Blog | Monday, August 29, 2011

Shame on you, New England Journal of Medicine

For specialists in internal medicine, the New England Journal of Medicine is one of the journals you really read. It's not a free throwaway journal or bathroom reading--it's where you find good original research, interesting case studies, cogent editorials. Usually. More or less.

Right now it's "less." A few days ago I posted my review of a recent study on placebos. I found it interesting but somewhat problematic. It's real benefit seems to have been that it has sparked substantive and vigorous discussions about placebos. To save you from reading my entire review, the study basically took asthmatics and gave them either real medicine, fake medicine, "sham" acupuncture, or nothing at all. All the patients reported feeling at least somewhat better, but only the patients treated with real medicine had significant improvement in measured lung function. Another way to state the findings might be "The placebos and the real medicine all made the patients feel better. Oh, and only the real medicine made them actually better." I have a problem with this presentation, as you will read below.

What we've learned about so-called placebos over the years is that "placebo" is not an intervention like a medication or a surgery. It is an artifact of observation. A certain amount of change can be expected any time you study a group of people. "Placebo" is simply all of the change that can't be explained by the primary intervention. Taking the asthma study as an example, simply enrolling people in the study and doing nothing else caused them to feel a bit better. But treating them with real medicine caused them to feel better and get significantly better physically. The bit of "better" that was seen simply by enrolling is referred to as placebo effect, and is a mix of various factors, such as patients' being cared for, regression to the mean, desire to please researchers, and other effects not due to a "real" intervention. It is likely that a good deal of placebo is subsumed in standard care: if you go to the doctor for a broken leg, being cared for and listened to makes you feel better, but setting the bone and placing the cast does most of the work. Good doctors maximize our ability to make people "feel" better along with treating the underlying illness.

The current object of my ire is an editorial published in the Journal to accompany the asthma study. It was written by an anthropologist named Danial Moerman who completely misreads the study, the meaning of placebo, and what a disease actually is. He first fails to understand that there were actually four interventions: "They found that three of the interventions, active albuterol, sham albuterol, and sham acupuncture, were all equally effective in controlling asthma symptoms, as judged by patient-reported improvement. ... The fourth intervention was "no treatment," in which patients were told to wait for several hours and then return home. Waiting had no effect on either subjective asthma symptoms or lung function.

Perhaps I misread the results and the graphs, but it appears to me that the "do nothing" group did in fact report feeling better, just not as much as the other groups. The importance of this lies in the fact that part of the placebo phenomenon is simply being cared for or enrolled in the study (in this case it also involved repeated lung function testing). If this were subtracted out in some way, we might find a much less significant effect. But we are still speaking of "subjective" improvement, an important factor, but not one nearly as important as being able to breathe better.

Professor Moerman, perhaps being used to dealing with less concrete ideas, misses the importance of objective vs. subjective outcomes in medicine. Holding a cancer patient's hand can make them feel better, a lot better in the short term than chemotherapy. But it won't shrink a tumor. Moerman thinks we have it the wrong way 'round: "It is the subjective symptoms that brought these patients to medical care in the first place. They came because they were wheezing and felt suffocated, not because they had a reduced FEV1. The fact that they felt improved even when their FEV1 had not increased begs the question, What is the more important outcome in medicine: the objective or the subjective, the doctor's or the patient's perception? This distinction is important, since it should direct us as to when patient-centered versus doctor-directed care should take place."

First, I hate it when people misuse "begs the question," but that's not important. What's important is that he's asked the wrong question. It's not whether subjective or objective is most important, or whether a "patient-" vs. "doctor-centered" care (whatever that means) is the best model. In medicine, we assess both how a patient feels, and how well they are doing physiologically. We do this in the exam room and we do this in our research. We (meaning doctors and medical scientists) don't think one is "more important" than the other; we know that any intervention is a balance between changing physiology and making a patient feel better. Reading this editorial makes me think of Columbus "discovering" America: it was already here, the folks living here obviously knew it, and he really had no idea where he was anyway.

Another example of his profound ignorance is his complete lack of understanding of common medical conditions: "For subjective and functional conditions, for example, migraine, schizophrenia, back pain, depression, asthma, post-traumatic stress disorder, neurologic disorders such as Parkinson's disease, inflammatory bowel disease and many other autoimmune disorders, any condition defined by symptoms, and anything idiopathic, a patient-centered approach requires that patient-preferred outcomes trump the judgment of the physician."

None of the conditions he mentions above are what he thinks they are. There is nothing "subjective" about the cognitive dysfunction of schizophrenia or the tremors and stiffness of Parkinson's disease. And there are drugs and other physiologic interventions that improve both the way patients feel and objective measures of how they are doing.

It's not so much Moerman's ignorance that disturbs me: anyone can be ignorant. But this piece of idiocy was published in one of the world's most respected medical journals. Well, his ignorance really does disturb me too. He closes with a false dichotomy: "Do we need to control for all meaning in order to show that a treatment is specifically effective? Maybe it is sufficient simply to show that a treatment yields significant improvement for the patients, has reasonable cost, and has no negative effects over the short or long term. This is, after all, the first tenet of medicine: 'Do no harm.'"

As a physician and a patient, I'm unwilling to settle for "no negative side effects over the short or long term." There are no such things as "side effects"; only "effects", some of which we desire, some of which we do not, so risk can only be minimized, never eliminated. The precept is "First, do no harm", not "Do nothing and hope for the best."

Moerman, Daniel E. Meaningful placebos--controlling the uncontrollable. N Engl J Med. 365(2):171-172 (2011). DOI:10.1056/NEJMe1104010.

Peter A. Lipson, ACP Member, is a practicing internist and teaching physician in Southeast Michigan. After graduating from Rush Medical College in Chicago, he completed his internal medicine residency at Northwestern Memorial Hospital. This post first appeared at his blog, White Coat Underground at the Scientopia Blogs network. The blog, which has been around in various forms since 2007, offers "musings on the intersection of science, medicine and culture." His writing focuses on the difference between science-based medicine and "everything else," but also speaks to the day-to-day practice of medicine, fatherhood, and whatever else migrates from his head to his keyboard.