If only they knew! A non‐inferiority randomized controlled trial comparing deceptive and open‐label placebo in healthy individuals

Abstract

BackgroundPlacebo use is widespread in clinical practice. However, they are most often administered deceptively rather than openly. It is often suggested that open‐label placebos (OLP) are less effective than deceptive placebos (DP). This study aimed to compare the use of DP and OLP treatments to reduce pain in healthy volunteers.MethodsWe conducted a non‐inferiority, parallel, randomized, controlled trial, which also included a nested cross‐over no‐treatment condition. This study was conducted at a university clinic in France.ResultsWe included 60 subjects and the main result shows that the OLP was not inferior to the DP by a margin of 10 mm. The mean difference between both groups regarding intensity of pain was 0.7 mm with a 95% compatibility interval (95% CI) of ]−∞; 5.4], and 97.5% CI of ]−∞; 6.3]. Secondary outcomes require cautious interpretation of the effect of placebo versus no treatment due to a time–treatment interaction.ConclusionThe study indicates that OLP may perform just as well as DP and could provide support for the use of OLP as an ethical alternative to DP when they are to be used in a clinical setting. If only patients knew about the placebo nature of some treatments they are receiving, unnecessary lies could be avoided while maintaining similar placebo effects.SignificanceThis study is the first to show non‐inferiority of placebos administered honestly, also called OLP, compared to DP in reducing pain. This suggests that OLP could be as effective as their deceptive counterparts while having the ethical advantage of not being required to lie. If deception is not a necessary condition for efficacy, OLP should be preferred over DP.

Rethinking placebo: Exploring the effectiveness of open‐label placebos

“…This journal recently published a paper by Druart et al (2023), 'If only they knew! A non-inferiority randomized controlled trial comparing deceptive and openlabel placebo in healthy individuals'.…”

“…The study by Druart et al (2023) pioneers noninferiority testing between OLP and DP effects and reveals that OLP is not inferior to DP. However, in one out of two comparisons between placebo (both OLP and DP) and control conditions, no significant differences were found, meaning that the placebo effects were not clear.…”

“…In conclusion, the study by Druart et al (2023) opens a new avenue for investigating the effectiveness of OLP; it calls for not only replication but also intensified studies to uncover the mechanisms of OLP and understand patient perspectives. These future studies hold promise for developing effective and acceptable OLP interventions for individuals suffering from acute and chronic pain.…”