Enhancing Assay Sensitivity in Chronic Pain Clinical Trials Through Placebo Lead-in Design

Music City Center 

Placebo response in chronic pain clinical trials presents a significant challenge to demonstrating treatment efficacy, often obscuring potential therapeutic benefits of investigational analgesics. High placebo response rates in chronic pain studies are attributed to multiple factors, including heightened expectation effects, trial design elements, and participant characteristics. These factors encompass conditioning from previous treatment experiences, intensive contact with healthcare providers, regression to the mean, natural symptom fluctuation, and psychological factors. This work examines how implementing a placebo lead-in design can enhance assay sensitivity by identifying and stratifying participants based on their initial placebo response patterns. The placebo lead-in approach involves an initial blind placebo phase before randomization, based on pre-specified criteria, participants are then stratified into "placebo responders" and "non-responders" before randomization to active treatment or control arms. This methodology helps identify participants whose responses may confound treatment effects and enables more balanced allocation of placebo responder across treatment arms

Placebo lead-in, enrichment design, signal detection, chronic pain clinical trial 

Biopharmaceutical Section