"Pre-cebo": an unrecognized issue in the interpretation of adequate relief during irritable bowel syndrome drug trials.

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.