title: 'Pre-endoscopy point of care test (Simtomax- IgA/IgG-Deamidated Gliadin Peptide) for coeliac disease in iron deficiency anaemia: diagnostic accuracy and a cost saving economic model'.
abstract: BACKGROUND
  International guidelines recommend coeliac serology in iron deficiency anaemia, and duodenal biopsy for those tested positive to detect coeliac disease. However, pre-endoscopy serology is often unavailable, thus committing endoscopists to take routine duodenal biopsies. Some endoscopists consider duodenal biopsy mandatory in anaemia to exclude other pathologies. We hypothesise that using a point of care test at endoscopy could fill this gap, by providing rapid results to target anaemic patients who require biopsies, and save costs by biopsy avoidance. We therefore assessed three key aspects to this hypothesis: 1) the availability of pre-endoscopy serology in anaemia; 2) the sensitivities and cost effectiveness of pre-endoscopy coeliac screening with Simtomax in anaemia; 3) whether other anaemia-related pathologies could be missed by this targeted-biopsy approach.
  
  
  METHODS
  Group 1: pre-endoscopy serology availability was retrospectively analysed in a multicentre cohort of 934 anaemic patients at 4 UK hospitals. Group 2: the sensitivities of Simtomax, endomysial and tissue-transglutaminase antibodies were compared in 133 prospectively recruited patients with iron deficiency anaemia attending for a gastroscopy. The sensitivities were measured against duodenal histology as the reference standard in all patients. The cost effectiveness of Simtomax was calculated based on the number of biopsies that could have been avoided compared to an all-biopsy approach. Group 3: the duodenal histology of 153 patients presenting to a separate iron deficiency anaemia clinic were retrospectively reviewed.
  
  
  RESULTS
  In group 1, serology was available in 361 (33.8 %) patients. In group 2, the sensitivity and negative predictive value (NPV) were 100 % and 100 % for Simtomax, 96.2 % and 98.9 % for IgA-TTG, and 84.6 % and 96.4 % for EMA respectively. In group 3, the duodenal histology found no causes for anaemia other than coeliac disease.
  
  
  CONCLUSIONS
  Simtomax had excellent diagnostic accuracy in iron deficiency anaemia and was comparable to conventional serology. Duodenal biopsy did not identify any causes other than coeliac disease for iron deficiency anaemia, suggesting that biopsy avoidance in Simtomax negative anaemic patients is unlikely to miss other anaemia-related pathologies. Due to its 100 % NPV, Simtomax could reduce unnecessary biopsies by 66 % if only those with a positive Simtomax were biopsied, potentially saving £3690/100 gastroscopies.
  
  
  BACKGROUND
  The group 2 study was retrospectively registered with clinicaltrials.gov. Trial registration date: 13(th) July 2016;
  
  
  BACKGROUND
  NCT02834429 .
authors.affiliation: Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK. michellelau@doctors.org.uk.
authors.forename: Michelle Shui Yee
authors.initials: MS
authors.lastname: Lau
authors.affiliation: Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Mooney
authors.affiliation: Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK.
authors.forename: William
authors.initials: W
authors.lastname: White
authors.affiliation: Department of Gastroenterology, Bradford Royal Infirmary, Bradford, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Appleby
authors.affiliation: Department of Gastroenterology, Bradford Royal Infirmary, Bradford, UK.
authors.forename: Sulleman
authors.initials: S
authors.lastname: Moreea
authors.affiliation: Department of Gastroenterology, Whipps Cross University Hospital, London, UK.
authors.forename: Ismail
authors.initials: I
authors.lastname: Haythem
authors.affiliation: Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Joshua
authors.initials: J
authors.lastname: Elias
authors.affiliation: Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Kiran
authors.initials: K
authors.lastname: Bundhoo
authors.affiliation: Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Gareth
authors.initials: G
authors.lastname: Corbett
authors.affiliation: Department of Gastroenterology, Hull Royal Infirmary, Hull, UK.
authors.forename: Liam
authors.initials: L
authors.lastname: Wong
authors.affiliation: Department of Gastroenterology, Hull Royal Infirmary, Hull, UK.
authors.forename: Her Hsin
authors.initials: HH
authors.lastname: Tsai
authors.affiliation: Academic Unit of Pathology, Department of Neuroscience, Faculty of Medicine, Dentistry & Health, The University of Sheffield, Sheffield, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Cross
authors.affiliation: Department of Gastroenterology, Northern General Hospital, Sheffield Teaching Hospitals, Sheffield, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hebden
authors.affiliation: Department of Gastroenterology, Whipps Cross University Hospital, London, UK.
authors.forename: Sami
authors.initials: S
authors.lastname: Hoque
authors.affiliation: Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK.
authors.forename: David
authors.initials: D
authors.lastname: Sanders
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018798:Anemia, Iron-Deficiency / Q000097:blood* / Q000209:etiology / Q000601:surgery; D001706:Biopsy; D002446:Celiac Disease / Q000150:complications / Q000175:diagnosis* / Q000601:surgery; D017046:Cost Savings; D004386:Duodenum / Q000473:pathology; D005260:Female; D005773:Gastroscopy; D005903:Gliadin / Q000097:blood; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D018803:Models, Economic; D010455:Peptides / Q000097:blood; D000067716:Point-of-Care Testing / Q000191:economics* / Q000706:statistics & numerical data*; D011237:Predictive Value of Tests; D011300:Preoperative Care / Q000191:economics / Q000379:methods*; D011446:Prospective Studies; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012698:Serologic Tests / Q000191:economics / Q000379:methods / Q000706:statistics & numerical data; D006113:United Kingdom; D055815:Young Adult
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010455:Peptides; D005903:Gliadin
keywords: Coeliac disease; Diagnostic tests; Endoscopy; Health economics; Histopathology; Iron deficiency anaemia; Screening; Small intestine