Placebo Response In Clinical Trials: Challenges And Mitigation

By Gary Sachs, MD, Juliet Brown, PhD, Marcela Roy, MA, & Alex Pavel, MD, PhD

Placebo response presents a significant challenge in clinical trials, contributing to failures and financial losses, particularly in regions like the U.S. The placebo effect refers to positive outcomes in participants receiving an inactive treatment, while the nocebo effect leads to adverse symptoms from the same treatment. Both are real phenomena influenced by various biopsychosocial factors, including participant genetics and site practices. The complexity of placebo response necessitates tailored, culturally sensitive mitigation strategies. Cultural differences impact expectations and participant interactions, affecting trial outcomes. This article explores how effective strategies involve understanding and addressing both true and pseudo-placebo responses through thoughtful study design, training of research staff, and culturally adapted communication.