title: Evolving Concepts in Phases I and II Drug Development for Crohn's Disease.
abstract: The highest attrition rates during drug development programmes occur at the proof of concept stage. Given the large number of molecules under development for Crohn's disease, a need exists to improve the efficiency of early drug development by fast-tracking promising agents and terminating ineffective ones. Multiple opportunities are available to achieve these goals, including the use of more responsive outcome measures, and the incorporation of sophisticated pharmacokinetic modelling and/or highly specific pharmacodynamic markers into exposure-based dosing regimens and novel trial designs. In this article we review these strategies and propose an integrated paradigm of early drug development in Crohn's disease.
authors.affiliation: Department of Medicine, University of Western Ontario, London, ON, Canada.|Robarts Clinical Trials Inc., Robarts Research Institute, University of Western Ontario, London, ON, Canada.|Nufﬁeld Department of Experimental Medicine, University of Oxford, Oxford, UK.
authors.forename: Vipul
authors.initials: V
authors.lastname: Jairath
authors.affiliation: Robarts Clinical Trials Inc., Robarts Research Institute, University of Western Ontario, London, ON, Canada.|Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
authors.forename: Barrett G
authors.initials: BG
authors.lastname: Levesque
authors.affiliation: Robarts Clinical Trials Inc., Robarts Research Institute, University of Western Ontario, London, ON, Canada.|Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.|KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.
authors.forename: Niels
authors.initials: N
authors.lastname: Vande Casteele
authors.affiliation: Department of Medicine, University of Western Ontario, London, ON, Canada.|Robarts Clinical Trials Inc., Robarts Research Institute, University of Western Ontario, London, ON, Canada.
authors.forename: Reena
authors.initials: R
authors.lastname: Khanna
authors.affiliation: Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mosli
authors.affiliation: Robarts Clinical Trials Inc., Robarts Research Institute, University of Western Ontario, London, ON, Canada.|University Hospital of Ghent, Ghent, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Hindryckx
authors.affiliation: Nufﬁeld Department of Experimental Medicine, University of Oxford, Oxford, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Travis
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Marjolijn
authors.initials: M
authors.lastname: Duijvestein
authors.affiliation: Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Rimola
authors.affiliation: Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: Julian
authors.initials: J
authors.lastname: Panes
authors.affiliation: Robarts Clinical Trials Inc., Robarts Research Institute, University of Western Ontario, London, ON, Canada.|Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: D'Haens
authors.affiliation: Robarts Clinical Trials Inc., Robarts Research Institute, University of Western Ontario, London, ON, Canada.|Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Department of Medicine, University of Western Ontario, London, ON, Canada brian.feagan@robartsinc.com.|Robarts Clinical Trials Inc., Robarts Research Institute, University of Western Ontario, London, ON, Canada.|Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
mesh_terms: D003424:Crohn Disease / Q000188:drug therapy*; D017277:Drug Approval / Q000458:organization & administration*; D055808:Drug Discovery / Q000379:methods; D005765:Gastrointestinal Agents / Q000145:classification / Q000494:pharmacology; D006801:Humans; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents
keywords: Crohn’s disease; clinical trials