title: Evolution of clinical trials for irritable bowel syndrome: issues in end points and study design.
abstract: Irritable bowel syndrome (IBS) involves a broad range of physiological and psychological alterations that may affect brain-gut dysregulation, gut function, visceral perception, and mucosal integrity and function. Despite advances in our understanding of basic neuroenteric mechanisms and the role of effectors and transmitters in the brain-gut axis, a reliable biologic marker of IBS has yet to be identified. IBS diagnosis and status depend entirely on an assessment of IBS signs and symptoms. This has made development of optimal end points and study design for evaluation of efficacy of IBS drugs a challenge. This article addresses three main topics: the evolution of primary end points for IBS clinical trials; a potential path forward for IBS end points in new clinical trials; and recommendations for the future development of patient-reported outcome (PRO) instruments for use in IBS clinical trials.
authors.affiliation: Study Endpoints and Labeling Development, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland 20993, USA. annmarie.trentacost@fda.hhs.gov
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Trentacosti
authors.forename: Ruyi
authors.initials: R
authors.lastname: He
authors.forename: Laurie B
authors.initials: LB
authors.lastname: Burke
authors.forename: Donna
authors.initials: D
authors.lastname: Griebel
authors.forename: Dianne L
authors.initials: DL
authors.lastname: Kennedy
mesh_terms: D002986:Clinical Trials as Topic; D017408:Guidelines as Topic; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000175:diagnosis / Q000628:therapy*; D012107:Research Design; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration