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

Sonal Ghura,1 Dawn Wiese Adams,2 Marilyn G Geller,3 Daniel A Leffler,1,4 Edwin Liu,5 Lori D McLeod,6 Lisa M Meckley,1 Muna J Tahir,1 Ragy Saad,1 Nicholas J Rockwood6 1Takeda Development Center Americas, Inc., Cambridge, MA, USA; 2Vanderbilt University Medical Center, Nashville, TN, USA; 3Celiac Disease Foundation, Woodland Hills, CA, USA; 4Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School Celiac Research Program, Boston, MA, USA; 5Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA; 6RTI Health Solutions, Research Triangle Park, NC, USACorrespondence: Sonal Ghura, Takeda Development Center Americas, Inc., 500 Kendall Street, Cambridge, MA, 02142, USA, Tel +608-770-9058, Email [email protected]: 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