The placebo response in functional dyspepsia – reanalysis of trial data

Abstract

Clinical trial data rarely identify factors contributing to the placebo response. We reanalysed the data from the placebo arm (n = 157) of a functional dyspepsia (FD) trial to determine predictors of placebo response including total GIS score, change in GIS score during run-in, type of FD symptoms, duration of illness, age, gender, body mass index (BMI), family occurrence of FD-like symptoms, smoking and alcohol consumption. The same response criteria were applied to the drug arm (n = 158) of the study. Based on the initial 40% response criterion of the study, 35 (22.2%) were classified as placebo responders (PR), whilst 122 (78.8%) were placebo non-responders (PnR). Response rates for the drug arm were 41.1 and 56.9% respectively. PR had significantly lower GIS scores compared to PnR at visit 1 (10.6 +/- 0.6 and 12.3 +/- 0.4, respectively, P = 0.035), but not at visit 2 with study medication dispensing (10.9 +/- 0.5 and 11.3 +/- 0.4). Hence, PR symptoms increased during run-in by 4.2% whilst PnR symptoms decreased by 6.3% (P < 0.005). Gender, age and duration and type of FD symptoms were not different between PR and PnR. Smoking was less prevalent in PR (3%) compared to PnR (21%) (P < 0.025). Increasing the criteria for the placebo response resulted in higher BMI for PR than for PnR (P = 0.035). None of the predictors for placebo response were able to distinguish responders from non-responders to the drug. Variables predicting the PR point towards behavioural and biological mechanism of the PR, operating simultaneously and independently.