Participant expectancies in double-blind randomized placebo-controlled trials: potential limitations to trial validity

Abstract

Background Randomized controlled trials (RCTs) that use placebo controls to achieve double-blinding intend to establish the efficacy of a treatment over and above expectancy and other forms of bias. Despite this, a growing body of research suggests that participant expectancies can influence the outcomes of these trials. Purpose and Methods This nonsystematic review examines research assessing the role of participant expectancies in double-blind placebo-controlled RCTs in order to determine if and how they can limit these types of trials. Results There appear to be at least three ways in which participant expectancies can limit the validity of double-blind placebo-controlled RCTs. First, when blinding fails researches cannot determine whether any observed improvement in the group receiving active treatment resulted because of the treatment’s effect or because of participants’ expectancies. Second, participant expectancies could create ceiling effects if there are strong placebo effects in each treatment arm and this may falsely suggest that the active treatment is ineffective without expectancy. Third, the knowledge that a participant will be allocated active treatment or placebo in double-blind placebo-controlled RCTs is likely to lead to weaker treatment responses than would be expected in standard clinical practice, in which patients are unlikely to doubt that they have been given an active treatment. Conclusions Participants’ expectancies can undermine the validity of double-blind placebo-controlled RCTs. Researchers conducting these trials should assess participants’ beliefs about their treatment allocation and actively investigate if and how these beliefs may have influenced the trial’s outcome. Clinical Trials 2010; 7: 246—255. http://ctj.sagepub.com