Methods for handling missing segments in Crohn’s disease clinical trials: analysis from the EXTEND trial

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 …