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Endoscopy and central reading in inflammatory bowel disease clinical trials: achievements, challenges and future developments
  1. Klaus Gottlieb1,
  2. Marco Daperno2,
  3. Keith Usiskin3,
  4. Bruce E Sands4,
  5. Harris Ahmad5,
  6. Colin W Howden6,
  7. William Karnes7,
  8. Young S Oh8,
  9. Irene Modesto9,
  10. Colleen Marano10,
  11. Ryan William Stidham11,
  12. Walter Reinisch12
  1. 1 Immunology, Eli Lilly and Company, Indianapolis, Indiana, USA
  2. 2 A.O. Ordine Mauriziano di Torino, Torino, Italy
  3. 3 Immunology, Celgene Corp, Summit, New Jersey, USA
  4. 4 Dr Henry D Janowitz Division of Gastroenterology, Mount Sinai School of Medicine, New York, New York, USA
  5. 5 Immunoscience, Bristol-Myers Squibb Co, New York, New York, USA
  6. 6 Gastroenterology, Univ Tennessee, Memphis, Tennessee, USA
  7. 7 Gastroenterology, UC Irvine, Irvine, California, USA
  8. 8 Immunology, Genentech Inc, South San Francisco, California, USA
  9. 9 Inflammation & Immunology, Pfizer Inc, New York, New York, USA
  10. 10 Janssen Research & Development, Spring House, Pennsylvania, USA
  11. 11 Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  12. 12 Department of Medicine IV, Medical University Vienna, Vienna, Austria
  1. Correspondence to Dr Klaus Gottlieb, Immunology, Eli Lilly and Company, Indianapolis, Indiana 46225, USA; klaus.gottlieb{at}lilly.com

Abstract

Central reading, that is, independent, off-site, blinded review or reading of imaging endpoints, has been identified as a crucial component in the conduct and analysis of inflammatory bowel disease clinical trials. Central reading is the final step in a workflow that has many parts, all of which can be improved. Furthermore, the best reading algorithm and the most intensive central reader training cannot make up for deficiencies in the acquisition stage (clinical trial endoscopy) or improve on the limitations of the underlying score (outcome instrument). In this review, academic and industry experts review scoring systems, and propose a theoretical framework for central reading that predicts when improvements in statistical power, affecting trial size and chances of success, can be expected: Multireader models can be conceptualised as statistical or non-statistical (social). Important organisational and operational factors, such as training and retraining of readers, optimal bowel preparation for colonoscopy, video quality, optimal or at least acceptable read duration times and other quality control matters, are addressed as well. The theory and practice of central reading and the conduct of endoscopy in clinical trials are interdisciplinary topics that should be of interest to many, regulators, clinical trial experts, gastroenterology societies and those in the academic community who endeavour to develop new scoring systems using traditional and machine learning approaches.

  • CLINICAL TRIALS
  • INFLAMMATORY BOWEL DISEASE
  • ENDOSCOPY
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  • Contributors KG, in conjunction with WR, devised the project, the main conceptual ideas and wrote the first and subsequent drafts and circulated them among all coauthors. The coauthors revised the drafts in an iterative fashion until consensus was achieved. All authors participated in the drafting and all approved the manuscript and secured organisational permission where required.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests Klaus Gottlieb is an employee and stockholder of Eli Lilly and Company. Marco Daperno reports personal fee from AbbVie, Chiesi, Ferring, Janssen, MD, Pfizer, and Quintiles, grants and personal fees from Takeda, and nonfinancial support from SOFAR and Mundifarma.Keith Usiskin is an employee of Celgene now Bristol Myers Squibb. Bruce Sands has received personal fees from AbbVie, Akros Pharma, Amgen, Arena Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Forward Pharma, Bristol-Myers Squibb, Immune Pharmaceuticals, Shire, Synergy Pharmaceuticals, Theravance Biopharma R&D, TiGenix, TopiVert Pharma, Receptos, Allergan, EnGene, Target PharmaSolutions, Lycera, Lyndra, Ironwood Pharmaceuticals, Salix; grants, personal fees and non-financial support from Celgene, Takeda, Pfizer, Janssen, personal fees and non-financial support from Prometheus Laboratories, Hoffman-La Roche, MedImmune, Lilly, Vivelix Pharmaceuticals, UCB, Oppilan Pharmaceuticals, Gilead, Rheos Medicines, Seres Therapeutics, 4D Pharma, Capella Bioscience, Otsuka, Ferring, Protagonist Therapeutics, Palatin Technologies.Harris Ahmad is an employee of Bristol-Myers Squibb. Colin Howden reports being a consultant for Phathom Pharmaceuticals, Ironwood, RedHill Biopharma, Alfasigma, OtsukaStockholder in Antibe Therapeutics andCo-Editor of Alimentary Pharmacology & Therapeutics.William Karnes reports that he is CMO, cofounder, shareholder and paid contractor for Docbot.Young Oh is an employee of Genentech, a member of the Roche Group and a Roche stock holder. Irene Modesto is and employee and stockholders of Pfizer. Colleen Marano is an employee of Janssen. Ryan Stidham reports consultancy for Abbvie, Janssen, Merck, Takeda. Investigator initiated research support from Abbvie. University of Michigan has filed a provisional patent on behalf of RWS related to machine learning for endoscopic evaluation in IBD.Walter Reinisch has served as a speaker for Abbott Laboratories, Abbvie, Aesca, Aptalis, Astellas, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MD, Otsuka, PDL, Pharmacosmos, PLS Education, Schering-Plough, Shire, Takeda, Therakos, Vifor, Yakult, as a consultant for Abbott Laboratories, Abbvie, Aesca, Algernon, Amgen, AM Pharma, AMT, AOP Orphan, Arena Pharmaceuticals, Astellas, Astra Zeneca, Avaxia, Roland Berger, Bioclinica, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, DSM, Elan, Eli Lilly, Ernest & Young, Falk Pharma, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, LivaNova, Mallinckrodt, Medahead, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MD, Nash Pharmaceuticals, Nestle, Nippon Kayaku, Novartis, Ocera, OMass, Otsuka, Parexel, PDL, Periconsulting, Pharmacosmos, Philip Morris Institute, Pfizer, Procter & Gamble, Prometheus, Protagonist, Provention, Robarts Clinical Trial, Sandoz, Schering-Plough, Second Genome, Seres Therapeutics, Setpointmedical, Sigmoid, Sublimity, Takeda, Therakos, Theravance, Tigenix, UCB, Vifor, Zealand, Zyngenia, and 4SC, as an advisory board member for Abbott Laboratories, Abbvie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, DSM, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Sandoz, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Zealand, Zyngenia, and 4SC, and has received research funding from Abbott Laboratories, Abbvie, Aesca, Centocor, Falk Pharma, Immundiagnsotik, MD.

  • Patient consent for publication Not required.

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

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