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Pre-cebo: An Unrecognized Issue in the Interpretation of Adequate Relief During Irritable Bowel Syndrome Drug Trials

Kim, Sharon E. MD; Kubomoto, Scott MD; Chua, Kathleen BHS; Amichai, Meridythe M. BS; Pimentel, Mark MD, FRCP(C)

Journal of Clinical Gastroenterology:
doi: 10.1097/MCG.0b013e31825828a7
ALIMENTARY TRACT: Original Articles
Abstract

Objectives: In drug trials involving subjects with irritable bowel syndrome (IBS), the placebo effect seems to be very important. However, events even before starting the study may also impact patient expectations. In this study, we utilized consent language from prior studies of diarrhea predominant IBS (D-IBS) drug trials to determine whether the knowledge imparted during this process affects the response to different therapies.

Methods: Consecutive IBS subjects who met the Rome III criteria for IBS were enrolled. Patients were presented with a mock trial and randomized to 1 of 3 questionnaires with consent using similar language from consent forms of 3 drugs used in D-IBS: desipramine, alosetron, and rifaximin. Demographics, IBS symptoms using visual analog scale, and percent improvement needed for patients to report adequate relief of IBS from theoretically taking their assigned drug was asked. Data were expressed as mean±SE.

Results: Subjects who were anticipating rifaximin had the highest expectation of improvement to determine adequate relief of 87.3±10.9% compared with 73.4±18.0% for desipramine (P<0.01) and 76.8±20% for alosetron (P=0.049). There was no major difference in expectation of response from any medication to satisfy adequate relief on the basis of a belief that IBS is psychologic or organic in origin. In addition, sex and previous use of a drug did not influence the expectation of adequate relief.

Conclusions: Benefits of drugs in D-IBS drug trials have the potential to be influenced by preconceived notions derived from familiarity of drug class and the consent process even before the study begins which we refer to as the “pre-cebo” effect. The higher pre-cebo effect for rifaximin may be an obstacle to successful treatment effect during drug trials compared with drugs such as desipramine. The pre-cebo effect may need to be taken into account when formulating consent forms for IBS study.

Author Information

GI Motility Program, Cedars-Sinai Medical Center, Division of Gastroenterology, Los Angeles, CA

Supported by the Beatrice and Samuel A. Seaver Foundation for their ongoing support of our research in the GI Motility Program at Cedars-Sinai Medical Center.

S.E.K.: study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content. S.K.: study concept and design; acquisition of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content. K.C. and M.M.A: acquisition of data; administrative, technical, or material support; critical revision of the manuscript for important intellectual content. M.P.: study concept and design; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; statistical analysis; obtained funding; study supervision.

M.P. is a consultant for and has grants from Salix Pharmaceuticals. This project was not funded by Salix Pharmaceuticals. Cedars-Sinai has a licensing agreement with Salix Pharmaceuticals. The remaining authors declare that they have nothing to disclose.

Reprints: Mark Pimentel, MD, FRCP(C), GI Motility Program, Cedars-Sinai Medical Center, Division of Gastroenterology, 8730 Alden Drive, Suite 225E, Los Angeles, CA 90048 (e-mail: pimentelm@cshs.org).

Received July 18, 2011

Accepted March 30, 2012

© 2012 Lippincott Williams & Wilkins, Inc.