Development and validation of the Crohn’s disease patient-reported outcomes signs and symptoms (CD-PRO/SS) diary

Abstract

BackgroundThe clinical course of Crohn’s disease (CD) and the effect of its treatment are monitored through patient-reported signs and symptoms (S&S), and endoscopic evidence of inflammation. The Crohn’s Disease Patient-reported Outcomes Signs and Symptoms (CD-PRO/SS) measure was developed to standardize the quantification of gastrointestinal S&S of CD through direct report from patient ratings.MethodsThe CD-PRO/SS was developed based on data from concept elicitation (focus groups, interviews; n = 29), then refined through cognitive interviews of CD patients (n = 20). Measurement properties, including item-level statistics, scaling structure, reliability, and validity, were examined using secondary analyses of baseline and two-week clinical trial data of adults with moderate-to-severe CD (n = 238).ResultsFindings from qualitative interviews identified nine S&S items covering bowel and abdominal symptoms. The final CD-PRO/SS daily diary includes two scales: Bowel S&S (three items) and Abdominal Symptoms (three items), each scored separately. Each scale showed evidence of adequate reliability (α = 0.74 and 0.67, respectively); reproducibility (intraclass correlation coefficient > 0.80), and validity, with the last including moderate correlations with the Inflammatory Bowel Disease Questionnaire bowel symptom score and select items (ranging from r = 0.43–0.54). Scores distinguished patients categorized by patient global ratings of disease severity (p < 0.0001).ConclusionsResults suggest the CD-PRO/SS is a reliable and valid measure of gastrointestinal symptom severity in CD patients. Additional longitudinal data are needed to evaluate the ability of the CD-PRO/SS scores to detect responsiveness and inform the selection of responder definitions.Electronic supplementary materialThe online version of this article (10.1186/s41687-018-0044-7) contains supplementary material, which is available to authorized users.

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 . It is well established that Crohn's disease symptoms do not correlate with the severity of endoscopic disease, 27‐29 and that clinical assessments of disease activity are susceptible to bias 30 .…”

“…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 ].…”

Treatment Evaluation in Inflammatory Bowel Diseases: a Move towards Validated Patient-Reported Outcome Measures (PROM)

“…Recently the Crohn's Disease patient-reported outcomes signs and symptoms (CD-PRO/SS) measure was developed to standardize the quantification of gastrointestinal signs and symptoms due to Crohn's disease through direct reports from patient ratings [25]. Findings from qualitative interviews identified nine items covering bowel and abdominal symptoms.…”