TOWARDS A COMMON VALIDATED METHODOLOGY FOR HISTOLOGIC MEASUREMENT OF MUCOSAL HEALING IN ULCERATIVE COLITIS: INTRODUCING A NEW PROJECT OF THE BIOMARKERS CONSORTIUM OF THE FOUNDATION FOR THE NIH

Abstract Ulcerative colitis is a chronic, debilitating disease characterized by damage to the mucous membrane (mucosa) lining the lower gastrointestinal tract. Endoscopic and histological evidence of healing of the damaged mucosa, referred to as mucosal healing, is increasingly accepted as an important endpoint in clinical practice and in clinical trials due to its association with improved clinical outcomes. In fact, in a draft guidance to industry, the Food and Drug Administration encouraged incorporating histologic evaluation in ulcerative colitis clinical trials. However, there is no community consensus regarding how to define mucosal healing and the field lacks standardized protocols for measuring this treatment target endpoint. Standardized assessment of histologic disease activity in clinical trials is challenging for many reasons, including variability in collection of mucosal biopsies (e.g., number and location), lack of fully validated histology scoring systems, and absence of standard definitions of histologic improvement and remission. The lack of standardized measurement of mucosal healing constitutes a major challenge for drug development and negatively impacts optimization of clinical management for patients. Therefore, the Biomarkers Consortium of the Foundation for the National Institutes of Health recently launched a consortium project, with governmental, nonprofit and industry partners, to address this gap by establishing a common methodology for a histologic measurement of mucosal healing in ulcerative colitis. The project will: 1) Establish the optimum number and locations of biopsies required to determine histological inflammation in ulcerative colitis; 2) Establish a standardized histopathologic measurement of mucosal healing that correlates with clinical outcomes; and 3) Develop an automated machine learning-based methodology for histopathological scoring of mucosal healing. The final results of this project will contribute to a consensus methodology with the goal of establishing a regulatory standard for future industry-sponsored clinical trials, with the potential to contribute to improved tools for clinical monitoring of disease activity in ulcerative colitis.