{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T11:00:10Z","timestamp":1781780410315,"version":"3.54.5"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:00:00Z","timestamp":1714003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alimentiv Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Regulatory guidance for Crohn\u2019s disease trials recommends coprimary efficacy end points that evaluate both symptoms and mucosal inflammation. We aimed to characterize the operating properties of commonly used disease activity assessments alone and in combination.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Endoscopic and clinical data were available for 129 participants from the Study of Biologic and Immunomodulator Na\u00efve Patients in Crohn\u2019s Disease trial. Readers scored the Simple Endoscopic Score for Crohn\u2019s Disease and the Crohn\u2019s Disease Endoscopic Index of Severity using standardized conventions. Index reliability was determined using intraclass correlation coefficients. Index responsiveness was assessed using standardized effect sizes based upon treatment assignment. Outcomes were evaluated for optimal sensitivity to treatment effect.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Substantial inter-rater reliability was observed when the Simple Endoscopic Score for Crohn\u2019s Disease and Crohn\u2019s Disease Endoscopic Index of Severity were used as continuous measures (intraclass correlation coefficient, 0.64; 95% confidence interval [CI], 0.50-0.73; and 0.62 95% CI, 0.36-0.77) compared with moderate reliability when dichotomized (0.46; 95% CI, 0.26-0.65; and 0.51; 95% CI, 0.00-0.78). The Simple Endoscopic Score for Crohn\u2019s Disease, Crohn\u2019s Disease Endoscopic Index of Severity, patient-reported outcome-2, and Crohn\u2019s Disease Activity Index were similarly responsive (standardized effect size, 0.43, 95% CI, 0.05-0.81; 0.38, 95% CI, 0.0-0.76; 0.53, 95% CI, 0.15-0.91). A composite outcome of Crohn\u2019s Disease Activity Index score\u2005&amp;lt;150 and Crohn\u2019s Disease Endoscopic Index of Severity score\u2005&amp;lt;6 was most sensitive to treatment effect (28.9%; 95% CI, 11.0%-46.8%; P\u2005=\u2005.003).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Endoscopic indices were more reliable as continuous measures. Composite outcomes including endoscopy improved sensitivity to treatment effect.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izae089","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T13:34:11Z","timestamp":1714052051000},"page":"706-715","source":"Crossref","is-referenced-by-count":4,"title":["Reliability and Responsiveness of Clinical and Endoscopic Outcome Measures in Crohn\u2019s Disease"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8679-2541","authenticated-orcid":false,"given":"Reena","family":"Khanna","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Western Ontario , London, Ontario ,","place":["Canada"]},{"name":"Department of Biostatistics and Epidemiology, University of Western Ontario , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6914-3822","authenticated-orcid":false,"given":"Brian G","family":"Feagan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Western Ontario , London, Ontario ,","place":["Canada"]},{"name":"Department of Biostatistics and Epidemiology, University of Western Ontario , London, Ontario ,","place":["Canada"]},{"name":"Alimentiv Inc. , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyong","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Epidemiology, University of Western Ontario , London, Ontario ,","place":["Canada"]},{"name":"Alimentiv Inc. , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry W","family":"Stitt","sequence":"additional","affiliation":[{"name":"Alimentiv Inc. , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W D","family":"McDonald","sequence":"additional","affiliation":[{"name":"Alimentiv Inc. , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Bressler","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, University of British Columbia , Vancouver, British Columbia ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5247-940X","authenticated-orcid":false,"given":"Remo","family":"Panaccione","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Calgary , Calgary, Alberta ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M","family":"Shackelton","sequence":"additional","affiliation":[{"name":"Alimentiv Inc. , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"VanViegen","sequence":"additional","affiliation":[{"name":"Alimentiv Inc. , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Edward V","family":"Loftus","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science , Rochester, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Daperno","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Division of Gastroenterology), Azienda Ospedaliera Ordine Mauriziano di Torino , Torino, Piemonte ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipul","family":"Jairath","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Western Ontario , London, Ontario ,","place":["Canada"]},{"name":"Department of Biostatistics and Epidemiology, University of Western Ontario , London, Ontario ,","place":["Canada"]},{"name":"Alimentiv Inc. , London, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2784-4046","authenticated-orcid":false,"given":"Geert","family":"D\u2019Haens","sequence":"additional","affiliation":[{"name":"Alimentiv Inc. , London, Ontario ,","place":["Canada"]},{"name":"Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Location AMC , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J","family":"Sandborn","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, University of California San Diego , La Jolla, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,25]]},"reference":[{"key":"2025030423093461600_CIT0001","volume-title":"Crohn\u2019s Disease: Developing Drugs for Treatment Guidance for Industry","author":"U.S. Department of Health and Human Services Food and Drug Administration","year":"2022"},{"key":"2025030423093461600_CIT0002","article-title":"Guideline on the development of new medicinal products for the treatment of Crohn\u2019s Disease","author":"European Medicines Agency","year":"2018"},{"issue":"3","key":"2025030423093461600_CIT0003","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S0016-5085(76)80163-1","article-title":"Development of a Crohn\u2019s disease activity index. National Cooperative Crohn\u2019s Disease Study","volume":"70","author":"Best","year":"1976","journal-title":"Gastroenterology."},{"issue":"4","key":"2025030423093461600_CIT0004","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/s0016-5107(04)01878-4","article-title":"Development and validation of a new, simplified endoscopic activity score for Crohn\u2019s disease: the SES-CD","volume":"60","author":"Daperno","year":"2004","journal-title":"Gastrointest Endosc."},{"issue":"7","key":"2025030423093461600_CIT0005","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1136\/gut.30.7.983","article-title":"Development and validation of an endoscopic index of the severity for Crohn\u2019s disease: a prospective multicentre study. Groupe d\u2019Etudes Th\u00e9rapeutiques des Affections Inflammatoires du Tube Digestif (GETAID)","volume":"30","author":"Mary","year":"1989","journal-title":"Gut."},{"issue":"1","key":"2025030423093461600_CIT0006","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/apt.13001","article-title":"A retrospective analysis: the development of patient reported outcome measures for the assessment of Crohn\u2019s disease activity","volume":"41","author":"Khanna","year":"2015","journal-title":"Aliment Pharmacol Ther."},{"issue":"7","key":"2025030423093461600_CIT0007","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1136\/gutjnl-2014-308973","article-title":"Reliability among central readers in the evaluation of endoscopic findings from patients with Crohn\u2019s disease","volume":"65","author":"Khanna","year":"2016","journal-title":"Gut."},{"issue":"10","key":"2025030423093461600_CIT0008","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1038\/ajg.2016.580","article-title":"Responsiveness of endoscopic indices of disease activity for Crohn\u2019s disease","volume":"112","author":"Khanna","year":"2017","journal-title":"Am J Gastroenterol."},{"issue":"9","key":"2025030423093461600_CIT0009","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1093\/ecco-jcc\/jjw120","article-title":"Effect of standardised scoring conventions on inter-rater reliability in the endoscopic evaluation of Crohn\u2019s disease","volume":"10","author":"Dubcenco","year":"2016","journal-title":"J Crohns Colitis."},{"issue":"5","key":"2025030423093461600_CIT0010","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1053\/j.gastro.2013.08.010","article-title":"Validation of endoscopic activity scores in patients with Crohn\u2019s disease based on a post hoc analysis of data from SONIC","volume":"145","author":"Ferrante","year":"2013","journal-title":"Gastroenterology."},{"issue":"15","key":"2025030423093461600_CIT0011","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1056\/NEJMoa0904492","article-title":"Infliximab, azathioprine, or combination therapy for Crohn\u2019s disease","volume":"362","author":"Colombel","year":"2010","journal-title":"N Engl J Med."},{"issue":"8","key":"2025030423093461600_CIT0012","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1093\/ptj\/74.8.777","article-title":"Statistical methodology for the concurrent assessment of interrater and intrarater reliability: using goniometric measurements as an example","volume":"74","author":"Eliasziw","year":"1994","journal-title":"Phys Ther."},{"issue":"1","key":"2025030423093461600_CIT0013","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2307\/2529310","article-title":"The measurement of observer agreement for categorical data","volume":"33","author":"Landis","year":"1977","journal-title":"Biometrics."},{"key":"2025030423093461600_CIT0014","volume-title":"Statsitical Power for the Behavioral Sciences.","author":"Cohen","year":"1988"},{"issue":"11","key":"2025030423093461600_CIT0015","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1016\/j.cgh.2008.06.010","article-title":"Relationships between disease activity and serum and fecal biomarkers in patients with Crohn\u2019s disease","volume":"6","author":"Jones","year":"2008","journal-title":"Clin Gastroenterol Hepatol."},{"issue":"3","key":"2025030423093461600_CIT0016","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1111\/apt.14853","article-title":"An expert consensus to standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Crohn\u2019s disease","volume":"48","author":"Rieder","year":"2018","journal-title":"Aliment Pharmacol Ther."},{"issue":"21","key":"2025030423093461600_CIT0017","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1056\/NEJMoa2212728","article-title":"Upadacitinib induction and maintenance therapy for Crohn\u2019s disease","volume":"388","author":"Loftus","year":"2023","journal-title":"N Engl J Med."},{"issue":"10340","key":"2025030423093461600_CIT0018","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.1016\/S0140-6736(22)00466-4","article-title":"Risankizumab as maintenance therapy for moderately to severely active Crohn\u2019s disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial","volume":"399","author":"Ferrante","year":"2022","journal-title":"Lancet."},{"issue":"5","key":"2025030423093461600_CIT0019","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/j.cgh.2019.08.025","article-title":"Response to Placebo, measured by endoscopic evaluation of Crohn\u2019s disease activity, in a pooled analysis of data from 5 randomized controlled induction trials","volume":"18","author":"Duijvestein","year":"2020","journal-title":"Clin Gastroenterol Hepatol."}],"container-title":["Inflammatory Bowel Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ibdjournal\/advance-article-pdf\/doi\/10.1093\/ibd\/izae089\/57332291\/izae089.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article-pdf\/31\/3\/706\/57332291\/izae089.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article-pdf\/31\/3\/706\/57332291\/izae089.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T23:10:42Z","timestamp":1741129842000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article\/31\/3\/706\/7658207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,25]]},"references-count":19,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,4,25]]},"published-print":{"date-parts":[[2025,3,3]]}},"URL":"https:\/\/doi.org\/10.1093\/ibd\/izae089","relation":{},"ISSN":["1078-0998","1536-4844"],"issn-type":[{"value":"1078-0998","type":"print"},{"value":"1536-4844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,3]]},"published":{"date-parts":[[2024,4,25]]}}}