Psychometric Evaluation of the Celiac Disease Symptom Diary 2.1 © Using Data from the Virtual Celiac Symptoms Study

Purpose: Validated patient-reported outcome measures (PROMs) are required for use in clinical trials of celiac disease (CeD) therapies. The Celiac Disease Symptom Diary 2.1 © (CDSD 2.1 © ), which measures the daily severity of core CeD symptoms (abdominal pain, bloating, diarrhea, nausea, tiredness), was developed according to the latest regulatory guidelines for fit-for-purpose PROMs. This study evaluated the psychometric properties of CDSD 2.1. Methods: Psychometric properties of CDSD 2.1 were evaluated using data from a 12-week US observational study, the Virtual Celiac Symptoms Study (NCT05309330), in patients with CeD maintaining a gluten-free diet. Participants completed CDSD 2.1 daily and other PROMs (Patient Global Impression of Severity [PGIS], Gastrointestinal Symptom Rating Scale [GSRS], and Celiac Symptom Index [CSI]) at specified time points to evaluate the reliability, validity, and responsiveness of CDSD 2.1. Results: Overall, 480 participants (338 adults, 142 adolescents) completed the study. Cronbach’s alpha (baseline = 0.77 adults/adolescents) indicated high internal consistency reliability of weekly average gastrointestinal (GI; abdominal pain, bloating, nausea, diarrhea) CDSD 2.1 scores. An intraclass correlation coefficient of 0.89 (adults)/0.88 (adolescents) demonstrated high test-retest reliability among stable patients on PGIS. Moderate-to-strong correlations between weekly average GI CDSD 2.1 scores and GSRS domains at baseline and CSI at Week 3 confirmed construct validity (r = 0.44– 0.76; p < 0.05). Weekly average GI CDSD 2.1 score changes followed expected patterns based on PGIS change groups, demonstrating responsiveness. Conclusion: This evaluation provides evidence to support the use of CDSD 2.1 in clinical trials as a reliable and responsive measure of CeD symptom severity. Keywords: celiac disease, celiac disease symptom diary, gastrointestinal symptoms, psychometric validation, patient-reported outcome measure, virtual celiac symptoms study