Placebo control

Definition

A placebo is an inert substance (such as a sugar pill or saline injection) that has no pharmacological activity. A placebo control is a comparison group of research participants who receive a placebo instead of the active investigational treatment. The use of a placebo control group allows researchers to distinguish between the true biological effects of an active treatment and placebo response (improvement due to expectation, attention, or natural history of disease). In many conditions, placebo responses are substantial; for example, in pain or depression studies, 30-50% of placebo recipients may report improvement. Without a placebo control group, it is impossible to determine what portion of observed improvement is due to the active compound versus placebo response. Double-blind placebo-controlled trials are considered the gold standard for evaluating treatment efficacy. However, placebo controls are not always ethical or appropriate; if an effective treatment already exists for a serious condition, giving some patients a placebo instead of the existing treatment may be unethical. In such cases, active comparator trials (comparing the new treatment to the existing standard treatment) may be used instead.

Placebo responses are mediated through physiological mechanisms involving expectation and the nervous system; they are not merely 'in the head' but involve measurable physiological changes. Understanding and controlling for placebo responses is essential for credible drug evaluation. Strict placebo controls work only when the placebo is indistinguishable from the active treatment in appearance, taste, and administration method. For injectable compounds, this may mean using identical syringes and injection sites.

Ethics committees carefully consider whether placebo controls are acceptable in clinical trials. Placebo controls are generally acceptable when (1) no effective treatment exists, (2) the condition is minor or self-limiting, or (3) the new treatment is not expected to be dramatically more effective than current standard treatment. For serious conditions with existing effective treatments, placebo-controlled trials are generally not approved, and comparisons to the existing standard treatment are required instead. In research peptide trials, investigators must justify the use of placebo controls to ethics committees before commencing the study.