title: Disease activity indices in coeliac disease: systematic review and recommendations for clinical trials.
abstract: Although several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for coeliac disease, there is currently no widely accepted measure of disease activity used in clinical trials. We conducted a systematic review of coeliac disease activity indices to evaluate their operating properties and potential as outcome measures in registration trials.
  
  
  
  MEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or paediatric patients with coeliac disease that included coeliac disease activity markers in their outcome measures. The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA).
  
  
  
  Of 19 123 citations, 286 studies were eligible, including 24 randomised-controlled trials. Three of five PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA. All histological and endoscopic scores identified lacked content validity. Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales. Endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy.
  
  
  
  Current best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in coeliac disease registration trials. Morphometric histology should be included as a key secondary or co-primary end point. Further work is needed to optimise end point configuration to inform efficient drug development.
authors: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.|Department of Gastroenterology, University of Ghent, Ghent, Belgium.
authors: Pieter
authors: P
authors: Hindryckx
authors: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.|Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
authors: Barrett G
authors: BG
authors: Levesque
authors: Department of Gastroenterology, University of Ghent, Ghent, Belgium.
authors: Tom
authors: 0000-0002-4540-4012
authors: T
authors: Holvoet
authors: Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
authors: Serina
authors: S
authors: Durand
authors: Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, UK.|Oxford University Clinical Academic Graduate School, John Radcliffe Hospital, Oxford, UK.
authors: Ceen-Ming
authors: 0000-0003-3850-4442
authors: CM
authors: Tang
authors: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.
authors: Claire
authors: C
authors: Parker
authors: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.|Department of Medicine, University of Western Ontario, London, Ontario, Canada.
authors: Reena
authors: R
authors: Khanna
authors: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.
authors: Lisa M
authors: LM
authors: Shackelton
authors: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.|Inﬂammatory Bowel Disease Centre, Academic Medical Centre, Amsterdam, The Netherlands.
authors: Geert
authors: G
authors: D'Haens
authors: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.|Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
authors: William J
authors: WJ
authors: Sandborn
authors: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.|Department of Medicine, University of Western Ontario, London, Ontario, Canada.|Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada.
authors: Brian G
authors: BG
authors: Feagan
authors: Celiac Disease Center, Columbia University, New York, New York, USA.
authors: Benjamin
authors: B
authors: Lebwohl
authors: The Celiac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors: Daniel A
authors: DA
authors: Leffler
authors: Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada.|Department of Medicine, University of Western Ontario, London, Ontario, Canada.|Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada.
authors: Vipul
authors: V
authors: Jairath
mesh_terms: D015415:Biomarkers / Q000097:blood; D002446:Celiac Disease / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D002986:Clinical Trials as Topic / Q000379:methods; D016099:Endoscopy, Gastrointestinal; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000379:methods; D015203:Reproducibility of Results; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers
keywords: CLINICAL TRIALS; COELIAC DISEASE; GLUTEN SENSITIVE ENTEROPATHY