Why use placebos in clinical trials? A narrative review of the methodological literature

Researchers have a number of different options for their choice of control or comparison intervention in randomized trials. We surveyed the methodological literature looking for reasons why a researcher might choose to administer a placebo (i.e., a mimic intervention) to control subjects. Two implicit assumptions were that the issue of placebo is pertinent only to drug trials and that the nonplacebo effect of a treatment is the "real" or "true" effect. Explicit reasons given in the literature for the use of placebos were facilitating blinding and controlling for the placebo effect. The importance of the latter was often inadequately argued. Reasons to avoid placebos in controlled trials, other than ethics and feasibility, are that placebos do not inform real decisions, and may interfere with accurate estimation of effect size and with nonspecific aspects of treatment. Placebo-controlled trials have high internal validity but may be difficult to apply to clinical practice; the situation is reversed for trials without placebo control.