The placebo response in functional dyspepsia – reanalysis of trial data P. ENCK,* B. VINSON,  P. MALFERTHEINER, à S. ZIPFEL* & S. KLOSTERHALFEN*, § *University Hospital, Department of Psychosomatic Medicine, Tu ¨ bingen, Germany  Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany àOtto-von-Guericke-University, Department of Internal Medicine, Magdeburg, Germany §University of Du ¨ sseldorf, Institute for Clinical Neurosciences and Medical Psychology, Du ¨ sseldorf, Germany Abstract Clinical trial data rarely identify factors contributing to the placebo response. We reanalysed the data from the placebo arm (n = 157) of a func- tional 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. Keywords body mass index, drug trial, functional dyspepsia, placebo response, smoking. BACKGROUND Placebo response rates are thought to be high in functional bowel disorders (FBD). 1 They can range from 5% to 85% in the irritable bowel syndrome (IBS) 2 and in functional dyspepsia (FD), 3 whilst in inflamma- tory bowel diseases (IBD) 4,5 this is much less the case (20% to 40%). It appears, therefore that the placebo response is not higher but more variable between FBD study, and responders may represent a subsample of patients prone to psychological interventions, psycho- therapy and placebo treatment. 6 It has been speculated that this may be due to variance in trial duration, patient selection, recruit- ment issues and other study design factors. 7 However, as we showed recently, 1 the only reliable factor explaining variability in response rates was the number of subjects included in the study: with the placebo response averaging around 40% in studies with high patient numbers (n > 250), in trials lasting up to 1 year, 8 and with similar magnitudes in IBS trials with alternative medicines. 9 Several attempts have been made to identify predic- tors of the placebo response in FBD clinical trials, either using meta-analysis of published trials 9–11 or statistical reanalysis of previously published data. 12,13 Neither approach has produced consistent results. Whilst the two IBS meta-analyses completed 10,11 both identified the number of doctor visits during a trial as a potential predictor of the placebo response, they came to opposite conclusions with respect to the direction of the effect. In IBD trials, higher placebo Address for correspondence Professor Dr Paul Enck, University Hospitals Tu ¨ bingen, Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, Frondsbergstr 23, 72076 Tu ¨ bingen, Germany. Tel: +49 7071 29-89118; fax: +49 7071 29-4382; e-mail: paul.enck@uni-tuebingen.de Received: 19 September 2008 Accepted for publication: 29 October 2008 Neurogastroenterol Motil (2009) 21, 370–377 doi: 10.1111/j.1365-2982.2008.01241.x Ó 2009 The Authors Journal compilation Ó 2009 Blackwell Publishing Ltd 370