title: Design of Treatment Trials for Functional Gastrointestinal Disorders.
abstract: This article summarizes recent progress and regulatory guidance on design of trials to assess the efficacy of new therapies for functional gastrointestinal disorders (FGIDs). The double-masked, placebo-controlled, parallel-group design remains the accepted standard for evaluating treatment efficacy. A control group is essential, and a detailed description of the randomization process and concealed allocation method must be included in the study report. The control will most often be placebo, but for therapeutic procedures and for behavioral treatment trials, respectively, a sham procedure and control intervention with similar expectation of benefit, but lacking the treatment principle, are recommended. Investigators should be aware of, and attempt to minimize, expectancy effects (placebo, nocebo, precebo). The primary analysis should be based on the proportion of patients in each treatment arm who satisfy a treatment responder definition or a prespecified clinically meaningful change in a patient-reported outcome measure. Data analysis should use the intention-to-treat principle. Reporting of results should follow the Consolidated Standards for Reporting Trials guidelines and include secondary outcome measures to support or explain the primary outcome and an analysis of harms data. Trials should be registered in a public location before initiation and results should be published regardless of outcome.
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute and Department of Medicine, St Michael's Hospital, Toronto, Canada.
authors.forename: E Jan
authors.initials: EJ
authors.lastname: Irvine
authors.affiliation: Departments of Clinical and Experimental Medicine and Gastroenterology, Translational Research Center for Gastrointestinal Disorders, University Hospital KU Leuven, Leuven, Belgium. Electronic address: jan.tack@med.kuleuven.be.
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Crowell
authors.affiliation: Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Kok Ann
authors.initials: KA
authors.lastname: Gwee
authors.affiliation: Peking Union Medical College Hospital, Center of FGID and MGID, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Meiyun
authors.initials: M
authors.lastname: Ke
authors.affiliation: Facultad de Medicina, Universidad Nacional Autónoma de México, Laboratorio de Hígado, Páncreas y Motilidad, Unidad de Investigación en Medicina Experimental, Hospital General de México, Mexico City, Mexico.
authors.forename: Max J
authors.initials: MJ
authors.lastname: Schmulson
authors.affiliation: University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: William E
authors.initials: WE
authors.lastname: Whitehead
authors.affiliation: Cedars-Sinai Health System, Cedars-Sinai Center for Outcomes Research and Education, Los Angeles, California.
authors.forename: Brennan
authors.initials: B
authors.lastname: Spiegel
mesh_terms: D005767:Gastrointestinal Diseases / Q000628:therapy*; D012107:Research Design
keywords: Controlled Trial; Functional Gastrointestinal Disorders; Intention to Treat; Patient-Reported Outcome Measure