Placebo effect studies are susceptible to response bias and to other types of biases

Objective: Investigations of the effect of placebo are often challenging to conduct and interpret. The history of placebo shows that assessment of its clinical significance has a real potential to be biased. We analyze and discuss typical types of bias in studies on placebo. Study Design and Setting: A methodological analysis and discussion. Results: The inherent nonblinded comparison between placebo and no-treatment is the best research design we have in estimating effects of placebo, both in a clinical and in an experimental setting, but the difference between placebo and no-treatment remains an approximate and fairly crude reflection of the true effect of placebo interventions. A main problem is response bias in trials with outcomes that are based on patients' reports. Other biases involve differential co-intervention and patient dropouts, publication bias, and outcome reporting bias. Furthermore, extrapolation of results to a clinical settings are challenging because of a lack of clear identification of the causal factors in many clinical trials, and the nonclinical setting and short duration of most laboratory experiments. Conclusions: Creative experimental efforts are needed to assess rigorously the clinical significance of placebo interventions and investigate the component elements that may contribute to the therapeutic benefit. (C) 2011 Elsevier Inc. All rights reserved.