Abstract Background Histological scoring is central to assessing disease activity and remission in ulcerative colitis (UC) clinical trials. However, there are two key challenges in the histological assessment of UC: high inter-rater variability and the lack of a standardised scoring system. The low agreement between pathologists increases the sample size required to power the endpoint effectively and increases costs and timelines to accommodate adjudication or consensus. The absence of standardised scoring across trials means sponsors must commit to a scoring system that may be suboptimal and limits comparability between studies. Our objective was to evaluate the impact of adopting a universal scoring template that can translate to any of the most common scoring systems and the introduction of a reading plan to increase pathologist alignment for active and remission ulcerative colitis. Methods Two expert pathologists with 14-40+ years of individual experience independently scored 51 whole-slide images (WSIs) from 10 UC patients using a universal scoring template derived from Simplified Geboes Score (SGS), Nancy Index (NI), and Robarts Histopathology Index (RHI) across 2 scoring rounds (R1, R2). Remission cut-offs were defined as SGS≤2A. 1, NI ≤ 0, and RHI≤3. After R1 and a washout period, the pathologists were guided through a reading alignment and documentation process. Inter-rater reliability was calculated with pairwise overall percentage agreement and weighted Cohen’s kappa. The effect of including a reading plan and scoring template on future trial cost and timelines was modelled using these data and published literature from the VIVID-1 trial1 as an example of a large IBD phase 3 clinical trial. Results Targeted reader-alignment sessions using a standardised reading plan improved SGS inter-rater reliability from 49% to 73% agreement (Cohen’s k = 0. 56 to 0. 61). Agreement in R1 for SGS groupings (i. e. , 0, 1, 2A, 2B, 3) improved by 23. 5% in R2 (Fig. 1). Agreement for remission (≤2A. 1) and active (≥2B. 1) groupings for SGS increased by 4% from R1 to R2 (Fig. 2). For a clinical trial of 1056 IBD participants (5 biopsies at two time points), the estimated number of biopsy slides requiring adjudication by approximately 3000 WSIs without a reading plan. The inclusion of such an approach would reduce the number of adjudications by ∼745, equivalent to ∼75 patients. Conclusion The universal scoring system did not worsen inter-rater variability compared with typical clinical trial performance, and the structured reading plan markedly improved alignment between readers. The impact of these tools on trials will result in significant time, cost, and risk savings through reduced scoring burden and patient enrolment requirements. Reference: 1. Magro F, Jairath V, De Hertogh G, et al. DOP054 Early Histologic Response and Remission are Associated With Objective Control of Inflammation After One Year of Treatment With Mirikizumab in Moderately-to-Severely Active Crohn’s Disease. Journal of Crohn’s and Colitis. 2025;19 (Supplement₁): i188-i189. Conflict of interest: Dr. Windell, Dylan: I disclose the following financial relationship (s) with a commercial interest: Perspectum Ltd. Magness, Alastair: I am an employee of Perspectum Ltd. Li, Rongxue: I disclose the following financial relationship (s) with a commercial interest: Perspectum Ltd Davis, Tom: I disclose the following financial relationship (s) with a commercial interest: Perspectum Ltd Beyer, Cayden: Employee of Perspectum Thomaides Brears, Helena: I disclose the following financial relationship (s) with a commercial interest: Perspectum Ltd Larkin, Sarah: I disclose the following financial relationship (s) with a commercial interest: Perspectum Ltd Aljabar, Paul: Employee of Perspectum Ltd. Kainth, Reema: I disclose the following financial relationship (s) with a commercial interest: Perspectum Ltd Wakefield, Phil: I disclose the following financial relationship (s) with a commercial interest: Perspectum Ltd Langford, Caitlin: I disclose the following financial relationship (s) with a commercial interest: Perspectum Ltd Fryer, Eve: No conflict of interest Goldin, Rob: None Landy, Jonathan: No conflict of interest
Windell et al. (Thu,) studied this question.