V Jairath1,2, R Khanna3,4, G Y Zou3,5, L Stitt3, M Mosli3,4,6, M K Vandervoort3, G D'Haens3,7, W J Sandborn3,8, B G Feagan3,4,5, B G Levesque3,8. 1. Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK. 2. Oxford Clinical Trials Research Unit, Oxford, UK. 3. Robarts Clinical Trials, University of Western Ontario, London, ON, Canada. 4. Department of Medicine, University of Western Ontario, London, ON, Canada. 5. Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada. 6. Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. 7. Inflammatory Bowel Disease Centre, Academic Medical Centre, Amsterdam, The Netherlands. 8. Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA.
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. AIM: 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. CONCLUSION: 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.
RCT Entities:
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. AIM: 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. CONCLUSION: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: Siddharth Singh; James A Proudfoot; Parambir S Dulai; Ronghui Xu; Brian G Feagan; William J Sandborn; Vipul Jairath Journal: Clin Gastroenterol Hepatol Date: 2019-05-18 Impact factor: 11.382
Authors: Jurij Hanžel; Nejc Sever; Ivan Ferkolj; Borut Štabuc; Nataša Smrekar; Tina Kurent; Matic Koželj; Gregor Novak; Griet Compernolle; Sophie Tops; Ann Gils; David Drobne Journal: United European Gastroenterol J Date: 2019-03-19 Impact factor: 4.623
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Authors: Christopher Ma; William J Sandborn; Geert R D'Haens; Guangyong Zou; Larry W Stitt; Siddharth Singh; Ashwin N Ananthakrishnan; Parambir S Dulai; Reena Khanna; Vipul Jairath; Brian G Feagan Journal: Clin Gastroenterol Hepatol Date: 2019-09-20 Impact factor: 11.382
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