OBJECTIVES: Severity and frequency of symptoms are critical endpoints in clinical trials for celiac disease (CD) in order to assess response to therapy. Valid and reliable instruments are therefore needed to assess symptoms as a key, and frequently primary, endpoint. This study evaluated evidence regarding validity and reliability of existing outcome measures and explored key stakeholders’ views on measuring CD symptoms and impacts. METHODS: A targeted literature review identified PRO measures and studies detailing their development or validation for comparison against FDA evidentiary standards. Stakeholders in the US, EU, and UK, i.e. patient advocates (n=1), clinicians (n=7), and payers (n=13), were then interviewed to understand which patient-centered aspects of CD are most important to treat, feasible to measure as PRO endpoints, and valued for reimbursement. RESULTS: Several PRO instruments relevant to CD were identified. Two were deemed most suitable for measuring CD symptoms accurately: the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient Reported Outcome tool (CeD-PRO), though each had limitations in terms of conceptual coverage, evidence for validity, reliability, and responsiveness, and readiness for implementation in clinical trial settings. In parallel, clinicians and patient advocate interviews showed that GI symptoms are most burdensome, though extra-intestinal symptoms are negatively impactful as well. Both the disease and the gluten-free diet (GFD) can impair patients’ quality of life. Payers emphasized the importance of measuring both symptom frequency and severity, particularly for GI symptoms, and the need to better understand and target patients who are non-responsive to GFD. CONCLUSIONS: With emerging therapeutic options in celiac disease (CD) beyond a strict GFD, further work is needed to finalize an appropriate PRO instrument to assess CD symptoms and to operationalize an endpoint in clinical trials in a way that is meaningful to patients, valued by payers, and acceptable to regulators in demonstrating efficacy.