...is one of my favorite surgeon-bloggers Sid Schwab when he discusses what happens when naturopaths actually subject their "healing art" to scientific examination. In the wake of the rather--shall we say--vigorous discussion that ensued after my post last week about the recently passed law in the State of Minnesota to license and regulate naturopaths, today I can't resist taking a look at the widely publicized study of St. John's Wort for Attention-Deficit Hyperactivity Disorder (ADHD) that by coincidence was published in JAMA last week and that Sid discusses.
What he's discussing is a study done by Bastyr University, that stonghold of naturopathy "at the heart of natural medicine education" in the Pacific Northwest, in which St. John's Wort was tested in children with ADHD. The results? What do you think? It was a negative study (direct link to study here). Basically, in a randomized, double-blind, placebo-controlled trial 54 children between the ages of 6 and 17 were randomized to St. John's Wort or placebo and treated for eight weeks after a placebo run-in phase of one week, and participants who were less than 80% adherent as assessed by pill count or who had a dramatic placebo response during the run-in phase were excluded from the trial prior to randomization. At the end of the treatment period, there was no detectable difference between the groups in various measures of ADHD. Studies don't get much more negative than this, and I do applaud the naturopaths at Bastyr for producing compelling evidence suggesting that one of their favorite herbal medicines, St. John's Wort, just plain doesn't work for ADHD.
Of course, the authors had to try to find a silver lining in this dark cloud of a study:
This trial was designed as a single-agent clinical trial, so the results pertain only to the use of H perforatum in isolation for the treatment of ADHD. It is possible that H perforatum may work synergistically with other botanicals, vitamins, minerals, or supplements. In addition, independent testing at the beginning of the trial confirmed that the product was standardized to 0.3% hypericin. Initially in the study of H perforatum, focus was on the constituent hypericin, a napthodianthrone, which was believed to work as a monoamine oxidase inhibitor, but it was not found to reach levels in the blood that would be physiologically active. More recently, the attention has turned to hyperforin, a phloroglucinol derivative, which is believed to be responsible for the reuptake inhibition of serotonin, dopamine, and norepinephrine. The product used for this study was not one of the newly marketed "high-hyperforin" products that range from 3% to 5% hyperforin. The product used in this trial was tested for hypericin and hyperforin content at the end of the trial and contained only 0.13% hypericin and 0.14% hyperforin. Hyperforin is a very unstable constituent that quickly oxidizes and then becomes inactive, which is likely what happened to the product used in this clinical trial. The majority of H perforatum products on the market are at risk of oxidation due to their delivery as 2-part capsules. It is possible that a product standardized to at least 3% hyperforin could benefit children with ADHD symptoms if it were delivered in a method that limits oxidation.
Of course, few indeed are the agents that perform synergistically with other agents without showing at least a modicum of activity on their own. It's possible that St. John's Wort may work this way, but unlikely given the results of this trial. It's also not unreasonable to wonder if a higher dose might have worked. (After all, that's what they're basically saying with all that business about the hyperforin and hypericin.) Fair enough; that's what is said after many "conventional" drugs fail to show efficacy in RCTs. Of course, no increase in dose is without a cost. Increase the dose, and you increase the chance of side effects and toxicity. You can't escape that. Also, if either of these two constituents of St. John's Wort are indeed active against ADHD, that begs the question: Why not just isolate and purify the postulated active compounds from the plant and test them under highly controlled dosages and conditions? What possible advantage is there to using an impure mix derived from a plant compared to the pure active compound, if either of these compounds are indeed active? That's just what those "unimaginative" pharmacologists and natural products chemists have been doing for decades, if not centuries, and it works pretty darned well. Think digoxin, taxol, and a host of other plant-derived pharmaceuticals.
In fact, the only weaknesses of this study were the above and somewhat of a mismatch in the percentage of boys in each group. The trial wasn't the largest, either, but it was certainly well-designed enough and large enough to have been powered to detect an effect equivalent to that of currently used drugs for ADHD, as described by the authors:
Sample size calculations were performed to determine the number of participants needed to detect effect sizes similar to those that have been reported in recent ADHD medication trials.
After all, isn't that what naturopaths are claiming anyway, that herbal medications can do as well or better than pharmaceuticals for various conditions? That's exactly what this trial was designed to test, and St. John's Wort failed to demonstrate an effect at all, much less an effect equivalent to that of Ritalin or other drugs used for ADHD. If there is indeed an treatment effect against ADHD attributable to St. John's Wort that this study was underpowered to detect, it is almost certainly much smaller than the effect of good, old-fashioned Ritalin. "Naturally" (sorry, couldn't resist), there was an accompanying editorial by a doctor named Eugenia Chan. As is the case with many of these editorials about so-called "complementary and alternative medicine" (CAM), particular when apparently written by an apparnetly woo-friendly physician, there is a lot of hand-waving about why this trial was negative. There was also a bit of the tu quoque fallacy thrown in for good measure:
Most studies of CAM efficacy, both in adults and children, are generally of poor quality; this is true for many conventional medical practices as well. In mainstream medicine, the concepts of outcomes research, evidence-based medicine, and the need for rigorous methods and quality standards for reporting clinical trials have emerged just in the past few decades. Only very recently have these standards been extended to RCTs of nonpharmacologic treatments.
All true, but it's also all pretty much irrelevant to the study at hand. Even if the rest of "conventional" medicine were truly not based on high quality evidence (an exaggeration that, aside from the infiltration of CAM into medical academia, bears less and less resemblance to reality these days), Dr. Chan is simply muddying the waters by shouting "you, too" back at scientific medicine, just because an "alternative" medical treatment has failed the test of scientific medicine in this trial. Unfortunately for her, two wrongs don't make a right, and the point that I emphasize again and again is that--finally--medicine is moving away from what I like to call tradition- or dogma-based medicine to seriously trying to rigorously systematize science- and evidence-based medicine, examining scientifically treatments both new and old to discern which ones work (and in what situations) and which ones don't. This is a very good thing, and long overdue. Sadly. although Dr. Chan plays lip service to the concept of EBM and the importance of RCTs, she still can't help but bring out the usual attacks on RCTs as inadequate for addressing CAM therapies, complete with the obligatory appeal to other ways of knowing:
While the RCT should remain the gold standard for providing evidence of treatment efficacy for both CAM and conventional therapies, many interventions pose unique challenges to rigorous RCT methodology. For example, randomizing participants may be difficult or impossible when the therapy to be evaluated relies on participants' belief in the treatment or relationship with the practitioner. Use of placebo and blinding may be difficult in therapies such as acupuncture, yoga, psychotherapy, or surgery, although techniques such as placebo needles that do not actually enter the skin have been developed. Even when a plausible placebo can be used, placebo and expectation effects can be very large in both CAM and conventional interventions and may be part of the mechanism of treatment efficacy.
Researchers may have difficulty defining precise and measurable outcomes for therapies for which the main effect is subjective (eg, general well-being, level of energy) or dependent on the skill of the practitioner (eg, therapeutic touch, psychotherapy). Some CAM therapies (eg, homeopathic remedies, traditional Chinese medicine) are tailored for an individual's specific needs and may not be able to be studied at a conventional "active ingredient" or "dose" level. Moreover, individuals often use a variety of CAM modalities simultaneously (eg, meditation, aromatherapy, herbs) or adjunctively with conventional therapies, and secular trends in lifestyle values such as diet, exercise, yoga, and massage may attenuate or magnify treatment effects.
Need I remind Dr. Chan that "conventional" therapies are often used in combinations too and therefore must control for the same things? Or that there is an increasing move towards "personalized" medicine in "conventional" medicine as well? The difference between "personalized" medicine in CAM and science-based medicine, of course, is that choices of treatments in science-based medicine are to the extent possible based on measurable, objective standards, such as gene expression, genomic profiling, and metabolic measurements, among other criteria. The "individualization" of CAM treatments, on the other hand, tends to be based on fairy dust such as "life energy" or "auras" or other pseudoscientific measurements of questionable accuracy and relevance from dubious labs. Naturally, the CAM-friendly don't see it that way, and neither, apparently, does Dr. Chan, who uses another favorite gambit of the CAM crowd:
Some of these challenges could be addressed through alternative study designs; for example, multiple N of 1 trials could be used to test the effectiveness of highly individualized CAM therapies, and preference RCTs can empirically test the effects of patient preferences on outcomes. Placebo and expectation effects can be addressed by excluding high placebo responders, as in the Hypericum trial, or by experimentally manipulating such effects as its own variable (eg, as graded dose-responses). "Attribute by treatment interaction" research methods can evaluate the extent to which interactions between individual patient and treatment characteristics, as opposed to the treatment's overall effect across a group of patients, explain variability in outcomes.
At its heart, calling for "multiple N of 1 trials" is really nothing more more than a call to use poor quality anecdotal evidence instead of high quality evidence from RCTs to study CAM, a strategy that, because of the placebo effect, is guaranteed to produce "positive" results. (Of course, that is the very intent of such calls.) As usual, this call is cleverly buried under a barrage of verbiage truly deserving of being included in Dr. Kimball Atwood's Weekly Waluation of the Weasel Words of Woo (although, admittedly, not quite as dramatic as this example). Dr. Chan then tops it all off with a spectacular example of the false equivalence fallacy:
Ultimately, increased attention to and emphasis on deepening a rigorous evidence base for all health care practices will benefit patients and families. The time for bad science, whether in conventional or unconventional medicine, is past.
Actually, I'd go further than that and say that there never was a time for bad science, and I'm very happy that medicine has been becoming more and more rigorously scientific during the two decades since I graduated from medical school. The vast majority of CAM modalities, which with the exception of herbal medicines, are at their heart bad science, because they are nearly all based on either pre-scientific notions of disease (vitalism being the most common one) or on religious or "spiritual" ideas (the concept of the life force qi, which is a combination of vitalism and religion). Some, like homeopathy, are based on concepts found in magic rather than science (for example, the Law of Similars). Yet CAM advocates keep telling us that we must "integrate" pseudoscience with science-based medicine to produce so-called "integrative medicine." How on earth can that be good science? Worse, pseudoscience abounds in naturopathy, including homeopathy, electrodiagnostic testing, chelation therapy for all manner of illnesses besides acute heavy metal poisoning, galvanic therapy, "glandular" therapy (in reality this is probably nothing more than "live cell therapy," which usually involves grinding up animal glands and administering them), and hydrotherapy, among many, many others.
Perhaps what's more disturbing is the alliance with the University of Washington that was necessary for Bastyr University naturopaths to carry out this study, as Wally Sampson pointed out:
In reality, N'paths hold no fund of knowledge not available to MDs and other medical practitioners. At the same time, N'paths warp that knowledge's application to fit ideological frames containing life forces, anti-technology, anti-public health measures and irrational fears of progress. Worse, N'paths believe a mass of unproved and false information that they claim as their exclusive area of expertise and which they apply on the basis of hunches and feelings. A N'path supplies no additional positive substance to healing the sick or to the science of medicine. In this sense, UW is an enabler of quackery, even if the short run product for the university could be algebraically positive. The overriding social consequence of enabling quackery, which is taught to Npathy students, is to spread a system of pseudo- and anti-science throughout the society.
One must grant the UW some degree of understanding for taking on this alliance, out of ignorance, innocence, and misplaced beneficence, but the establishing of precedent is an act they will one day regret and will find progressively more difficult to reverse. Bastyr's existence and UW's acceptance materialized in a social environment lacking an overarching theory of scientific social beneficence and a sense that something is wrong with anti-science.
Even though this study was completely negative, Bastyr gained far more from this collaboration than the University of Washington ever could. This sort of collaboration serves the purposes of Bastyr well in that it allows them to insinuate their woo into respected medical schools like the University of Washington and gives them an undeserved patina of respectability. After all, if the real medical doctors at such a prestigious institution are willing to collaborate with Bastyr naturopaths, there must be something to naturopathy, right?
Wrong. Aside from the potential that some herbal medicines might have as drugs, there ain't. Naturopathy is nothing if not one-stop shopping for woo.
Amusingly enough, some in the "natural medicine" crowd are very angry with the naturopaths at Bastyr. In a hilariously over-the-top article appearing on the always hilariously over-the-top "natural medicine" website NaturalNews.com, conspiracy theorist supreme and chief cheerleader for woo Mike Adams sees in this study a dark and horrible plot by big pharma to discredit "natural medicine," with the naturopaths at Bastyr having been the naïve dupes of this evil cabal:
Keep in mind that one of the study's authors, Dr. Biederman, is not merely on the take from drug companies that sell competing pharmaceuticals, but that he also lied about how much money he was being paid by drug companies, hiding the truth about his income by underreporting $1.6 million he took from psychiatric drug companies. See my report on that here: http://www.naturalnews.com/023408.html
Dr. Biederman has a clear financial interest in promoting patented prescription drugs for brain chemistry disorders while discrediting competing natural alternatives such as St. John's Wort. This blatant conflict of interest was not disclosed by JAMA, nor was it mentioned in the text of the study on ADHD and St. John's Wort. It appears Dr. Biederman would prefer his financial ties to Big Pharma continue to remain secret, even while producing questionable studies that desperately attempt to show that herbs don't work.
Mike Adams is lying here, plain and simple. Whatever Dr. Biederman may or may not have done with regards to reporting all of his income from drug companies, in the case of the Bastyr-UW study Dr. Biederman did disclose his conflicts of interest with regard to this particular article. At the very end of the article, where disclosures of conflicts of interest always appear in JAMA articles, I find this text:
Dr Biederman reports that he currently receives research support from the following sources: Alza, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen Pharmaceuticals, McNeil, Merck, Organon, Otsuka, Shire, the National Institute of Mental Health, and the National Institute of Child Health and Human Development; that he is currently a consultant/advisory board member for the following pharmaceutical companies: Janssen, McNeil, Novartis, and Shire; that he is currently a speaker for the following speaker's bureaus: Janssen, McNeil, Novartis, Shire, and UCB Pharma; and that in previous years, he received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, AstraZeneca, Celltech, Cephalon, Eli Lilly, Esai, Forest, Glaxo, Gliatech, the National Alliance for Research on Schizophrenia and Depression, the National Institute on Drug Abuse, New River, Novartis, Noven, Neurosearch, Pfizer, Pharmacia, the Prechter Foundation, the Stanley Foundation, and Wyeth. No other disclosures were reported.
That's a pretty comprehensive disclosure of conflicts of interest, wouldn't you say? I'll say it again: Either Mike Adams lied and is a lying liar, or he didn't bother to look at the article itself before composing his hysterical screed. Either way, it reflects very poorly on him. (So what else is new?) Not that that his own error or lie stops him from going on to paint Bastyr University as even more of a dupe than I've painted UW as being:
In the world of naturopathy, by the way, there is quite a chasm between the more "conventional" N.D.s (like Bastyr graduates) and the holistic, natural, salt-of-the-Earth kind of naturopathic healers who have no sponsoring institution. The Bastyrs of the world are working hard to get naturopathic medical practice legalized in many states, but they're also disliked by the non-accredited naturopaths who end up being labeled criminals for practicing their own brand of natural medicine in those same states.
Many non-accredited naturopaths insist that Bastyr is just a "green" replacement for organized medicine's tyranny. Without a doubt, when people see Bastyr graduates collaborating with top psychiatric drug pushers on a study that clearly seeks to discredit a valuable herb, it just fans the flames of dissent against Bastyr among more holistic practitioners.
What's my take on the issue? I think Wendy Weber must be a complete fool to lend her name to such a study, because the very title of the study presupposes something that's entirely false to begin with: That ADHD is a bonafide "disease" in the first place. She even based the entire scoring of the participants' symptoms on the American Psychiatric Association's DSM-IV -- the tome of psychobabble "disorders" invented by a truly evil industry that seeks to label every person still breathing with some sort of brain chemistry disorder (and then demand that they all be "treated" with mind-altering drugs that just happen to enrich their corporate sponsors, the drug companies!).
Of course, Adams' other charge, namely that the study used an "inactive" form of St. John's Wort because big pharma (represented by Dr. Biederman, wanted this study to fail, strains credulity. Does he honestly believe that the naturopaths at Bastyr didn't want to design this study to give it the maximal chance of showing a treatment effect due to St. John's Wort? Or maybe he believes the naturopaths at Bastyr are utterly clueless about what is supposed to be one of their favorite and most well-known herbal medicines. Whatever I think of naturopathy, even I don't think that naturopaths at the largest and most famous school of naturopathy in the U.S. would be so ignorant about their own supposed craft as not to be able to come up with what they consider to be an appropriate formulation of St. John's Wort for this particular trial.
Aside from herbal and plant-based medicines, which in reality is nothing more than administering and studying unpurified and unstandardized medicines, there is little in naturopathy that could be said to be based on science or on anything other than the placebo effect. (Naturopaths embrace the ultimate in pseudoscience, homeopathy, for crying out loud!) People don't realize that most medical doctors are not scientists and that post-modernist relativism (or even just a desire not to be perceived as close-minded) can lead physicians into either not resisting the infiltration of pseudoscience into academia or even embracing it. Collaborations such as the one between Bastyr University and UW are one result of this, as well as a carefully crafted strategy by CAM advocates to coopt science-based medicine to give pseudoscientific CAM modalities the appearance of scientific validity. Unfortunately, all these collaborations serve to accomplish is to blur the line further between scientific medicine and woo, between medicine and quackery. The naturopaths definitely have their foot in the door, but will scientific medicine have the courage to slam the door shut on it in spite of the yowls of pain doing so will no doubt cause?
REFERENCE:
1. Weber, W., Stepp, A., McCarty, R., Weisse, N., Biederman, J., McClellan, J. (2008). Hypericum perforatum (St John\'s Wort) for Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: A Randomized Controlled Trial. Journal of the American Medical Association, 299(22), 2633-2641.
This trial was designed as a single-agent clinical trial, so the results pertain only to the use of H perforatum in isolation for the treatment of ADHD. It is possible that H perforatum may work synergistically with other botanicals, vitamins, minerals, or supplements.
I understand that it works well combined with Ritalin, a rock-solid activity schedule that includes lots of fresh air and exercise, and a balanced diet.
It is genius what you write about Dr. Chan's editorial, Orac. Those were my thoughts exactly.
I agree Mike Adams is an idiot and a liar. The annoying thing is that his articles seem to get picked up by other websites and spread all over the web like a virulent form of verbal diarrhea.
Marilyn
Once again proof that there is no such thing as alternative medicine. There are treatments and drugs that go through the process of testing and studies and come out shown to have efficacy for treating the target problems. That is called medicine. Medicine can contain "natural" herbs or plants that pass the tests, or drugs that have been created in labs.
Then there are treatments "natural" or not that show no efficacy at all compared to placebos. This is not alternative medicine, this is junk.
There is no alternative medicine.
And pseudoscience abounds in naturopathy, including homeopathy, electrodiagnostic testing, chelation therapy for all manner of illnesses besides acute heavy metal poisoning, galvanic therapy, "glandular" therapy (in reality this is probably nothing more than "live cell therapy," which usually involves grinding up animal glands and administering them), and hydrotherapy, among many, many others.
Are they still injecting chicken embryos?
Orac said: "What possible advantage is there to using an impure mix derived from a plant compared to the pure active compound, if either of these compounds are indeed active? That's just what those "unimaginative" pharmacologists and natural products chemists have been doing for decades, if not centuries, and it works pretty darned well. Think digoxin, taxol, and a host of other plant-derived pharmaceuticals."
One of the pillars of woo is that "impure mix(es) dervied from a plant" are far superior to the purified active ingredient(s), due to a natural synergy that Mother Gaia programmed into the plants, seeing that plants were created to serve the needs of man. It is commonly explained that any lack of efficacy or side effects due to "natural" compounds are caused by man's tampering with plants to create a purified extract.
The theme that any cooperation with Evil Allopathy/Big Pharma on the part of alties makes them dupes or conspiracists is also common in the world of woo. Vociferous advocates of "natural" medicine don't want it to be "complementary" to mainstream medicine. They're like religious extremists who don't want to pollute the One True Faith.
It is commonly explained that any lack of efficacy or side effects due to "natural" compounds are caused by man's tampering with plants to create a purified extract.
So, varieties of Feverfew developed by humans to have a higher (and more standardized) content of parthenolide are actualy less effective than low-dose, variable varities.
It's plant homeopathy?
The one teenager I know with ADHD drinks several cans of Mountain Dew each day. Have studies been done linking ADHD with sugar or caffeine intake, or with low quality or insufficient sleep?
From my brief stint in the world of medicine, it seems that changing harmful habits often works miracles that no amount of medicine (real or woo) can work.
randomizing participants may be difficult or impossible when the therapy to be evaluated relies on participants' belief in the treatment or relationship with the practitioner
So it's essentially faith healing, voo-doo or other witchcraft. It also leaves the practitioner with the easy out of "you just didn't bee-lieve in the therapy enough", and "If you prayed harder/right/more often/to a different God .... it would have worked."
I prefer my medicine to work even when administered by strangers, and when I'm unconscious.
From my brief stint in the world of medicine, it seems that changing harmful habits often works miracles that no amount of medicine (real or woo) can work.
Umm... changing dietary habits to avoid harmful effects from allergies/overintake would be called "medicine".
"Umm... changing dietary habits to avoid harmful effects from allergies/overintake would be called" --
"parenting" (along with turning off the Boob-tube, video games & PC, and getting the kids outside to exercise).
Bastyr has a variety of other failed research projects listed on their site
http://bastyr.edu/research/projects/default.asp?view=Publications
Like:
Efficacy and safety of Echinacea in treating upper respiratory tract infections in children. Taylor J, W Weber, L Standish, H Quinn, J Goesling; M McGann, and C Calabrese, ND, MPH. Journal of American Medical Association 290(21), December 2003.
That concluded:
Conclusions Echinacea purpurea, as dosed in this study, was not effective in treating URI symptoms in patients 2 to 11 years old, and its use was associated with an increased risk of rash.
The one teenager I know with ADHD drinks several cans of Mountain Dew each day. Have studies been done linking ADHD with sugar or caffeine intake, or with low quality or insufficient sleep?
From my brief stint in the world of medicine, it seems that changing harmful habits often works miracles that no amount of medicine (real or woo) can work.
Studies were done to see whether caffeine could have beneficial effects against ADHD similar to Ritalin and other stimulants, after parents had anecdotally reported good results. I seem to recall the results were disappointing. However, caffeine was not found to aggravate ADHD. However, lack of sleep *did* aggravate it. ADHD sufferers are much worse when they're sleep-deprived. Getting enough sleep won't cure a real case of ADHD, but it'll make it a heck of a lot easier to cope.
Another interesting study (not blinded, and performed by somebody who works in this field and thus has a conflict of interest) was done with people who are overstressed at work -- not enough sleep, overstimulated with e-mails and phone calls and meetings, working on multiple tasks simultaneously -- and found that over time, they developed symptoms similar to ADHD. If they went on vacation for two weeks, the symptoms disappeared. So ordinary people can get ADHD symptoms -- but unlike ADHD sufferers, they are very easily cured by the time-honored remedy of a vacation. ;-)
Regarding the St John's Wort study, I remember reading of a study about ten years ago looking at ADHD sufferers who were given tricyclic antidepressants. It found that for a minority of the patients, the antidepressants relieved their ADHD symptoms. For the majority, however, the antidepressants did nothing. However, that group showed that traditional ADHD drugs like Ritalin seemed to relieve their symptoms of depression.
This research is probably what prompted the use of St John's Wort for ADD. But I seem to recall that the effect of the depressants was relatively mild. And since St John's Wort is generally quite mild in relation to prescription antidepressants like Prozac, it would seem to me to be a waste of time to use it. Especially since it has a dangerous interaction with a number of lifesaving drugs.
This whole St John's Wort thing has been going around in woo-ville for quite some time. It's yet another substance which has been touted as being effective for multiple conditions with no real science behind it.
A good starting rule for ADHD is that anything that improves overall health goes double for improving ADHD:
Of course, all of those are hard to apply for neurotypical adults. Multiply the difficulty for teens, and then take some hideous exponent for ADHDers.
While caffeine and sugar may help somewhat to arouse the normally-underactive parts of an ADHD brain, the cost in terms of sleep quantity and quality (and remember, teens need them more than children or adults) more than makes up for any benefits.
On the other hand, it works -- in testimony whereof, my ADHD son who finally got the clue that Dad may actually know what he's talking about and put The Program into action -- and is now getting A grades in classes at one of the most brutal physics programs in the US.
Well whereas I gave the study some mention, you gave it a thorough academic going-over. Much more impressive!
What possible advantage is there to using an impure mix derived from a plant compared to the pure active compound, if either of these compounds are indeed active?
Cost. St. John's wort is very easy to grow in most temperate climates, so if you have a modest yard you can supply yourself with impure mixes basically for free, rather than paying for the purification and recouping R&D costs for whoever isolates and patents the active compounds.
Orac
I think you might be misrepresenting N-of-1 trials here. They are in fact a rigourous and accepted method of investigation in certain rare clinical conditions. Ignore for the moment that ADHD is hardly rare enough to ever warrant N-of-1 trials. Imagine instead a very rare condition or a patient who through sheer bad luck has two relatively rare conditions that will mean that no one will ever do a randomised controlled trial that is relevant to that patient because such patients are too rare to ever build an experimental sample.
These trials can involve the one patient being randomised to various sequences of treatment that involve repeated placebos and washouts interspersed with multiple exposure to various (or one) treatment/s that are suspected to be helpful to that patient. They are in fact the very highest level of evidence when considering the care of that particular patient. As long as normal double-blinding and randomisation techniques are used, of course.
http://www.jr2.ox.ac.uk/bandolier/booth/glossary/No1.html
The problem with what Chan is saying is that multiple n-of-1 trials are in fact just normal randomised cross-over trials but with somewhat complex design. Nasty to analyse but perfectly acceptable within rational medicine. Dose finding trials are perhaps an easy to understand example.
I don't think so. N of 1 trials, as you point out, are only appropriate for rare diseases or conditions for which studying more cases is just not possible. Proposing to do N of 1 studies for the common diseases for which CAM is generally used. That's where I was coming from.
"These trials can involve the one patient being randomised to various sequences of treatment that involve repeated placebos and washouts interspersed with multiple exposure to various (or one) treatment/s that are suspected to be helpful to that patient."
Sounds like we keep trying something different and then calling whichever therapy that the patient was on when he finally got better the one that worked.
I think it's called 'personalised' or 'individualised' medicine. :)
...that explains a lot.
I really wish I known that last year.
angry doc,
I learned the following from a consultant after we spent 8 hours troubleshooting a problem:
Q: "What approach ALWAYS works?"
A: "GUR YNFG GUVAT LBH GEL".
Use ROT-13 to decrypt the answer, http://web.forret.com/tools/rot13.asp.
Orac said: "Yet CAM advocates keep telling us that we must "integrate" pseudoscience with science-based medicine to produce so-called "integrative medicine." How on earth can that be good science?"
Science and pseudoscience put different emphasis on negative results, and controls in research. As a patient I see this as a quality control issue and I want to know what importance my doctor puts on these. Unfortunately, as you said, "most medical doctors are not scientists." Some don't know the difference. Integrative medicine in my opinion means it will be even harder for me to have an expectation about how my doctor is determining the effectiveness of his methods.
As a patient with an idiopathic rare disorder I know what it is like to depend on medicine where the science is weak, studies are small, case studies are often cited, every surgeon experiments, err should I say tinkers, with the procedures and disagreements between them are common. Even so I am comforted by their attempts to apply science as well as possible. Maybe some day I will want the hope that CAM provides, but for now I want what science-based medicine I can get and I want some idea of which is which.