Abstracts Division 2
30. Placebo response in pharmacological trials in patients with functional dyspepsia - a systematic review and meta-analysis
M. Bosman, MD1, F. Smeets, MD, PhD1, S. Elsenbruch, PhD2, J. Tack, MD, PhD3, M. Simrén, MD, PhD4, N. Talley, MD, PhD, FRACP, FAHMS5, B. Winkens, PhD6, A. Masclee, MD, PhD1, D. Keszthelyi, MD, PhD1.
1Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center, The Netherlands. 2Department of Medical Psychology and Medical Sociology, Faculty of Medicine, Ruhr University Bochum, Germany; Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany.
3Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University of Leuven, Belgium; Division of Gastroenterology and Hepatology, University Hospitals Leuven, Belgium.
4Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden; Centre for Functional GI and Motility Disorders, University of North Carolina, United States.
5NHMRC Center of research Excellence in Digestive Health, University of Newcastle, Australia.
6Department of Methodology and Statistics, Care and Public Health Research Institute, Faculty of Health, Medicine, and Life Sciences, Maastricht University, The Netherlands.
Background
Pharmacological trials in functional dyspepsia (FD) are associated with high placebo response rates. We aimed to identify the
magnitude and the contributing factors to the placebo response.
Methods
We conducted a systematic review and meta-analysis including randomized controlled trials
(RCTs) with a dichotomous outcome in adult patients with FD that compared an
active pharmacotherapeutic treatment with placebo treatment. Our main outcome
was identification of the magnitude of the pooled placebo response rate for the
following endpoints: symptom responder, adequate relief responder, and combined
endpoint responder (ie, the primary endpoint of each specific trial regarding
treatment response). Several putative moderators were examined, including patient,
disease, and trial characteristics.
Results
Of the 9829 publications identified, 25 RCTs were included in our analysis. The pooled placebo response rate was 33.4% (95%
CI 26.9-40.6) using the symptom responder definition, 37.6% (32.1-43.5) using
the adequate relief responder definition, and 35.6% (31.5-40.0) using the
combined endpoint responder definition. A lower overall baseline symptom score
was significantly associated with a higher placebo response rate. No other
moderators were found to significantly impact the placebo response rate. Due to
lack of data, no analyses could be performed according to individual FD
subtypes or symptoms.
Conclusion
The pooled placebo response rate in pharmacological trials in FD is 33-38% depending on the
responder definition. Future trials should consider applying an entry criterion
based on minimal level of symptom severity in order to decrease the placebo
response. We also suggest separate reporting of the core FD symptoms pending
more concrete harmonization efforts in FD trials.
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