Biology 202

2002 Second Web Report

On Serendip

The purpose of this paper is to investigate whether the Placebo Effect is overestimated through misinterpretation of the data. Specifically, the objective is to explore whether the passage of time during clinical trials accounts for many results widely attributed to the placebo effect. That is, the passage of time in itself-through a combination of spontaneous changes in symptoms, regression effects, and homeostatic changes-produces most of the favorable results credited to the placebo.

Despite its widespread acceptance for approximately fifty years, the Placebo Effect has recently become controversial, with several researchers claiming that the presumed benefits of placebos are overestimated. Dr. Asbjorn Hrobjartsson and Dr. Peter C. Gotzsche of the University of Denmark and the Nordic Cochran Center reviewed journal articles looking for the original research stating that 35% of patients improve if given a placebo. Interestingly, none of the papers they examined included original research on the placebo effect, but all cited the same reference. The original source was a 1955 article, "The Powerful Placebo," published in the Journal of the American Medical Association and written by Henry Beecher, chief of anesthesiology at Massachusetts General Hospital in Boston. Dr. Beecher had analyzed about a dozen studies and had come up with the 35% figure (1).

Challenging the validity of this finding, Drs. Hrobjartsson and Gotzsche hypothesized that two important factors were ignored. First, that the natural course of many diseases is to wax and wane. Second, that a patient who feels terrible one day will almost certainly feel better the next day.

Hrobjartsson and Gotzsche analyzed 114 studies conducted between 1946 and 1998 that used not the usual two, but three groups of patients. One group received appropriate medical treatment, one group received placebo treatment, and the third group received nothing. (The studies involved 7,500 patients with 40 different medical conditions, including high blood pressure, high cholesterol levels, asthma, behavior disorders, such addictions as alcohol abuse and smoking, and such neurological diseases as Alzheimer's Disease, Parkinson's Disease, epilepsy, as well as bacterial infections and the common cold (5). As Hrobjartsson and Gotzsche predicted, the patients in this third group improved as often as the patients in the placebo group (1).

Carol Hart (2) cites Shapiro and Shapiro, who offer possible confounds that lead to overestimation of the placebo effect. Observations of the third control group-the group with neither treatment, nor placebo-may have improved because of three mechanisms. The first possibility was Spontaneous Improvement. Chronic pain conditions or mood disorders wax and wane, and often show improvement with no provocation (3). Patients may choose to enter treatment or a medical trial when the symptoms of the complaint have reached a high degree of variability. Pain, depression, cholesterol levels may have peaked, and, thereafter, improvement may follow without any intervention.

The second possibility was Fluctuation of Symptoms, particularly Regression to the Mean, the tendency for random increases or decreases to be followed by observations closer to the average (3). When a patient is in great pain on day #1, it is possible that the pain may diminish somewhat on day #2. Very bad experiences are followed by improved experience. Rheumatoid Arthritis and Multiple Sclerosis are examples of diseases whose symptoms may change from day to day (4). Regression accounts for natural and inevitable fluctuations. Periods of pain are followed by periods of remission of pain. The intensity and duration of pain from arthritis, chronic backache, gout, and other illnesses, fluctuate, and eventually move toward the average-away from the extremes. [Sir Francis Galton, in a study in 1885, coined the term regression in a study called Regression Toward Mediocrity in Heredity Stature, which was a study of average heights of sons of very tall and very short parents (5).]

A third possibility to account for the improvement of symptoms with no intervention is the body's natural process to achieve a state of homeostasis. This natural occurrence precipitates Time Based Healing. The body will attempt to repair itself. Illnesses and injury often heal spontaneously as the body's immune and hormonal systems act to regulate and return the body to a healthy state (4). Except for extreme illnesses and severe conditions, most ailments are self-limiting and improve with time, regardless of treatment. There is a common saying: If you treat a cold, the symptoms will last for a week, but if you leave it alone, the cold will be gone in seven days. Even serious diseases have periods of exacerbation and remission. Some cancers inexplicably disappear. The main logical error (fallacy) in plotting disease progress is known by the Latin expression post hoc, ergo propter hoc-after it; therefore because of it (6). Spontaneous healing occurs because something inside the body causes a major response in the immune system. The dozens of types of white blood cells produced by our lymphatic system, spleen, and thymus literally flood the body and attack everything that is foreign and might cause illness (7).

If new studies show that the Placebo Effect is overestimated, then its apparent benefits may be attributable to the passage of time. Placebos are best known for their use as inactive substitute treatments in randomized clinical trials of drugs. Placebos are meant to provide a benchmark for measuring the efficacy of those compounds, but instead often confound results by seeming to be effective themselves. Placebos do not help disease, only the way patients perceive disease (8).

A variety of researchers have argued that a combination of expectancy (suggestion) and endorphin release accounts for the benefits of placebos. Still others believe that the researchers in a double blind study may be exhibiting a Hawthorne Effect, an increase in productivity, merely because they are involved in an investigation, which affects patient outcomes (9).

Indeed, many holistic and alternative therapies are generally held to be based upon the phenomenon of the placebo effect. If the hypothesis in this report is true, then one must be skeptical toward the variety of holistic and alternative therapies available that claim to exploit the Placebo Effect for the benefit of patients. According to Lawrence Sullivan, a historian of religion at the Harvard Divinity School, the placebo is a "toxic waste site, nobody wants to own it. Even shaman and witch doctors would be offended by the idea that their healing powers depended on the Placebo Effect" (8).

Some interesting background information: The word, placebo entered the English language through a particular mistranslation of the 116th Psalm that read "I will please the Lord" rather than "I will walk before the Lord." In the medieval Catholic liturgy, this verse opened the Vespers for the Dead; because professional mourners were sometimes hired to sing vespers, "to sing placebos" came to be a derogatory phrase describing a servile flatterer. By the early 19th century, "placebo" had come to mean a medicine given "more to please than to benefit the patient" (2).Outside the context of modern clinical trials, "placebo" has been a term reserved for characterizing the substandard practices of other less ethical or knowledgeable healers. Using treatment drugs that have no efficacy against an ailment is considered by some another form of placebo. For example, some physicians today will prescribe antibiotics for viral colds and flu, because the patient requests them, even though the physician knows that the antibiotics are useless in treating viral infection (2). The dangers that exist within the belief that placebos have curative powers have allowed charlatans and alternative curative practices to perpetrate a fraud on the gullible.

WWW Sources

2) MDD July 1999: The Mysterious Placebo ,

3) Spontaneous Remission and the Placebo Effect ,

4) The Placebo Effect ,

5) Regression and the Regression Fallacy ,

6) Skeptical Inquirer/January/1997/ The Mysterious Placebo ,

7) Health News Network-The Placebo Effect ,

8) Mind, Brain, Behavior: The Pleasing Placebo ,

9) Clinical Research-Journal of Prosthetics and Orthotics ,

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