{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T06:49:44Z","timestamp":1784357384178,"version":"3.55.0"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T00:00:00Z","timestamp":1718323200000},"content-version":"vor","delay-in-days":74,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In 2022, the Food and Drug Administration (FDA) updated its draft guidance for drug development in ulcerative colitis, replacing the version from 2016. Several changes from the 2016 version merit further discussion as they impact clinical trial design and the interpretation of trial results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We compared both documents and critically appraised the changes and implications for future clinical trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The 2022 guidance recommends full colonoscopy, rather than flexible sigmoidoscopy, to document disease activity in all involved segments of the colon. The concordance between the findings of the 2 procedures is very high and there is little evidence to support colonoscopy over sigmoidoscopy. The use of colonoscopy, rather than sigmoidoscopy, is also associated with a higher burden to trial participants who must undergo full bowel preparation, cost, and a potential for more adverse events. The definition of the Mayo endoscopic score of 0 was changed from the original publication to \u201cnormal appearance of mucosa,\u201d which suggests that endoscopic signs of prior disease, such as pseudopolyps and scarring, are incompatible with a score 0, even though they are not associated with active disease. The term \u201cmucosal healing\u201d has been abolished and histologic outcomes defined as exploratory. A welcome change is that shorter washout periods than 5 half-lives will be considered to reduce patient exposure to corticosteroids as bridging therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The 2022 FDA draft guidance includes changes which for the most part are not informed by empirical evidence, which may ultimately complicate interpretation of future trials and preclude comparisons with past trials.<\/jats:p><\/jats:sec>","DOI":"10.1093\/crocol\/otae038","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T13:27:26Z","timestamp":1718371646000},"source":"Crossref","is-referenced-by-count":3,"title":["Differences Between the 2016 and 2022 Food and Drug Administration Guidance\u2014Implications for Design and Interpretation of Clinical Trials in Ulcerative Colitis"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3158-8014","authenticated-orcid":false,"given":"Jurij","family":"Hanzel","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Faculty of Medicine, University of Ljubljana , Ljubljana , Slovenia"},{"name":"Alimentiv Inc. , London, Ontario , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4698-9948","authenticated-orcid":false,"given":"Christopher","family":"Ma","sequence":"additional","affiliation":[{"name":"Alimentiv Inc. , London, Ontario , Canada"},{"name":"Division of Gastroenterology & Hepatology, Cumming School of Medicine, University of Calgary , Calgary, AL , Canada"},{"name":"Department of Community Health Sciences, Cumming School of Medicine, University of Calgary , Calgary, AL , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Peyrin-Biroulet","sequence":"additional","affiliation":[{"name":"INSERM, NGERE, University of Lorraine , Nancy , France"},{"name":"INFINY Institute, Nancy University Hospital , Vand\u0153uvre-l\u00e8s-Nancy , France"},{"name":"FHU-CURE, Nancy University Hospital , Vand\u0153uvre-l\u00e8s-Nancy , France"},{"name":"GroupeHospitalier Priv\u00e9 Ambroise Par\u00e9 \u2013 Hartmann, Paris IBD Center , Neuilly sur Seine , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7341-1351","authenticated-orcid":false,"given":"Silvio","family":"Danese","sequence":"additional","affiliation":[{"name":"Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce E","family":"Sands","sequence":"additional","affiliation":[{"name":"Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1092-0033","authenticated-orcid":false,"given":"Vipul","family":"Jairath","sequence":"additional","affiliation":[{"name":"Alimentiv Inc. , London, Ontario , Canada"},{"name":"Department of Medicine, Division of Gastroenterology, University of Western Ontario , London, ON , Canada"},{"name":"Department of Epidemiology and Biostatistics, University of Western Ontario , London, ON , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,14]]},"reference":[{"key":"2024062813411699700_CIT0001","volume-title":"Ulcerative Colitis: Developing Drugs for Treatment","author":"Food and Drug Administration","year":"2022"},{"key":"2024062813411699700_CIT0002","volume-title":"Ulcerative Colitis: Clinical Trial Endpoints","author":"Food and Drug Administration","year":"2016"},{"issue":"26","key":"2024062813411699700_CIT0003","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1056\/NEJM198712243172603","article-title":"Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. a randomized study","volume":"317","author":"Schroeder","year":"1987","journal-title":"N Engl J Med."},{"issue":"2","key":"2024062813411699700_CIT0004","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1053\/j.gastro.2015.10.016","article-title":"Agreement between rectosigmoidoscopy and colonoscopy analyses of disease activity and healing in patients with ulcerative colitis","volume":"150","author":"Colombel","year":"2016","journal-title":"Gastroenterology."},{"issue":"4","key":"2024062813411699700_CIT0005","doi-asserted-by":"crossref","first-page":"e750","DOI":"10.1016\/j.cgh.2021.02.007","article-title":"Spatial evolution of histologic and endoscopic healing in the left and right colon in patients with ulcerative colitis","volume":"20","author":"Jangi","year":"2022","journal-title":"Clin Gastroenterol Hepatol."},{"issue":"1","key":"2024062813411699700_CIT0006","doi-asserted-by":"crossref","first-page":"17562848221098849","DOI":"10.1177\/17562848221098849","article-title":"Clinical relevance of endoscopic peri-appendiceal red patch in ulcerative colitis patients","volume":"15","author":"Reijntjes","year":"2022","journal-title":"Therap Adv Gastroenterol"},{"issue":"2","key":"2024062813411699700_CIT0007","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.1093\/jcag\/gwaa001","article-title":"Systematic review: patient perceptions of monitoring tools in inflammatory bowel disease","volume":"4","author":"Goodsall","year":"2021","journal-title":"J. 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