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http://www.google.ch/patents/US8219419

Am I right to infer that these are all subjectively experienced clinical features patients giving responses to 'please' researchers in the context of the study rather than actually feeling better would all get rolled up into the claimed 'placebo effect' in Kaptchuk's studies?

He has also, by his recruitment strategy seeded his trial with suggestible/compliant subjects who are prone to give confirmatory responses.

And with all those advantages, the placebo effect looks pretty puny.

[Damn me for formatting replies on a little iPhone screen]

Am I right to infer that these are all subjectively experienced clinical features? Patients giving responses to 'please' researchers in the context of the study rather than actually feeling better would all get rolled up into the claimed 'placebo effect' in Kaptchuk's studies.

He has also, by his recruitment strategy seeded his trial with suggestible/compliant subjects who are prone to give confirmatory responses.

And with all those advantages, the placebo effect looks pretty puny.

It is interesting that these researchers chose to look at GI symptoms, which are strongly influenced by emotional factors, even in patients with actual diseases. They also tend to be quite subjective. I suspect that if they had chosen to look at an objective end point in some other condition, perhaps one based upon a laboratory value, they would have had much more difficulty spinning their results.

Orac or his double should send a long letter to the editor to the LA Times in response. It would be interesting to see if it got published. I suspect that someone there has an agenda, so perhaps it would not.

And yes, I misspelled my own name in the previous comment. Groan.

@ Orac
"There’s no way to convince a patient that an inert sugar pill (or whatever else is being used as a placebo) will do anything useful to relieve their symptoms without lying to the patient. "
- There's a way: the doctor must believe in the power of the sugar pill! What we need is to train physicians stupid enough to believe in the power of inert sugar pills. Maybe one day Universities funded by the Homeopathy pharma will select their MD students according to this criterion.

Part of the problem is that during the consent process, patients hear what they want to hear. See PMID: 27174578. In Kaptchuk's trial, he overloaded the consent with "good news" about the power of treatment, and de-emphasized accurate description of the lack of content of his placebo. So, of course, many patients heard only that they would receive a pill that will make them better. What was missing was a test of patient comprehension. In essence, what he proved is that you can hide a complex true statement in a thicket of confounding and misleading statements.

Michael Finfer, MD @ 4, that smell clunker gets us all from time to time.
Oh! That's spell checker!
Dammit. ;)

@Orac, so a statistically insignificant number of a statistically insignificant number of pre-selected participants, selected for suggestibility and psychosomatic complaints, managed to prove a week - at a level of noise to signal in this study and hence, that is significant.
Yes?
One ponders what any peer review would say.
I'm thinking, "Bird cage liner" for the ultimate destination of the paper.

There are placebos and then there are woocebos.

There’s a way: the doctor must believe in the power of the sugar pill!

Ah yes, the old "it's not lying if you believe it" dodge. I'm not familiar with the laws in your jurisdiction, so maybe it would work there. Here in the US the typical phrasing of such laws is, "... knew, or should have known, ...." A medical doctor should know that a placebo will have no pharmaceutical effect, so just because he believes it will doesn't mean he is justified in making claims that it will.

To illustrate this distinction, consider the contrast between claiming in 1998 that vaccines might cause autism versus making the same claim today. In 1998 the Wakefield et al. Lancet study had just been published, and the fact that it was based on fraudulent data would not be discovered for several years. So in 1998 a reasonable person could have believed that there was evidence of vaccines causing autism. Now that Wakefield et al. has been thoroughly debunked (in addition to being based on fraudulent data, the finding was never replicated by any researcher not connected with Wakefield), it is no longer reasonable to believe that claim.

Placebo narrative and patents:

System and method for reducing the placebo effect in controlled clinical trials Fava, et al. 8,219,419, July 10, 2012

The inventors write, "It has been suggested that addressing the placebo response issue is one of the most important challenges facing the future of industry-sponsored psychopharmacologic drug development. "

These were patented as well, it doesn't mean that they worked as intended and in some cases, worked at all.
http://www.museumofquackery.com/devices/devindx.htm

@ Eric
"A medical doctor should know that a placebo will have no pharmaceutical effect". What about homeopathy? If a medical doctor thinks that homeopathy has an effect, what does the US law say? Is there any information that has been concealed to him as in the Wakefield case?

psychopharmacologic

It's difficult to know exactly what you're saying here. It's just that your history suggests that it's shit.

Daniel@12: Anybody who has had high school chemistry should know that Avogadro's number is finite, and therefore that homeopathy is bunk. I tend to let Hahnemann of the hook because in his day Avogadro's number wasn't known (Avogadro, who was a contemporary, did not know the number, only that it was finite). More recent homeopaths--especially the ones who came after quantum mechanics was shown to explain almost all of chemistry and a big chunk of physics--are not entitled to that charity.

Of course, IANAL, TINLA, and even if it were it would be worth at most what you paid for it.

@ Eric
Even if they are told that Avogadro's number is finite, they may think that molecules do not explain everything and since they believe there is an effect, it is not a problem for them. I am convinced that most of the doctors specialized in homeopathy really believe it works.

Rich - that goes to mood and behavior effects, whereas neuropsycho would be changes on neural cell function. Not that mjd actually has an understanding, as he's just cutting and pasting.

Way OT here, but a *very* common printer, which is extremely popular with hospital pharmacies and retail pharmacies has a recall on the power supply for the label printer.
Zebra printers manufactured between October 1, 2010 and December 31, 2011 may be effected.
https://www.zebra.com/us/en/power-supply-recall.html

Three fires have been reported, with one fire damaging the workspace and printer.

@ Daniel #15 Which really doesn't make it any better. Being self deluded is not a defense for selling overpriced water.

1) Selling overpriced: all the luxury industry is based on overpricing.
2) If a MD is self deluded why wouldn't a judge be deluded too?
3) The initial post was about the fact that the idiot is not lying.
Finally, as I said in RI already, if a MD believes in homeopathy, it is better if he does not prescribe active drugs.
The real problem is to give degrees to students lacking judgement.

BadlyShavedMonkey @1 & 2

IIRC, and I really cannot face rummaging back through Kaptchuk's papers at the moment (it's still dark here and I haven't finished my first coffee), they are all self-report...

Cue rant about use of self-report in any medical research without the back up of even a semi-objective measure...

The placebo narrative: Justifying integrative medicine through exaggeration

oracknows — Mon, 19 Dec 2016 02:00:24 +0000

The placebo narrative: Justifying integrative medicine through exaggeration

I write quite a bit about placebo effects. Of course, part of the reason is that placebo effects are just plain interesting from a scientific perspective. After all, if one can relieve symptoms with inert sugar pills or other ineffective interventions because of the power of expectation, that’s something we should want to understand. Also, given the mission of this blog, another major reason is that placebo effects are inextricably bound to the question of whether the alternative medicine modalities that are being “integrated” into medicine through the brand of integrative medicine actually have any useful therapeutic effects or not, aside from placebo effects. Of course, as we’ve discussed time and time again, pretty much all “complementary and alternative medicine” (CAM) or “integrative” medicine modalities that are not herbal medicine, nutrition, or exercise (which can have measurable physiological effects due to understandable physical mechanisms) have no detectable effects above and beyond placebo effects, no matter how much proponents of integrative medicine try to show that they do. There’s a reason why, given the utter implausibility of many of these treatments, such as homeopathy, reiki, and the like, I refer to integrative medicine as “integrating” quackery with real medicine; that is, when integrative medicine is not rebranding perfectly respectable science-based modalities like diet and exercise as somehow “alternative” or “integrative,” so that they can claim at least some efficacious modalities in their armamentarium and thereby imply that the quackery has value too.

That’s why I was so disturbed when a reader e-mailed me a link to a credulous article in National Geographic that basically promotes every pseudoscientific trope about acupuncture entitled, "Here's What Placebos Can Heal—And What They Can't" by Simon Worrall, with the subtitle "The latest research in biochemistry reveals that your brain can actually self-medicate." Yes, that’s like waving the proverbial cape in front of the proverbial bull, particularly given how ScienceBlogs was for a time in essence owned by National Geographic. The article is an interview with Erik Vance about his new book, Suggestible You: The Curious Science of Your Brain’s Ability to Deceive, Transform, and Heal. Its blurb is not encouraging:

This riveting narrative explores the world of placebos, hypnosis, false memories, and neurology to reveal the groundbreaking science of our suggestible minds. Could the secrets to personal health lie within our own brains? Journalist Erik Vance explores the surprising ways our expectations and beliefs influence our bodily responses to pain, disease, and everyday events. Drawing on centuries of research and interviews with leading experts in the field, Vance takes us on a fascinating adventure from Harvard’s research labs to a witch doctor’s office in Catemaco, Mexico, to an alternative medicine school near Beijing (often called “China’s Hogwarts”). Vance’s firsthand dispatches will change the way you think—and feel.

Expectations, beliefs, and self-deception can actively change our bodies and minds. Vance builds a case for our “internal pharmacy”—the very real chemical reactions our brains produce when we think we are experiencing pain or healing, actual or perceived. Supporting this idea is centuries of placebo research in a range of forms, from sugar pills to shock waves; studies of alternative medicine techniques heralded and condemned in different parts of the world (think crystals and chakras); and most recently, major advances in brain mapping technology. Thanks to this technology, we're learning how we might leverage our suggestibility (or lack thereof) for personalized medicine, and Vance brings us to the front lines of such study.

You know, someone should tell whoever wrote the blurb that being referred to as “Hogwarts” is not a good thing in medicine. Of course, I can’t resist indulging in one of my favorite quips here regarding Hogwarts and alternative medicine: What’s the difference between magic Harry Potter’s world and alternative medicine? In Harry Potter’s world, magic works. Alternative medicine, not so much.

Unfortunately, this article promotes what we at SBM have come to refer to as the “placebo narrative” in apologia for integrative medicine. If what Vance says in his interview reflects what’s in his book (and there’s no reason to think it doesn’t), then the book is basically promoting the same message. Before I look at the interview itself, though, let’s recap what we mean by the “placebo narrative.”

The placebo narrative

I consider it a truism that, as more and more rigorous clinical trials with proper blinding and controls show that popular alternative medicine modalities like acupuncture, reiki, and the like that are furiously being “integrated” into medicine have no detectable specific effects on any disease or condition distinguishable from placebo effects, increasingly integrative medicine proponents have shifted to arguing that that’s OK, that these modalities actually work through the “power of placebo.” Thus was born what Steve Novella has referred to as the “placebo narrative.” I like that term, but I sometimes refer to the placebo narrative as the myth that “thinking makes it so,” which is the basis for the rebranding of integrative medicine as harnessing “the power of placebo” or, alternatively, the power of positive thinking. Never mind that it’s highly questionable whether it’s ever worthwhile to do so and that trying to use placebo effects to intervene in real disease processes could potentially have deadly consequences by making the patient think he feels better without actually affecting the underlying pathology.

That’s not to say that there aren’t still believers out there trying to demonstrate through “bait and switch” studies that, for example, acupuncture is more potent than antidepressants (it’s not); that acupuncture is effective in relieving hot flashes, be they due to menopause or breast cancer chemotherapy or hormonal therapy (no, it doesn’t work for either); or that acupuncture is effective in improving the pregnancy rate in women undergoing in vitro fertilization (it’s not). There are even meta-analyses claiming that acupuncture “works.” One meta-analysis by Andrew Vickers claiming that acupuncture is effective for pain, is cited almost as gospel by acupuncture advocates, even though its methodological deficiencies are significant and the effect “detected” is almost certainly not clinically significant, issues detailed by Steve Novella, Mark Crislip, and, of course, yours truly. (Let’s just say that the corresponding author of that study did not take the criticism well.) I could go on, but you get the idea. In fact, I’d argue that it’s because of how difficult it has been for acupuncture advocates to show that acupuncture and other alternative therapies work for anything that the narrative has shifted to placebos. It’s also why integrative medicine advocates like pragmatic trials so much.

Still, those who still think various highly implausible alternative medicine treatments actually work notwithstanding, increasingly the placebo narrative has become the dominant message among integrative medicine advocates to explain how the woo in integrative medicine “works.” Basically, any time you hear someone referring to the “mind-body” connection, they’re invoking a disguised form of the placebo narrative, wrapped in discredited mind-body dualism to boot.

The problem with the placebo narrative

As you might imagine if you’ve been reading SBM a while, there’s a problem with the placebo narrative—many problems, actually. These fall into two categories, in general: The scientific and the ethical. The ethical problem is easy to understand, and it’s very, very daunting for the promoters of the placebo narrative. Basically, in medicine it is very unethical to lie to patients, and inducing placebo effects requires lying to patients. Period.

That’s why integrative medicine believers have made such an effort to provide evidence that it is not actually necessary to lie to patients to induce placebo effects. The big name in integrative medicine who has done the most to promote this narrative of “placebos without deception” is without a doubt Ted Kaptchuk at Harvard. Indeed, Kaptchuk has tried repeatedly to demonstrate that it is possible to trigger placebo effects “without deception,” and three of his clinical trials are the ones often cited to argue that placebo effects don’t require lying to the patient. Unfortunately, it takes very little in the way of a critical reading of all three studies to realize that there was indeed deception in them, as well as selection bias. The advertising and the consent forms for both trials basically served the purpose of the physician telling a patient that the treatment would work. For instance, in one of Kaptchuk’s studies, which tested placebo pills on patients with irritable bowel syndrome (a syndrome very sensitive to placebo effects) emphasized how “placebo pills, something like sugar pills, have been shown in rigorous clinical testing to produce significant mind-body self-healing processes.” Another of his studies, which tested the drug Maxalt versus placebo pills for their effect on migraine headache symptoms, included in its language about the placebo: “Our second goal is to understand why placebo pills can also make you pain-free.” Not to understand why placebo pills might be able to make you pain-free or could possibly make you pain free. “Can make you pain free." The other study, billed an open-label placebo trial for chronic low back pain, included this language:

After informed consent, all participants were asked if they had heard of the “placebo effect” and explained in an approximately 15-minute a priori script, adopted from an earlier OLP study, the following “4 discussion points”: (1) the placebo effect can be powerful, (2) the body automatically can respond to taking placebo pills like Pavlov dogs who salivated when they heard a bell, (3) a positive attitude can be helpful but is not necessary, and (4) taking the pills faithfully for the 21 days is critical. All participants were also shown a video clip (1 minute 25 seconds) of a television news report, in which participants in an OLP trial of irritable bowel syndrome were interviewed (excerpted from: http://www.nbcnews.com/video/nightly-news/40787382#40787382).

So basically, they used the same talking points from the previous study, plus clips from a news reports about happy study participants to prime the patients that placebo effects can be “powerful.” In pretty much every study of “placebo without deception,” you will find a problem like this.

None of this doesn’t mean that the science of placebo effects isn’t worth studying. The problem is that integrative medicine proponents have taken over much of the research and tried to make it conform to their preferred narrative

Enter Erik Vance

When I encountered Worrall’s interview with Vance on NatGeo, I thought Vance’s name sounded vaguely familiar. A quick search revealed him to be a science writer whose work has appeared in Discover and the New York Times. When I saw how much Vance has written about placebo effects before, I was surprised that, as far as I could tell, neither I nor any of the other SBM bloggers had written about one of his articles before, particularly given that he’s written articles like "Power of the Placebo," complete with a placebo narrative trope, 'Once dismissed as a curiosity, the placebo effect is now recognized as the key to the brain's "inner pharmacy." If only doctors knew how to open the medicine cabinet.' Is it? Is it really?

In the introduction to the interview, Worrall informs us a bit about Vance, including that he trained as a biologist but had been raised in a Christian Science household. That’s probably why Worrall’s first question was about whether faith healing actually can work, to which Vance answered:

Wow, that’s tough! I was brought up in Christian Science, which, at its heart, believes that the world, including our bodies, is a reflection of our minds. So, if you change your mind, you can change your body.

Growing up in Christian Science I saw a lot of healings, which piqued and sustained my interest in this subject. I saw people who claimed to be healed of cancer, or a guy who cut off his toe and the toe grew back. But my hope for this book is not to prove or disprove these things I saw as a child. Do placebos and the power of the mind work? What I’ve found is yes, but not with everything. There are rules and conditions in which healing can be incredibly effective. Parkinson’s, chronic pain, irritable bowel syndrome, depression, anxiety, certain types of asthma, and autoimmune deficiencies are all very placebo-responsive. But cancer is not.

Christian Science, homeopathy, or other unproven alternative medicines may make someone feel better, but when it comes to curing a life-threatening tumor, that isn’t an appropriate place to be using these methods.

At least Vance isn’t completely unreasonable. At least he attributes some limitations to placebo medicine. (Would that some others were a bit more circumspect!) He’s also not antivaccine, as we learn when he states that his kids have all their shots and how he understands how vaccines work and therefore has full faith in them. In fact, part of the problem with the placebo narrative is how it’s taken in people who believe themselves to be scientific and who are generally pretty reasonable.

Vance is, however, dead wrong about asthma being particularly placebo-responsive—and my choice of the word “dead” is intentional because placebo medicine could easily lead to the death of asthmatic patients. Indeed it’s worth expanding a bit on a point to state that one of Kaptchuk’s own studies showed just how dangerous using placebo effects in asthma is. The CliffsNotes version is that placebos made asthma patients undergoing an asthma attack feel as though they were breathing better, but the cold, hard evidence from incentive spirometry showed that their breathing function did not improve. As Peter Lipson pointed out, that’s a good way to kill a patient, because that patient could feel less short of breath even though he is on the verge of respiratory collapse.

Vance is not incorrect when he discusses how placebo effects impact Parkinson’s disease:

Parkinson’s is the perfect disease to talk about placebos. It is a chronic deficiency of dopamine, which is one of those brain chemicals that does a lot of jobs in our bodies. One of [dopamine’s] important roles is in reward processing: how we think about good things we might get in the future.

Expectation drives placebos. And dopamine is a chemical that’s very responsive to our expectations. Parkinson’s happens to be a deficiency in the very chemical that’s very important in placebo effects and rewards.

If you look at Alzheimer’s, which does not have a high placebo response, you start to see that there are rules at play when it comes to placebos. It’s not your brain magically doing all these crazy things. There are certain chemicals we have access to and others we don’t.

It is true that clinical trials of Parkinson’s disease do report significant placebo effects. For example, Dr. Christopher Goetz examined 11 clinical trials with 858 patients and found that in drug trials 0-27% of patients experienced improvement in their symptomatology, while in surgical trials the number could be as high as 42%. (More invasive placebos produce more significant placebo effects.) Overall, 16% of patients in the placebo groups of the trials experienced improvement. Of course, I would point out that most patients with a serious disease would not be particularly happy to have only a 16% chance of improving due to a treatment. Yes, there are pharmaceuticals that are that poorly effective, usually against bad diseases, but those are exactly the drugs that integrative medicine proponents often rail against—with some justification. Yet here, Vance likes an intervention that produces such a modest result.

He also doesn’t consider that even that modest result is probably illusory.

The illusion of placebo effects

One thing not mentioned here is that placebo effects can only be quantified in clinical trials, which are, by their nature, highly artificial treatment situations. We at SBM often point out that it’s incorrect to refer to “the placebo effect,” because there is not just one placebo effect. Instead, we refer to placebo effects. Much of what is lumped together as “the placebo effect” include study artifacts that have little or no bearing on real world outcomes and/or modulation of the patient’s perception of his symptoms. Indeed, there are those who question, based on evidence, whether there is even such a thing as placebo effects. For example, in 2001 Hróbjartsson and Gøtzsche published an article in which they asked whether the placebo was powerless based on 214 studies with a total of 8,525 patients in which they concluded:

We found little evidence in general that placebos had powerful clinical effects. Although placebos had no significant effects on objective or binary outcomes, they had possible small benefits in studies with continuous subjective outcomes and for the treatment of pain. Outside the setting of clinical trials, there is no justification for the use of placebos.

In support of the idea that much of what passes for “placebo effects” is in reality a sum of artifacts of clinical trials, Jean Brissonnet in a French language article translated by Harriet Hall pointed out that clinical trials are different. We measure many more things—and measure them more intensively. Treatments are much more standardized. Brissonnet proposes defining the placebo effect thusly, “Observed effect = specific effect + natural course of healing + a residual effect that we will provisionally call the placebo effect.”

When you look at placebo effects this way, they become a lot less impressive than proponents like Vance portray them. I’m not sure I’m quite ready to go as far as Mark Crislip in rejecting the idea that placebo effects are even a real thing, but I have been convinced that, if placebo effects are real apart from artifacts in clinical trial construction, measurement biases, and the like, they are quite modest at best and, in the case of alternative medicine, not worth lying to the patient.

None of this is to say that placebo effects might not be useful, because it is certainly possible that doctors can enhance the perceived effectiveness of evidence- and science-based treatment by using strategies that enhance placebo effects, in particular the doctor-patient relationship. One of my favorite studies was another Kaptchuk study that actually told us something interesting about placebos. Basically, Kaptchuk randomized patients with irritable bowel disease into three groups. Subjects in Group 1 were in the wait list control and received no intervention. Subjects in Group 2 received placebo acupuncture treatments from an acupuncturist showing no empathy. Subjects in Group 3 received the same acupuncture treatments as patients in group 2 under the same conditions and in the same room, except that the practitioners interacted with them extensively. The difference was that subjects experienced an “augmented” patient interaction (45 minutes) at the first visit in which detailed questions about their symptoms were asked, including how their IBS symptoms affected their lifestyles and relationships. The interviewers asked if subjects understood the “cause” and “meaning” of their conditions and at each visit incorporated at least five primary behaviors, including a warm, friendly manner; active listening (repeating the patient’s words and asking for clarifications); empathy; 20 seconds of thoughtful silence while feeling the patient’s pulse or contemplating a treatment plan; and communication of confidence and positive expectation. At each visit, the acupuncturist would place the placebo needles and then leave the subject in a quiet room for 20 minutes. When the practitioner came back to remove the needles, he or she also made sure to exchange some words of encouragement.

The results? At the end of six weeks, Kaptchuk observed an improvement of 28%, 44%, and 62% in groups 1, 2, and 3, respectively, concluding, “Non-specific effects can produce statistically and clinically significant outcomes and the patient-practitioner relationship is the most robust component.” Basically, what we used to call a good bedside manner matters.

Even Vance seems to realize that the trappings of medicine and the practitioner-patient relationship are very important, as he says:

I also traveled to Catemaco, a town in Vera Cruz famous for its witch doctors. I met with one of the leading witch doctors there to try and understand what we call the theater of medicine—all the trappings that go into the healing practice, like the stethoscope and white lab coat. In different cultural contexts, those things change. What was interesting in Catemaco is that many of the traditional healers have adopted the theater of modern medicine. They wear lab coats, cut their hair short, and use long words, which gives them the "flavor" of what we recognize as conventional medicine.

And:

The message for doctors is the importance of being more empathetic and taking more time. You may be throwing away 30 percent of your cure just by having a poor bedside manner. If you do, you can’t be surprised if people go looking for other means of healing. The witch doctors, traditional Chinese medicine practitioners, and homeopaths I spoke to all understand this.

Of course, the proper response to this is to point out that, yes, bedside manner matters. That’s why training physicians to be more empathetic is a far better course than to embrace witchcraft like homeopathy, acupuncture, and other forms of magic that make up much of the alternative medicine being “integrated” into medicine through integrative medicine.

The seductiveness of the placebo narrative

Paul Ingraham summed up placebo effects well:

Placebo gets more love than it deserves. I am interested in the biology and psychology of placebo, but it is not a magical mind-over-matter phenomenon, or even a good consolation prize when treatment is otherwise ineffective. Many medical problems are entirely immune to positive thinking and expectation (try treating tuberculosis with a sugar pill and see how many Nobel Prizes you pick up for that innovation). The power of belief is strictly limited and accounts for only some of what we think of as “the” placebo effect. There are no mentally-mediated healing miracles. But there is an awful lot of ideologically motivated hype about placebo…

There’s a reason for this hype, though. The placebo narrative is very seductive, as I’ve pointed out many times before, for reasons that are not hard to guess. First and foremost, it taps into a deep, longstanding aspect of humans. Specifically, the placebo narrative offers the patient—and, truth be told, the physician as well—an illusion of control. What is the reward for the physician? That’s simple. These days medicine is a collaboration between doctor and patient, and, although the doctor still holds most of the power, the patient must be involved in the decision-making process. However, part of the appeal of being a physician is actually rooted in paternalism (these days, disguised under the term “patient-centered care,” where we are the nearly all-knowing physician who does what is necessary to heal the sick and the patient simply accepts whatever we deem necessary. We don’t have to tell them everything, and they don’t expect to be told everything. There is also a very real appeal to being a “shaman-healer,” who takes care of the “whole patient” spiritually as well as physically. Being able to perceive oneself as teaching a patient to “heal himself” could thus be very tempting, and there’s a reason why anthropologists are attracted to alternative medicine.

As for patients, placebo medicine literally tells them that their mind—and therefore they—can relieve their symptoms and “heal” their bodies just by unleashing some innate power within oneself to heal the body. You don’t have to have chronic pain or a serious illness to understand how appealing such an idea is. Patients love it, for much the same way that people love The Secret. It tells you that you attract what you want to yourself and that, basically, if you only want something bad enough, including healing, the universe will provide.

It’s not for nothing that I coined the term “the central dogma of alternative medicine” and concluded that that central dogma is: Wishing makes it so. The placebo narrative fits perfectly with that and is of a piece with previous religious healing traditions in which the ill pray for healing and, if that healing comes, God did it. The main difference here is that we’re told that, instead of the universe providing through a god or spirit, the universe provides through your mind—as though the mind and the body were separate things.

The reality of course, is much more prosaic and much less “sexy,” as even Vance seems to realize. Late in the interview he notes that he’s “tried a lot of alternative medicines and haven’t stuck with any of them.” Why not? If placebo effects are so powerful, you’d think Vance would have found an alternative medicine modality that he liked enough to stick with.

He also cautions:

The message for the patient is that [alternative medicine] can be effective. But I do lay out some rules for when to do it and when not to.

One is, don’t hurt yourself. If you have a life-threatening disease, that’s not the time to play with expectations.

Don’t go broke. I’ve talked to many people who’ve spent their life’s fortune chasing after healings that were never going to happen.

The last one is, don’t harm the environment. If your placebo involves endangered animals, it might be a good idea to pick a different one.

Within those rules and within certain diseases, there’s a lot you can do. Just because it’s a placebo doesn’t mean it won’t work. This has been shown again and again in laboratories.

Except that it hasn’t “been shown again and again in laboratories” that placebos “work.” It’s still not even clear that placebo effects are anything but artifacts of clinical trials. In brief, the myth of placebo effects is far more impressive than the reality.

Placebo research can be valuable, but it has, unfortunately, been largely hijacked by integrative medicine, whose adherents want to demonstrate that alternative medicine works and that placebo medicine is efficacious and therefore worthwhile. (Would that it were true!) What placebo research has shown us is not that alternative medicine works, nor has it shown us that the brain is the body’s “pharmacy” that can be tapped at will to heal all manner of ailments. Rather, what it has done is to reinforce something known since ancient times, the importance of empathy and a trusting practitioner-patient relationship. That’s more than good enough.

oracknows Sun, 12/18/2016 - 21:00

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Brain and Behavior

How would the effects of something like Rescue Remedy be explained in terms of its effect on anxiety. I came up against this the other day and found myself a bit tonge tied trying to explain to a friend why it was just a placebo. She said she didn’t care because it “worked” (she was very anxious, used the stuff and very quickly felt much better). I have read this, and all the highlighted bits, and I still don’t see how to answer my friend. What’s wrong with the “power of suggestion”, “power of positive thinking” with something like anxiety? It certainly shouldn’t cost $12 or more per bottle, but that argument doesn’t work very well either. Of course she threw out the naturalistic fallacy as well, at which point I kinda gave up. I need something simple and to the point to someone who barely got through high school and doesn’t read (probably barely can). Why bother? It just bugs me to hear that, “oh, you know that stuff I got? It really works!”. It seems like a gateway drug.

"It certainly shouldn’t cost $12 or more per bottle"

Yes it should, and even much more. The amount a person spends on something the more they are personally invested in it working (filling a need or a want). The same is true of cars, clothes, house, phone, personal trainer, or whatever. The more they spend the more they will strive to convince you, and themselves, that it works and was therefore worth the price.

How would the effects of something like Rescue Remedy be explained in terms of its effect on anxiety.

I was given a bottle by a friend. Consuming the entire thing worked for a little while, but it's awfully expensive for a digestif.

It certainly shouldn’t cost $12 or more per bottle

Real prescription medications usually do cost $12 or more per bottle--they need to set a higher price to recover manufacturing costs, amortized R&D costs, distribution costs, and reasonable retail markup. Some drug manufacturers get greedy and charge far more than justified by their costs, but even the ones that don't generally end up charging more. Of course the insured patient rarely sees that full cost because their cost is limited to the co-payment while the insurance company covers the difference.

OTC medications are a different story. Volume and competition help to drive prices down. But I recall from the time I almost bought a homeopathic remedy by mistake (N=1) that the homeopathic remedy was triple the price of the real stuff, and that was for the store brand homeopathic remedy (there was also a name brand version of the homeopathic remedy for about twice the price of the store brand).

I don't think rs@2 is entirely wrong about people equating higher price with superior product. That certainly does happen, whether justified (e.g., in real estate you are almost always getting something for the additional money you pay, whether it's a bigger lot, more square footage, or a more desirable location) or not (e.g., I can't reliably distinguish a $20/bottle wine from a $2k/bottle wine, but many wine snobs will always take the latter if they can afford it). I don't think that's necessarily the case with placebo medicine. There are lots of folk remedies that qualify as placebo medicine that don't cost a bundle of money, e.g., chicken soup for relief of cold symptoms. Some people get desperate enough to pay lots of money for treatments, and certainly there are charlatans who take advantage of this, but it's not the whole story.

The price should have an impact on the placebo effect. If an injection has more effect than two pills and two pills has more effect than one pill then it makes a kinda sense that an expensive remedy has more effect than a cheap one. Can you tell I've just been rereading Ben Goldacre's Bad Science?

Everything we pay for in life is worth only what we're willing to spend on it. Fake products can cost what they do because the people who are willing to buy them are willing to pay it. If they think they are getting value for their money, then the value is there to them . . . until their kid dies from an untreated infection, or they have a stroke because the "natural" remedy for their high blood pressure didn't do them a damn bit of good.

There's a reason why snake oil salesmen did so well 100+ years ago. Partly because anyone really sick would be dead by the time they came through town again, and partly because their products contained something else that created the illusion of feeling better that worked long enough that a change for the worse wasn't attributed to the snake oil, but the fact they'd run out of it and the salesman had moved on to the next town of marks.

Funny how the snake oil of the day contained a lot of alcohol and/or laudanum or cocaine.

Which makes me want to know what was really in the placebo that darwinslapdog's friend takes, Rescue Remedy. It didn't take long to find that brandy is one of the ingredients.

Go figure. Placebo effect my ass. She's getting a buzz. Probably not enough to get her pulled over or get her a DUI, unless she gets a drink after work with her friends.

Many years ago I started taking the much-maligned fluoxetine. I started feeling better in a couple of days. I knew perfectly well that it was extremely unlikely that it was actually doing anything yet, and suspect that I felt better in large part because I'd finally come to the point of giving myself permission to feel better.

I really doubt that darwinslapdog's friend was getting a buzz - the standard product contains "27% Grape Based Brandy as a preservative" and a standard bottle of drops is only 20 mL, so 5.4 mL of ethanol in a whole bottle. For comparison, a UK "unit" of alcohol is 10 mL or 8 g, equivalent to 25 ml of typical 40%-alcohol hard liquor. A typical "shot" in Canada or the US is about 43 mL, containing about 17 mL of alcohol.

Oh, Jebus, Doctors Phil & Oz recommend Rescue Remedy, according the mfr's web site.

Isn't rescue remedy supposed to be delivered in a small cask attached to the collar of a St. Bernard?

***
Here's a link to an old photo of placebo bottles. I ran across it early this morning while trying to find out about the rise and fall of "hypodermic tablets", which came up in a conversation last evening.

Many years ago I started taking the much-maligned fluoxetine. I started feeling better in a couple of days. I knew perfectly well that it was extremely unlikely that it was actually doing anything yet, and suspect that I felt better in large part because I’d finally come to the point of giving myself permission to feel better.

I had a similar experience when I first started on Celexa during my first year of grad school, when I finally had healthcare; I figure the mere act of finally seeking help probably provided some relief. Or it could have kicked off some hypomania that helped me get through my second semester of grad school without throwing me totally off kilter, who knows. I was on a variety of antidepressants for years, on again off again. Wellbutrin definitely made me unbalanced and I went off it after a few weeks.

Isn’t rescue remedy supposed to be delivered in a small cask attached to the collar of a St. Bernard?

I once bought a bottle of homeopathic cough syrup by accident. It helped, but I suspect it was the contents of the syrup itself, not the magical mystical whatever-it-is that's not even in there.

Eric Lund: Chicken soup for a cold is not a placebo. The hot liquid helps to clear the nasal passages. In addition, some research suggests that something in chicken soup may have properties beyond just being a hot liquid: http://well.blogs.nytimes.com/2007/10/12/the-science-of-chicken-soup/?_…
doug: As to amounts of alcohol imbibed from a patent medicine, some people are acutely sensitive to alcohol. My wife gets loopy on a sip of wine or about one ounce of beer. This is most certainly not any kind of anticipation effect. Besides, many people taking these "harmless" remedies figure that more is better and take lots more than the recommended dose.

doug: from the manufacturer's FAQ: http://feelbach.com/faq.asp?qid=5344790&act=bq

They have several products with varying levels of alcohol "as a preservative."

1) "We preserve the essence in Brandy and spring water, wherein the alcohol level per volume is 25%." That's 50 proof.

2) "In addition, we sell ready-mixed essences (Bach flower formulas). These essences are intended for common situations such as insomnia, tension, and smoking cessation. These essences are sold in 20 ml bottles. We preserve these essences with Brandy at an alcohol level of 40% per volume, and they retain their potency for 10 years." That's 80 proof. No doubt it lasts ten years. I want to know if it ages well, like a good whiskey.

3) "Lastly, we sell each of the 38 basic Bach essences in 20 ml bottles. These too are preserved in Brandy at an alcohol level of 40% per volume, and are also potent for 10 years." That's also 80 proof.

Now granted, they instruct you to further dilute in water. Still, I'd be interested to know what it does to the BAC. And we all know that patient who thinks if a little is good, more is better, as Dave also pointed out.

I scare the socks off people with tales of people routinely taking 5 or more tablets of Vicodin at a time because they're so addicted to hydrocodone, and wondering why their livers are failing.

I also wonder if they have to have a liquor license to ship interstate. Hope they're not selling to minors.

Hope they’re not selling to minors.

I take it that you missed this story.

You can even get your dog drunk on homeopathic remedies!

Narad: I did miss that story.

What does it say that my first reaction was, "Holy shit!" :D

@NumberWang #5
I also enjoyed Bad Science and some of Ben Goldacre's other work, but I have noticed a bit of pushback against some of his comments on placebos.

For example, I recently listened to a podcast from Merseyside Skeptics Society where they went through some of the studies he was quoting and argued that they didn't necessarily show what Ben was claiming they did: that the 'placebo' response due to the variations in specific placebo treatment (number of pills etc.) could not fully be untangled from other non-specific effects.

IIRC, one of the issues mentioned was that the comparisons of different placebos against each other were partly based on comparing placebo arms of two different studies with each other, so that as well as comparing two different placebo treatments, it was effectively a comparison of two different groups of patients and two different groups of 'testers'. Hence maybe the difference in response was partly down to different biases in the testers or different makeup of the treatment groups etc.

Well I can't claim to know if BG looked at those studies in depth but I'm fairly sure he would be delighted to know that they were being questioned.

Check out the podcast themselves, it's number 187 and 188 of skeptics with a K:
http://www.merseysideskeptics.org.uk/podcasts/

One of the studies was painkillers in brand packaging versus generic.
The 4 arms was placebe in generic packaging, placebo in brand packaging, and painkillers in generic and brand packaging.

In the placebo arms the brand packaging had better effect, and in the drug arms the brand had better effects, however, the placebo branded effect was less than the drug generic effect, and the scale was curios, a 1 to 6 with 1 worse, 2 the same, 3 slightly better 4 a Little better, 5 better and 6 much better, with the placebos fooling around between 2 and 3.

The point was that the study did not look at placebo versus drug interactions, as BG claimed, it did not test or show that placebo was on par with drugs.

They argued that BG must have misremembered the study, especially since he attributed a different drug to the test, than the one that was used.

I think the conclusion was that the placebo narrative is a powerful one, and that BG had fallen for it, at least partly.

The part of the book I'm remembering mentioned nothing about testing against drugs. Just one placebo compared to another. Specifically that the more serious the intervention is considered, the greater the effect.

I do wonder about ginger for motion sickness and the placebo affect. Here's how the train of thought usually goes:

This is probably just a placebo.
Then it won't work because I know it's a placebo.
But maybe you've built a conditioned response to feel better.
And there is a little bit of research that says it might work.
Look, it will either help, do nothing, or maybe make you hurl and you'll feel better. Eat it!
*eats ginger candy*
It BURNS!
Oh, well, maybe it works by overwhelming your brain with pain so you can't feel anything else?
*suffers*

In Nepal they have a 'sweet' that I was given for anti nausea. Some kind of concentrated salty....lemony....something. Tasted foul but it really did the job. I thought it was medicine until they gave me an entire jar to bring back to the UK. No idea what category that would fit in to. Herbal? Placebo? Maybe the strong taste just distracted me from the feeling I wanted to puke.

NumberWang@20: My mom told me that the old-time remedy for nausea was straight Coke syrup. And the one time I tried an OTC anti-nausea syrup it was the same thing: unspeakably sweet (and totally ineffective, as the taste/texture made me gag and then, well).

I've wondered how that's supposed to work, being so sweet. Some hydroscopic property? (i'm pretty sure that's how couch syrups work, just by mechanically coating to sooth.)

Blast & darnnation! I went to the yeast pee dispensary this evening and forgot to have a look for green Chartreuse. If a few flowers in some 25-40% ethanol can "rescue" and calm the anxious, Chartreuse ought to resurrect the dead and make methamphetamine with a dash of strychnine seem like a sedative by comparison. I don't think I've had any (Chartreuse, that is) this millennium. I hate to think what the price is these days.

On straight Coke syrup - I presume the syrup doesn't contain the phosphoric acid. If it did it would make a bit of a twist on the first part of
Through the teeth,
Over the gums,
Look out stomach,
Here it comes.

Was Coke syrup actually sold at retail in the past?

"... mechanically coating to sooth"

Forsooth! They gave Grandpa Joad "soothing syrup". I thought it was probably just heavy on the EtOH, but Wikipedia says morphine!

They fed him short ribs and coffee and soothing syrup;
And Grandpa Joad did die.
They buried Grandpa Joad by the side of the road,
Grandma on the California side,
They buried Grandma on the California side.

Ballad of Tom Joad by Woodie Guthrie

Justatech: Oh dear. I just bought my sister in law a few ounces of ginger tea for Christmas, as she's having a terrible time with nausea and doesn't have many herbal teas. (She's trying to cut down on caffeine due to pregnancy). Maybe I should have saved my money.

I am disappointed.

Much ado about cost (everyone knows all that and I was talking more about the profit to the quacks, not people’s attitudes) and little about the rest. My friend is a functioning alcoholic who consumes large quantities every day, so I don’t think it was the bit in the few drops she consumed. Her testimony was dramatic and she was very distressed that I tried to debunk her “miracle”. I am always conflicted about pipiing up when people testify to woo, especially as it usually does no good anyway, but my sceptical side just can’t be kept in check.

Coca Cola and Coke syrup are well-known folk remedies for nausea and to my anecdotal experience work pretty well. The syrup does contain phosphoric acid, and it's worth noting that Emetrol, an OTC anti-emetic, has phosphoric acid and sugar as it's active ingredients. Coke is cheaper.
As for ginger, it's a common home remedy for a number of things in the Far East. My wife, a nurse from the Philippines, slices ginger root in the soft rice she cooks up when someone at home has diarrhea or nausea. It does help, although that may be due to the rice itself, or the salt in it, or the soothing feeling of having something hot and digestible in the stomach.
She also swears by ginger root for coughing. She will give it in tea or or just a sliver of the raw root, and it seems to help. I know this is all anecdotal, but when she gives me something with ginger it's been harmless at worst.

PGP @24: No, no, you're good! I'm pretty sure (if I'm remembering the things I found on PubMed correctly) that ginger has been found to be more effective than placebo for morning sickness. And at least it's a clear fluid so it's no *hurting*.

@ JP, doug, and anyone else who's ever been prescribed an anti-depressant...

I started taking the much-maligned fluoxetine. I started feeling better in a couple of days. I knew perfectly well that it was extremely unlikely that it was actually doing anything yet, and suspect that I felt better in large part because I’d finally come to the point of giving myself permission to feel better.

Granted that you're just talking about feeling better after a couple days, which would be 'placebo' not effect of the drug itself, there are a lot of folks who think all common anti-depressants have no effect beyond placebo and point to some research that supposedly supports that conclusion.

I don't buy that at all. In my travels through depression-land, I was prescribed Zoloft, Paxil, Effexor, Serzone, Cymbalta, Wellbutrin, Celexa, and Lexapro at different times, most during a fairly short period when I wasn't responding well to medication. I had heard of Prozac, of course, and had been on desipramine during an earlier really bad spell, so I had a general expectation that anti-depressant would do something – not make me feel 'good' in any way, but keep the depressive downward spirals from sinking past a certain point, acting something like a peak limiter in electronics or a drive-train governor in a truck. Though my expectations and my mental state were essentially constant, the anti-depressant effect, or lack thereof, was all over the place from one pill to another that were all supposed to be similar in action, and some (most notably Celexa vs. Lexapro) that had very similar chemical composition.

For one thing, I wouldn't call SSRIs 'placebos', since they all had fairly unpleasant 'side effects'. They were all definitely doing something, of course, how that affected my mental state I can't say. In listening to other depressives, I'd say the anecdotal reports are pretty much univocal in describing prescription of anti-depressants as a blindfolded psydoc tossing darts in the general direction of a wall until one of them sticks in the target. That is, they couldn't find any rhyme or reason to what 'worked' or what didn't any more than I could. Nor was there any pattern across this unscientifc sample. The 'hits' and 'misses' all seemed idiosyncratic and individualized.

This experience is one reason I wish there was more good research into 'placebo effects', including those that accompany meds that do have some physiological mechanism of action. For example, how might my little survey square with the resaerch casting doubt that SSRIs do anything at all. I suspect there may be the usual methodological flaws in studies that try to quantify some form of self-reports. But beyond that, I wonder if any study across a representative sample population could account for the sort of dartboard/it-all-depends-on-the-individual hypotheses, or whether somehow these specific differential effects disappear when you examine the aggregate...

In the UK, 'Integrated' healthcare generally means the integration of primary, secondary, tertiary and social care - not the integration of cow pie and apple pie (nonsense/scientific sense) as in the US.

The term 'Integrative medicine' is only slowly being applied in the UK - and is not understood by most doctors, medical institutions and patients, even though our Prince of Wales did found his 'Foundation for Integrated Health' some years ago (meaning cow/apple pie integration). It went bust!

For that reason I am happy with the 'placebo narrative' which I find helpful to explain to anyone who will listen how it is that so many patients report 'benefit' from CAM (which I term 'camistry').
It is not good enough to say a CAM 'doesn't work' without differentiating the type I effects of a constructive therapeutic relationship with an empathic practitioner from the type II effects of the specific modality (the pill, prick, pummel, potion, what have you.) Camistry provides no type II effects - or it would be 'medicine'.

But I cannot differentiate the response expectancies achieved by placebos from those achieved by hypnosis. And since all hypnosis is auto-hypnosis (even if facilitated), are not placebo effects a manifestation of hypnotic effects (and thereby, purely imaginary)?

I try to explore this theme more in 'Real Secrets of Alternative Medicine (Amazon).

The revenge of the son of the myth of "placebos without deception"

oracknows — Tue, 18 Oct 2016 04:30:06 +0000

The revenge of the son of the myth of "placebos without deception"

Back when advocates of “alternative” medicine were busily trying to legitimize their quackery by first renaming it “complementary and alternative medicine” (CAM), long before CAM “evolved” into “integrative medicine,” they really believed that if their favorite woo were to be studied scientifically it would be shown to be efficacious. Thus was born the Office of Alternative Medicine in the NIH, which later became the National Center for Complementary and Alternative Medicine (NCCAM), which more recently became the National Center for Complementary and Integrative Health (NCCIH), thus utterly purging itself of the word “alternative.” Both reflecting and influenced by NCCIH, over the last 25 years, increasingly academic medical centers have been feverishly studying quackery, often funded by NCCIH, and “integrating” it into real medicine. Thus was born the phenomenon of quackademic medicine, the infiltration of quackery into medical schools and academic medical centers.

There’s just one problem. As the actual double blind placebo-controlled randomized clinical trials (RCTs) of acupuncture, reiki, homeopathy, and various forms of the quackery advocates associated with NCCIH and investigators in bastions of quackademic medicine were done, it rapidly became very clear that these treatments produced effects indistinguishable from placebo controls; in other words, they didn’t work. Normally in medicine, when that happens the treatments that fail randomized clinical trials are abandoned. True, the process of abandoning such treatments is messier and longer than we might like to admit, but eventually they are abandoned.

When it comes to integrating quackery into medicine, however, because it was never science that motivated quackademics to begin with, when RCTs come up negative for acupuncture, homeopathy, reiki, or whatever, they cannot accept that their woo doesn’t work and simply walk away. So instead, for example, they make excuses. They do “pragmatic studies” without placebos, even though such studies are only appropriate after a treatment has been validated as efficacious in RCTs. Alternatively, they basically concede that their treatment doesn’t do anything better than placebo but then start arguing that they “work” by “harnessing the power of placebo” effects to “induce natural healing,” misrepresenting placebo effects as the power to use one’s mind to heal oneself. Never mind that this argument never flies with conventional science-based medicine and represents a flagrant double standard in which CAM is held to a much lower standard of evidence. Again, this is about belief, not evidence. Never mind that lying to patients to invoke placebo effects is the resurrection of medical paternalism.

The need for deception is, of course, a major problem with arguing that physicians should be able to use placebos, to tell them that a sugar pill is something effective. Ethically, this has always been a dubious thing for a doctor to do, but in the era of shared decision-making between doctors and their patients that has emerged from the paternalistic “doctor knows best” era of 50 or 60 years ago it’s even more problematic than before. To combat this narrative, there has emerged the narrative of “placebo without deception.” The foremost advocate of this narrative is our old buddy Ted Kaptchuk, who first promoted it in a big way six years ago with an open label study of placebo pills plus standard of care versus standard of care alone on irritable bowel syndrome. I discussed this study when it came out.

Unfortunately, Kaptchuk is back in the news saying virtually identical things:

Conventional medical wisdom has long held that placebo effects depend on patients' belief they are getting pharmacologically active medication. A paper published in the journal Pain is the first to demonstrate that patients who knowingly took a placebo in conjunction with traditional treatment for lower back pain saw more improvement than those given traditional treatment alone.

"These findings turn our understanding of the placebo effect on its head," said joint senior author Ted Kaptchuk, director of the Program for Placebo Studies and the Therapeutic Encounter at Beth Israel Deaconess Medical Center and an associate professor of medicine at Harvard Medical School. "This new research demonstrates that the placebo effect is not necessarily elicited by patients' conscious expectation that they are getting an active medicine, as long thought. Taking a pill in the context of a patient-clinician relationship -- even if you know it's a placebo -- is a ritual that changes symptoms and probably activates regions of the brain that modulate symptoms."

I was half tempted to direct you to my discussion of Kaptchuk’s first “placebo without deception” study and leave it at that because this study suffers from virtually the same flaw as the last one, but that’s not what you come to this blog here. You come here because you like your Insolence Insolent and ~~verbose~~ detailed.

One thing I’ve learned when evaluating these studies is that you really, really have to look long and hard at the methodology, because when you do you will almost always find that there is deception involved. For example, like this new trial, Kaptchuk designed his IBS trial so that the patients knew they were getting placebos, even going so far as to label the pill bottles “Placebo.” Back then, then he and his team observed a difference in reported symptoms between those taking the placebo pills plus usual care compared to those with usual care and proclaimed that they had successfully invoked placebo effects without deception. There was just one problem, and it was in the script doctors used when discussing placebo effects with patients:

Patients who gave informed consent and fulfilled the inclusion and exclusion criteria were randomized into two groups: 1) placebo pill twice daily or 2) no-treatment. Before randomization and during the screening, the placebo pills were truthfully described as inert or inactive pills, like sugar pills, without any medication in it. Additionally, patients were told that “placebo pills, something like sugar pills, have been shown in rigorous clinical testing to produce significant mind-body self-healing processes.”

And the study was advertised thusly:

Participants were recruited from advertisements for “a novel mind-body management study of IBS” in newspapers and fliers and from referrals from healthcare professionals. During the telephone screening, potential enrollees were told that participants would receive “either placebo (inert) pills, which were like sugar pills which had been shown to have self-healing properties” or no-treatment.

So basically, right off the bat the investigators recruited patients who were interested in “mind-body” effects and then told them that placebo effects could produce powerful “mind-body self-healing processes” in rigorous clinical testing. There was the deception, because even the most generous and sympathetic characterization of the rigorous research existing on placebo effects would not justify such a description. As I said at the time, not only did Kaptchuk et al deceive their subjects to trigger placebo effects, whether they realized or would admit that that’s what they did or not, but they might very well have specifically attracted patients more prone to believing that the power of “mind-body” interactions. Yes, patients were informed that they were receiving a placebo, but that knowledge was tainted by what the investigators told them about what the placebo pills could do.

So what about this study? This time around Kaptchuk is not the first author; Cláudia Carvalho is. He’s also not the senior listed author. Irving Kirsch is. Be that as it may, this study has Kaptchuk’s fingerprints all over it. Entitled Open-label placebo treatment in chronic low back pain: a randomized controlled trial, it is basically that. The verbiage is very similar:

Administrating fake pills to harness placebo effects poses an ethical conundrum for physicians in clinical practice due to the widespread belief that deception is necessary for placebo pills to work (eg, pretending sugar pills are drugs or, more commonly, giving genuine medications that have no known effect on the condition).²⁹ However, 4 studies have directly tested the effect of an open-label placebo (OLP) prescription, and all indicated that patients reported benefits after taking pills presented honestly as placebos. Three were small pilot studies.^19,25,28 The fourth was a controlled trial in irritable bowel syndromeand showed significant, clinically meaningful benefits over no-treatment controls.¹⁷

The received wisdom is that clinical administration of a placebo requires deception (or double-blind conditions) to be effective. How is it that a placebo treatment is able to produce effects even when the participants know that the pill is inert?

This is the spin. Even though that controlled trial did indeed invoke deception to promote placebo effects by greatly exaggerating what placebo effects were, Carvahlo et al blithely ignore that and simply declare the study to be strong evidence that one can invoke placebo effects without deception. They even move on to assume that the point has been demonstrated and ask how such a thing could be true? Then they go on to do the same thing that Kaptchuk did six years ago.

From the methods section:

Participants were recruited from advertisements for “a novel mind–body clinical study of chronic low back pain” in flyers, posters, Facebook posts, magazine advertising, and referrals from health care professionals.

And:

After informed consent, all participants were asked if they had heard of the “placebo effect” and explained in an approximately 15-minute a priori script, adopted from an earlier OLP study,¹⁸ the following “4 discussion points”: (1) the placebo effect can be powerful, (2) the body automatically can respond to taking placebo pills like Pavlov dogs who salivated when they heard a bell, (3) a positive attitude can be helpful but is not necessary, and (4) taking the pills faithfully for the 21 days is critical. All participants were also shown a video clip (1 minute 25 seconds) of a television news report, in which participants in an OLP trial of irritable bowel syndrome were interviewed (excerpted from: http://www.nbcnews.com/video/nightly-news/40787382#40787382).

So basically, they used the same talking points from the previous study, plus clips of happy study participants to prime the patients that placebo effects can be “powerful.” Again, people that patients tend to believe, doctors and nurses and other health care professionals, telling them that sugar pills coule invoke powerful healing effects. In other words, this study is just like the IBS study, only with back pain.

Its design was fairly simple. There were two groups: open label placebo (OLP) + treatment as usual (TAU) versus TAU. Participants were eligible if they were over 18 years old and had persistent back pain for more than three months’ duration. Exclusion criteria included usage of opioid pain medications within the prior 6 months or if they had a history of refusing to take oral medication. Other exclusion criteria included pain due to cancer, fratures, infections, prior back surgery, disk degeneration due to trauma or aging, conditions that make treatment difficult (e.g., paralysis or psychosis), and other conditions thought to interfere with interpretation, such as fibromyalgia, rheumatoid arthritis, etc. Then there were the pretty standard exclusions: pregnancy, breastfeeding, surgery within the last 30 days, and the like. So basically what investigators were left with were patients with chronic low back pain, almost certainly musculoskeletal in nature, and no major anatomic abnormalities from trauma, prior surgery, or cancer who had not taken opioids in the last six months. In other words, this is mild chronic back pain, a condition that’s very likely to be prone to placebo effects, which is likely why this group was chosen. Overall, 97 subjects were randomized, and ultimately there were 42 subjects in the TAU group, 41 in the TAU + OLP group. There were three dropouts in the TAU group and 4 in the TAU + OLP group, leaving 38 in each group, but an intent-to-treat analysis was used, so that all 83 of the original participants were analyzed. Outcomes were measured at baseline and after 11 and 21 days using questionnaires measuring total pain score and the Roland–Morris Disability Questionnaire.

One thing that bothered me looking at Table I. (The paper is open access; so you can look for yourself if you’re curious.) There are no statistics. By the “eyeball” test, the two groups look pretty comparable in all the baseline characteristics measured, but I like to see statistics. I’m funny that way. Be that as it may, the results of this study were utterly predictable, given its design:

Compared to TAU, OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale (P , 0.001), with moderate to large effect sizes. Pain reduction on the composite Numeric Rating Scales was 1.5 (95% confidence interval: 1.0-2.0) in the OLP group and 0.2 (20.3 to 0.8) in the TAU group. Openlabel placebo treatment also reduced disability compared to TAU (P , 0.001), with a large effect size. Improvement in disability scores was 2.9 (1.7-4.0) in the OLP group and 0.0 (21.1 to 1.2) in the TAU group. After being switched to OLP, the TAU group showed significant reductions in both pain (1.5, 0.8-2.3) and disability (3.4, 2.2-4.5).

And:

A reduction in pain of 27.9% has been found to correspond to clinical ratings of “much improved” and a 30% reduction has been recommended as an indication clinical significance.7,9 There was a clinically significant 30% reduction in both usual and maximum pain in the placebo group compared to reductions of 9% and 16% in usual and maximum pain, respectively, in the continued usual treatment group. Open-label placebo reduced minimum pain by 16% compared to an increase in pain of 25% with TAU. There was also a 29% reduction in pain-related disability in placebo group compared to 0.02% in the TAU arm.

So, basically, both groups improved, but the OLP group improved more, just as one would expect from placebo effects. Yet, none of this stopped Carvalho et al from concluding:

Our data suggest that harnessing placebo effects without deception is possible in the context of a plausible rationale. More research on this possibility is warranted in cLBP and other conditions defined by self-appraisal.

As is frequently the case when investigators are interviewed by the press, no doubt excited about their results, they went beyond these claims in a non-peer-reviewed source. You saw Kaptchuk regurgitate pretty much the same nonsense he did six years ago with the IBS study. To that, he added more, and Carvalho chimed in:

"It's the benefit of being immersed in treatment: interacting with a physician or nurse, taking pills, all the rituals and symbols of our healthcare system," Kaptchuk said. "The body responds to that."

"Our findings demonstrate the placebo effect can be elicited without deception," said lead author, Claudia Carvalho, PhD, of ISPA. "Patients were interested in what would happen and enjoyed this novel approach to their pain. They felt empowered." Kaptchuk speculates that other conditions with symptoms and complaints that are based on self-observation (like other kinds of pain, fatigue, depression, common digestive or urinary symptoms) may also be modulated by open-label treatment.

"You're never going to shrink a tumor or unclog an artery with placebo intervention," he said. "It's not a cure-all, but it makes people feel better, for sure. Our lab is saying you can't throw the placebo into the trash can. It has clinical meaning, it's statically significant, and it relieves patients. It's essential to what medicine means."

"Taking placebo pills to relieve symptoms without a warm and empathic relationship with a health-care provider relationship probably would not work," noted Carvalho.

One more time: No, Mr. Kaptchuk and Dr. Carvalho. Your results do not show that the placebo effect can be elicited without deception. They do not. You can keep saying that, keep spinning your results that way, but the exact same problem applies to this study as to the IBS study in 2010. You had to hype up what placebo effects were and tell participants, without justification, that they produced “powerful” mind-body effects, priming them with advertisements touting the same thing. The “placebo without deception” narrative was not supported by evidence in 2010, and this new study doesn’t support the narrative either.

Finally, we already know that interacting with a kind physician or nurse makes people think they feel better. That’s something that can be done honestly, without deception. Using placebos can’t.

oracknows Tue, 10/18/2016 - 00:30

Tags

randomized clinical trial

Cláudia Carvalho

deception

placebo

Ted Kaptchuk

Categories

http://scienceblogs.com/insolence/2016/04/13/once-again-acupuncture-doe…
http://scienceblogs.com/insolence/2016/04/25/yet-again-acupuncture-does…
http://scienceblogs.com/insolence/2014/02/14/more-tooth-fairy-science-s…
http://scienceblogs.com/insolence/2013/07/03/more-tooth-fairy-science-a…

I see another deception, which CAM advocates rarely talk about.
People lied to the doctors because they felt they "should have" had better results and wanted to make all those nice people happy.
Frequently they even lie to the themselves. People who are frustrated and in pain will do that.

Christine writes: "I see another deception, which CAM advocates rarely talk about.
People lied to the doctors because they felt they “should have” had better results and wanted to make all those nice people happy."

Isn't that what's known as confirmation bias?

Now, I may be wrong about this, but I see a lot of confidence intervals that include 1 (e.g., the Numeric Rating Scale comparison). Doesn't that suggest that there was no difference between groups? Also, what's with listing the CI low-high for the OLP group and high-low for the TAU group?

Finally, as with last time, you're right that they actually showed that you can elicit placebo effects with deception, which we all already know. Why do they find it so difficult to not use deception in these studies?

Oh, and while we're on the subject of Kaptchuk and his team's penchant for deceiving study patients, let's not forget the Wechsler et al. study of acupuncture vs. albuterol for asthma study, where subjects were told they might get one of the following treatments: albuterol, a placebo inhaler, "real" acupuncture, sham acupuncture. The only problem is that "real" acupuncture was never going to be given to any study subjects, and there was no indication that any of the subjects were ever told of this deception.

@tgobbi

"Isn’t that what’s known as confirmation bias?"

I'd say no, it isn't. Confirmation bias is the tendency to attribute the real improvements to the treatment and the real deteriorations to bad luck or missing a pill. This is a tendency to willfully overestimate the results, whether consciously or not.

That may not be someone's definitions, but I don't think they are the same thing.

@ Christine, tgobbi

“Isn’t that what’s known as confirmation bias?”

I think that what Christine described is more akin to "being agreeable" (voluntary mis-spelling)
i.e. saying "yes" to the nice person in front of you because anything else would be unpolite/antagonistic.
Saying "yes I feel better" may also seem the fastest way to get out of the room and back in control of your life.

I think the fact the double blind RCT of acupuncture, reiki etc can make it past an Ethics Review Board is kind of an admission that these treatments have no real effect outside of placebo.

Okay lads and lasses, I'm a bit lost on one part of this. How can a trial on Reiki be Double Blinded?

Surely the practitioner will be aware that it's either bolllocks; or genuinely believes it. Which makes it a Single Blind.

Or have I got this completely arse upwards?

@Todd #4: I'm curious; WHY wouldn't they use real accupuncture in their study? Were they afraid it would fail?

tgobbi @2: No, it's not confirmation bias, it's something else (which is of course escaping me at the moment). It's a real issue in survey design, particularly when you have an in-person interviewer. The study subject will (intentionally or not) tell the interviewer what they think the interviewer wants to hear (or what is socially acceptable).

It's really hard to work around, which is why you might have to use a phone or paper survey for the kind of stuff people don't want to admit in person (how much do you drink, do you hit your kids, how many sexual partners have you had).

Socialization bias, maybe?

One obvious lesson of the whole NCCIH experience is that it's important to stick to the Science when determining which treatments are safe and effective, and that the use of political muscle to ram approval through does not generally lead to good outcomes.

@Panacea

I'd have to go back and check, but I don't think they explained that anywhere in the protocol.

Wow. I was so distracted by all the "quackery" language that I got bored trying to extract the point of the article. I am passionate about science, many fields of science and I don't project my ignorance, fear, or judgment on those that use alternative methods for healing. That's because I am all grown up now, and my mind is free and open to - possibility, curiosity and imagination. Poorly written article and I lost all respect for what you are trying to say. Cocky and arrogant.

So let's see. I used the word "quack," "quackademic," or "quackery" a few times in the first three paragraphs. After that, I didn't use the term once and soberly discussed the study. So ask yourself this: If I were to remove the first three paragraphs, would this post have made you think or change your mind? I rather suspect that the answer is no, and you just latched on to the language as an excuse to reject it.

Alternatively, how about this? Try ignoring the first three paragraphs and then telling me what, in the rest of the post, I got wrong and why. I'm sure you can base your arguments on science and evidence, right?

Ironic that someone purportedly concerned about tone so readily engages in name-calling.

Too bad. I was interested in hearing what Amber had to say about alternative methods for healing.

I found it very disappointing to read the obvious bias expressed in this narrow minded piece. I have to admit, that there us some 'quackery' associated with so-called. 'complimentary medicine', especially in so.e corners of TCM and other traditional approaches.

*Continued from above*

However, to lump a manual therapy like acupuncture in with reiki and the like is a mistake. The sensations and therapeutic effect from acupuncture is profound, and comparable to that of the rarely criticized approaches of massage, chiropractic and physio therapy. So say that the insertion of a fine, sterile needle into appropriately sensitive areas carries no more than illegitimized placebo, or 'quackery' as you so eagerly put, only highlights your own preconceived notions of acupuncture. In actuality, there are distinctly measurable physiological, neurological and endocrine effects that are consistent with current neuroscience and pain science coming out of Australia, notably from the NOI group and affiliates.

If you were to pay attention to the details, you would understand that placebo cannot apply when studying any manual therapy like acupuncture, massage, chiropractic, or PT, because it is impossible to pretend to stick an needle, massage, adjust, etc, let alone convince the patient they are receiving sham, or placebo approaches.

I understand the need to unblind the patient and practitioner in growing our understanding of what the limitations and benefits of placebo are, but to use this as a podium to deride 'quackery' is far beside the point.

You may be correct in pointing out biases in the above studies, but you miss the forrest for the trees.

Sad, narrow minded, biased, and overall negative stance on an essential practice.

However, to lump a manual therapy like acupuncture in with reiki and the like is a mistake. The sensations and therapeutic effect from acupuncture is profound, and comparable to that of the rarely criticized approaches of massage, chiropractic and physio therapy. So say that the insertion of a fine, sterile needle into appropriately sensitive areas carries no more than illegitimized placebo, or ‘quackery’ as you so eagerly put, only highlights your own preconceived notions of acupuncture. In actuality, there are distinctly measurable physiological, neurological and endocrine effects that are consistent with current neuroscience and pain science coming out of Australia, notably from the NOI group and affiliates.

Citation needed.

I've written many times about why acupuncture is nothing more than a theatrical placebo. Type the word "acupuncture" into the search box, and there are literally dozens of posts on the topic. Some examples:

There are many more. Because this post was about a study about placebos, I used acupuncture as an example. However, the post was already long enough that I don't have to list every single thing I've ever written about acupuncture. If you want an overview of why acupuncture is an elaborate placebo, I recommend this article:

http://www.dcscience.net/2013/05/30/acupuncture-is-a-theatrical-placebo…

Basically, acupuncture has no specific effects on any condition yet studied.

so-called. ‘complimentary medicine’

You're looking good! Your liver is in amazing health for a man of your habits! Your kidneys are the greatest! That will be $50, please.

Amber Brown Skylar
Wow. I was so distracted by all the “quackery” language that I got bored trying to extract the point of the article.

I sympathise with Amber's distractability. With me it's squirrels. And shiny objects.

re " Poorly written article"

SRSLY.

"If you were to pay attention to the details, you would understand that placebo cannot apply when studying any manual therapy like acupuncture, massage, chiropractic, or PT, because it is impossible to pretend to stick an needle, massage, adjust, etc, let alone convince the patient they are receiving sham, or placebo approaches."

Untrue.

Placebo-controlled trials of acupuncture have been done, and have served to demonstrate that perceptions of improvement occur whether or not the needle punctures the skin (or is inserted in locations that have nothing to do with sites that supposedly improve the flow of "qi".

Placebo intervention is also possible with manual techniques like chiropractic.

https://www.ncbi.nlm.nih.gov/pubmed/26246937

The sensations and therapeutic effect from acupuncture is profound [sic]

Do go on about these sensations.

All hail the awesome miraculous power of mind/faith. Belief can cure. Or if not cure, make one feel better. Not actually be better but feel as if one is better. And that’s an amazing grace in itself, Kaptchuk thinks. It’s okay for doctors to tell their patients that this pill is a placebo, it’s powerless in itself, but if you put your faith in it – and in me – then you will feel better. Your faith will heal you. Trust me, it’s been scientifically proven.
Only it hasn’t been. It’s just smoke and mirrors dressed up in white coats. It’s duplicitous hocus-pocus. It’s a lie.

Additionally, patients were told that “placebo pills, something like sugar pills, have been shown in rigorous clinical testing to produce significant mind-body self-healing processes.”

--
How did anyone think that was ok to tell patients? What the hell?

" ... when RCTs come up negative for acupuncture, homeopathy, reiki, or whatever, they cannot accept that their woo doesn’t work and simply walk away. So instead, for example, they make excuses ... "

It all sounds very familiar ... for example in the above statement substitute PSA screening or mammography for the woo and the "they" would be a whole lot of unethical real doctor's with m.d.'s after their names.

It's not about science ... and its definitely not about "do no harm" ... its about money.

for example in the above statement substitute PSA screening or mammography for the woo

Do go back to the thread you started in. Randomly interjecting the PSA monomania because you're not getting enough attention is thoroughly irritating.

@ Ed Dwulet
RCTs came up positive for mammography.

Daniel @#29

You could have gone all the way and said I was completely wrong by claiming there were positive RCT's for PSA screening too.

My response would be: barely "positive" ... and had they all been performed BEFOREHAND -- neither would or could ever be rationally used to justify implementation of widespread screening because the barely positive came at the cost of tremendous harm.

The RCT's were all performed long 'after the fact" -- not before -- by a "system" with a financial interest in "proving" they were right all along -- and to justify continuing the status quo.

So every few years we get to read another "Study Says Mammograms Saves Lives" headline ... OK, you're right ... after the statistical numbers games are played to generate an abstract artifact called "significance" -- meanwhile lots of real lives are being ruined.

THINK PINK!

I just read a news item that said someone was finally organizing a RCT for DCIS -- about 40 years late, wouldn't you say? A famous epidemiologist once advised "Randomize the FIRST patient." I doubt that they'll be able to recruit any patients from the USA after the 40 years of breast scare mongering that's gone on here.

@ Ed Dwulet
Tabar et al. (Lancet, 1985) found a 31% reduction in breast cancer mortality, 7 years after the beginning of the trial. Nationwide screening began later in most countries.

Daniel @#41

Wow! 31% Sounds impressive! It isn't! 31% of what?
And at what costs in harm? No to mention that 31% completely disappears when the stats game is played another way.

"Why cancer screening has never been shown to “save lives”
http://www.bmj.com/content/352/bmj.h6080

@ Ed Dwulet
31% of breast cancer mortality, as I said, and after 7 years of screening. Lumpectomy causes harm, but not death. And the benefit in breast cancer mortality vanishes in longer studies, because cancer incidence increases.
The BMJ paper does not answer the question for breast cancer.

The New York Times reported on the study in today's paper and seems to have swallowed the conclusion hook line and sinker. No critical analysis in it.

"“It’s the benefit of being immersed in treatment: interacting with a physician or nurse, taking pills, all the rituals and symbols of our healthcare system,” Kaptchuk said. “The body responds to that.”
Well, of course. That has already been well-documented. So why are there no studies where the "rituals and symbols" are also removed? A triple or quadruple blind RCT? Nobody in the role of patient or practitioner, with the scientists remaining deeply hidden beneath several layers of protocol. A candid camera kind of thing. "Move along please. No test going on here. Nothing to see."
"Surprise, surprise, Mr IBS. You've been wondering why your pooping is less painful? You've been secretly administered a sugar pill over the last 21 days and a hidden camera has been following you in the rest room..."
I conducted an as yet unpublished study in 2008: "VooDoo, suggestibility and the placebo effect: real arsenic kills 100% whereas only 14% of subjects who were told they had been administered arsenic after swallowing sugar pills. actually died within two months."
Telling the patient that they were receiving sugar pills when being administered arsenic killed with the same frequency as those who were told it was arsenic AND the control group who were unaware of receiving a fatal dose.
Our conclusion was that real arsenic is significantly more effective in killing people than VooDoo, suggestion or a hate-filled relationship.

"Finally, we already know that interacting with a kind physician or nurse makes people think they feel better."
This sentence would be more accurate with two edits:
"Finally, we already know that interacting with a (*) physician or nurse makes people (**) feel better."
I demonstrate this in my book, "Help! OK."

NCCIH research: Nothing much there behind the curtain

oracknows — Thu, 07 Jan 2016 07:50:32 +0000

NCCIH research: Nothing much there behind the curtain

It's an understatement to say that I'm not exactly a fan of the National Center for Complementary and Integrative Health (NCCIH), the institute formerly known as the National Center for Complementary and Alternative Medicine (NCCAM) and, even a year after its name change, probably still better known by its old moniker. Just type "NCCAM" or "NCCIH" into the search box of this blog if you don't believe me. Basically, it's an institution forced upon the National Institutes of Health in the 1990s by Senator Tom Harkin (D-IA), a woo-friendly senator who believed that bee pollen cured his allergies and a man who seven years ago famously chastised NCCAM for not having "validated" enough complementary and alternative medicine (CAM).

While on the surface, it doesn't seem unreasonable to want to study "unconventional" treatments that fall under the rubric of CAM or "integrative medicine," skeptics' criticisms of NCCIH have basically boiled down to these: First, NCCIH has been wasting money on magic, treatments like reiki (faith healing substituting Eastern mysticism for Christian belief), homeopathy (although in fairness I haven't been able to find an NCCIH-funded homeopathy study since 2008), and the like. Second, NCCIH promotes the "integration" of pseudoscience into medicine through its funding of "training programs" in CAM in medical schools, as with Georgetown. Third, it is unnecessary. There is nothing that NCCIH studies that couldn't or wouldn't be studied through grants by other Centers and Institutes at the NIH. As Harriet Hall says about naturopathy, what is good about NCCIH is not unique, and what is unique about NCCIH is not good. It's not as though, if NCCIH ceased to exist, the various areas "rebranded" as "CAM" or "integrative medicine," such as placebo effects, the effect of lifestyle interventions on disease and health, or supplements, to name a few, wouldn't be studied if there were scientific merit. All NCCIH brings to the table is a culture with a willingness to study pseudoscience, complete with quacks such as chiropractors, naturopaths, on its advisory council. Finally, little of value has ever been demonstrated using NCCIH grants or by NCCIH investigators. Studies of supplements have been disappointing at best, and no truly "alternative" treatment has ever been validated by the NCCIH.

Of course, Josephine Briggs, the current director of NCCIH, would apparently beg to differ. The other day, she published a post on the NCCIH blog about what she considers to be notable research from 2015 funded by the center.

Christina Smolke, Ph.D., of Stanford University was featured as one of Nature’s 10 People Who Mattered This Year for her team’s successful engineering of a yeast strain capable of making opioids. This achievement—the most complicated chemical synthesis ever engineered in yeast—was also highlighted as one of the runners-up for “Breakthrough of the Year” in Science.

Ted Kaptchuk’s work on placebo was recently featured in The New Yorker as one of “The Most Notable Medical Findings of 2015.” Ted, a longtime NCCIH grantee, published several articles last year, including about how genes affect the placebo response.

U.S. News and World Report highlighted the work of Dr. Beth Bock at Miriam Hospital in Providence, Rhode Island for her research on yoga as an effective therapy for smoking cessation, particularly for individuals who either cannot use medications, or who choose not to use medications while quitting.

At this, I scratched my head, particularly the first one. Smolke's work, as impressive as it sounds, also doesn't sound as though it has anything to do with "alternative" or "integrative" health. Take a look at Nature's description of her research. About a year ago, there was a race to engineer a strain of yeast that can produce opioids because a more stable production method would be highly useful, given the unpredictable yields of poppy crops. However, no one had been able to identify an enzyme that converts reticuline, a chemical building block of morphine and other narcotics, from one form to another. Smolke used a very clever approach to solving this problem:

Most other labs hunting for the enzyme were working to isolate it from poppies directly. But Smolke and her team at Stanford University, California, took a different approach: they combed through genetic databases, looking for snippets of sequence that looked as if they might be involved in reticuline metabolism. When they found a hit from several different poppy species, they ordered a synthetic version of the gene that had been built letter-by-letter by a machine. They plugged it into yeast and it worked. “I was super excited, really proud and also relieved,” Smolke says. “It was a bit of a Hail Mary.”

The discovery enabled Smolke’s lab to stitch together a pathway of 23 different genes from plants, mammals, bacteria and yeast to produce the world’s first narcotic through synthetic biology (S. Galanie et al. Science 349, 1095–1100; 2015). It was a crowning achievement for a biological wunderkind who started her own lab at the California Institute of Technology in Pasadena at the age of just 28. The opioid-producing yeast cells contain the most complex synthetic-biology pathway developed so far, and mark a turning point for the field by showing how step-by-step engineering can turn microbes into drug factories. “This will significantly impact our future ability to produce many more chemicals through biotechnology,” says Jens Nielsen, a synthetic biologist at the Chalmers University of Technology in Gothenburg, Sweden.

This is truly an impressive achievement, clearly a breakthrough, allowing yeast to turn sugar into thebaine, the precursor of synthetic opioids like hydrocodone and oxycodone, but what does it have to do with "integrative health." Pretty much nothing that I can see. It's standard biotechnology cleverly exploited and pushed beyond its previous limits to do something new. Nature points out that her goal is not just to produce opioids but to design new opioids free of the most troublesome side effects, such as dependency and addiction. This is standard medicinal chemistry, only using a new technology to approach the problem. Science also notes that, as yet, this process is very inefficient and would likely require thousands of liters of culture to produce a single dose. Of course, Smolke is now working on increasing the yeast's output to levels that could be used to manufacture opioids.

I looked up the grant funding Smolke's research, Synthetic Biology Platforms for Natural Products Discovery. This grant was indeed funded by NCCIH and was funded through the NIH Director's Pioneer Award (DP1) mechanism, which is described as a program that "complements NIH’s traditional, investigator-initiated grant programs by supporting individual scientists of exceptional creativity who propose pioneering and possibly transforming approaches to addressing major biomedical or behavioral challenges that have the potential to produce an unusually high impact on a broad area of biomedical or behavioral research." I'd agree that Smolke's work qualifies, but I fail to see anything traditionally considered "integrative" about it. After all, she's trying to develop a technique to manufacture opioids more efficiently and then improve upon them! Most "integrative" techniques try to avoid opioids.

Does anyone think the NIH wouldn't have funded this work if NCCIH didn't exist? I don't, particularly given that this was funded through the Director's Pioneer Award. In fact, given that such special mechanisms usually don't go through specific institutes or centers brings up the question of how, when this grant achieved a fundable score, it got assigned to NCCIH. That might be a more disturbing thing about Smolke's work than anything else, that someone at NIH thought it appropriate to have NCCIH fund this. This is an example of what is good about NCCIH not being unique to NCCIH.

Moving on, I've written about Ted Kaptchuk more times than I can remember. As you might recall, he's the traditional Chinese medicine maven on faculty at Harvard Medical School who's done a lot of research on placebo effects and tried to spin it as evidence that placebo effects can actually have therapeutic effects. Of course, his research hasn't exactly shown that, such as when he showed that a placebo intervention for asthma did indeed make asthmatics feel as good as a real intervention (namely an albuterol inhaler) without having any detectable effect on the pathophysiology of the disease. As I pointed out, that's a very dangerous situation because it could deceive an asthma sufferer into thinking he's doing much better than he is. He could be moments from a respiratory arrest and not realize it. Other times, Kaptchuk tried to show that there can be placebo effects without deception while in actuality showing exactly the opposite. The list of examples goes on.

What I can't figure out is why he's on this list, in particular why Jerome Groopman included him on a list of the most notable medical findings of 2015, as I don't recall any significant findings by Kaptchuk this year. Indeed, a reader showed me Groopman's article a week or two ago, and I briefly considered blogging it. I decided not to because the gruel was so thin:

Ted Kaptchuk is a pioneer in elucidating the placebo effect, acting as a nodal point among researchers ranging from anthropology to genomics. This year, he and his colleagues published a paper that highlights how people may be genetically predisposed to, or resistant to, the placebo effect. The relevant genes govern molecules that shape our moods and goal-driven behaviors. Also this year, Kaptchuk published on the ethics of placebos, which physicians once prescribed routinely for diseases that had no remedy. He and his co-authors emphasize how the placebo effect arises not only from swallowing an inert pill from a bottle but also, as I experienced, from the intimate interaction between the sufferer and the healer. Reading these articles, I couldn’t help but recall a headline that appeared in The Onion, in 2003: “FDA Approves Sale of Prescription Placebo.”

It's interesting that Groopman cites Michael Specter's somewhat misguided article on Ted Kaptchuk and placebo effects. In any case, after this I still couldn't figure out why Groopman would include Kaptchuk as someone with notable scientific achievements in 2015 because, well, I don't really recall there being any. In any case, what article was Groopman referring to when he mentioned an article on the the ethics of using placebos is this New England Journal of Medicine article Placebo Effects in Medicine. It's a Perspective article, which means it's not original research but rather commentary. It's basically the same stuff Kaptchuk has been saying for years, admitting that placebo effects don't have significant effects on disease pathophysiology but insisting that they are not "bogus."

As for the genetics research, all I could find was a review article in which Kaptchuk refers to the "placebome" (because, you know, in this ages of genomes, proteomes, metabolomes, etc., everything has to be an "-ome," even the "woo-ome," as I like to call it). He also published a meta-analysis of placebo responses in genetically determined intellectual disability in PLoS One. Overall, Kaptchuk's output last year hasn't included anything particularly interesting. The "placeboes without deception" study, as poorly interpreted as it does, was at least interesting. Ditto the asthma study. Anything in 2015? Not so much. In any case, Groopman is closer to the truth than he realizes when he compares Kaptchuk's editorial to The Onion. Basically Ted Kaptchuk is an example of what is unique to NCCIH not being good. Instead of objectively studying placebo effects, Kaptchuk has an agenda to promote a message that CAM "works" through placebo effects and that placebo effects have real therapeutic effects.

Finally we come to Beth Bock. This is what the US News & World Report said about her:

Though medications have been effective at helping smokers quit, the majority of smokers don't use them, and more than 40 percent of smokers report failed attempts each year. Researchers at Miriam Hospital in Providence, Rhode Island, are turning to yoga as an alternative therapy for tobacco sensation.

For this research, the NIH awarded the hospital a grant of $593,064.

Basically, it's an R01 grant, Efficacy of yoga as an alternative therapy for smoking cessation. The clinical trial funded by this can be found here. It's still recruiting and apparently hasn't been published. Basically it's an open label study comparing smoking cessation plus yoga consisting of twice weekly, 1-hour yoga classes delivered for 8 weeks combined with once-weekly, 1-hour cognitive-behavioral smoking cessation classes with smoking cessation plus wellness training, consisting of twice-weekly, one-hour Wellness classes given on a variety of health topics twice weekly to match schedule of the yoga classes, plus 1-hour per week of cognitive-behavioral smoking cessation.

What's the rationale for the study? This:

Our research, and the research of other investigators, has demonstrated that traditional (Western) exercise (e.g., brisk walking, bicycling) improves smokers' ability to successfully quit. Exercise may help smokers quit by reducing concerns regarding post-cessation weight gain, and by reducing nicotine withdrawal and enhancing mood. Recent research suggests that yoga is an acceptable and potentially effective alternative therapy for smoking cessation for several reasons: As a form of exercise, yoga shares many of the same properties as traditional (Western) aerobic exercise in that yoga has been shown to improve mood, physical fitness, weight control, self-image and quality of life in healthy and ill populations. Moreover, features of yoga, including a focus on breathing, mental concentration, meditation, stress reduction and enhanced mood are likely to have special relevance for smokers who are trying to quit. Thus, yoga may be particularly attractive as an alternative for individuals who either cannot use medications, or who choose not to use medications while quitting.

I fail to see what's so special here. The investigators state that exercising can help smokers quit. Yoga is a form of exercise. Big deal. Assuming exercise improves smokers' ability to successfully quit, I expect that this study will likely be positive also because it adds a regular exercise program in the form of yoga to cognitive-behavioral therapy for smoking cessation. What would be interesting is what's not being studied: Exercise known to help smokers quit versus yoga. This appears to be yet another example of what is good about NCCIH not being unique. Unfortunately, because pretty much all exercise and lifestyle interventions for health have been "rebranded" as CAM or "integrative," they get lumped in with all the pseudoscience in CAM, such as traditional Chinese medicine, acupuncture, naturopathy, reiki, and the like, and it's frequently the same people studying lifestyle and exercise interventions who also engage in quackademic research into rank pseudoscience. Again, there's no need for an NCCIH to fund this research; it could be perfectly well handled by another center or institute in the NIH.

Presumably, Briggs picked the three best examples of good science she could find from the entire NCCIH portfolio of grants. If that's the case, her list strikes me as pretty pathetic. It includes research that has little or nothing to do with CAM and everything to do with molecular biology, biotechnology, and synthetic biochemistry, research that oversells placebo effects, and a clinical trial that reinvents the wheel by testing yoga as yet another form of exercise to help people quit smoking. More than anything else, this thin research portfolio indicates that NCCIH has no real scientific rationale to continue to exist.

oracknows Thu, 01/07/2016 - 02:50

Tags

Pseudoscience

National Center for Complementary and Alternative Medicine

Josephine Briggs

National Center for Complementary and Integrative Health

Categories

So two of the three examples Briggs listed are there solely because they were mentioned in the popular press, rather than on the basis of any solid scientific results? And these are supposed to be her best examples? With most government funding agencies, that kind of lack of productivity tends to get your project/mission terminated.

I agree that Smolke's work is significant, but as you say, it seems odd that NCCIH rather than some other NIH program is funding it. This looks like an example of a blind squirrel finding an acorn.

I see ninjas from Mercola stealing these genetically engineered yeast to sell as "All-natural pain relief Baker's Yeast" on woo web sites.

Next up: yeast engineered to make naloxone.

"...traditional (Western) exercise..."

Heh!

“…traditional (Western) exercise…”

Heh!

Bronco bustin', calf ropin", headin' 'em off at the pass?

Dogie rollin?

I thought it was *hard( to get grants, and that your study proposal/plan/protocol had to be beyond reproach? Clearly not when your money comes from NCCIH.
If I designed a study that compared two such different things as "yoga" and "wellness classes" in a study about if yoga is as good as aerobic exercise for supporting smoking cessation, my boss would laugh at me.

Dr. Do-little's (back) in the house. Of course. :-)

-Jamie (Ariel) Parsons

(Look up the meaning of the names.)

Dr. Do-little’s (back) in the house

It is tempting to approach NCCIH with a research proposal for talking to the animals.

It looks a lot like Briggs has dredged up references in the popular press to research funded by her agency and is promoting these as notable research. Well, there were notable in that they were noted in the popular press, but other than Smolke's work not that notable as science.

If this is all you have to show for $124 million of funding spent, I would be embarrassed.

OT but really...

Orac, when I click on some of the 'Insolence returned' I get security warnings about the site -
Danger Danger! blah blah blah.
I thought you should know in case it means anything.

Denice, for some reason those are the ones where the "http" has been turned into an "https", which is for those with secure certification. Just remove the "s."

@ Chris:

Thanks but now it's not doing it.

Yeah, it is kind of an inconsistent annoyance.

And I just got it at "The Spudd."

Hi, Orac! Great to see you're still blogging here.
Not sure if you remember me, but I used to blog at the now-defunct Signout, and am trying to get back into my account to manage a few things. Do you know the contact info of the administrator, who might be able to help me regain access?
My email address should show up with this comment, but let me know if not and I can leave it in a second comment.
Thanks in advance, and big regards all around!

Have they lost their minds? As you point out, none of the examples should have qualified for funding under the program. Given those examples, anything goes.

The National Center for Complementary and Integrative Health (NCCIH) is about the most inane title for an institute as I have ever seen, so I suppose I shouldn't be entirely surprised by their confusing behavior. At least the former moniker brandished the word "Medicine", but as you explained in a previous blog, that flew in the face of what the FDA deems to be legal and any treatments funded under the program would therefore become de facto claims in violation of the law, so the name had to be changed to protect the purveyors of so-called alternative and complementary medicines, which are plainly drugs marketed under the guise of dietary supplements. The same goes for anything else used in the treatment or prevention of disease. As a result, clinical trials of dietary supplements will increasingly be conducted elsewhere.

On the basis of an apparent soft spot for rehab professionals, acquired from his history of treatment for back pain, Groopman includes a paper on genetic predisposition to the placebo effect amongst the most notable medical findings of the year. He doesn't explain what makes the paper medically notable, as he does for his other six most notables.

Instead he links to an interview with the author of the placebo paper - by a very sympathetic placebo-friendly interviewer.
All of which is re-cited by the NIH's institute for placebo medicine: NCCIH. Who just happen to have dished out lots of dosh to the particular placebo researcher in question.

Shame on the lot.

The inclusion of yoga in alternative medicine continues to baffle me; the only reason I can see why yoga would be lumped in with other woo-ly modalities is the insistence of most of its practitioners on needlessly incorporating dollops of Eastern mysticism into the practice, with a view to roping in the gullible.

As useless as SETI

@Gary - at least SETI has a chance of paying off....

Lawrence@19

@Gary – at least SETI has a chance of paying off….

Super off topic, but I heard an interesting thought on SETI a while back. The idea was that an advanced civilization would have encrypt their communications (as we do now) and therefore would be indistinguishable from random noise. For all we SETI has been receiving alien broadcasts this entire time.

SETI is scientifically plausible, unlike, say, homeopathy.

We might find some sort of life in our solar system, but a program like SETI is the only way we stand a chance of finding intelligent life somewhere other than earth.

PING times will be outrageous.

For your education and amusement:
http://www.cracked.com/blog/what-4-mystical-healing-techniques-actually…

@Julian Frost: For pete's sake....your #23 needs a "DO NOT DRINK" warning. I laughed until I cried AND inhaled my water.

Thanks for making my lousy snowy Friday better. (hmmmmm...back ache after shoveling the heavy wet snow...acupuncture or reiki?)

Acupuncture bait and switch: Electrified hot flash edition

oracknows — Wed, 26 Aug 2015 07:45:25 +0000

Acupuncture bait and switch: Electrified hot flash edition

It's always disappointing to see a good journal fall for bad medicine, particularly when it's in your field. For example, the Journal of Clinical Oncology (affectionately referred to by its abbreviation JCO) is the official journal of the American Society of Clinical Oncology (ASCO) and probably the most read clinical journal by those involved in the clinical care of cancer patients. Just as most oncologists, surgeons, and radiation oncologists who specialize in the care of cancer patients belong to ASCO, most of them also at least peruse JCO on a regular basis because major results of large cooperative group trials are often published there. Basically, everyone wants to publish his oncology clinical trial in JCO. Getting into Clinical Cancer Research is good, but getting in JCO is great.

So when I see a study that some of you have been e-mailing and Tweeting at me in JCO, I can't help but wonder what the hell happened to peer review at the journal. I also realize that, being in the biz myself, by criticizing the peer review at JCO I might endanger my own chances of ever publishing in there given that my meatspace identity isn't exactly a particularly well-kept secret (nor is it meant to be anymore). Oh, well. It needs to be said. Earlier this week there appeared in the Early Release Articles a study by Jun J. Mao and colleagues at the University of Pennsylvania entitled Electroacupuncture Versus Gabapentin for Hot Flashes Among Breast Cancer Survivors: A Randomized Placebo-Controlled Trial. Sounds neat, right? Sounds like a head-to-head battle between every acupuncturist's version of transcutaneous electrical nerve stimulation (TENS), electroacupuncture (EA), versus gabapentin (a.k.a. Neurontin) in a battle royale to see which can alleviate hot flashes the best.

And make no mistake, hot flashes are an incredibly important problem in oncology, particularly for breast cancer patients. Patients who have breast cancer that is estrogen receptor positive, which means that the cells are responsive to estrogen, are frequently treated with drugs that block estrogen action. If a woman is postmenopausal, the usual drug used is a member of a class of drugs called aromatase inhibitors. If the woman is premenopausal, the usual drug used is Tamoxifen. In either situation, the most common—and frequently the most troubling—side effect of the drug is menopausal symptoms, mainly hot flashes. What a lot of people who aren't cancer doctors or patients don't understand is that these hot flashes can be horrible. Believe it or not, I learned this lesson with the very first patient I treated as an attending surgeon, lo these many years ago. This woman had such horrendous hot flashes from her Tamoxifen, as well as psychological symptoms, that she and her oncologist, after attempts at dose reductions and other strategies to ameliorate her symptoms, jointly decided that she couldn't take it any more. Unfortunately, for patients with hormone-responsive breast cancers, the most bang for the buck in terms of preventing recurrence comes from the hormonal therapy, at least equal to that of any chemotherapy. So the degradation of quality of life and sometimes even symptoms necessitating cessation of hormonal therapy are a major problem in oncology. Unfortunately, our existing treatments are not the greatest, which opens the door to woo such as acupuncture. Where there's woo, there's quackademic medicine to study the woo, and that's just what this study is.

Basically, this study is a bait-and-switch. I realize that I just discussed another bait-and-switch acupuncture study less than a week ago, but sometimes a doc's gotta do what a doc's gotta do.

So where's the bait and switch? In this case, it's on more levels than you think. In fact, before I dive into the story itself, let's look at the spin being put on the results. I like to call this how not to report on an acupuncture study:

Needles beat pills for treating hot flashes in breast cancer survivors, according to a new trial that compared acupuncture, "sham" acupuncture, the medication gabapentin and a placebo pill.

Interestingly, sham acupuncture came in second place for effectiveness, the researchers said.

Furthermore, the effects of acupuncture were "significant and enduring for hot flashes while gabapentin's effect only happened when a patient was taking the medication," said study first author Dr. Jun Mao, an associate professor of family medicine and community health at the University of Pennsylvania in Philadelphia.

The study was published Aug. 24 in the Journal of Clinical Oncology.

As usual, the reporting that "acupuncture beat pills for hot flashes" is a completely inaccurate assessment of what the study actually showed. The study showed nothing of the sort. Barring an incredibly strong effect, it couldn't possibly have (more on that later). Sadly, dissecting the BS attached to acupuncture studies is a rather specialized skill set; so perhaps I'm being too harsh. There were others who fell for this. When this study was presented as an abstract at the San Antonio Breast Cancer Symposium in December, similar stories were written about it. Of course, given the depth and breadth of science presented at the SABCS, it never ceases to amaze me how the press always seems to zero in on studies like this one, which tell us very little but give the appearance that acupuncture works.

Acupuncture is, of course, a theatrical placebo. Its effects are nonspecific, which is why it is such an adaptable placebo. As I joked sarcastically last time, if you believe its practitioners and adherents, acupuncture can treat almost any disease or health problem to which human beings are prone, which is why last week I could be blogging about a bait and switch study of acupuncture to treat hypertension and this week I can be writing about a bait and switch study of acupuncture to treat hot flashes caused by hormonal treatment in breast cancer patients. That's why several years ago I was writing about worthless acupuncture studies examining acupuncture for hot flashes.

This study, in fact, shares a major flaw with the one I blogged about in 2008. Specifically, it has no control group that received no treatment at all. For a study that goes on and on about placebo effects and how acupuncture provides more of a placebo effect than pills, that's a rather glaring omission. So let's look at the study design. Basically it's a four arm study, two arms of which look at electroacupuncture (EA) versus acupuncture and the other two at gabapentin versus a placebo. Interestingly in this study compared to most electroacupuncture studies, the EA is considered the "real" acupuncture and the standard acupuncture (SA) is described as the "sham," which, I have to admit, is not inappropriate, given that acupuncture is a sham and electroacupuncture is basically transcutaneous electrical nerve stimulation rebranded as the sham that is acupuncture. (We all know that those ancient Chinese must have had access to electricity, right?) It is funny, though, because the SA group did use retractable needles and really were sham acupuncture. Consequently, the investigators weren't really comparing EA versus the same acupuncture without the current but rather EA to at true sham.

So basically, the groups were as follows: electroacupuncture (EA); standard acupuncture (SA), gabapentin (GP), and placebo pill (PP). There were 120 patients with stage I to III breast cancer treated for cure at the Abramson Cancer Center of the Hospital of the University of Pennsylvania in Philadelphia and with no evaluable disease (i.e., no detectable disease left after treatment) and at least two hot flashes per day for at least a month. They excluded patients with stage IV disease, active breast cancer treatment, initiation or change in hormonal adjuvant therapy within the past 4 weeks, plans to initiate or change hormonal treatment in the coming 14 weeks, pregnancy or breast feeding, bleeding disorders or use of warfarin/heparin, an allergy to or previous use of GP for hot flashes, current use of an anticonvulsant, or documented renal failure in the past 12 months. They were then randomly assigned to one of the four groups according to this schema (click to embiggen):

In any case, the EA and SA groups received their "acupuncture" treatment for 30 minute sessions, twice a week for two weeks, then once a week for six more weeks. Meanwhile, in the GP versus PP groups, the GP group received 900 mg per day of gabapentin or placebo for eight weeks. Outcomes were measured once a week using the average hot flash composite score (HFCS) as measured by the Daily Hot Flash Diary, a commonly used instrument to measure hot flash severity and frequency. Adverse events were also monitored. Patient outcomes were followed for 24 weeks.

Of course, in any acupuncture study, blinding is of critical importance; so whenever you see an acupuncture study, look at the blinding. In this case, monitors blinded to treatment group tallied adverse events (AEs). That's good. The patients were blinded to treatment group between EA and SA and between GP and PP, but were not blinded to whether they fell into one of the acupuncture groups or the medication groups. So was the principal investigators, study investigators, study staff, and the statistician. The acupuncturists, however, were not blinded to whether the patients received EA or SA, which is another huge flaw, almost as bad as the lack of a no treatment control group. In fact, it's bad that they didn't even blind patients between the acupuncture and pill groups. All that would have required would have been to give all the patients in the two acupuncture groups a placebo pill and all the patients receiving pills sham acupuncture and then blind the acupuncturists to experimental group by using a needle that retracts in such a way that the acupuncturist can't tell if it really went into the skin or not (such needles do exist) and then having every patient hooked up to the current generator, which could be set to light up and have its gauge show that it's producing current whether it actually is or not. That way, everyone can be blinded. Then add a wait list/no treatment control. But that's not what they did. I realize my way would be more difficult and expensive, but it is the only way likely to generate anything resembling useful data.

Here's another aspect:

Because placebo response to a pill has been previously reported to be approximately 20%,20 assuming baseline HFCS had a mean of 16 with a standard deviation of 4, we needed 26 participants in each placebo group to detect a 20% difference (3.2 HFCS/day) with 80% power using a two-sided significance level of .05. Assuming a 15% dropout rate, we needed to recruit 30 subjects per arm, for a total of 120 subjects. Our trial was not designed to evaluate the efficacy of EA or GP because sample size requirements would be much larger on the basis of previous literature. Evaluations of the short- and long-term effects between EA and other groups were secondary aims.

In other words, this study shows nothing about whether EA is actually efficacious, because it wasn't designed to. It's too small. So right away, any results must be interpreted in light of this knowledge, which is why all the discussion of placebo effects. First, however, here is the singularly unimpressive result of the study in the form of a single graph:

First, notice that all groups appeared to be improving right up until the end of the eight week treatment phase and are bunched up. How the authors interpret this result is rather interesting:

By week 8 (end of the intervention), acupuncture produced a significantly greater placebo effect than did pills, with the SA group having a significantly lower HFCS than the PP group (−2.39; 95% CI, −4.60 to −0.17; P = .035). Compared with PP, EA also had improvement in hot flashes (−4.1; 95% CI, −7.0 to −1.3; P = .005), whereas GP showed nonsignificant improvement (−1.8; 95% CI, −3.9 to 0.2; P = .085). We observed differences among treatment groups in the HFCS score (P

So, in other words, everyone improved (which is usually what happens on clinical trials of symptoms with a large subjective component), and somehow the authors see this as evidence that "sham acupuncture" produces a stronger placebo effect than the placebo pills. They also state that the SA group had less nocebo effect (equated with AEs, which I don't consider appropriate given that some of the AEs included bruising In actuality, this might be true, but we really don't know if that's true. For one thing, there is no control group receiving no treatment. How do we know that a no treatment group wouldn't also show a roughly 20% decline in HFCS composite scores just due to the subjects being on a clinical trial? We don't. In fairness, the authors acknowledge this limitation. They also acknowledge that their study wasn't powered to detect efficacy, which puzzled me to no end. Why bother to do the study if it can't demonstrate efficacy? And why say things like this at the end:

In conclusion, acupuncture is associated with enhanced placebo effects and lower nocebo effects when compared with taking pills for hot flashes among survivors of breast cancer. Eight weeks of EA produced promising short- and long-term treatment outcomes for hot flashes compared with other comparators and had fewer adverse effects than GP. These preliminary findings need to be confirmed in larger studies with long-term follow-up. For survivors of breast cancer experiencing hot flashes, acupuncture could be preferable to GP because of sustained benefit after treatment and fewer adverse effects, whereas patients who dislike needles or do not have the time required for acupuncture treatments may prefer GP.

Here's why:

The results with the sham acupuncture, which bested gabapentin, suggest that "there is more than a placebo effect with the sham acupuncture," said Dr. Gary Deng, interim chief of the integrative medicine service at Memorial Sloan Kettering Cancer Center in New York City. "There is a component of behavior of doing a sham procedure, so it psychologically may trigger a different kind of reaction from patients versus taking the placebo pill."

Deng pointed out that clinicians have come to realize that the placebo effect is very important in treatment. "In fact, in clinical practice, every doctor uses it all of the time," he said. "The so-called bedside manner or communication with patients -- all of these enhance the effect of the patients feeling they're getting something."

No one is quite sure why placebos work for some people and not for others, said Deng. "It's like psychotherapy," he added. "Why does it work for some people and not others?" He suggested that differences in anatomy and genetics might be possible explanations, but said "there is a fertile field for further research."

Because the most rigorous studies of acupuncture (and other "complementary and alternative medicine" or "integrative medicine" therapies) are almost always negative and the totality of the literature on acupuncture is consistent with its being a "theatrical placebo," acupuncture advocates, like CAM advocates in general, are now selling it as the "power of placebo." Of course, we know that more invasive interventions produce a stronger placebo effect. For instance, injections tend to produce stronger placebo effects than pills and surgical interventions produce the strongest placebo effects of all. So it would not be surprising if as theatrical a procedure as acupuncture produced a stronger placebo effect than a pill. If you accept that what was measured were placebo effects (and I do not without a no treatment control), then all this study basically showed was that SA is a better placebo than a pill, a result we could already have surmised from the literature, meaning that there was really no need to do this study.

In any event, I've never argued that placebo effects can't be important. However, there is an inherent problem with using them, and that's that you have to lie to the patient, attempts to demonstrate the existence of "placebo effects without deception" that show nothing of the sort notwithstanding. Worse, when a fantasy treatment based on a prescientific understanding of human physiology and disease retconned by Chairman Mao into a seemingly effective therapy is used as the placebo, the message is not so much that we could get the same effects using ethical means of increasing placebo effects, such as good bedside manner, encouraging words, and the like. It's that magic works through placebo effects, which is exactly how this study will be sold.

In the end there are two bait and switches in this study: electroacupuncture sold as acupuncture and acupuncture sold as a powerful placebo that has clinical utility. Same as it ever was.

oracknows Wed, 08/26/2015 - 03:45

Tags

1. http://www.scilogs.com/in_scientio_veritas/authors-of-plos-one-study-on…

Categories

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To my mind, major journals are complicit in this infiltration of quackery into medicine. To cite a recent set of examples, I am beginning to think that there is an effort at PLOS One to pass off acupuncture studies with minimal and inadequate reviews. Otherwise, I cannot find a reason why these studies, with so many glaring lacunae in methodology and interpretations, would find their way into a journal, such as PLOS One:

2. http://www.scilogs.com/in_scientio_veritas/cam-peer-review-plos-problem/

3. http://www.scilogs.com/in_scientio_veritas/plos-one-acupuncture-lacks-c…

I did complain rather loudly on Twitter, but I am yet to hear from the PLOS One folks.

Of additional potential concern is the underdosing of gabapentin in this study.
In someone with normal kidney function, the target dose for gabapentin for this indication should be at least 900 mg three times daily. This study used one-third of that dose. If the patient were not having dose-limiting side effects or modified dosing requirements due to decreased kidney function, then that dosing scheme is inadequate.

This is a bit of a side point. But it is a problem that also occurs in pharmaceutical trials as well. (Comparison of one drug to an inadequate dosing of the standard treatment.)

My own practice is to prefer venlafaxine rather than gabapentin as the first choice pharmacologic treatment, all else being equal, due to some (limited) evidence that patient tolerability is higher. http://jco.ascopubs.org/content/28/35/5147.full

I am ashamed that such a great place, where I did two years of fellowship, is promoting such nonsense. At least they had the sense not to offer it to me when I was a patient there. They would have gotten an earful.

In the end there are two bait and switches in this study: electroacupuncture sold as acupuncture and acupuncture sold as a powerful placebo that has clinical utility. Same as it ever was.

Amen.

...are now selling it as the “power of placebo.”

When the health industry starts selling placebo treatments to me is when I start paying them in placebo money.

Yeah, I hope that 1 million dollar check I am going to write them makes them feel wonderful before it ceases to do anything for their bank account.

@Kausik Datta
haha. funny i was just going to link your comment on SBM.

Oh, is that live now? *toddles off to check*

But seriously, for me, both Orac's and Dr. Novella's analyses have separate values. I love Orac's attention to the scientific details.

@ Kausik Datta
"Otherwise, I cannot find a reason why these studies, with so many glaring lacunae in methodology and interpretations, would find their way into a journal, such as PLOS One"
These papers are reviewed by acupuncture experts. Peer review does not make science.
But "hot" papers make high impact.

@Daniel,
"These papers are reviewed by acupuncture experts. Peer review does not make science."

True. To me, that points to a failure of the peer review system, because these reviewers seem to be reviewing acupuncture, and not the science.

This hearkens to what Dr. Novella wrote in the SBM piece: [I quote] "It seems almost that these types of studies are designed not to ask if acupuncture works, but to show that it works..." [End quote]

I suppose the bottom line here is that gabapentin is a pretty crappy drug for treating hot flashes.

Does the paper show the absolute values of HFCS (average, median or range) for each subgroup at time 0? Since a subjective measure like this cannot be linear, especially near the top and bottom boundaries, the subsequent deltas may not be comparable between subgroups.

As a perimenopausal woman, I can vouch that hot flashes can be miserable. Mine have dropped off with time, (and HRT treatment), but for a while I was having 1 ever 1-2 hours. I can't imagine knowing I couldn't treat them - I went flying to the doctor for HRT after the first week of that frequency. I would have tried gabapentin if I'd known that was an option, as I had used it for restless leg syndrome, to see if it worked. But not acupuncture.

These papers are reviewed by acupuncture experts.

This failure mode of peer review is not limited to acupuncture studies, or even medicine in general. It's a particular problem in medicine because medicine is such a large field that it's particularly easy to game the review system.

Here's how it works. The authors will suggest potential reviewers, and the editor will (or should) draw other potential reviewers from (a) his knowledge of who's who in the field and (b) whose papers are cited in the manuscript. The bigger the field, the greater reliance the editor has to put in the latter option. It's too easy for an editor to fail to notice that the literature review in the manuscript is unbalanced (or worse, not care because he agrees with the authors' views), and select reviewers who are sympathetic to that view. Of course the authors' suggested reviewers are likely to be sympathetic as well, which is why only the most foolish or desperate editors will pick more than one reviewer from the list the authors provide.

Also, reviewers can't be expert in everything. So maybe you get a reviewer who is expert on one specific aspect of the paper, and makes the authors improve that part, but overlook some other mistake that would be obvious to an expert in that aspect, but not to the reviewer. This happens routinely in my field, which is a good deal smaller than biomedical fields. I've read several papers in my field which left me thinking, "How the #$&% did that get past the referees?"

Maybe I've forgotten too much of what I was taught about statistics over the last 30 years, but the graph labelled Fig.2 raises hackles. The error bars overlap in all measurements up to 12 weeks, but can then be read as fantastically singular at 24 weeks. What am I missing?

@ Eric Lund
The problem is not related to the field. If one defines "excellence" in science by the number of peer reviewed papers with high short term impact (and two years is very short in science), one should not be surprised to see all this bullshit.
Before giving positions in scientific institutions, it would be better to evaluate individuals on their basic knowledge in the domain and, if possible, their creativity.

And Lo! I have invented a new treatment: Kitten-puncture.

We know from studies like this one that acupuncture is a theatrical placebo, where someone listens to you, and cares about you, and then pokes you a little bit, and you feel better.

Come to my (imaginary) clinic where you'll get a nice cold glass of tea, a big fluffy robe, and then you lie down on a nice soft table with soothing music, and I plop a pile of kittens on your back. It's a pleasant environment, you get stabbed slightly (kitten paws and claws are cleaned between patients) and then you go home.

Now I just need a cat-allergy alternative.

kitten paws and claws are cleaned between patients

I'd pay money to see how that's done.

Kittens are self-cleansing.

MO'B: Oh, that's easy! First you have them walk across a sticky pad, then dip their little feet in hand sanitizer. The trick is to keep them from licking the sanitizer.

First you have them walk across a sticky pad, then dip their little feet in hand sanitizer.

JustaTech - I admit to fairly limited kitting (kitten sounds ungrammatical - see "Elderly Man River") experience. However, the kittings I've known would not willingly walk across a sticky pad nor dip their paws into the entirely inappropriate hand sanitizer (shouldn't it be paw sanitizer? And if so, would that be for male cats only?).

The advocates of CAM love to have it both ways: when criticized that their treatments are no better than placebo, they elevate the placebo to a sort of venerated status, as if it is equivalent to actual effective medical treatments. As has been said often, there is a placebo effect, but the placebo itself has no affect.

If one defines “excellence” in science by the number of peer reviewed papers with high short term impact

I'm aware that it is standard practice to rate journals that way, and I agree it is foolish to do so. I haven't heard of individuals being rated in this fashion, but that would be even more foolish. There is no reason why a good paper shouldn't continue to get citations 10, 20, or even 50 years after publication. There is, however, a reason not to evaluate potential hires on this basis: early-career scientists will not have been in the field long enough to have any ten-year-old papers to cite. And those are the people who are generally considered for assistant professor positions in the US, or the equivalent in other countries.

The pressure for journals to boost their "impact factor" produces a fair amount of pathology. This article is a mild example. It may not mean what the authors think it means, but at least we have no reason to suspect that the described studies didn't happen more or less as described in the paper. Wakefield et al (1998, Lancet) was fraudulent, and there have been many other prominent cases. Nature and Science, which are derisively called "glamour mags" for a reason, are particularly susceptible because they specialize in "hot research" regardless of field; about two thirds of the papers retracted in the wake of the Jan-Hendrik Schön scandal were published in those two journals.

I wouldn't be so sure that kittehs would always avoid sticky surfaces as one of my own willingly ambled across newly varnished- still wet- wood which necessitated a concerted effort on my part in removing said varnish before she licked it or she stuck to something somewhere.

AND my Very Large Cat is quite adept at inserting his own puncturing implements into skin although he knows nothing about meridians.

I'm 50-ish years old, and take gabapentin for neuropathic pain (an approved use) - and I still get hot flashes. Interestingly, I didn't know the drug is used this way, though off-label. I suspect that since the drug makes a person feel drowsy, that the women who are awoken at night time due to hot flashes, find it easier to sleep through them.
This still doesn't explain why the placebo pills have such a marked effect on patients reporting fewer hot flashes (or less severe ones).

@ Eric Lund
The whole process of evaluating science by productivity is insane. And this is why I like quackademics: it's a very good illustration of this.

To Eric "I’m aware that it is standard practice to rate journals that way, and I agree it is foolish to do so."
A two year impact factor was important for librarians in order to know which journals they had to buy. It makes sense. The H index is frequently used by "scientists" to evaluate others. This is stupid and dangerous.

I have a question aboput the following statement:
"the EA is considered the “real” acupuncture and the standard acupuncture (SA) is described as the “sham,”

I don't have access to the paper, but I had a quick look at the protocol (which was available online), and they mention Streitberger needles. To my extent of knowledge, these are supposed to be fake needles that never pierce the skin, but only create the illusion of doing so by hiding in a sheath. Can anyone with access to the paper clarify what type of needles were actually used?

Thanks!

It doesn't matter how robust the evidence is patients are just people that are affraid of pain, loss, death or debilitating illness they are not rational by any means but they are our core buisness. banging this drum is pointless.

Orac,
Would a concisely couched letter to the editor of JCO not achieve your purpose?

ORAC~
A well placed review of a flawed study.
Ii's unnecessary to refer to Jun J. Mao as "Chairman Mao" if even he is the chariman of a dept. or the supporting institution. Reserve sarcasm for you own acquaintances.

I didn't refer to him as "Chairman Mao." I was referring to the real Chairman Mao, who ruled China for decades. Follow the link on his name. It explains all. In fact, it never even occurred to me that Dr. Mao shared Chairman Mao's name, although now in retrospect it's pretty funny to me and I wish I had thought of riffing on Dr. Mao's name in this post.

As for sarcasm, even though there was no sarcasm about Dr. Mao in my post (again, I was referring to the real Chairman Mao from history), I will be sarcastic when and where I damned well feel like it on this blog. If you don't realize that, you obviously haven't been reading very long. I have no intention of changing that.

Not A Troll @ 4: Ouch!, That almost cost me a new keyboard;-) Someone ought to try it as a defence against passing bad cheques. 'That wasn't a bad cheque, it was an acupuncture cheque! An homeopathic cheque if you will, a very good cheque with prosperous financial energy and a most righteous and honourable history!!'

JustATech@ 15: 'Kitten-puncture:' also has the relaxing benefits of a good massage. To get the little moggies to walk across the sticky pad, just place windup mice on the other side of it. A sanitiser gel made from ethanol wouldn't be quite so acutely toxic as one made from methanol, so you'd have time to intervene if they started licking their paws. Just don't make any claims about 'the healing energy of soft fluffy kitties' and we'll recommend you to our friends.

Seriously though, why didn't the nefarious study in question use a TENS arm as a control against EA? Someone needs to do this one: EA, TENS, and a no treatment arm. Thereby demonstrating that any claimed effect of EA is indistinguishable from that of TENS, and removing the magic from the medicine.

@ Lurker
If you remove the magic, then you lose the impact. This paper has been published because of the magic. This blog is popular because of the magic. Orac has published in a high impact factor journal about magic, could he do this with serious issues?

Riard Fitzgerald:

As distinct, I suppose, from you and your friends and acquaintances, who are not at all afraid of pain, loss, death, or debilitating illness? Brave, brave sir Riard.

Most people are afraid of at least some of these things. Some people who aren't actually afraid of pain know that it interferes with most other things, including clear thinking and ability to get things done, even relatively simple things like laundry. I have a relative who tried acupuncture for pain, in the hope that it would let her focus better and/or reduce her doses of narcotics, acetominophen, and NSAIDs. (The acupuncture significantly increased her pain levels, as well as being a waste of money and her limited time and energy.)

Come to my (imaginary) clinic where you’ll get a nice cold glass of tea, a big fluffy robe, and then you lie down on a nice soft table with soothing music, and I plop a pile of kittens on your back

This would be as effective as acupuncture is. Heck, it would probably work better than acupuncture for a lot of people.

Seriously though, why didn’t the nefarious study in question use a TENS arm as a control against EA? Someone needs to do this one: EA, TENS, and a no treatment arm. Thereby demonstrating that any claimed effect of EA is indistinguishable from that of TENS, and removing the magic from the medicine.

I briefly looked around for just such a thing, and didn't find much.

I rather suspect that the EA fanbois don't want to know what we suspect it will show (that is, no difference between EA and TENS), and everyone else suspects it would be a waste of time and money, with little chance of publication.

In 2015, you will find that Acupuncture is both an art and science.

You all are playing around with incomplete concepts and remedies. PLUS you are behind the science. Unfortunately most are behind the science even the schools of Acupuncture.

The art is --- well profoundly well balanced within that time in history, the culture and the real-life observations.

The science is in the book of C. Chan Gunn, MD and an old study done by Cannon Law of denervation.

Gunn lays out the perfect 1 to 1 cause and effect reality based problem + solution = resolution. Muscle pain + the needle as the remedy = resolution of the pain.

If you want more evidence you can study Gunn works. Then you can blend his work into that of Travell, Simons, Rachlin, Hackett et al for the complete 360 view of what is not very observable in the bits and pieces of RCT research.

Psychological correlates of the placebo that is acupuncture

oracknows — Tue, 17 Feb 2015 02:02:29 +0000

Psychological correlates of the placebo that is acupuncture

If there's one thing that's become clear to me over the years about acupuncture, it's that it's nothing more than a theatrical placebo. Many are the times that I've asked: Can we finally just say that acupuncture is nothing more than an elaborate placebo? Most recently, I asked this question in 2012. What science-based medicine answers is yes. However, there's a large contingent of physicians under the sway of practitioners of traditional Chinese medicine (TCM) who have fallen under the spell of that theatrical placebo, leading to a whole subdiscipline of quackademic medicine in which tooth fairy science is used to try to convince people that acupuncture actually works, even if they involve misinterpreting adenosine signaling or rebranding regional anesthesia as a form of acupuncture they dubbed PAPupuncture.

While I grudgingly admire the imaginative creativity of some of the attempts to torture acupuncture into seeming scientific, I also take note of studies that go against the seeming flow of propaganda designed to convince you that acupuncture has real, specific effects. Remember, it wasn't so long ago that I considered acupuncture, of all alternative medical treatments, as the one that might actually have something to it. The reason, at the time at least, was that acupuncture actually involved sticking needles into people. Perhaps there was some sort of physiological effect. Then I actually started paying close attention to the acupuncture literature. There, I learned that it doesn't matter where you stick the needles, thus invalidating any concepts of acupuncture meridians. Nor does it even matter if you stick the needles in at all; twirling toothpicks against the skin produces a similar effect. Basically, when compared to usual care or wait list controls, patients treated with acupuncture report improvement in pain and other subjective measures. However, when a rigorous sham acupuncture control is included in such studies, the apparent differences between acupuncture and control disappear. Acupuncture effects are virtually all nonspecific placebo effects.

With that in way of background, I just saw another study that sheds light on acupuncture effects by way of story in Medical News Today story entitled Acupuncture back pain success determined by psychological factors. It's a story about study by George T. Lewith's group at the University of Southhampton. He's bit of a controversial figure, as no doubt David Colquhoun could tell you, given that he apparently still prescribes homeopathy even though he's published studies showing that it isn't effective. Be that as it may, this study is called Psychological Covariates of Longitudinal Changes in Back-related Disability in Patients Undergoing Acupuncture.

Basically, it's longitudinal study using a questionnaire mailed to patients undergoing acupuncture for chronic back pain. Data were collected at baseline (pretreatment), 2 weeks and then at three and six months on a total of 485 patients from 83 different acupuncturists. The questionnaires were designed to measure variables from four theories (fear-avoidance model, common-sense model, expectancy theory, social-cognitive theory). In addition, clinical and sociodemographic characteristics, and disability were surveyed. The primary outcome was back pain-related disability. This was assessed using the 24-item Roland Morris Disability Questionnaire (RMDQ), which asks patients to think about “today” and to indicate whether their back pain interferes with 24 activities. An example: "I stay at home most of the time because of my back." High scores indicate greater back-related disability. At the same time, a variety of psychosocial scales were also examined to try to hone in on what psychological factors most contribute to the patient-perceived efficacy of acupuncture.

You can tell that Lewith is a believer by the introduction to the study:,

Personally, economically, and socially, back pain is costly. Acupuncture is recommended by UK clinical guidelines for low back pain (LBP) and is commonly used for LBP. In randomized clinical trials acupuncture has shown large effects on chronic pain compared with usual care or waiting list controls but often only small effects compared with sham acupuncture. This suggests acupuncture has large nonspecific effects, that is, factors other than needling characteristics contribute to patients’ outcomes. Indeed, acupuncture can be conceptualized as a complex intervention in which changes in patients’ health are produced not only by needling but also by more psychosocial factors such as empathic therapeutic relationships and holistic consultations in which discussions of lifestyle and self-care can trigger changes in how patients think and feel about their symptoms and their ability to manage them. However, little is known about the psychosocial factors and processes that might be involved in acupuncture for LBP: established psychological models have not been applied to understand acupuncture’s effects. Although variables from such models may not be explicitly addressed by acupuncturists, this does not mean they are not involved in patients’ ongoing LBP in this treatment context. Therefore, a comprehensive and theoretically informed investigation of psychological covariates of acupuncture’s effects on LBP was designed, drawing on major theoretical frameworks that have predicted LBP outcomes in patients undergoing other interventions: the fear-avoidance model (FAM), common-sense model (CSM), expectancy theory, and social-cognitive theory (SCT).

It is rather interesting to me that UK clinical guidelines for LBP would include the use of a placebo. One wonders why, if acupuncture is viewed as an acceptable clinical option for LBP in the UK, UK medical authorities don't also allow doctors to prescribe placebo sugar pills. It's basically the same thing. Of course, homeopathy is still common in the UK, albeit not recommended, and that's a placebo, too. Be that as it may, it's interesting that Lewith admits to conceptualizing acupuncture as an interaction in which it's not "just" the needling that causes supposed therapeutic effects but also the empathetic therapeutic relationship and the "holistic" consultation. In fact, reading the introduction, I could tell that this would be almost certainly what Lewith's group found, particularly given that a more rigorously designed study from a few years ago found that an empathetic acupuncturist expressing high expectations for the treatment would do better; i.e., that patient expectation and practitioner attitude influence the placebo effect caused by the whole theatrical placebo that is acupuncture.

So what were the findings? Within individuals (individuals compared to themselves), reductions in back-related disability compared to the individual's mean were associated with reductions in fear-avoidance beliefs about physical activity, consequences, concerns, emotions, and pain identity. Similarly, within person reductions in disability were associated with increases in personal control, comprehension, and self-sufficiency for coping. It was also noted that people who were less disabled had more positive outcome expectancies. In other words, they expected to get better.

These results are, of course, completely consistent with acupuncture being a theatrical placebo. Unfortunately, instead of making the most obvious conclusion (that acupuncture is a placebo and that these various psychological constructs modulate placebo effects), the authors just can't let acupuncture go. As lead author of the study, Felicity Bishop, said in an interview:

People who started out with very low expectations of acupuncture - who thought it probably would not help them - were more likely to report less benefit as treatment went on.

Which is, of course, an unremarkable observation that is usually true for any treatment with a large placebo component. In the paper itself, Bishop et al write:

The findings also have implications for understanding acupuncture’s large nonspecific effects and, more generally, for understanding the processes whereby acupuncture may result in decreased disability. Given that similar variables predict disability in other settings, patients’ perceptions of pain and self-efficacy could be influencing disability outcomes in patients receiving both real and sham acupuncture in clinical trials. These psychological variables offer one means by which major components of acupuncture as a complex intervention, such as ritual, the therapeutic relationship, and lifestyle advice, could trigger positive clinical outcomes. In the context of a warm relationship and therapeutic ritual, providing positive self-help advice encouraging physical activity could help patients to develop more positive illness perceptions, confront their fear of activities and become more active, breaking the negative cycle proposed in the fear-avoidance model and triggering a more positive perception of back pain as controllable and enabling an increasing sense of self-efficacy for coping. According to social-cognitive theory, enhanced self-efficacy for coping could then trigger a positive feedback loop increasing actual coping ability and reducing disability.

And at the very end:

Acupuncture patients experience less back-related disability when they are less afraid and avoidant of physical activity and work, perceive fewer symptoms emotions and consequences of LBP, perceive their LBP as less threatening, and when they feel greater control over, understanding of, and ability to cope with their back pain. Future studies should test whether integrating acupuncture and psychological interventions targeting these constructs can enhance patient outcomes.

Of course, the science-based view would be to ask this: Why is acupuncture even needed at all in this model? All of these observations could be used to use placebo mechanisms to accentuate the perceived benefits of science- and evidence-based treatments. Given that rigorous studies of acupuncture for low back pain routinely fail to find a difference between the acupuncture group and a well-designed sham control while finding significant differences between both sham control and acupuncture groups versus usual treatment or wait list controls, the results of this study can best be viewed as what psychological factors modulate placebo effects, and, to be honest, not a very rigorous study given that there is no control group, waitlist or sham, and the data were all collected using various questionnaires designed to assess back-related disability and various model measures.

I have an idea. Placebo effects are definitely a worthy area of study, even though in the world of "complementary and alternative medicine" (CAM), or, as it's becoming more commonly called, "integrative medicine" (really the integration of pseudoscience with science-based medicine) they are often endowed with downright magical, mystical, and even religious properties that far outstrip the magnitude and utility that placebo effects are, in fact, likely to have. The problem with CAM practitioners is that, rather than seeking ways by which placebo effects might enhance the patient-perceived effectiveness of actual medical interventions that have been shown to work, they just can't give up their ineffective modalities like acupuncture despite all the evidence showing they don't work.

Quackademic medicine marches on.

oracknows Mon, 02/16/2015 - 21:02

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