Factors Associated With Placebo Treatment Response in Functional Dyspepsia Clinical Trials

INTRODUCTION: Controlling for potential placebo effects is an important aspect of gaining an accurate estimate of how much the therapy alone changes patient symptoms or other end points. When the placebo effect is large, this can lead to only a small fraction of changes seen in the active therapy group being attributed to the therapy itself. This problem has been well studied in some disorders of brain-gut interaction but not in functional dyspepsia where placebo response rates of 40% and higher have been reported. Understanding risk factors for placebo response might lead to changes in trial design that could reduce the magnitude of the problem. This study sought to identify risk factors for the placebo effect in a functional dyspepsia clinical trial with a longer-term aim of suggesting trial design changes that might minimize the problem.METHODS: A secondary analysis of the clinical trial data was undertaken using 2 arms deemed to involve placebo therapy. Potential predictors were drawn from a wide range of patient characteristics including psychological, clinical, and physiological features.RESULTS: Predictors of a stronger placebo effect on the gastrointestinal symptom rating scale included higher functional dyspepsia symptom burden at baseline (b = -0.101), coexisting irritable bowel syndrome (b = -0.436), and higher scores on the Nepean Dyspepsia Index eat/drink domain (-0.005). Baseline symptom burden and coexisting irritable bowel syndrome were found to be independent placebo predictors, explaining 13% of the variance in change in gastrointestinal symptom rating scale. Anxiety, childhood sexual abuse, sleep amount, and frequent abdominal pain were also found to be predictors of change in individual symptom scores.DISCUSSION: The findings of this study yield actionable insights into trial methodology that may help to reduce the magnitude of the placebo effect in future functional dyspepsia treatment trials.