Do physicians really believe in placebos?

ResearchBlogging.orgIn a previous post, I argued that placebo is an artifact of certain clinical interactions, rather than a treatment that we can exploit. Apparently, there are a whole lot of doctors out there who don’t agree with me. Or are there?

A recent study published in the British Medical Journal is getting
a lot of enk (e-ink) in the blogosphere. As a practicing internist, I have some pretty strong opinions (based in fact, of course) about both this study and placebos in general.

The Study

The current BMJ study defines placebo as “positive clinical outcomes caused by a treatment that is not attributable to its known physical properties or mechanism of action.”  I’ve got a lot of problems with this definition, but we’ll get to that later.  It also allowed physiologically active medications to “count” as placebos.  Oops.

The study surveyed internists and rheumatologists practicing in the U.S. They tried to control negative responses to the term “placebo” thusly (from the Methods section):

Because the term “placebo” and behaviours surrounding its use can be contentious, we devised a series of non-judgmental questions beginning with broad questions that avoided the term “placebo” and then gradually gained more specificity, culminating in items whose responses used a clear definition of a “placebo treatment.” By constructing a series of items in this manner we allowed respondents to describe their attitudes and experiences as accurately as possible.

The first set of three items began with a hypothetical scenario in which a dextrose tablet was shown in clinical trials to be superior to a no treatment control group (thus establishing its efficacy as a placebo treatment). To avoid biasing responses these three questions did not use the term “placebo,” “placebo treatment,” or “placebo effect.”

I know a lot of doctors.  They tend to be fairly bright.  I don’t think any of them would be deceived by this scenario.  When you read “dextrose pill”, you think “placebo”.  It might as well be the same word.

Respondents were then asked to indicate which of several treatments they had used within the past year primarily as a placebo treatment, defined as a treatment whose benefits derive from positive patient expectations and not from the physiological mechanism of the treatment itself; and how they typically described placebo treatments to patients. By asking these five questions both without the term “placebo” and then using the term, we aimed to assess physicians’ practices as accurately as possible.

All docs would recognize this as a placebo scenario.  However, the definition above is rather problematic.   Is a placebo “a treatment whose benefits derive from positive patient expectations and not from the physiologic mechanism of the treatment itself”?

The validity of this study hinges on the answer to this question.

Placebo—I do not think it means what you think it means

The concept of placebo, and the way it is used in this study are both problematic.  First, we have an elephant in the exam room.  When we observe a so-called placebo effect, we are very susceptible to the post hoc ergo propter hoc fallacy.  Just because the patient’s condition changes doesn’t mean we have done anything to cause that change.  In fact, due to the remarkably inexact human pattern-recognition software, we are likely to attribute a change in a patient’s condition to something, and if we don’t know what that something is, we may label it “placebo”.  So the very concept of placebo may be an artifact of our way of thinking, a label to place on a co-incidence, rather than a “thing”.  We may have wrongly reified a rather fuzzy concept.

So, I’m not quite sure what a placebo is. In the current study, a placebo is defined as “positive clinical outcomes caused by a treatment that is not attributable to its known physical properties or mechanism of action.” This implies that the physician either knows the treatment shouldn’t work, or doesn’t understand how it works. This isn’t just semantics; we have many treatments available whose exact mechanism of action isn’t known, but whose effectiveness has been proved. If you interpret the definition less strictly, it oxymoronically defines a placebo as something that works despite it’s lack of efficacy. If I prescribe something expecting a predictable effect, and it produces that effect, by definition it isn’t a placebo. If I prescribe something I expect to work, and it doesn’t, then it isn’t a placebo. If I prescribe something expecting failure, but it works, I’m a lucky idiot. This would seem to imply that there is no such thing as a placebo (and I might agree).

Earlier work lays down some less problematic definitions by dividing out the “components” of the placebo effect. One scheme divides placebo effects into effects due to assessment and observation, due to therapeutic ritual (placebo treatment), and due to supportive patient-practitioner relationship.  (It leaves out coincidence.)  Each of these effects is easy to remove from the shadow of placebo.  Effects due to assessment and observation occur with all patients.  Therapeutic rituals exist independent of traditional placebos—for example, simply doing a thorough exam is a useful ritual, and is often therapeutic.  And a supportive doctor-patient relationship is (should be) standard.  When you try to divide placebo into its components, you’re left with standard components of medical care.

Modern medicine has a bit of a Clarkian quality to it. Most patients don’t know how medicine works, and that’s OK. It’s not necessary that every patient be a trained physician. Given the power of modern, science-based medicine,  it can seem like magic to the uninitiated.  To someone who doesn’t apply too much thought to the problem, a placebo can seem to be another tool on the shelf along with acetaminophen, appendectomies, and atenolol.  Each of these tools can have a positive clinical effect. And positive effects can occur with no treatment at all.  Is it right to label that which we do not understand “placebo”?

The best definition of placebo that I’ve seen, snatched right from Wikipedia, is ” a substance or procedure a patient accepts as medicine or therapy, but which has no specific therapeutic activity.”  This seems more accurate.  It takes out the necessity for a placebo to actually work.  Some might say that this eviscerates the concept entirely, and that’s really the point—a placebo treatment is not a treatment at all, only the perception of one.

In sum…

A placebo is a tool used in clinical studies to separate out effects of the treatment in question from doing nothing.  If there are improvements in subjects in the placebo arm, it is usually called a “placebo effect”, but may just be either random changes in the patient’s condition, or the effect of standard medical care such as being observed and cared for. A placebo cannot be used as a treatment, and cannot be observed outside of this setting.  After all, how would you test a placebo?  Against a different placebo?  And trials that do exist measure only subjective outcomes, such as pain, rather than something objective, such as tumor size. Would you be willing to be a subject in a trial of placebo vs. nothing at all for your colon cancer? The ethical problem of deceiving a patient in order to achieve a placebo effect is dealt with in detail in Dr. Gorski’s post from earlier today.  I would add to his argument that since placebo effects don’t really exist outside of clinical studies, there is never a good reason to use one.

Finally, placebo is a refuge for cult medicine enthusiasts.  When homeopaths, naturopaths, chiropractors, and other modern shamans are confronted with the utter implausibility of their offerings, they may retort, “well, it at least has a powerful placebo effect, and the patient feels better.”

A careful examination of the nature of placebo shows this argument to be bankrupt.  Placebo is not a treatment. It is unethical.  And, as it is commonly understood, placebo treatments may in fact be non-existent, an ephemeral  change in a patient’s condition.  To claim credit for it is disingenuous at best.


J. C Tilburt, E. J Emanuel, T. J Kaptchuk, F. A Curlin, F. G Miller (2008). Prescribing “placebo treatments”: results of national survey of US internists and rheumatologists BMJ, 337 (oct23 2) DOI: 10.1136/bmj.a1938

T. J Kaptchuk, J. M Kelley, L. A Conboy, R. B Davis, C. E Kerr, E. E Jacobson, I. Kirsch, R. N Schyner, B. H. Nam, L. T Nguyen, M. Park, A. L Rivers, C. McManus, E. Kokkotou, D. A Drossman, P. Goldman, A. J Lembo (2008). Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome BMJ, 336 (7651), 999-1003 DOI: 10.1136/bmj.39524.439618.25

A Hróbjartsson (2002). What are the main methodological problems in the estimation of placebo effects? Journal of Clinical Epidemiology, 55 (5), 430-435 DOI: 10.1016/S0895-4356(01)00496-6

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16 thoughts on “Do physicians really believe in placebos?

  1. Harriet Hall says:

    Words can be misleading. Disagreements about whether a placebo effect exists may boil down to semantic quibbling. Placebos themselves don’t have any effect, but if patients believe they are receiving a treatment and if they believe they feel better, that perception IS the placebo effect. It does happen, whether it’s due to suggestion or false perception or distraction or any other explanation.

    I wish we had a better term to describe the phenomenon. What I mean by “the placebo effect” is really the complex web of psychosocial effects surrounding medical treatment, effects that occur with effective treatments too, not just with inert treatments.

  2. Peter Lipson says:

    I’ve been going back and forth with a few folks about whether this is all about semantics or whether we have hitched ourselves to a concept that isn’t especially powerful.

    Hróbjartsson divided placebo into several different components, but as far as i can tell, each of them separately is a concept different from “placebo”—the aggregate effect may or may not best be called “placebo”. After much thinking, I really feel that the clinical concept of placebo, vs the RCT concept, really isn’t that useful, especially in clinical medicine, the one area where it should be most powerful. When I have a patient with symptoms not amenable to science-based treatments, I give them all the “components” of a placebo—assessment and observation, therapeutic ritual, and a supportive patient-practitioner relationship.

    I’m left wondering if there’s any “there” there.

  3. pmoran says:

    All you have shown is that the word is used loosely and in different senses, with which I heartily agree. But I think everyone can understand that the placebo “does” nothing in itself. Any influence that it has on medical outcomes, including via such suggested means as endorphin release or activation of symptom-relieving neural pathways, is due to *everything else* about the therapeutic encounter including how the patient perceives both the practitioner/adviser and the particular sham treatment chosen.

    The focus has been inappropriately on the sham treatment when it should have been on the “everything else”. We still don’t know what that is capable of ( — AS “placebo”) and whether any effects on clinical outcomes can be fully invoked without at least a symbolic act of treatment. The Kaptchuk article you reference above certainly suggests that the combination may well have usefulness in some troublesome clinical conditions.

    Can anything be wholly unethical if it is done with the undiluted interests of the patient in mind? Who is to say in each case? I don’t trust ethical absolutes and sweeping generalisations that happen to fit a political agenda, even ones that I largely approve of.

    Doctors are, in any case, clearly having to sidestep the ethical questions by using as placebos treatments that have some credibility as medical treatment in other contexts. I suspect (actually I know, through observing what doctors do from the specialist vantage point) that they do this kind of thing far more often than they will admit to in any survey. I think this also partly explains a considerable use of “alternative” methods, even homeopathy, by conventional doctors in some countries, perhaps recognising that it is prudent not to use unnecessarily powerful pharmaceuticals as placebos.

    It’s not so awful. It is just that medicine is messy. Not a lot of everyday medical practice fits wholly into our idealistic and somewhat romanticised EBM/SBM model.

  4. Peter Lipson says:

    Good points. I agree that ethical absolutes don’t fit in well with real life. The fact that most patients aren’t in a position to fully understand their care makes the idea of perfect informed consent impossible.

  5. Peter Lipson says:

    BTW, I completely expect people to disagree with me on this one, and I hope that these disagreements will continue to help me think it through, as Harriet’s and pmoran’s comments have.

    So, please have at it—you aren’t gonna hurt my feelings… : )

  6. The current BMJ study defines placebo as “positive clinical outcomes caused by a treatment that is not attributable to its known physical properties or mechanism of action.” I’ve got a lot of problems with this definition, but we’ll get to that later. It also allowed physiologically active medications to “count” as placebos. Oops.

    I’m confused about why that definition counts as an oops. Antibiotics are physiologically active, but they don’t work on viruses. So, if a doctor prescribes antibiotics for a virus and the patient reports that she feels better, then the antibiotics might be acting as placebos.

    It’s possible that therapeutic rituals are beneficial all by themselves. Reassurance and care tend to make people feel good and do better in all areas of life, including medicine. But I always assumed that the placebo effect posited something more involved than that. I thought that placebos were treatments that worked because the patient believed the treatment was effective, even if the treatment had no curative or palliative effects of its own.

    A test for such a placebo effect would be to compare patients who got an exam and a prescription for a sugar pill to those who got the exam and no pill.

    It’s an empirical question whether the placebo effect exists over and above the benefits of being reassured and cared for.

  7. Mark Crislip says:

    I am unaware if this literarture has been evaluated in a systematic way, and I may be suffering from confirmation bias, but when clinical studies have a placebo wing and outcomes have both an objective end point and a subjective endpoint, the only consistent effect is for the subjective component and not the objective component.

    Attitude changes, function does not. The pain is less, but you still have same functional limitations from the pain. This suggests to me that placebo does nothing.

    I am limited in my understanding to SCAM studies; we do not use much placebo in infectious diseases.

  8. wertys says:

    The late great Patrick Wall (of Melzack and Wall gate control theory fame) proposed near the end of his career that the placebo situation was not best understood as a ‘stimulus’ ie the pill, the sham intervention, but as a ‘response’. He postulated that a person in pain is similar to a person who is hungry or thirsty, that is a person who is aware of a physiological sensation, and simultaneously driven towards action which might consummate that need. At the onset of pain a person’s first instinct is to avoid the inciting factor, protect the injured body part and seek help. The reduction of symptomatic pain would then occur as the psychological need for assistance is met, independently of any measurable physiological parameter. He compared this also to hunger and thirst in that there is no clear physiological parameter to define the feeling of hunger or thirst. They are need states which are mediated by the brain alone and experienced as emotional motivators for action. Once you have eaten or drunk, there is again no measurable value at which you are ‘unhungry’ but rather a reduction in hunger and altered behaviour to the postprandial state.

    This concept I think is useful in contemplating placebo responses, and does away with the imperative for deception in defining when it has occurred. If one does not experience a reduction in pain with a treatment encounter, the pain tends to drive a search for other ways of pain reduction, and people can become ludicrously superstitious about what they need to do to experience pain relief. This irrational behaviour is nonetheless psychologically satisfying as it meets the perceived need for appropriate care and this mediates symptom reduction.

  9. Fifi says:

    wertys – Yes! But then I would agree and have a bias having been raised around these ideas and having worked in a pain clinic for a brief period ;-)

  10. daedalus2u says:

    I suspect there is more than a fair amount of denialism regarding the placebo effect among physicians.

    You can lump all error and fraud and deception, mistaken improvement and self-delusion, wishful thinking and investigator error into “the placebo effect”, and then claim that there isn’t anything beyond that. That would be an instance of denialism (in my opinion).

    If you look at this article, they have instrumental measures of gastric motility which are different depending on expectations. When people are given a pharmacologically inert material and told it will make nausea worse, it doesn’t, it makes it better. When people are given the same pharmacologically inert material and told it will make nausea better, it doesn’t, it makes it worse.

    Is that a “placebo effect” because expectations changed a physiological outcome?

    My interest is in the physiology behind the placebo effect, not the ethics of giving placebos (which I think is universally unethical). My interest is due my interest in nitric oxide, which I feel is intimately connected with the placebo effect, and which I think is one of the fundamental causes of the placebo effect, the neurogenic regulation of the basal NO level to end the “fight or flight” physiologic state where resources can then be allocated to healing.

    I completely agree that virtually all of the CAM treatments are pure placebos, homeopathy, Riki, acupuncture, and most chiropractic. Relaxation techniques invoke the placebo effect through the neurogenic production of NO.

    My interest is because I am quite sure that the source of NO that I am working with will be capable of invoking the placebo effect pharmacologically. Once that is done, there is nothing more than any placebo can do. If you could invoke the placebo effect pharmacologically, then the CAM treatment modalities can do nothing extra (because they are only placebos).

    Until you can invoke the placebo effect pharmacologically, the woo-meisters will have the advantage. I think this is the way to attack CAM, with a “placebo effect” that is superior to what the woo-meisters can invoke.

  11. yeahsurewhatever says:

    Defining placebo as “positive clinical outcomes caused by a treatment that is not attributable to its known physical properties or mechanism of action” is a self-contradiction. If the outcome is not attributable to any known physical property or mechanism of action of a treatment, it is not attributable to the treatment at all. There is a word for this: coincidence.

    Also, I love the Princess Bride reference.

  12. yeahsurewhatever says:

    “I wish we had a better term to describe the phenomenon.”

    Treatment bias. Subject-expectancy effect. Wishful thinking. Self deception. Subjective validation. Reification of natural regression to the mean. Voodoo treatment. Abracadabrism. Patient mollification. Nothing for the price of something.

    Also, for those who like such things:

  13. daedalus2u says:

    YSW, a positive effect could be due to an as yet unknown physiological mechanism or action.

    If insulin could be transported back 100 years, would its use by those ignorant of its physiological effects be called a “placebo”?

    Or, as you say “Treatment bias. Subject-expectancy effect. Wishful thinking. Self deception. Subjective validation. Reification of natural regression to the mean. Voodoo treatment. Abracadabrism. Patient mollification.”?

    It certainly would be a “positive clinical outcomes caused by a treatment that is not attributable to its known physical properties or mechanism of action”

  14. pmoran says:

    It is fairly obvious from the differences of opinion whenever placebos are discussed that we don’t know what “the placebo” (meaning herein generic medical care containing a pretend treatment), can do for patients. All we know is that there are major limitations to its ability to influence objective disease processes, as Mark says .

    We have suggestive evidence for clinically useful activity otherwise. Look at the Kaptchuk trial, Also, YSW and others, the Hrobjartsson systematic review can be interpreted as showing that placebo-based management can influence symptom levels even within clinical studies designed to inhibit them. In fact, the very intricacies of the EBM system testify to the belief that the “placebo effect” (meaning, again, patient responsiveness to a package of care that includes a placebo) is potent enough to easily leak through most safeguards and corrupt clinical studies.

    Of course, as Daedalus2 points out, we can explain away much of the benefits commonly attributed to placebo as illusory (e.g. spontaneous events and patient reporting biases), but can we honestly claim that we have disposed of them all? Does it even matter if any benefits are due to altered patient perceptions, or better ability to cope with illness, or a reconsideration of abnormal illness behaviors, or even due to the satisfaction of the (Wertys) urge to “do something” while a bad patch of symptoms works its way through ( as always with the unspoken proviso that there is no obviously superior science-based method and there are no significant risks to the kind of placebo chosen)?

    Let’s also not forget the nocebo effects expected whenever we disappoint patient expectations by, for example, not having an easily understandable explanation for an illness and not supplying simple souls “something to take for it”. Harriet and others will say that we should be able to help patients manage their problems without drifting off into make-believe, which is partly true, but I am sure they will admit that there are many hurdles for “talk only” treatment in everyday practice including time constraints and varying levels of patient intelligence and insight. Sometimes it will be the right approach, quite often it is a futile endeavour.

    We are not entitled as scientists to choose answers that our inclinations dictate. Sure, homeopathy and acupuncture and “Detox” have no right to work — they are ridiculous treatments from any theoretical viewpoint. It is a practical joke on all rational people if they can. in fact, satisfy many of the needs that people bring into medical encounters and make them feel genuinely better. But to my mind, the available evidence seems to be heading in that direction. Should skeptics be preparing for such a mind-shift and thinking twice before using words like “worthless” and “ineffective” in relation to medical treatments that don’t work better than placebo?

  15. Fifi says:

    “Sure, homeopathy and acupuncture and “Detox” have no right to work — they are ridiculous treatments from any theoretical viewpoint. It is a practical joke on all rational people if they can. in fact, satisfy many of the needs that people bring into medical encounters and make them feel genuinely better.”

    Well, from my perspective they have a “right” to work, they just don’t appear to “work” how the person doing them claims they work. So, the proposed mechanisms may be ridiculous but that doesn’t mean that another very rational (and simple) explanation for why they work doesn’t exist. There are all kinds of very direct and rational psychosocial reasons for why people receive comfort from attention and being touched caringly and listened to, or from paying attention to their actions and state and performing a ritual with a specific intent, or being told they’re not going to die, or whatever.

    The question really is whether it’s part of a doctor’s role to fill these kinds of psychosocial needs for people (that were previously often provided by religion, if we think about it a bit)? Or are doctors essentially biomechanics that deal purely with the biological aspects of a person’s well being or also the psychosocial. (It’s no coincidence that many CAM practices often have a “community” around them that a patient then becomes part of and feels supported by – with everyone reinforcing each other’s belief in the system they’re using.) The reality is that most GPs do end up filling the psychosocial role for people (the quintessential family doctor who understands what’s going on in a family not just an individual), while more specialists fill the more biomechanical role (GPs often end up translating and making sense of information from a specialist for their patients). I’d say that the ever growing lack of GPs has a lot to do with people turning to woo instead of medicine, and is also why so many CAM practitioners are trying to muscle in on the role of the GP. Which, incidentally, would be disasterous since it’s GPs who direct patients towards appropriate tests and treatments by the appropriate specialists. Since it demands such a broad knowledge of medicine (and ongoing updating of knowledge), it seems to me that general practice is THE most important area to keep woo out of. As a whole, medicine needs to be looking at how to stop privileging specialists over GPs – on some level it seems to me that medicine itself doesn’t have adequate respect for the role of the GP.

  16. daedalus2u says:

    To expand on the two thoughts that PM and Fifi mention;

    “Sure, homeopathy and acupuncture and “Detox” have no right to work — they are ridiculous treatments from any theoretical viewpoint.”

    ”Well, from my perspective they have a “right” to work, they just don’t appear to “work” how the person doing them claims they work. “

    Homeopathy and detox are “top down” therapies. Someone had an idea made up out of nothing and then tried to force reality to fit into that idea. Sure, they can fool themselves, and fool other people, but they can’t fool reality. Because they don’t correspond with reality, they can’t work.

    Any system that is going to “work” has to be built from the bottom up, it has to be built up from smaller structures that “work” with those built of still smaller structures that “work”. The building up of a system that is going to “work” has to use as building blocks only smaller systems that work.

    A “top down” system can’t work unless each and every detail assumed at the “top” is in fact correct. If you already know that each and every detail is correct, then it isn’t a “top down” system but a “bottom up” system. If the system is built on facts that are known, then it is built from the bottom up. If the system assumes ideas and then tries to test them and make sure they work, that system is being built from the top down. When a “top down” system finds a fact that doesn’t fit, the normal human inclination is to reject the fact rather than the “top down” edifice that the fact is incompatible with.

    Most human enterprises have a “top down” hierarchy. There is a natural human inclination to follow a “top down” hierarchy. An example of that is parents teaching their children. The children learn from the top down, they learn the overall structure and then fill in the details. An abstract lays out the “big picture” and then the rest of the paper fills in the details. A prophet lays out the big picture and then fills in the details.

    It is human nature to see a “big picture” first and then try and work out the details. It is overactive human pattern recognition that forces the type 1 error, the false positive rather than remain in doubt or allow the type 2 error the, false negative.

    This is how humans communicate, they do pattern recognition on the tiny scraps of data that are transmitted via language and use their Theory of Mind to extract (and to some extent project) what the person speaking the language actually “means”.

    The Theory of Mind is the “big picture”, and once the data stream matches it well enough, there is pattern recognition and the “idea” is communicated. That works for communication with other humans with a shared Theory of Mind, it doesn’t work for trying to figure out reality.

    That is how reality gets anthropomorphized, via people using their Theory of Mind to try and understand reality. Objects act a certain way because there is a demon inside the object animating it. Treat the demon as another human, and it will do what you want it to do.

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