Reproducibility of histological assessments of disease activity in UC

Mahmoud H Mosli; Brian G Feagan; Guangyong Zou; William J Sandborn; Geert D'Haens; Reena Khanna; Cynthia Behling; Keith Kaplan; David K Driman; Lisa M Shackelton; Kenneth A Baker; John K MacDonald; Margaret K Vandervoort; Mark A Samaan; Karel Geboes; Mark A Valasek; Rish Pai; Cord Langner; Robert Riddell; Noam Harpaz; Maida Sewitch; Michael Peterson; Larry W Stitt; Barrett G Levesque

doi:10.1136/gutjnl-2014-307536

Reproducibility of histological assessments of disease activity in UC

Gut. 2015 Nov;64(11):1765-73. doi: 10.1136/gutjnl-2014-307536. Epub 2014 Oct 30.

Authors

Mahmoud H Mosli¹, Brian G Feagan², Guangyong Zou³, William J Sandborn⁴, Geert D'Haens⁵, Reena Khanna⁶, Cynthia Behling⁷, Keith Kaplan⁸, David K Driman⁹, Lisa M Shackelton¹⁰, Kenneth A Baker¹⁰, John K MacDonald¹⁰, Margaret K Vandervoort¹⁰, Mark A Samaan¹⁰, Karel Geboes¹¹, Mark A Valasek¹², Rish Pai¹³, Cord Langner¹⁴, Robert Riddell¹⁵, Noam Harpaz¹⁶, Maida Sewitch¹⁷, Michael Peterson¹⁸, Larry W Stitt¹⁹, Barrett G Levesque⁴

Affiliations

¹ 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.
² 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.
³ Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
⁴ Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
⁵ Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands.
⁶ Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada Department of Medicine, Western University, London, Ontario, Canada.
⁷ Pacific Rim Pathology Medical Corporation, San Diego, California, USA.
⁸ Carolinas Medical Center, Charlotte, North Carolina, USA.
⁹ Department of Pathology, Western University, London, Ontario, Canada.
¹⁰ Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada.
¹¹ Department of Pathology, University Hospital of KU Leuven and UZ Gent, Leuven, Belgium.
¹² Department of Pathology, University of California, San Diego, California, USA.
¹³ Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁴ Department of Pathology, Medical University of Graz, Graz, Austria.
¹⁵ Department of Pathology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
¹⁶ Department of Pathology, Mount Sinai Hospital, New York, New York, USA.
¹⁷ Department of Medicine, McGill University, Montreal, Quebec, Canada.
¹⁸ Department of Pathology, Western Washington Pathology and Multicare Health System, Tacoma, Washington, USA.
¹⁹ Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.

PMID: 25360036
DOI: 10.1136/gutjnl-2014-307536

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.

Design: 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.

Keywords: CHRONIC ULCERATIVE COLITIS; CLINICAL TRIALS; IBD; INFLAMMATORY BOWEL DISEASE.

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MeSH terms

Adult
Biopsy
Colitis, Ulcerative / pathology*
Female
Humans
Male
Reproducibility of Results