Someone's High On Placebos
    By Barry Leiba | December 29th 2010 04:30 PM | 16 comments | Print | E-mail | Track Comments

    Last Wednesday, this paper, published in PLoS ONE, hit the popular news in the medicine/science category, with articles such as this one from MedPage Today and this, from Reuters. The headlines are consistent, implying that the study has shown that the placebo effect works even when patients know that they’re getting placebos.

    From the MedPage article:

    While this may seem counterintuitive, the results suggest that physicians don’t have to resort to deception to harness the power of the placebo effect, Kaptchuk explained in an interview.

    Conventional wisdom says that in order for a placebo to work you have to convince the patient that they are taking a real drug, he told MedPage Today.

    However, the brain appears to respond to placebo in a way that conditions like IBS are susceptible to, Kaptchuk noted.

    Counterintuitive, indeed, and enough so that it merits some serious scrutiny. My first thought was that the headlines are misrepresenting the study and the claims of the researchers, a common problem in the reporting of research in the popular press. But it seems that they are, indeed, reporting exactly what the researchers are saying, here.

    I’ll note that the paper appears in a Public Library of Science (PLoS) journal, rather than in some other, more respected medical journal (such as NEJM or BMJ). I’ll also note that the lead researcher, Ted Kaptchuk, is associated with Harvard’s Division for Research and Education in Complementary and Integrative Medical Therapies, a connection the press just puts forth as Harvard, downplaying the fact that he does complementary medicine.

    Those aren’t reasons to ignore his research or his results, of course. But they are points that should make us ask questions. On the other hand, we should ask questions with any study; that’s what science is about.

    Now, the study is on IBS, which is a very subjective, catch-all condition of unknown etiology. They mention in the article that they expect this effect to work also with conditions such as fibromyalgia and chronic pain — also subjective conditions of unknown etiology — and depression and anxiety, more highly subjective stuff. And the study itself is entirely subjective, using self reporting exclusively, and not measuring anything.

    That could be OK. If we’re looking for cures, we need to measure; if we’re looking for symptom relief, well, if you think you feel better, then you feel better. Where I have to scratch my head, though, is in wondering what their hypothesis was.

    When you go into a study, you go in with a hypothesis, which your study might support or disprove. Even if it seems like you’re just wildly trying any drug that might work, you have a hypothesis: This drug might work. What’s the hypothesis, here? Placebos might work even if the patients know they’re placebos, is a valid hypothesis, I suppose, but to whom would it occur to even try that?

    The answer shows up in the study: it would occur to people who think they can show mind-body self-healing processes. OK... again, a valid thing to consider. But that’s where we get into some problems.

    We start with some very typical problems with medical studies... again, from MedPage:

    Limitations of the trial included a relatively small sample size, too short duration to examine long-term effects, and the possibility of self-selection bias in that the trial may have selectively attracted IBS patients interested in mind-body interventions.

    Many, many studies are too small, too brief, and suffer from various sorts of selection bias, and this one is no different. But to get the real kicker, we have to go into the paper itself and see how the placebos were presented to the patients:

    Patients were randomized to either open-label placebo pills presented as placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes or no-treatment controls with the same quality of interaction with providers.

    Read that again. The patients were not told just that they were getting placebos. They were not told that what they were getting is an inert substance with no medical effect. They were told that what they were getting has been shown in clinical studies to produce significant improvement in IBS symptoms.

    In other words, these pills are having exactly the same placebo effect as is well documented in pretty much every other medical study that involves placebos. And, to put the point forth directly, far from making this deception-free, they are deceiving the patients in the same way patients are deceived in every other administration of placebos.

    Let’s line it all up:

    1. You recruit people who have a condition that makes them feel horrible, that no one can tell them the cause of, and that no one has effective treatment for.
    2. You give them a pill and you tell them that this has been shown to provide significant improvement for their condition.
    3. They report that the pills did, indeed make them feel better.
    4. You claim that you did not deceive them, because you told them they were getting placebos.

    Bullshit. Whether or not you put the label placebo on it, you told them they were getting effective treatment. That biased the outcome, and the result should be no surprise to anyone. And it says... nothing. This study is worthless garbage.


    Gerhard Adam
    I think you're being unnecessarily harsh on the study, since they also stated that their aim was to ensure the patient understood that they were not receiving any medication, but they wanted to maximize the placebo effect.

    "Our rationale had a positive framing with the aim of optimizing placebo response."
    While you can argue about whether or not deception played any role in the doctor/patient interaction, the point regarding placebos was based on the assumption that the placebo effect was dependent on "intentional ignorance".  You can certainly make the point that the type or nature of the deception switched, but that gets into another area entirely.  

    After all, if the outcome is unknown, then it isn't a matter of deception as much as an opinion.

    At the beginning of the paper they clearly presented the problem of physician ethics in deceiving patients about the use of placebos.  Therefore, in this study, the attempt was made to inform the patient of the placebo while focusing on the positive aspects of the "treatment" and the physician/patient relationship.

    While there are clearly many other elements that need to be examined in the placebo effect, the results of this study help demonstrate that a placebo can be effective, even if the patient is told, so long as the point is framed in a positive fashion.

    That biased the outcome, and the result should be no surprise to anyone. And it says... nothing.
    Of course, it biased the outcome ... that's the point.  That the result can be biased (i.e. placebo effect) even with full disclosure that the patient is receiving no pharmaceutical treatment.  In their review with the patient, they disclosed  

    "...“four discussion points:” 1) the placebo effect is powerful, 2) the body can automatically respond to taking placebo pills like Pavlov's dogs who salivated when they heard a bell, 3) a positive attitude helps but is not necessary, and 4) taking the pills faithfully is critical.

    There's nothing deceptive in that briefing.
    Mundus vult decipi
    I guess we disagree on the deception point.  In the study, they told people they were getting "a placebo", but then were told that it works... and not just that someone's grandmother thinks it works, but that it's been clinically proven to work.  What's the real difference between that and what doctors otherwise do?

    We can possibly assume that at least some people in the study don't know what a placebo is in the first place.  And if I were told that I was getting "a placebo" that has been clinically proven to work, I'd be saying "What on Earth does that mean?  That contradicts the meaning of 'placebo'."

    So, no, I don't think these placebos are any different from what we've seen before, and this study is merely showing what we already know: that if people are given pills that they expect to work, many will perceive that they work.

    Now, it would be interesting to see a study with three groups, in which two get pills marked "PLACEBO", but half of them get an instruction sheet that says what these people were told, about the effectiveness, and the other half get an instruction sheet that says "These pills have no effect whatsoever."  I think we both know what the result would be likely to be.
    Gerhard Adam
    The provider clearly explained that the placebo pill was an inactive
    (i.e., “inert”) substance like a sugar pill that contained no medication.

    When participants in the placebo arm were asked: “ What did you think
    was in the placebo pills?” of the 29 who responded, 16 wrote “sugar”
    (12), “flour” (3) or “calcium” (1),” 6 responded “nothing,” 5 responded
    “did not know,” 1 responded “symbolic reminder,” and 1 responded
    “possible test medication.”

    Actually your statement is little better than what you're suggesting they did wrong.
    ...the other half get an instruction sheet that says "These pills have no effect whatsoever."
    Why would you think that your statement isn't also a placebo bias?  Your statement reflects your own bias that without pharmaceuticals the pills have no effect, but that isn't a completely true statement if they have a psychological effect.  They were correct in distinguishing the fact that the pills contained no pharmaceuticals and therefore there would be no medicinal effect from taking them. 

    I think your last paragraph illustrates precisely how difficult assessing the placebo effect is, because a negative bias is ultimately no different than a positive one.  Your results will still be skewed.
    Mundus vult decipi
    Why would you think that your statement isn't also a placebo bias?
    I don't think that; it's just that it introduces an opposite bias, and at least gives something to compare to.
    I think your last paragraph illustrates precisely how difficult assessing the placebo effect is, because a negative bias is ultimately no different than a positive one.  Your results will still be skewed.
    We're in absolute agreement here!
    Gerhard Adam
    I don't think that; it's just that it introduces an opposite bias, and at least gives something to compare to.
    I don't think there's a need to compare anything based on negative bias.  My basis for that, is that it should be clear that if there is a real mechanistic relationship between the problem and the treatment then there should be no placebo effect regardless of what is said or presented.

    The fact that something occurs anyway, then it is more important (in my view) to determine how far this can be exploited.  The null hypothesis indicates that nothing should occur, so I'm not convinced that adding a negative bias does anything except push the results towards the null hypothesis.  So, under the best circumstances, the only thing that could be demonstrated is that a negative bias leads to null results.  However, as I've said, the important point is that something happens at all, and it is this aspect of it that needs investigation. 

    One of the most troubling aspects of this, is to measure how much the placebo effect may have influenced positive results in drug trials that create the impression they are more effective than they are.  This is especially true when the problem being treated is more subjective to the patient and it is difficult to assess effectiveness.

    In some cases, there is a direct "mechanistic" relationship such that we're specifically trying to kill a strain of bacteria, and in doing so, we are affecting the outcome.  However, many other results are subject to much variation and having a better understanding that the placebo effect occurs even when people are being told about it, is a significant finding.  This corresponds to research indicating that the placebo effect even occurs in animals.
    Mundus vult decipi
    I am with Gerhard all the way. This study also gives some support to a hypothesis of mine: many of those who take homeopathic remedies/ follow some religion actually know quite well that homeopathy does not work/ the god concept makes no sense. Nevertheless, they also believe that there are no side effects and on some level humans all seem to practically (rather than intellectually) 'know' that they can (should/it is OK to) commit self-deception along the lines of: I first bring myself to doubt (Maybe there is something more to homeopathy after all?), then I add ritual (take something out of an expensive bottle, pray), and then it actually does have an effect on me. This is a highly effective method especially absent other options (thus, we are evolved to actively employ irrational basing of our usual rationalizations unconsciously).

    In the study that you suggest, I would as a patient think: this is a study - I get told it is placebo - well maybe they just want to study what my disbelief in the real drug does to its effect - so I am actually getting the real meds here! Such a study is useless. The study they did however ensures that the patients really know they get a placebo that works via belief into the placebo effect. And that is actually a great study with many implications that should have been done a long time ago.
    I propose the following IBS clinical trial protocol. Enrolees are told the nature of the groups to which they will be randomly allocated. One group will receive a drug proven to be significantly more effective for IBS than a placebo. A second group will receive the placebo proven to be significantly less effective than the drug. A third group will receive no treatment. All subjects will be informed which group they have been allocated to. I predict the drug group will do far better than in the original blinded trial and the "placebo" group much worse. I predict that this group will do little better than the no treatment group - the drug group will entirely capture the placebo effect. The placebo effect is predictably fickle!
    I predict this on the basis of what is well known, which is that specific and non-specific components of treatment are always present. What subjects are told impacts on the non-specific component in predictable ways. One needs to take account of this fact - thus randomised blinding. The result of the PLOS study was not in the least surprising given the enrolment procedure and trial protocol. Non-deceptive? In an "I did not have sex with that woman" sort of way, maybe... but really with this kind of protocal one could produce any desired result one wished.

    Gerhard Adam
    Why is it that no one suggests such a negative placebo effect during drug trials.  Why not take a drug that is supposed to be effective and tell people that it's not.  Would that have a detrimental effect on the treatment (especially in cases where results may be quite subjective)?

    So, I would suggest four groups.  One given the drug and told it is effective, One given the drug and told it is a placebo and not effective.  One given a placebo and told it is effective, and one given no-treatment.

    However, the point remains.  There should be no such thing as the placebo effect, therefore whatever is occurring is significant in its own right and doesn't require a real drug to demonstrate that something is taking place.  A placebo effect (positive or negative) throws a different light on ANY claims made.

    Mundus vult decipi
    Bonny Bonobo alias Brat
    For what its worth Gerhard, as someone who has an Erdos score of ∞ and who also just happens to be female (not many female commentators around here, anyone wondered why?) I totally agree!
    My article about researchers identifying a potential blue green algae cause & L-Serine treatment for Lou Gehrig's ALS, MND, Parkinsons & Alzheimers is at
    Gerhard Adam
    OK, I'll bite ... why so few female commentators?  :)
    Mundus vult decipi
    Bonny Bonobo alias Brat
    Probably because they think you're all a bunch of egocentric, elitist, opinionated, self-righteous members of an exclusive scientific boys club who regard their comments as nothing but trollipop.
    My article about researchers identifying a potential blue green algae cause & L-Serine treatment for Lou Gehrig's ALS, MND, Parkinsons & Alzheimers is at
    Bonny Bonobo alias Brat
    Oh dear Sascha, you can't delete this comment! But maybe Barry or an anonymous moderator will? According to this article methamphetamine is addictive and dangerous just a few famous methamphetamine addicts on the list of famous celebrities with this problem were :-
    Charlie Parker, Elvis Presley, Jean-Paul Sartre, John F. Kennedy, Adolf Hitler and Charles Manson
    Oh and Erdos of course!
    My article about researchers identifying a potential blue green algae cause & L-Serine treatment for Lou Gehrig's ALS, MND, Parkinsons & Alzheimers is at
    Gerhard Adam
    Hey! ... who are you calling a "boy"?  :)
    Mundus vult decipi
    The answer to your question is yes, undoubtedly there would be a detrimental effect. People are suggestible.
    One can play around with the permutations and watch the placebo effect being dragged around every which way.

    Kaptchuck has said he thinks the trial shows that the ritual of pill taking is a t work. Trouble is, he didn't control for that factor. He didn't have a non-pill group instructed that mind-body alone could do the trick. He would not have been able to claim scientific proof of that, but he may have been able to demonstrate that telling people that works as well as taking a placebo pill. Without a control all he has is a belief in the power of "ritual".

    One could replicate the trial with different groups being told different things. For example, the term "mind-body" could be swapped for the word or phrases: psychosomatic, psycho-biological, neuro-linguistic, positive thinking, etc etc. Would they all have the same effect? I doubt it. Some might show a greater placebo effect, some less, according to the suggestibility of the groups.

    I wonder which would prove the more effective: rhino horn or tiger penis? One would only need a vanishingly tiny trace - as demonstrated by homeopathy - I'm sure these placebos would run Viagra close. Imagine: two words converted by the brain into chemicals resulting in a stiiffy. The placebo effect really is wonderful and needs to be harnessed.

    Suggestibility is more subtle than mere gullibility and/or desperation. Placebos promise to please. People like to be told that they are going to given something which they really want/need. They want to please in return, out of gratitude. If a doctor or nurse is being empathetic and offering something which they say has been proven to work, it's natural to be thankful and want to give back. Who wants to report to the kind person trying to help that it's not worked? It's natural to respond to kindness with kindness. Yes, I do feel a bit better... I think. Not sure? Better to err on the side of kindness - it's only human.