This article is cross-posted at Science-Based Medicine. Check it out. --PalMD
In 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.
References
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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Would you consider the placebo effect to perhaps be a statistical threshold of therapeutic effect, used to attempt to gauge a transient change the patient's body is exerting on its own from the actual impact of a treatment? It seems like the semantics of the term placebo causes a bit of trouble when it comes to testing it. Great post for scientists, physicians, and physician hopefuls(like myself) to ponder.
Yes, I just hadn't thought of how to phrase it.
Im confused about why that definition counts as an "oops."
Antibiotics are physiologically active, but they dont 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 a complicated empirical question whether an antibiotic might do something that actually makes a patient with a particular virus feel better or get better, but that's not a weakness in the definition of "placebo."
Not quite an x-post, but I left a similar comment at Science-Based Medicine.
Okay, I'm going to be a bit less suspicious in the future when my allergist writes a prescription and says "Here, this seems to work for some of my patients. Let's try it."
I'm curious as to what you think of the body of literature showing that there is a naloxone-sensitive component of the placebo response to pain. It would seem to be your own elephant in the room with regards to this post.
I can haz citation pleaze?
levine et al 1978 the mechanism of placebo analgesia was the first to discover it. since then it's been widely reproduced and studied, with placebo response to pain being separated into opioid mediated and non-opioid mediated components.
here's another paper:
http://www.jneurosci.org/cgi/content/full/19/1/484
ty
This seems weird. I do remember reading statistical studies that showed how placebo-treated patients fared better then nontreated ones (here placebo=dextrose pill).
Plus, as a mother not a doctor, I think placebos have an important role: namely, in some illnesses you just don't do anything, but sit and wait. Many parents (at least among those I know) feel that just sitting and waiting is unacceptable. In that case I find placebos much more appropriate then unnecessary medications, that tend to have side effects.
Among the parents I know, some will change and change pediatrician (and, I think, their own doctor - but that's something they don't discuss with me) until they find one that _always_ prescribes something. If so, I think many doctors would be happier for a child to be given unnecessary dextrose then unnecessary antibiotics. Have you considered this viewpoint at all?
IMHO, the only legit role placebo has is as a control arm in clinical studies, and even then it is not of much value unless there is also a no treatment, no placebo arm to compare it with.
I'd be concerned about getting this sort of response from a patent. I certainly wouldn't be prescribing something for -everything-, especially when a lot of the minor cases I see require no prescription.
I'm not a paediatrician, but I would be trying to talk to the parents and explain why I won't prescribe something every time. If they insisted, and changed Doctors because of this, well, that is a patient I don't think i'd miss.
PalMD, I think you allow yourself to be needlessly confused about, and to unhelpfully confuse and sophistrize, the subject of "placebo." It is rather clear from history and common usage, that the concept of "placebo" is about administering something for which we have no reasonable expectation that it, in itself, has inherent ability to affect the patient in a way relevant to the situation or condition at hand. For example, that might be a sugar pill given to someone with MS. That placebo however, is represented by the physician or experimenter to the patient as being likely to be effective (or, the patient believes it is apart from anyone telling him that directly.)
If the placebo "works" despite being "inactive" according to any rational assessment of its intrinsic powers of influence (such as chemical properties etc.) then we figure that attitudes of the patient much have effected the changes. (Well, what else could have, unless you really want to reassess the actual powers per se of simple sugar pills - do you?) Also, I think you are mistaken here: "And trials that do exist measure only subjective outcomes, such as pain, rather than something objective, such as tumor size." Really? I think there are plenty of placebo studies that look into objective measures.
The standard of whether it "works" can well be the same standard we'd apply to any "real drug", since the latter might also be mimicked in their effectiveness by an inherent tendency to get better over time in some case, etc. Placebos do need a control standard, so the standard is taken as versus literally "doing nothing" - not even having someone say, this is yadda and will help you.
There are also reports of effects due to hypnotism, which is a direct suggestion effected a noticeable result.
@AusMed:
If they insisted, and changed Doctors because of this, well, that is a patient I don't think i'd miss.
Wouldn't you be sorry for those innocent antibiotics-filled kids? Wouldn't you be sorry for someone who is just suffering from a lack of education not due to laziness but to an inefficient school system? How about poorly educated elderly patients? It's hard to change your way of thinking as a grownup.
thanks