{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T17:54:09Z","timestamp":1773942849168,"version":"3.50.1"},"reference-count":9,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001872"],"award-info":[{"award-number":["UL1 TR001872"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UCSF Bakar Computational Health Sciences Institute"},{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\n Background<\/jats:title>\n Randomized trials are the gold-standard for clinical evidence generation, but they can sometimes be limited by infeasibility and unclear generalizability to real-world practice. External control arm (ECA) studies may help address this evidence gaps by constructing retrospective cohorts that closely emulate prospective ones. Experience in constructing these outside the context of rare diseases or cancer is limited. We piloted an approach for developing an ECA in Crohn\u2019s disease using electronic health records (EHR) data.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We queried EHR databases and manually screened records at the University of California, San Francisco to identify patients meeting the eligibility criteria of TRIDENT, a recently completed interventional trial involving an ustekinumab reference arm. We defined timepoints to balance missing data and bias. We compared imputation models by their impacts on cohort membership and outcomes. We assessed the accuracy of algorithmic data curation against manual review. Lastly, we assessed disease activity following treatment with ustekinumab.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Screening identified 183 patients. 30% of the cohort had missing baseline data. Nonetheless, cohort membership and outcomes were robust to the method of imputation. Algorithms for ascertaining non-symptom-based elements of disease activity using structured data were accurate against manual review. The cohort consisted of 56 patients, exceeding planned enrollment in TRIDENT. 34% of the cohort was in steroid-free remission at week 24.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n We piloted an approach for creating an ECA in Crohn\u2019s disease from EHR data by using a combination of informatics and manual methods. However, our study reveals significant missing data when standard-of-care clinical data are repurposed. More work will be needed to improve the alignment of trial design with typical patterns of clinical practice, and thereby enable a future of more robust ECAs in chronic diseases like Crohn\u2019s disease.<\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0282267","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T13:41:52Z","timestamp":1677764512000},"page":"e0282267","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Creation of an ustekinumab external control arm for Crohn\u2019s disease using electronic health records data: A pilot study"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1789-3004","authenticated-orcid":true,"given":"Vivek A.","family":"Rudrapatna","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao-Wen","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3352-9934","authenticated-orcid":true,"given":"Colin","family":"Feuille","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arman","family":"Mosenia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Shih","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongmei","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia","family":"Roberson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Rubin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atul J.","family":"Butte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uma","family":"Mahadevan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Skomrock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ngozi","family":"Erondu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christel","family":"Chehoud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saquib","family":"Rahim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Apfel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Curran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Najat S.","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Terry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin D.","family":"Martini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"pone.0282267.ref001","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1172\/JCI129197","article-title":"Opportunities and challenges in using real-world data for health care","volume":"130","author":"VA Rudrapatna","year":"2020","journal-title":"J Clin Invest"},{"key":"pone.0282267.ref002","author":"Office of the Commissioner","year":"2018","journal-title":"Framework for FDA\u2019s Real-World Evidence Program. In: FDA [Internet]. FDA"},{"key":"pone.0282267.ref003","article-title":"Transforming Clinical Trials with Real-World Evidence.","author":"S Graterman","year":"2021","journal-title":"In: BCG Global [Internet]."},{"key":"pone.0282267.ref004","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1158\/1078-0432.CCR-19-2580","article-title":"FDA Approval Summary: Palbociclib for Male Patients with Metastatic Breast Cancer","volume":"26","author":"S Wedam","year":"2020","journal-title":"Clin Cancer Res Off J Am Assoc Cancer Res"},{"key":"pone.0282267.ref005","doi-asserted-by":"crossref","first-page":"e100337","DOI":"10.1136\/bmjhci-2021-100337","article-title":"Utility of routinely collected electronic health records data to support effectiveness evaluations in inflammatory bowel disease: a pilot study of tofacitinib","volume":"28","author":"VA Rudrapatna","year":"2021","journal-title":"BMJ Health Care Inform"},{"key":"pone.0282267.ref006","unstructured":"Janssen Research & Development, LLC. A Phase 2b, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Multicenter Study to Evaluate the Safety and Efficacy of JnJ-64304500 in Subjects With Moderately to Severely Active Crohn\u2019s Disease. clinicaltrials.gov; 2021 Jul. Report No.: NCT02877134. Available: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02877134"},{"key":"pone.0282267.ref007","author":"S. Van Buuren","journal-title":"Flexible Imputation of Missing Data"},{"key":"pone.0282267.ref008","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1056\/NEJMoa1602773","article-title":"Ustekinumab as Induction and Maintenance Therapy for Crohn\u2019s Disease","volume":"375","author":"BG Feagan","year":"2016","journal-title":"N Engl J Med"},{"key":"pone.0282267.ref009","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1001\/jamainternmed.2018.3931","article-title":"Estimated Costs of Pivotal Trials for Novel Therapeutic Agents Approved by the US Food and Drug Administration, 2015\u20132016","volume":"178","author":"TJ Moore","year":"2018","journal-title":"JAMA Intern Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0282267","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T13:42:12Z","timestamp":1677764532000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0282267"}},"subtitle":[],"editor":[{"given":"Sreeram V.","family":"Ramagopalan","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,3,2]]},"references-count":9,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0282267","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.11.12.21266064","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,2]]}}}