title: Systematic review: patient-reported outcome measures in coeliac disease for regulatory submissions.
abstract: New therapeutics are moving into phase 3 clinical trials for the treatment of coeliac disease, a condition with no established therapies other than gluten-free diet. These trials will require a meaningful, validated and fit for purpose patient-reported outcome measure (PROM) to quantify the symptomatic improvement of patients.
  
  
  
  To evaluate existing PROMs for suitability in a Food and Drug Administration (FDA) approval trial for a coeliac disease therapeutic.
  
  
  
  We performed a systematic search in five online databases (MedLine, EmBase, Web of Science, CENTRAL, CINAHL) for studies that enrolled patients with coeliac disease and used PROMs. Studies included in this review had to measure some PROM concept, be patient administered and based upon a previously validated instrument with published measurement properties.
  
  
  
  Our literature search identified 2706 unique records of which 199 ultimately qualified for abstraction. The majority of PROMs used in studies of coeliac disease was generic and did not measure numerous symptoms or concerns of interest to patients. Four PROMs were found to contain appropriate content for use in an FDA trial: the coeliac disease-specific modification of the Gastrointestinal Symptoms Rating Scale (CeD-GSRS), Psychological General Well-Being Index (PGWB), the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient Reported Outcome (CeD-PRO). The GSRS and PGWB are most often used together and are two of the most extensively used measures in coeliac disease. The CDSD and CeD-PRO were developed exclusively for trials in coeliac disease but have much less published information on their measurement properties.
  
  
  
  While we did not find PROMs that currently meet the stated expectations of the FDA for regulatory purposes, four PROMs (CeD-GSRS, PGWB, CDSD and CeD-PRO) appear to contain appropriate content and with modest additional validation work could meet scientific standards for valid and sensitive measures of disease and treatment outcome. Specifically, what is needed for these instruments is an understanding of how sensitive they are to real changes in-patient condition, how stable they are over a period of time when health status should not have changed (test-retest reliability) as well as how they correlate with other measures of patient functioning such as intestinal biopsy. All of these objectives could feasibly be accomplished over a short cohort study of patients with biopsy-defined coeliac disease undergoing gluten challenge.
authors.affiliation: Pharmaceutical Outcomes Research and Policy Program, University of Washington School of Pharmacy, Seattle, WA, USA.
authors.forename: W J
authors.identifier: 0000-0002-6577-1047
authors.initials: WJ
authors.lastname: Canestaro
authors.affiliation: Department of Health Services, Seattle Quality of Life Group, University of Washington School of Public Health, Seattle, WA, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Edwards
authors.affiliation: Department of Health Services, Seattle Quality of Life Group, University of Washington School of Public Health, Seattle, WA, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Patrick
mesh_terms: D002446:Celiac Disease / Q000523:psychology / Q000628:therapy*; D006801:Humans; D007878:Legislation as Topic; D000071066:Patient Reported Outcome Measures; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome