumentary “Vaccine Roulette” appeared on a local NBC TV affiliate. It purported to show the child victims of the DTwP vaccine, housed in a dark and dismal chronic care facility, damaged by doctors and forgotten by society. The show awakened the nation to the alleged dangers of this vaccine, and the fear quickly spread like wild fire. Fear of the DTwP vaccine and of vaccines in general enveloped the nation, and lawsuits against vaccine manufacturers over a host of alleged reactions rained down upon the courts. This torrent of legal action threatened the future of the vaccination program in this country. While in 1979 there was only 1 DTP-related lawsuit, by 1986 there were 255, with a total of over $3 billion sought by claimants. This clearly was not sustainable for the vaccine industry, and in fact manufacturers went out of business. In 1967 there were 26 US manufacturers of vaccines. By 1980 this number had dropped to 15, and by 1986 there were only 3 companies still making vaccines in this country. Vaccine prices skyrocketed, and manufacturers found it difficult to obtain liability insurance.

With the future of our vaccination program at risk, Congress passed the National Childhood Vaccine Injury Act (NCVIA) in 1986 and established the National Vaccine Injury Compensation Program (NVICP). Funded by an excise tax on each vaccine component administered, the NVICP was designed as a no-fault, expedited process to compensate families who claim their child has suffered a vaccine-related injury. No proof of causation is necessary to be eligible for compensation. A child simply has to have a documented problem that occurred in the specified time frame following a vaccination, and that problem has to be on the table of problems recognized by the NVICP as potential vaccine adverse events. Cases are reviewed by a Special Master, who makes a determination based on minimal evidence, with the primary goal being a prompt resolution. If a claim is successful, compensation is granted for medical, rehabilitation, counseling, special education, and vocational training expenses, and $250,000 when the claimed outcome is death. Patients may accept the ruling or take their case through the usual tort process by suing the manufacturer. However, a major aspect of this process, and the one which saved the vaccine program from total collapse in the 1980s, is the significant liability protection granted to the vaccine manufacturers. Before suing a vaccine manufacturer, a claimant must first go through the NVICP process, or the so called “Vaccine Court”. But if a parent rejects an NVICP ruling and decides to sue in court, the vaccine manufacturer is immune from liability, assuming they have complied with all regulatory requirements and have not committed outright fraud or other crimes in the manufacture of the vaccine. Most importantly, the NCVIA stipulates that,

No vaccine manufacturer shall be liable in a civil action for damages arising from a vaccine-related injury or death associated with the administration of a vaccine after October 1, 1988, if the injury or death resulted from side effects that were unavoidable even though the vaccine was properly prepared and was accompanied by proper directions and warnings.

Setting aside for the moment the fact that there is no evidence the DTwP vaccine can cause any of the adverse events listed in the original table, the statement above gets to the heart of the Supreme Court’s ruling. Specifically, the ruling centered around the words “unavoidable” and “even though” in the above excerpt. In April 1992, when Hannah Bruesewitz received the vaccine that allegedly injured her, her diagnosis “residual seizure disorder” had just been removed from the NVICP vaccine injury table. Her claim was denied by the Special Master, although she was still awarded $127,000 for legal fees. The family rejected this decision, and instead brought the case against Wyeth (which had acquired Lederle) to Pennsylvania state court. The Breusewitz’s asserted that the vaccine was defective, that the manufacturer knew it could cause harm, and that they had knowledge of a safer vaccine but failed to develop or use it. The Pennsylvania court rejected this claim, citing that such design-defect claims were preempted by the Vaccine Act. The case then ended up in The Supreme Court which finally, this past Tuesday, upheld the intent of the NVICP to protect the vaccine supply by preventing lawsuits based on design-defect claims. The Supreme Court’s opinion, delivered by Justice Antonin Scalia, interpreted the word “unavoidable” as written in the Vaccine Act, to apply to the specific vaccine administered to a claimant, and not to other hypothetical, alternate vaccines that might or might not be more or less safe and effectve. Justice Scalia argued that the use of the words “even though” in the excerpt above implies that the unavoidability referred to in the Act applies to the specific vaccine that was administered, and not to some other potential vaccine. In other words, the Breusewitz’s claim that their daughter’s condition was avoidable because a safer alternative vaccine could have been given was ruled to be a misreading of the Vaccine Act’s intent. The Opinion asserts that exclusion of design defects from the Act was intentional. The fact that the NCVIA and the FDA spell out in detail the manufacturing method and the warnings and directions that must be provided by a vaccine manufacturer, while making no mention of vaccine design requirements is a clear indication that such an exclusion was intentional. It was the Court’s opinion that any other reading of The Act would require very difficult determinations of relative vaccine safety and efficacy. Justice Scalia points out that these determinations are rightly the domain of the FDA and National Vaccine Program experts, and not the courts.

The Supreme Court’s ruling in this case was a huge victory for the health and well-being of our Nation’s children, and the Court should be applauded for its good sense and clarity on the issue. Undoubtedly, those who eschew rationality and oppose vaccines will find fault with the ruling, and cling to the mantra of conspiracy and collusion. Sadly, the fear and misinformation spawned from the DTwP-era lives on today. As technology improved, a version of the vaccine containing an “acellular” pertussis component did eventually become feasible. The DTaP vaccine, as it was called, was introduced in 1996 and nearly eliminated reactions to the vaccine. But the damage was done. As the media and a splintered cadre of like-minded conspiracy and anti-establishment groups took up arms against vaccines in general, a new anti-vaccinationism took hold. We’ve since been through the Wakefield crisis, the thimerosal debacle, and many other dangerous vaccine myths, nourished along by the media and the anti-vaccine cartel. The consequence of this spreading fear is an increasing distrust of vaccines, and the development of pockets of underimmunization around the country. We are now seeing outbreaks of completely preventable childhood disease, and children have died as a result. This was an important ruling, but we have a long way to go before we can bring rationality to the public discussion and understanding of vaccines in this country.

¹Pediatr Infect Dis J. 2006;25:768-773

Dr. Mehmet Oz is one of America’s most influential doctors.  Just ask him.  He has a TV show and everything.  And in the past, much of his advice had been practical and mundane, the same advice you might hear from your own (perhaps less charismatic) physician.  But lately, he’s been giving out frankly bizarre medical opinions.  Not all of Oz’s recommendations are over-the-top strange, but even some of his less-bizarre stuff is hyperbolic to the point of being—in my opinion—deceptive.  Let’s explore one example close to my heart, diabetes.  As an internist, one of my most important tasks is the prevention and treatment of diabetes.  I know something about it.  As a heart surgeon, Dr. Oz deals with one of the most serious complications of diabetes, coronary heard disease, so he must know a bit about it as well.

So I was a bit surprised to learn from his website that I’ve  been going after diabetes the wrong way.  Unknown to me is the “prevention powerhouse” of coffee and vinegar.  He recommends heavy consumption of these miracle foods to prevent diabetes and to help the liver and cholesterol, whatever that means.  Reading this, two questions come to mind (a few more, really, but two that we will focus on): is this plausible, and is this true?

There are a few epidemiologic studies that support the idea that coffee consumption is in some way associated with diabetes risk.  (For a bit of background on different types of studies, see here and here.)  There are a few bits of basic science that could explain this relationship, if it turns out to be causal.  But these large studies simply show relationships.  They have found that people who drink more coffee (regular or decaf) were less likely to develop diabetes during the study period.  Most of these studies tried to control for confounding variables (for example, caloric intake) but none of these truly shows cause and effects.

The two biggest potential problems here are recall bias and confounding variables.  Do people reliably report the data we ask them to?  We aren’t directly measuring it, so this is critical.  Do coffee drinkers simply have smaller appetites?  Or other habits that reduce the risk of diabetes?  These studies give us an interesting starting point.  The next step to look for actual cause and effect would be a randomized controlled trial (which obviously could not be double-blind), that takes non-diabetics and randomly has half drink coffee and half abstain, and follows them over a several year period.   The idea that coffee can affect blood glucose metabolism and the development of diabetes is not nuts, but the available data don’t allow us to go any further than that.

The data support the plausibility of the question of coffee and diabetes, but not the truth of the statement.   But let’s pretend it is true.  The next questions are are how much risk reduction is there, and at what cost?

We know that some drugs and proper diet and regular exercise reduce the risk of diabetes.  How do these interventions compare with coffee or vinegar?  Is one of them 100 times more potent than the other?  One thousand?  One fifth?  And what are the hazards of caffeine consumption?  Not that great in general (and lessened by drinking decaf), but even small amounts of caffeine can cause significant acid reflux, sleep problems, heart palpitations, headaches.

What Dr. Oz is suggesting is using an unproven drug (coffee or dilute acetic acid) that isn’t needed.  We have safe, effective ways to prevent diabetes.  Our biggest failure is in providing people with the education, health care, and other tools to follow through.

References

Salazar-Martinez E, Willett WC, Ascherio A, Manson JE, Leitzmann MF, Stampfer MJ, & Hu FB (2004). Coffee consumption and risk for type 2 diabetes mellitus. Annals of internal medicine, 140 (1), 1-8 PMID: 14706966

VANDAM, R., & FESKENS, E. (2002). Coffee consumption and risk of type 2 diabetes mellitus The Lancet, 360 (9344), 1477-1478 DOI: 10.1016/S0140-6736(02)11436-X

Tuomilehto, J. (2004). Coffee Consumption and Risk of Type 2 Diabetes Mellitus Among Middle-aged Finnish Men and Women JAMA: The Journal of the American Medical Association, 291 (10), 1213-1219 DOI: 10.1001/jama.291.10.1213

van Dam, R. (2006). Coffee, Caffeine, and Risk of Type 2 Diabetes: A prospective cohort study in younger and middle-aged U.S. women Diabetes Care, 29 (2), 398-403 DOI:10.2337/diacare.29.02.06.dc05-1512

Pereira MA, Parker ED, & Folsom AR (2006). Coffee consumption and risk of type 2 diabetes mellitus: an 11-year prospective study of 28 812 postmenopausal women. Archives of internal medicine, 166 (12), 1311-6 PMID: 16801515

Dam, R., Dekker, J., Nijpels, G., Stehouwer, C., Bouter, L., & Heine, R. (2004). Coffee consumption and incidence of impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes: the Hoorn Study Diabetologia, 47 (12), 2152-2159 DOI: 10.1007/s00125-004-1573-6

Last week David Gorski wrote a excellent post about why we have not yet cured cancer. It turns out, cancer is a category of many individual diseases that are very challenging to treat. We have made steady progress, and many people with cancer can now be cured – but we have not discovered the one cure for all cancer. I personally am not convinced that we will discover a single cure for all cancer, at least not with any extrapolation of current technology. But if we continue to make progress as we are cancer will become an increasingly treatable and even curable type of disease.

This topic also brings up a meme that has been around for a long time – the notion that scientists have already cured cancer but the cure is being suppressed by the powers that be, to protect cancer as a source of income. In the comments to David’s article, Zuvrick writes:

So we can find a cure. It has probably happened multiple times. But nobody wants to cure cancer. Too many researchers earn a living seeking a cure by remaining inside a narrow, restricted channel of dogma. Their institutions get grant money and survive from the funding. Big Pharma makes big bucks selling chemotherapy drugs, surgeons remove tumors and various radiation devices employ radiologists and firms making these machines. MRI and CT scans would not be needed for cancer if Rife technology were available today.

I have heard or read some version of this claim since before I entered medical school.  Superficially it may sound like profound wisdom (cynicism is a cheap way to sound wise) – but the idea collapses under the slightest bit of logical scrutiny.

First, as David thoroughly pointed out, the claim is implausible. Cancer is a complex set of diseases that defy sincere attempts at a cure. Those who promote the notion of the hidden cure often simultaneously promote wacky pseudoscientific treatments that they claim work – and Zuvrick is no exception. He believes that Royal Rife cured cancer 70 years ago. Rife was essentially a copycat of Albert Abrams who promoted his radio frequency devices. The concept is to use radio waves to alter the vibrations of cells in the body. This is pure nonsense. Here is a quick summary from Stephen Barret:

One of Abrams’s many imitators was Royal Raymond Rife (1888-1971), an American who claimed that cancer was caused by bacteria. During the 1920s, he claimed to have developed a powerful microscope that could detect living microbes by the color of auras emitted by their vibratory rates. His Rife Frequency Generator allegedly generates radio waves with precisely the same frequency, causing the offending bacteria to shatter in the same manner as a crystal glass breaks in response to the voice of an opera singer. The American Cancer Society has pointed out that although sound waves can produce vibrations that break glass, radio waves at the power level emitted a Rife generator do not have sufficient energy to destroy bacteria.

But let’s explore the logic of the hidden cure a bit further. Given that cancer is such a complex set of diseases, there is a vast and evolving science exploring the causes and behavior of cancers. This research takes place in numerous labs around the world. A cure for cancer would likely emerge from a collaboration among many researchers, in different labs and institutions, and even in different countries. Even if one lab made a significant breakthrough, it would be the capstone on top of a large body of research that was available to the entire community (and in fact the public). It would be impossible to keep other researchers from replicating the final steps that lead to a cure.

Often the hidden cure conspiracy idea is framed around the claim that a pharmaceutical company would hide such a cure to protect their profits from other cancer drugs. This claim fails not only for the reason above but for a separate practical reason. It would take about 100 millions dollars of research (if not more) to prove that a drug was actually a cure for one type of cancer (let alone all types of cancer). Why would a pharmaceutical company spend that kind of research money on a drug they know they have no intention of marketing, just so that they can suppress it? Also – where would they do such research? How could they get past all the regulatory hurdles to perform human research without revealing what they are doing?

Often those who claim that “they” are hiding a cure for cancer have only a vague notion of who “they” are. They generally have an image of the “medical establishment” as monolithic, but nothing could be further from the truth. The medical establishment is composed of universities, professional organizations, journals, regulatory agencies, researchers, funding agencies, and countless individuals – all with differing incentives and perspectives. The idea that they would all be in on a massive conspiracy to hide perhaps the greatest cure known to mankind is beyond absurd.

For those who think the profit motive is sufficient explanation, not all of the people and institutions named are for profit. And what about countries with socialized medicine who could dramatically reduce their health care costs if a cancer cure were found? Is Canada, the UK, all of the European Union, in fact, in on the conspiracy to protect American cancer treatment profits? It’s as if hidden cure conspiracy theorists forget that there are other countries in the world.

Hidden cancer cure conspiracies also are premised on a simplistic notion of how medicine and medical research progresses. The practice of medicine is constantly evolving in a process of creative destruction. New technologies render older ones obsolete. Resources ebb and flow to diseases as they emerge and are reduced or cured. There used to be entire hospitals dedicated to the chronic treatment of tuberculosis – and now, after antibiotics, those hospitals have been repurposed. Researchers, specialists, hospital space, and other resources shift over time to where they are needed.

If a cure for cancer were discovered it would not be as disruptive as is claimed by the conspiracy theorists. It would take years if not decades of research to explore how effective the treatment was for every type, grade, and stage of cancer. We could not assume that it cured all cancer even if it cured one type. And what about people who did not respond to the treatment, or could not tolerate it for some reason? (One might assume a 100% effective and side effect free cure for all cancer, but this gets progressively more unlikely.) Further, any real breakthrough cure would likely tell us something profound about the nature of cancer itself, and this would spawn entire research programs.

Research funding and researchers themselves would shift their focus where it was needed. Some might shift their skills to other diseases entirely, and perhaps fewer doctors and researchers would go into cancer research if a cure were already found. As with any other significant medical advance, the medical infrastructure would adapt.

Conspiracy theorists also tend to ignore the huge incentive to find a cure. For the researchers involved, it would mean fame, fortune, Nobel prizes and an enduring legacy within the halls of medicine. It is safe to say that it is every cancer researcher’s dream to be part of the team that finds the cure for cancer (or at least as big a breakthrough as is plausible).

The institution would also gain fame and prestige, which translates into more donations, better applicants, and also part ownership of any patents. A company that discovered the cure for cancer would make billions, even if it meant it would make existing drugs obsolete. Patents on drugs are finite, so companies are always looking for new drugs anyway. And imagine the public relations boon for the company that cured cancer – their name would forever be “Pharmaceutical Company – We Cured Cancer!” Even if the new treatment could not be patented, it would still be an enduring profit stream for the original company to market it – it would become their Tylenol, only bigger.

And of course the health care systems around the world would rejoice at the potential reduction in health care costs, which are now threatening to cripple the system. Doctors, hospitals, researchers – pretty much everyone, is making less money than they were a couple decades ago because of rising health care costs. The system is now being threatened by further cuts and restrictions to tame rising costs. A significant reduction in overall costs, by curing an expensive disease, would ease the pressure on the entire system, and free up resources for other diseases.

Finally, there is the human element. A hidden cure would require individual people to know that a cure for cancer is available but to deny this cure to dying patients in order to protect their or someone else’s profit. There may be people in the world who are that callous and evil, but think of all the people who would have to be that evil, over years or decades, to maintain a hidden cure. These are people who also have loved-ones who are likely to get cancer at some point in their lives, and who themselves are at risk for cancer. I would not casually assume that the medical establishment is full with such cartoonish maniacal villains.

Conclusion

The grand conspiracy of the hidden cancer cure is a meme that I wish would go away, but for some reason persists. It is like an urban legend – it appeals to some ill-formed fear or anxiety produced by the complexity of modern society. It gives a focus to these anxieties, and gives the illusion of control. No one wants to feel as if they are being deceived, and so assuming there is a conspiracy feels like a good way to avoid being duped. But ironically it is the conspiracy theorists who are being duped, or who are doing the deceiving.

The notion of a hidden cure is also dependent on seeing institutions with which one is not personally familiar as faceless and monolithic organizations, comprised of obedient drones. But these institutions are made of people – ordinary people with flaws and feelings and families just like everyone else.