Impact of various central endoscopy reading models on treatment outcome in Crohn's disease using data from the randomized, controlled, exploratory cohort arm of the BERGAMOT trial.

Background And Aims: Endoscopic assessment of mucosal appearance by independent central reading has become the standard method to assess Crohn's disease activity in clinical trials. The performance characteristics of various endoscopy reading models have yet to be systematically evaluated.

Methods: This substudy included patients with Crohn's disease in the exploratory induction cohort of the BERGAMOT trial (NCT02394028) randomly assigned to etrolizumab or placebo.

Central Endoscopy Reading in Inflammatory Bowel Diseases.

Endoscopic assessment of the presence and severity of endoscopic lesions has become an essential part of clinical trials in ulcerative colitis and Crohn's disease, for both patient eligibility and outcome measures. Variability in lesion interpretation between and within observers and the potential bias of local investigators in patient assessment have long been recognized. This variability can be reduced, although not completely removed, by independent evaluation of the examinations by experienced off-site (central) readers, properly trained in regard to lesion definition and identification, that should be removed from direct patient contact and blinded to any other clinical or study data.

The 2 + 1 paradigm: an efficient algorithm for central reading of Mayo endoscopic subscores in global multicenter phase 3 ulcerative colitis clinical trials.

Despite its importance and potential impact in clinical trials, central reading continues to be an under-represented topic in the literature about inflammatory bowel disease (IBD) clinical trials. Although several IBD studies have incorporated central reading to date, none have fully detailed the specific methodology with which the reads were conducted. Here we outline key principles for designing an efficient central reading paradigm for an ulcerative colitis (UC) study that addresses regulatory, operational and clinical expectations.

Bowel Preparations for Colonoscopy: A Regulatory Perspective.

Agents indicated for cleansing of the colon as a preparation for colonoscopy (bowel preps) are among the most frequently prescribed drugs for otherwise healthy patients. Better bowel preparation has been shown to translate into higher adenoma detection rates. Therefore, safety and efficacy standards need to be high.

Central Reading of Endoscopy Endpoints in Inflammatory Bowel Disease Trials.

Background: Central reading of endoscopy (CROE) is crucial in determining who qualifies for a trial but also has a role, independent of the selected scoring system, in decreasing measurement noise that can obscure separation between placebo and active drug. Benefits of CROE may not be independent of the method chosen, and controversy exists about the ideal approach.

Methods: Literature review and concept development.

Voting for image scoring and assessment (VISA)--theory and application of a 2 + 1 reader algorithm to improve accuracy of imaging endpoints in clinical trials.

Independent central reading or off-site reading of imaging endpoints is increasingly used in clinical trials. Clinician-reported outcomes, such as endoscopic disease activity scores, have been shown to be subject to bias and random error. Central reading attempts to limit bias and improve accuracy of the assessment, two factors that are critical to trial success.

Development of drugs for celiac disease: review of endpoints for Phase 2 and 3 trials.

Celiac disease is a lifelong disorder for which there is currently only one known, effective treatment: a gluten-free diet. New treatment approaches have recently emerged; several drugs are in Phase 2 trials and results appear promising; however, discussion around regulatory endpoints is in its infancy. We will briefly discuss the drugs that are under development and then shift our attention to potential trial endpoints, such as patient-reported outcomes, histology, serology, gene expression analysis and other tests.