[edit ] Modern clinical application

Experimenters typically use placebos in the context of a clinical trial. in which a "test group" of patients receives the therapy being tested, and a "control group " receives the placebo. It can then be determined if results from the "test" group exceed those due to the placebo effect. If they do, the therapy or pill given to the "test group" is assumed to have had an effect. The first well documented use of a placebo in a clinical trial was reported in "Streptomycin treatment of pulmonary tuberculosis". BMJ 1948;2:769--782, a research paper by the Medical Research Council. Thus, if a therapy or medicine has no effect beyond placebo, then it is said to have no effect or efficacy beyond non-specific effects.

[edit ] Confounders mistaken for placebo effect

Due to the difficulty in ascribing causation, many phenomena overlap with — and can thus mistakenly be included in — statistics on the placebo effect:

Natural termination of the disease process. Regression to the mean. Cyclical presentation of the disease. Errant diagnosis or prognosis. Temporary improvement confused with cure.

[edit ] Objective or subjective effects?

Hrobjartsson and Götzsche published a study in 2001 and a follow-up study in 2004 questioning the nature of the placebo effect. (Hrobjartsson 2001, Hrobjartsson 2004) They performed two meta-analyses involving 156 clinical trials in which an experimental drug or treatment protocol was compared to a placebo group and an untreated group, and specifically asked whether the placebo group improved compared to the untreated group. Hrobjartsson and Götzsche found that in studies with a binary outcome, meaning patients were classified as improved or not improved, the placebo group had no statistically significant improvement over the no-treatment group. Similarly, there was no significant placebo effect in studies in which objective outcomes (such as blood pressure) were measured by an independent observer. The placebo effect could only be documented in studies in which the outcomes (improvement or failure to improve) were reported by the subjects themselves. The authors concluded that the placebo effect does not have "powerful clinical effects," (objective effects) and that patient-reported improvements (subjective effects) in pain were small and could not be clearly distinguished from bias.

These results suggest that the placebo effect is largely subjective. This would help explain why the placebo effect is easiest to demonstrate in conditions where subjective factors are very prominent or significant parts of the problem. Some of these conditions are headache, stomachache, asthma, allergy, tension, and the experience of pain, which is often a significant part of many mild and serious illnesses.