Modulating Placebo Effects in Clinical Trials: Study Team Briefing to Optimize Drug–Placebo Differences

Clinical trials often face challenges with placebo effects that can mask actual drug effects. We evaluated whether briefing the study team members on placebo mechanisms influenced analgesia. In this study, we compared the analgesic effects of oxycodone and placebo in three groups of 32 subjects. The groups were treated by an untrained study team (Arm A), a team trained to maximize (Arm B) and a team trained to minimize placebo effects (Arm C). The primary outcome was the reduction of pain during the cold pressor test, assessed by the area under the pain curve of the visual analog scale before and after blinded administration of oxycodone or placebo. Oxycodone and placebo demonstrated the expected differences in pain reduction across all study arms. Briefing the study team did not significantly affect pain reduction or treatment expectation, regardless of treatment. However, treatment expectations were more pronounced with oxycodone compared to placebo, showing a positive correlation of expectation and treatment effect only in the oxycodone group, possibly reflecting the influence of unblinding due to adverse effects. These findings suggest that a brief training of the study team may not be sufficient to alter treatment expectations and placebo analgesia. This insight will inform future efforts to apply placebo research to optimize blinded trial design and drug treatments in clinical settings. Trial Registration: DRKS 00013586 (German Clinical Trials Register), registered on December, 22nd 2017; URL: https://www.drks.de/drks_web/setLocale_EN.do.