Meta-analysis: the effects of placebo treatment on gastro-oesophageal reflux disease.Cremonini F, Ziogas D, Chang HY, Kokkotou E, Kelly J, Conboy L, Kaptchuk TJ, Lembo AJ. Aliment Pharmacol Ther. 2010 Mar 26. [Epub ahead of print] Background: Gastro-oesophageal reflux disease (GERD) is a common chronic condition effectively treated in most patients with proton pump inhibitors (PPI) or H(2)-receptor antagonists (H2RA). There appears to be a significant placebo response rate in clinical trials for GERD. Despite this, little is known about the determinants and the circumstances associated with placebo response in the treatment of GERD. Aim: The purpose of this study is to estimate the magnitude of the placebo response rate in randomized controlled trials (RCTs) for GERD and to identify factors that influence this response. Methods: We performed a meta-analysis of published, English language, randomized, double-blind, placebo-controlled trials that included 20 or more patients with GERD who were treated with either a proton-pump inhibitor or H(2)-receptor antagonist for at least 2 weeks. Medline, Cochrane and EMBASE databases were searched. We considered only studies that reported a global response for ‘heartburn’. Eligible studies were synthesized using meta-analysis methods, including cumulative meta-analysis. Heterogeneity and study quality issues were explored. Results: 24 studies were included with 9,989 total patients with GERD. The pooled odds ratio (OR) for response to active treatment versus placebo was 3.71 [95% CI: 2.78-4.96]. The pooled estimate of the overall placebo response was 18.85% [range 2.94% – 47.06%]. Patients with erosive esophagitis had a non-significantly lower placebo response rate than patients without it (11.87% and 18.31%, respectively; p = 0.246). Placebo response was significantly lower in studies of PPI therapy versus studies of H(2)-receptor antagonists (14.51% vs. 24.69%, respectively; p=0.05). Conclusion: The placebo response rate in randomized controlled trials for GERD is substantial, although lower than that reported in other disorders of gastrointestinal function. A lower placebo response was associated with the testing of proton pump inhibitors, but not with the underlying presence of erosive esophagitis.