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

J Clin Epidemiol. 2011 Nov;64(11):1223-9. doi: 10.1016/j.jclinepi.2011.01.008. Epub 2011 Apr 23.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bias
  • Humans
  • Magnetic Resonance Imaging
  • Patient Dropouts
  • Placebo Effect*
  • Placebos
  • Positron-Emission Tomography
  • Publication Bias*
  • Randomized Controlled Trials as Topic / statistics & numerical data*
  • Research Design*
  • Research Subjects / psychology
  • Treatment Outcome


  • Placebos