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Original article
Outcome measures in coeliac disease trials: the Tampere recommendations
  1. Jonas F Ludvigsson1,2,
  2. Carolina Ciacci3,
  3. Peter HR Green4,
  4. Katri Kaukinen5,6,
  5. Ilma R Korponay-Szabo7,8,
  6. Kalle Kurppa9,10,
  7. Joseph A Murray11,
  8. Knut Erik Aslaksen Lundin12,13,
  9. Markku J Maki14,15,
  10. Alina Popp16,17,
  11. Norelle R Reilly18,19,
  12. Alfonso Rodriguez-Herrera20,
  13. David S Sanders21,
  14. Detlef Schuppan22,23,
  15. Sarah Sleet24,
  16. Juha Taavela25,
  17. Kristin Voorhees26,
  18. Marjorie M Walker27,
  19. Daniel A Leffler28
  1. 1 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  2. 2 Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
  3. 3 Coeliac Center at Department of Medicine and Surgery, Scuola Medica Salernitana, University of Salerno, Salerno, Italy
  4. 4 Celiac Disease Center at Columbia University, New York, USA
  5. 5 Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
  6. 6 Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
  7. 7 Coeliac Disease Centre, Heim Pál Children’s Hospital, Budapest, Hungary
  8. 8 Department of Paediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
  9. 9 Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
  10. 10 Department of Paediatrics, Tampere University Hospital, Tampere, Finland
  11. 11 The Mayo Clinic, Rochester, Minnesota, USA
  12. 12 Institute of Clinical Medicine and K.G. Jebsen Coeliac Disease Research Centre, Faculty of Medicine, University of Oslo, Oslo, Norway
  13. 13 Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
  14. 14 Science Center, Tampere University Hospital, Tampere, Finland
  15. 15 Tampere Centre for Child Health Research, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
  16. 16 Institute for Mother and Child Health Bucharest, University of Medicine and Pharmacy ’Carol Davila', Bucharest, Romania
  17. 17 Tampere Centre for Child Health Research, University of Tampere, Tampere University Hospital, Tampere, Finland
  18. 18 Division of Pediatric Gastroenterology, Columbia University Medical Center, New York, USA
  19. 19 Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, USA
  20. 20 Grupo IHP Pediatria, Sevilla, Spain
  21. 21 Academic Unit of Gastroenterology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK
  22. 22 Celiac Center, University Medical Center, Johannes-Gutenberg University, Mainz, Germany
  23. 23 Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
  24. 24 Coeliac UK, Buckinghamshire, UK
  25. 25 Tampere Centre for Child Health Research, University of Tampere, Tampere University Hospital, Tampere, Finland
  26. 26 Continuum Clinical, Northbrook, Illinois, USA
  27. 27 Faculty of Health and Medicine, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia
  28. 28 Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Jonas F Ludvigsson, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden; jonasludvigsson{at}yahoo.com

Abstract

Objective A gluten-free diet is the only treatment option of coeliac disease, but recently an increasing number of trials have begun to explore alternative treatment strategies. We aimed to review the literature on coeliac disease therapeutic trials and issue recommendations for outcome measures.

Design Based on a literature review of 10 062 references, we (17 researchers and 2 patient representatives from 10 countries) reviewed the use and suitability of both clinical and non-clinical outcome measures. We then made expert-based recommendations for use of these outcomes in coeliac disease trials and identified areas where research is needed.

Results We comment on the use of histology, serology, clinical outcome assessment (including patient-reported outcomes), quality of life and immunological tools including gluten immunogenic peptides for trials in coeliac disease.

Conclusion Careful evaluation and reporting of outcome measures will increase transparency and comparability of coeliac disease therapeutic trials, and will benefit patients, healthcare and the pharmaceutical industry.

  • celiac disease
  • gluten
  • gluten free diet
  • clinical trials

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors JFL and DL initiated the study. JFL coordinated the study and wrote the first draft, the text was then extensively revised by the coauthors. All authors contributed to the literature searches, contributed to the writing of the manuscript and approved the final version of the manuscript.

  • Funding JFL was supported by the Swedish Research Council (522-2A09-195) and the Swedish Society of Medicine while writing the draft of this paper. DS received research support from the German Research Foundation (DFG), the Ministry of Research and Development (BMBF) and the Leibniz Foundation. DSS received an educational grant from Biocard and Simtomax to undertake an investigator-led research study on point-of-care tests and an educational grant from Dr Schär (a gluten-free food manufacturer) to undertake an investigator-led research study on gluten sensitivity. KKa was supported by the Academy of Finland, the Competitive Research Funding of the Tampere University Hospital and The Sigrid Juselius Foundation. IRK-S was supported by the Hungarian Research Fund (Grant NKFI 120392). MJM was supported by the Competitive State Research Financing of the Tampere University Hospital (grant 9U038).

  • Competing interests PHRG: scientific advisory board of Alvine Pharmaceuticals, ImmunogenX and ImmusanT. JAM: serves on the advisory board of Celimmune, was a consultant to BioLineRx, GlaxoSmithKline (GSK), Genentech, UCB Biopharma and Glenmark Pharmaceuticals Ltd and is a consultant to ImunnosanT, Institute for Protein Design (PvP Biologics), Takeda Pharmaceutical Company, Ltd., Innovate Biopharmaceuticals, Inc., Intrexon, 2GPharma Inc., Boeringer-Ingelheim and ImmusanT. KEAL: ImmusanT, Regeneron and Alvine Pharmaceuticals. DSS: holds a patent and receives royalties for the TG2-antibody assay, has received an educational grant from Coeliac UK, Biocard, Simtomax and Dr Schär to undertake an investigator-led research study on CD and/or gluten sensitivity. NRR: clinical advisory board for ImmusanT. DAL: Medical Director for Takeda Pharmaceuticals AR-H: coauthor detecting gluten peptides in human fluids (Patent No. US 20170160288 A1), consultant for Vircell. IRK-S: patent on rapid coeliac antibody detection licensed by the University of Tampere to Labsystems Oy, Finland. MJM: serves on the Advisory Board of Celimmune, USA, ImmusanT, USA and Innovate Pharmaceuticals Inc, USA; is consultant to FinnMedi Oy, Finland and Jilab Oy, Finland via his own company Maki HealthTech Oy, Finland; is an inventor in the patent Methods and Means for Detecting Gluten-Induced Diseases, USA (Patent No. 7,361,480—USA, European Patent No. 1390753). The patent resulted in a commercial product from FinnMedi at the Tampere University Hospital and the University of Tampere, a coeliac disease point-of-care test, Biocard Celiac Test, licensed to Labsystems Diagnostics Oy (former AniBiotech Oy), Finland.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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