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Methods for handling missing segments in Crohn’s disease clinical trials: analysis from the EXTEND trial
  1. Christopher Ma1,
  2. Reena Khanna2,
  3. Leonardo Guizzetti3,
  4. Guangyong Zou4,
  5. Brian G Feagan5,
  6. Vipul Jairath4
  1. 1Division of Gastroenterology & Hepatology, University of Calgary, Calgary, Alberta, Canada
  2. 2Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada
  3. 3Alimentiv Inc, London, Ontario, Canada
  4. 4Department of Biostatistics and Epidemiology, Western University, London, Ontario, Canada
  5. 5Division of Gastroenterology, Western University, London, Ontario, Canada
  1. Correspondence to Dr Vipul Jairath, Department of Biostatistics and Epidemiology, Western University, London, ON N6A 3K7, Canada; vjairath{at}uwo.ca

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Recently in Gut, Gottlieb et al summarised considerations for endoscopy central reading in IBD clinical trials.1 Achieving endoscopic remission is an important measure of therapeutic efficacy, and most Crohn’s disease (CD) trials now require video-recorded ileocolonoscopy at screening and for evaluation of the primary outcome. While the Crohn’s Disease Endoscopic Index of Severity (CDEIS)2 and the Simplified Endoscopic Score for Crohn’s Disease (SES-CD)3 are commonly used instruments, Gottlieb et al correctly highlight that these scores are sensitive to missing data if one or more of the five ileocolonic segments are not examined. Bowel segments may not be visualised if there is an impassable stricture, when the bowel preparation is poor or if there are technical challenges precluding procedure completion. In these situations, appropriately handling missing data is essential because the total endoscopic score may not be reflective of the actual disease burden. We empirically evaluated the effect of different methods for handling missing data from non-visualised segments on the SES-CD and CDEIS.

Ileocolonoscopy videos from baseline and week 12 in the Extend the Safety and Efficacy of Adalimumab through Endoscopic Healing (EXTEND) trial were used.4 EXTEND was a randomised, placebo-controlled trial evaluating adalimumab in patients with moderate-to-severe CD. Six methods of handling missing segments were applied:

  1. No imputation: non-visualised segments ignored.

  2. Worst …

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Footnotes

  • Contributors All authors were involved in conception and design. LG and GZ were involved in data analysis and interpretation. CM and VJ were involved in manuscript drafting. All authors were involved in manuscript editing for important intellectual content. All authors have reviewed, contributed to and approved the final version of this manuscript. VJ is serving as the article guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests CM has received consulting fees from AbbVie, Amgen, AVIR Pharma, Janssen, Ferring, Fresenius Kabi, Takeda, Pfizer, Roche and Alimentiv (formerly Robarts Clinical Trials); speaker’s fees from AbbVie, Janssen, Takeda and Pfizer; and research support from Pfizer. RK has received consultancy fees from AbbVie, Encycle Innomar, Lilly, Janssen, Merck, Pfizer, Roche, Takeda and Amgen; speaker fees from AbbVie, Lilly, Janssen, Pendopharm, Roche, Shire and Takeda; and research study fees from Roche. LG is an employee of Alimentiv (formerly Robarts Clinical Trials). GZ has no conflicts of interest to declare. BGF has received grant/research support from AbbVie, Amgen, AstraZeneca/MedImmune, Atlantic Pharmaceuticals, Boehringer-Ingelheim, Celgene, Celltech, Genentech/Hoffmann-La Roche, Gilead Science, GlaxoSmithKline (GSK), Janssen Research & Development, Pfizer, Receptos/Celgene International, Sanofi, Santarus, Takeda Development Center Americas, Tillotts Pharma AG and UCB; consulting fees from Abbott/AbbVie, Akebia Therapeutics, Allergan, Amgen, Applied Molecular Transport, Aptevo Therapeutics, Astra Zeneca, Atlantic Pharma, Avir Pharma, Biogen Idec, BioMx Israel, Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, Galapagos, GiCare Pharma, Gilead, Gossamer Pharma, GSK, Inception IBD, JnJ/Janssen, Kyowa Kakko Kirin, Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nestle, Nextbiotix, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Receptos, Salix Pharma, Shire, Sienna Biologics, Sigmoid Pharma, Sterna Biologicals, Synergy Pharma, Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, Vivelix Pharma, VHsquared and Zyngenia; speakers bureau fees from Abbott/AbbVie, JnJ/Janssen, Lilly, Takeda, Tillotts and UCB Pharma; is a scientific advisory board member for Abbott/AbbVie, Allergan, Amgen, Astra Zeneca, Atlantic Pharma, Avaxia Biologics, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Elan/Biogen, Galapagos, Genentech/Roche, JnJ/Janssen, Merck, Nestle, Novartis, Novonordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Sterna Biologicals, Takeda, Teva, TiGenix, Tillotts Pharma AG and UCB Pharma; and is the Senior Scientific Officer of Alimentiv. VJ has received has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena pharmaceuticals, Genentech, Pendopharm, Pfizer, Fresenius Kabi, Bristol Myers Squibb, Roche, Ferring, Sandoz, Merck, Takeda, Janssen, Alimentiv (formerly Robarts Clinical Trials), Topivert, Celltrion, Mylan and Gilead; and speaker’s fees from Takeda, Janssen, Shire, Ferring, Abbvie and Pfizer. Alimentiv is a contract research organisation that provides centralised endoscopy imaging solutions for clinical trials.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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