March/April  2004

The Zen of Science

The placebo effect
By MARC RINGEL, MD

      "Red clover and placebo equally reduce the frequency of hot flushes. Providers should encourage patients to avoid spending money on supplements and instead add soy to their diet. In general, however, if patients are already convinced that something works, donıt discourage them [italics added]." - Journal of Family Practice, November 2003

      Dr. Andrea Gordon is the author of the above review of an article entitled "Phytoestrogen Supplements for the Treatment of Hot Flashes: The Isoflavone Clover Extract (ICE) Study: A Randomized Trial" that appeared recently in the Journal of the American Medical Association. Though they may not sound so to you, Gordonıs words are revolutionary. Let me deconstruct them.

      The ICE study compared menopausal symptoms of patients given extracts of the red clover plant, a rich source of plant-derived estrogen-like substances (phytoestrogens, also found in soy products) to symptoms experienced by patients who received an inactive placebo. Who got red clover and who got placebo was determined by a random process, like a coin toss, making this a randomized trial, as the report title states.

      Neither patient nor researcher knew who got what. This is called a double blind design, the gold standard for clinical research. Blinding both subject and scientist as to who receives the treatment and who the placebo minimizes the role that expectations of either patient or doctor might play in the outcome.

      Expectations to get better are lumped under the term "placebo effect." This phenomenon is not limited to little green sugar pills that make neurotic headaches go away. Placebo effect figures in virtually every health-related activity. Studies have shown, for example, that at least half of the pain relief produced by narcotics is attributable to patientsı anticipation that they will feel better.

      At the end of a double-blind trial, researchers break the code that kept them ignorant of the identities of intervention and placebo subjects, and the outcomes of the two groups are compared and analyzed statistically. The investigators should then be able to say, objectively, whether a treatment worked on the population studied and to predict whether it would be effective when administered to other patients similar to the ones in the report.

      Double blind design is how the scientific method wrings subjective content out of medical study findings. By adhering to the precepts of objective research, scientists minimize the placebo effect. In the study quoted above, if red clover extracts had been found to reduce menopausal symptoms, the authors could have concluded that the herb had an objective effect on these symptoms, not attributable to either the patientsı or the doctorsı expectation that the herbal substance would help.

      Too bad for the purveyors of red clover that the ICE study found no significant difference in incidence of hot flashes between treatment and placebo groups. Still, Gordon suggests that her physician readers "not discourage [patients]" who "are already convinced that something works" from taking it, in this case, red clover.

      Physicians are not just trained in the scientific method, we are basted in it. Throughout four years of medical school plus three or more years of post-graduate education, doctors-in-training endlessly analyze, weigh and apply medical studies to clinical practice. We learn to despise the placebo effect for being a confounder of real scientific fact.

      When Gordon refuses to condemn red clover extract in the face of convincing objective evidence that it doesnıt work, she is going against all of her medical training. Thatıs why I called her words "revolutionary." If red clover helps a woman with menopausal symptoms, never mind that the effect may be pure placebo, Andrea Gordon says she should take it. After all, the ultimate goal of our profession is not to apply scientifically validated evidence. It is to do what we can to help people be healthier and feel better.

      Traditional medicine is not nearly so scientific as we doctors would like to believe. Commentators have estimated that no more than a quarter of current standard practice is backed by the sort of objective evidence that medical science strives for. Even practices that are based on well-designed studies are subject not just to change, but to complete reversals of direction. The majority of what we doctors do is based on scientific deduction, tradition, personal experience and intuition, not on hard facts.

      Thanks to the scientific method, medicine has accomplished some truly incredible things, like eradicating smallpox, curing appendicitis, and transplanting kidneys. But the emphasis on science has its costs too. In our obsession to advance medical care by applying the lessons of objective truth weıve lost sight of the subjective truth of human life. Itıs way too easy for me, a doctor, as the self-appointed arbiter of objectivity, to tell my patient, "Stop taking red clover. Iıve read the latest study about it in the Journal of the American Medical Association, and it doesnıt work." What if, for that patient, it does work?

      The definition of placebo effect that I like best is, "A change in the patientıs health or bodily state that is attributable to the symbolic impact of medical treatment or the treatment setting." In other words, "placebo," is a synonym for "meaning." Meaning is not an aberration to be ruled out of the healthcare equation, but an absolutely crucial part of caring for a real, whole person.

      When I hand a patient a penicillin prescription for strep throat, I donıt say, "Here. This may or may not help you get better faster." I say, "Here. Penicillin is just the right antibiotic for the strep bug. You should feel better real soon." When I give diet instruction to the parent of a toddler with diarrhea, I write it down on a prescription form. Even though my scratchings donıt specify something to be filled by a pharmacist, the prescription form itself is a symbol of my power as a doctor, power to heal.

      Do my choice of words and notepad contribute to the placebo effect? You betcha. Do my patients get better faster? Though I suspect so, I donıt know for sure. Iıd have to do a scientific study to find that out.

      It is imperative to study by rigorously applied scientific method everything medical that we possibly can. When we shed the light of scientific scrutiny on traditional as well as alternative medical practices we will probably uncover a whole lot of placebo effect in both. No one can predict what will and wonıt show objective value.

      Traditional medicine is just getting around to investigating seriously the placebo effect. In many reputable published studies three-quarters of patients have gotten better with placebo pills. There is even a placebo effect in surgery. One report comparing patients who underwent arthroscopic knee surgery with patients who were anesthetized and got three scalpel wounds around the knee that didnıt even enter the joint space, found comparable functional improvement between the patients who received real operations and sham ones.

      When I see my acupuncturist, I am always impressed by the healing properties of his office: quiet; the smell of moxa; muted colors; well placed lighting; pretty magazines; trickling miniature fountain; a play zen garden, complete with miniature wooden rake. The space reminds me of the origin of the word "placebo," a conjugation of the Latin verb placere, meaning, "I shall please." Just being in Fredıs office pleases me and begins the healing, before Iıve been stuck with a single needle.

      By saying itıs okay to take red clover even though it might not work, Dr. Andrea Gordon has struck a small blow for personal meaning against the objectification of modern medicine. Sir Robert Hutchison, an English physician, was 82 years old when he wrote, "Sfrom too much zeal for what is new and contempt for what is old; from putting knowledge before wisdom, science before art; and cleverness before common sense; from treating patients as casesS Good Lord, deliver us."

      Marc Ringel, MD, is a family practitioner and writer based in Greeley, Colorado.