title: Reproducibility of histological assessments of disease activity in UC.
abstract: OBJECTIVE
  Histopathology is potentially an important outcome measure in UC. Multiple histological disease activity (HA) indices, including the Geboes score (GS) and modified Riley score (MRS), have been developed; however, the operating properties of these instruments are not clearly defined. We assessed the reproducibility of existing measures of HA.
  
  
  METHODS
  Five experienced pathologists with GI pathology fellowship training and expertise in IBD evaluated, on three separate occasions at least two weeks apart, 49 UC colon biopsies and scored the GS, MRS and a global rating of histological severity using a 100 mm visual analogue scale (VAS). The reproducibility of each grading system and for individual instrument items was quantified by estimates of intraclass correlation coefficients (ICCs) based on two-way random effects models. Uncertainty of estimates was quantified by 95% two-sided CIs obtained using the non-parametric cluster bootstrap method. Biopsies responsible for the greatest disagreement based on the ICC estimates were identified. A consensus process was used to determine the most common sources of measurement disagreement. Recommendations for minimising disagreement were subsequently generated.
  
  
  RESULTS
  Intrarater ICCs (95% CIs) for the total GS, MRS and VAS scores were 0.82 (0.73 to 0.88), 0.71 (0.63 to 0.80) and 0.79 (0.72 to 0.85), respectively. Corresponding inter-rater ICCs were substantially lower: 0.56 (0.39 to 0.67), 0.48 (0.35 to 0.66) and 0.61 (0.47 to 0.72). Correlation between the GS and VAS was 0.62 and between the MRS and VAS was 0.61.
  
  
  CONCLUSIONS
  Although 'substantial' to 'almost perfect' ICCs for intrarater agreement were found in the assessment of HA in UC, ICCs for inter-rater agreement were considerably lower. According to the consensus process results, standardisation of item definitions and modification of the existing indices is required to create an optimal UC histological instrument.
authors.affiliation: Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada Department of Medicine, Western University, London, Ontario, Canada Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia Department of Epidemiology, Biostatistics and Occupational Medicine, McGill University, Montreal, Canada.
authors.forename: Mahmoud H
authors.initials: MH
authors.lastname: Mosli
authors.affiliation: Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada Department of Medicine, Western University, London, Ontario, Canada Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.affiliation: Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
authors.forename: Guangyong
authors.initials: G
authors.lastname: Zou
authors.affiliation: Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.affiliation: Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: D'Haens
authors.affiliation: Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada Department of Medicine, Western University, London, Ontario, Canada.
authors.forename: Reena
authors.initials: R
authors.lastname: Khanna
authors.affiliation: Pacific Rim Pathology Medical Corporation, San Diego, California, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Behling
authors.affiliation: Carolinas Medical Center, Charlotte, North Carolina, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Kaplan
authors.affiliation: Department of Pathology, Western University, London, Ontario, Canada.
authors.forename: David K
authors.initials: DK
authors.lastname: Driman
authors.affiliation: Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Shackelton
authors.affiliation: Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Baker
authors.affiliation: Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada.
authors.forename: John K
authors.initials: JK
authors.lastname: MacDonald
authors.affiliation: Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada.
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Vandervoort
authors.affiliation: Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Samaan
authors.affiliation: Department of Pathology, University Hospital of KU Leuven and UZ Gent, Leuven, Belgium.
authors.forename: Karel
authors.initials: K
authors.lastname: Geboes
authors.affiliation: Department of Pathology, University of California, San Diego, California, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Valasek
authors.affiliation: Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Rish
authors.initials: R
authors.lastname: Pai
authors.affiliation: Department of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Cord
authors.initials: C
authors.lastname: Langner
authors.affiliation: Department of Pathology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Riddell
authors.affiliation: Department of Pathology, Mount Sinai Hospital, New York, New York, USA.
authors.forename: Noam
authors.initials: N
authors.lastname: Harpaz
authors.affiliation: Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Maida
authors.initials: M
authors.lastname: Sewitch
authors.affiliation: Department of Pathology, Western Washington Pathology and Multicare Health System, Tacoma, Washington, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Peterson
authors.affiliation: Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Stitt
authors.affiliation: Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
authors.forename: Barrett G
authors.initials: BG
authors.lastname: Levesque
mesh_terms: D000328:Adult; D001706:Biopsy; D003093:Colitis, Ulcerative / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D015203:Reproducibility of Results
keywords: CHRONIC ULCERATIVE COLITIS; CLINICAL TRIALS; IBD; INFLAMMATORY BOWEL DISEASE