title: Development of interim patient-reported outcome measures for the assessment of ulcerative colitis disease activity in clinical trials.
abstract: BACKGROUND
  Patient-reported outcomes (PROs) have an increasingly important role in the evaluation of new therapies for inflammatory bowel disease. The US Food and Drug Administration has issued formal guidance to describe the role of PRO instruments in evaluation of claims for product labelling. However, no validated PRO exists for ulcerative colitis.
  
  
  OBJECTIVE
  To investigate whether the PROs from the Mayo Clinic Score (MCS) for UC can be modified, to develop an interim PRO for use in clinical trials, alone or in combination with endoscopy.
  
  
  METHODS
  Data from an induction trial of a mesalazine (mesalamine) formulation were used to compare effect sizes between mesalazine and placebo for PRO items (stool frequency and rectal bleeding) alone and in combination with endoscopy. The operating properties of the PRO were validated using data from a phase 2 trial of MLN02, a humanised antibody to the α4β7 integrin in patients with UC.
  
  
  RESULTS
  A two-item PRO (PRO2) consisting of rectal bleeding = 0 and stool frequency ≤1 or ≤2, combined with an endoscopy subscore ≤1 yielded statistically significant differences between active drug and placebo. This combination yielded the most similar effect sizes and placebo rates for remission, compared to the primary trials. Use of PRO items alone yielded high placebo remission rates in both data sets, although rates were lower when the items were combined and remission defined as PRO2 = 0.
  
  
  CONCLUSIONS
  Patient-reported outcomes items derived from the Mayo Clinic Score combined with endoscopy as a co-primary endpoint may be an appropriate interim outcome measure for ulcerative colitis trials.
authors.affiliation: Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.|Oxford Clinical Trials Research Unit, Oxford, UK.
authors.forename: V
authors.initials: V
authors.lastname: Jairath
authors.affiliation: Robarts Clinical Trials, University of Western Ontario, London, ON, Canada.|Department of Medicine, University of Western Ontario, London, ON, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Khanna
authors.affiliation: Robarts Clinical Trials, University of Western Ontario, London, ON, Canada.|Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada.
authors.forename: G Y
authors.initials: GY
authors.lastname: Zou
authors.affiliation: Robarts Clinical Trials, University of Western Ontario, London, ON, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Stitt
authors.affiliation: Robarts Clinical Trials, University of Western Ontario, London, ON, Canada.|Department of Medicine, University of Western Ontario, London, ON, Canada.|Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: Mosli
authors.affiliation: Robarts Clinical Trials, University of Western Ontario, London, ON, Canada.
authors.forename: M K
authors.initials: MK
authors.lastname: Vandervoort
authors.affiliation: Robarts Clinical Trials, University of Western Ontario, London, ON, Canada.|Inflammatory Bowel Disease Centre, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: D'Haens
authors.affiliation: Robarts Clinical Trials, University of Western Ontario, London, ON, Canada.|Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Robarts Clinical Trials, University of Western Ontario, London, ON, Canada.|Department of Medicine, University of Western Ontario, London, ON, Canada.|Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada.
authors.forename: B G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: Robarts Clinical Trials, University of Western Ontario, London, ON, Canada.|Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA.
authors.forename: B G
authors.initials: BG
authors.lastname: Levesque
mesh_terms: D000328:Adult; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000503:physiopathology*; D004311:Double-Blind Method; D004724:Endoscopy / Q000379:methods; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D006801:Humans; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use*; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D063868:Patient Outcome Assessment; D014481:United States
chemical_list: D019804:Mesalamine