Recommendations for Standardizing Clinical Trial Design and Endoscopic Assessment in Postoperative Crohn's Disease.

2022-09-01

Hanzel, Jurij

Jairath, Vipul

De Cruz, Peter

Guizzetti, Leonardo

Shackelton, Lisa M

Bossuyt, Peter

Duijvestein, Marjolijn

Dulai, Parambir S

Grossmann, Johannes

Hirten, Robert P

Khanna, Reena

Panes, Julian

Peyrin-Biroulet, Laurent

Regueiro, Miguel

Rubin, David T

Singh, Siddharth

Stidham, Ryan W

Sandborn, William J

Feagan, Brian G

D'Haens, Geert R

Ma, Christopher

inflammatory bowel disease

medical therapy

randomized controlled trials

surgery

Journal Article

0000-0003-3158-8014

0000-0001-8603-898X

0000-0003-4027-7365

0000-0002-8679-2541

0000-0002-4971-6902

0000-0002-7681-8111

0000-0002-4698-9948

10.1093/ibd/izab259

The lack of standardized methods for clinical trial design and disease activity assessment has contributed to an absence of approved medical therapies for the prevention of postoperative Crohn's disease (CD). We developed recommendations for regulatory trial design for this indication and for endoscopic assessment of postoperative CD activity. An international panel of 19 gastroenterologists was assembled. Modified Research and Development/University of California Los Angeles methodology was used to rate the appropriateness of 196 statements using a 9-point Likert scale in 2 rounds of voting. Results were reviewed and discussed between rounds. Inclusion of patients with a history of completely resected ileocolonic CD in regulatory clinical trials for the prevention of postoperative recurrence was appropriate. Given the absence of approved medical therapies, a placebo-controlled design with a primary end point of endoscopic remission at 52 weeks was appropriate for drug development for this indication; however, there was uncertainty regarding the appropriateness of a coprimary end point of symptomatic and endoscopic remission and the use of currently available patient-reported outcome measures. The modified Rutgeerts Score, endoscopic assessment of the anastomosis, and a minimum of 5cm of neoterminal ileum were also appropriate; although the appropriateness of other indices including the Simple Endoscopic Score for CD for endoscopic assessment of postoperative CD activity was uncertain. A framework for regulatory trial design for the prevention of postoperative CD recurrence and endoscopic assessment of disease activity has been developed. Research to empirically validate end points for these trials is needed.

link

Inflammatory Bowel Diseases 2022; 28(9): 1321-1331

Inflammatory Bowel Diseases