The roles of expectation, comparator, administration route, and population in open-label placebo effects: a network meta-analysis.

Three meta-analyses have demonstrated the clinical potential of open-label placebos (OLPs). However, there is a need to synthesize the existing evidence through more complex analyses that would make it possible to answer questions beyond mere efficacy. Such analyses would serve to improve the understanding of why and under what circumstances OLPs work (e.g., depending on induced expectations or across different control groups). To answer these questions, we conducted the first network meta-analyses in the field of OLPs. Our analyses revealed that OLPs could be beneficial in comparison to no treatment in nonclinical (12 trials; 1015 participants) and clinical populations (25 trials; 2006 participants). Positive treatment expectations were found to be important for OLPs to work. Also, OLP effects can vary depending on the comparator used. While the kind of administration route had no substantial impact on the OLP effects, effects were found to be larger in clinical populations than in nonclinical populations. These results suggest that the expectation, comparator, administration route, and population should be considered when designing and interpreting OLP studies.