Development and validation of the Ulcerative Colitis patient-reported outcomes signs and symptoms (UC-pro/SS) diary

Abstract

BackgroundThe clinical course of ulcerative colitis (UC) and the effects of treatment are assessed through patient-reported signs and symptoms (S&S), and endoscopic evidence of inflammation. The Ulcerative Colitis Patient-Reported Outcomes Signs and Symptoms (UC-PRO/SS) measure was developed to standardize the quantification of gastrointestinal S&S of UC in clinical trials through direct report from patient ratings.DesignThe UC-PRO/SS was developed by collecting data from concept elicitation (focus groups, and individual interviews), then refined through a process of cognitive interviews of 57 UC patients. Measurement properties, including item-level statistics, scaling structure, reliability, and validity, were evaluated in an observational, four-week study of adults with mild to severe UC (N = 200).ResultsFindings from qualitative focus groups and interviews identified nine symptom items covering bowel and abdominal symptoms. The final UC-PRO/SS daily diary includes two scales: Bowel S&S (six items) and Abdominal Symptoms (three items), each scored separately. Each scale showed evidence of adequate reliability (α = 80 and 0.66, respectively); reproducibility (intraclass correlation coefficient = 0.81, 0.71) and validity, including moderate-to-high correlations with the Partial Mayo Score (0.79; 0.45) and Inflammatory Bowel Disease Questionnaire (IBDQ) total score (− 0.70; − 0.61). Scores discriminated by level of disease severity, as defined by the Partial Mayo Score, Patient Global Rating, and Clinician Global Rating (p < 0.0001).ConclusionsResults suggest that the UC-PRO/SS is a reliable and valid measure of gastrointestinal symptom severity in UC patients. Additional longitudinal data are needed to evaluate the ability of the UC-PRO/SS scores to detect responsiveness and inform the selection of responder definitions.

Development of the symptoms and impacts questionnaire for Crohn's disease and ulcerative colitis

“…While at least one other inflammatory bowel disease PRO initiative has cited the FDA guidance, endoscopy was not incorporated in the development of the CD‐PRO/SS and UC‐PRO/SS measures 7,8 . Participants in the CD‐PRO/SS development study were enrolled based on physician‐confirmed biopsy and clinical disease activity was assessed using the Sandler estimated Crohn's Disease Activity Index (SeCDAI), without endoscopy 7,26 .…”

“…Guidance documents issued by the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) indicate that a co‐primary endpoint consisting of a PRO measure and an endoscopic outcome is required in future inflammatory bowel disease registration trials 5,6 . While the Crohn's Disease Patient‐Reported Outcomes Signs and Symptoms (CD‐PRO/SS) diary 7 and Ulcerative Colitis Patient‐Reported Outcomes Signs and Symptoms (UC‐PRO/SS) diary 8 were established according to the FDA‐endorsed pathway, endoscopic disease activity was not evaluated in the development studies. This represents an important potential shortcoming given that objective measures of inflammatory bowel disease activity do not necessarily correspond to symptom‐based assessments.…”

Etrolizumab for the Treatment of Ulcerative Colitis and Crohn’s Disease: An Overview of the Phase 3 Clinical Program

“…In alignment with the focus on PROs by health authorities, Roche and Genentech, in cooperation with a small consortium, have worked to develop the UC-PRO and CD-PRO [18,19]. The UC-PRO and CD-PRO are modular instruments that were designed to comprehensively assess the signs, symptoms, and impact of UC and Crohn's disease, capturing the experience from the perspective of the patient.…”

“…PROs, including the Inflammatory Bowel Disease Questionnaire, EuroQoL-5D, UC-PRO tool (“signs and symptoms” and “systemic systems” modules), Crohn’s disease (CD)-PRO tool (“signs and symptoms” and “systemic systems” modules), components of CDAI (SF, AP, general well-being) and components of MCS [SF and rectal bleeding score (RB)], are collected daily using electronic PRO devices. The etrolizumab program uses the UC-PRO Signs and Symptoms (SS) and CD-PRO/SS, the first PRO tools to undergo a rigorous development process outlined by the FDA, with input from patients and clinical experts [ 18 , 19 ].…”

Disease monitoring strategies in inflammatory bowel diseases: What do we mean by ‘tight control’?

“…Since the STRIDE recommendations, newer PRO tools, including more clinical variables (abdominal pain and urgency for UC) in accordance with FDA guidance, have been developed, however their applicability in clinical trial design or everyday clinical practice still remain to be validated[34-36]. Various other PROs have already been used in clinical trials reporting depression, anxiety, disability and other quality of life parameters, however available data on these PROs in IBD are yet limited.…”