Michael Specter is a good science journalist. I particularly enjoyed his book, Denialism. In a recent New Yorker article he tackles the difficult question of the placebo effect in modern medicine. While he does a fair job of hitting upon the key points of this question, I think he missed some important aspects of this question and allowed the views of Ted Kaptchuk to overly influence the framing of the article. Specter fell for the typical journalist trap — frame the article around a charismatic “maverick”, complete with compelling anecdotes, bury the meat of legitimate skepticism deep in the article, but then bring it all back to the maverick in the end. Be sure to tell us how this is going to change everything. This is good story telling, but very problematic as science journalism.
Kaptchuk himself is an interesting character. He is heading Harvard’s Program in Placebo Studies and the Therapeutic Encounter. He has produced some good science on the placebo effect, but does not seem to want to draw the appropriate lessons from that research, and passes his bias on to Specter. From the article the quotes from Kaptchuk that most strike me are those about his personal experience with placebo medicine. Specter reports:
“There was no fucking way needles or herbs did anything for that woman’s ovaries,” he told me, still looking mystiﬁed, thirty-ﬁve years later. “It had to be some kind of placebo, but I had never given the idea of a placebo effect much attention. I had great respect for shamans—and I still do. I have always believed there is an important component of medicine that involves suggestion, ritual, and belief—all ideas that make scientists scream. Still, I asked myself, Could I have cured her? How? I mean, what could possibly have been the mechanism?”
To me this is no different than Ray Hyman being flabbergasted when his cook-book palm readings were found to be highly accurate by his clients. Hyman, however, took a step back and did what a scientist should do. He gave the opposite readings as was dictated by the reference book and found that his clients were just as pleased with the results. He concluded that the accuracy of palm reading (any cold reading, really) is just an illusion, one happily constructed by the client.
It is difficult to shake the sense, however, that something real is going on in such situations. We are struck by coincidences and apparent patterns and effect. The patterns may seem so real to us that, emotionally, we just can’t accept that they are illusory.
That is what I see in Kaptchuk’s memory of that one case, which is just representative of the many cases that apparently convinced him of the power of the placebo. All practitioners, like all psychics (regardless of how sincere they are), are subject to this illusion. We are all subject to confirmation bias, statistical effects like regression to the mean, expectation bias, and reporting bias. These psychological effects create the illusion of a real effect where none exists.
In fact, the analogy to psychics is very illuminating, because it demonstrates that people can be led to believe that there is a real effect when we know (as much as we can know anything in science) that none exists. Why should the placebo effect get any different treatment?
The real question is: how much of the placebo effect is due to illusions, like confirmation bias and regression to the mean, and how much is due to a real physiological response to the therapeutic interaction? This is an important question, and Kaptchuk is right to research it, as long as he is willing to listen to the answer.
We already have much research that addresses this question, and Specter references some of it in his article. In fact, Specter would have been better served to frame his article around Asbjörn Hróbjartsson and his research, rather than Kaptchuk (the same facts would then have been framed very differently, it seems). Hróbjartsson has been reviewing studies in which a placebo arm is compared to a no-treatment group. He first published his findings in 2001, but has updated his research. His most recent study concludes:
We did not find that placebo interventions have important clinical effects in general. However, in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting. The effect on pain varied, even among trials with low risk of bias, from negligible to clinically important. Variations in the effect of placebo were partly explained by variations in how trials were conducted and how patients were informed.
In other words, the best research we have strongly suggests that placebo effects are illusions, not real physiological effects. The possible exception to this are the subjective symptoms of pain and nausea, where the placebo effects are highly variable and may be due to subjective reporting. In a separate publication Hróbjartsson explores this question further and concludes that the existing research is consistent with reporting bias (i.e. illusion), but we need to creatively design studies to better answer this question.
Placebo effects are mostly just as much an illusion as precognition or talking with the dead. Pain is the notable exception, which makes physiological sense. Pain is a subjective experience, evolved to have adaptive features that are highly situational. There are times when pain should be very bothersome, and other times when it’s more adaptive to be able to ignore pain. So it is no surprise that mood and expectation can highly influence the reporting of pain.
There is another way to get at the question of how much of placebo effects is real and how much is illusion, and ironically Kaptchuk himself has authored one of the best studies of this kind — comparing subjective and objective outcomes. Kaptchuk performed the now famous (at least among medical skeptics) study of medical treatment vs placebo vs no treatment of asthma patients. David Gorski reviews the study here, pointing out that for subjective outcomes there was a measurable placebo effect. For objective outcomes, there was none. That is the key finding. In my opinion it is difficult to miss the implications of this — that at least when it comes to asthma the placebo effect is illusion, not real.
Kaptchuk, however, missed that. He concluded, rather (to quote Specter):
Kaptchuk concluded that objective data should not be the only criterion for doctors to consider. “Even though objective physiological measures are important,” he wrote in the study, published earlier this year in The New England Journal of Medicine, “other outcomes such as emergency room visits and quality-of-life metrics may be more clinically relevant to patients and physicians.”
I wonder what he would have concluded if the study showed there was an objective improvement with placebo? Anyway — Kaptchuk just wants to change the rules to suit the outcome, rather than listen to the outcome. Asthma is perhaps the perfect disease to demonstrate the folly of his approach. Asthma attacks can kill. If someone is made to feel that they are better because of expectation, investment justification, and other psychological effects — essentially biasing their reporting of their symptoms — while the physiological asthma attacks continues, they are theoretically at higher risk of complications, including death. Kaptchuk, however, pulls the standard — what are you going to listen to, numbers or people. He misses the point. The subjects of his study who received the placebo were not better. They just reported that they were because they felt they were expected to.
If the study were just a pain study, Kaptchuk might have a point. As I teach my students every day — you have to ask what the goal of treatment is. If it is solely to make the patient feel better, then it’s OK to assess a treatment (in clinical practice, not as a scientific study of efficacy) on whether or not the patient feels better. But when your goal is to change the course of a disease, or prevent a complication, then you have to use objective measures, not subjective report.
There is no question that if you give someone a treatment and ask them how they feel, they are likely to report that they feel better. There are numerous psychological ways to manipulate and maximize this response (type of treatment, cost of treatment, and the interaction of the practitioner). No one doubts this. The real question we have to ask, however, is — is the reported improvement the same type of illusion that makes people feel psychics have magical power, or is it a real physiological effect that can be exploited?
The best evidence we have strongly suggests that the answer (for everything but pain and nausea) is that the placebo effect is largely or entirely an illusion. It is something to be controlled for so that we do not fool ourselves into thinking that a worthless treatment has a real effect. For pain and nausea the question is a bit more complex, but still the best evidence suggests that any placebo effect is small and variable, and may also be largely biased reporting. To the extent that placebo effects for pain are real, we can get them by having a pleasant therapeutic interaction.
It is unlikely that spending billions of dollars on further research is going to give us the ability to exploit the placebo effect for pain any better than we can now, simply by being hopeful and supportive of the patient. That will not stop billions of dollars from being spent on asking and answering the same questions over and over again.
Specter missed, in my opinion, a major context to this question. Proponents of so-called CAM (complementary or alternative medicine) have been telling the world for decades that their treatments are real, and they can prove it once they are studied properly. Now that they have been (at least all the major CAM modalities) and found not to work any better than placebo, CAM advocates have come out with a range of special pleading, such as the bogus claim that “Western” science cannot study such mystical methods.
Recently the main special pleading we have been hearing is that CAM modalities work through the placebo effect. That is why they are so desperate to represent the placebo effect as something more than it is — as a real effect worthy of exploitation. If the placebo effect is all illusion, however, then CAM is all illusion.