{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T10:25:59Z","timestamp":1782210359012,"version":"3.54.5"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:p>Enrolling adequate numbers of patients into the control arm of randomized controlled trials (RCTs) often presents barriers. There is interest in leveraging real\u2010world data (RWD) from electronic health records (EHRs) to construct external control (EC) arms to supplement RCT control arms and form hybrid control (HC) arms. This investigation showed the use of an HC arm in second\u2010line metastatic pancreatic ductal adenocarcinoma (PDAC). The RCT experimental arm (atezolizumab\u2009+\u2009PEGylated recombinant human hyaluronidase (Atezo\u2009+\u2009PEGPH20)) was compared with an HC arm consisting of patients treated with modified FOLFOX6 or gemcitabine\/nab\u2010paclitaxel from the MORPHEUS PDAC internal control arm supplemented with data from a nationwide EHR\u2010derived de\u2010identified database as the EC arm. The EC arm was constructed by applying key inclusion\/exclusion criteria from the MORPHEUS PDAC trial to patients from the real\u2010world cohort. Baseline variables were balanced using propensity score matching and covariate adjustment. Three analysis approaches\u2014Cox model with pooled\u2010control data, Cox model with control arm\u2010specific frailty, and Bayesian analysis using a commensurate prior\u2014were assessed. Overall survival was similar between the treatment arms. The direction and magnitude of hazard ratios (HRs) from the multiple HC analyses (HRs ranged from 1.02 to 1.06) were comparable with the reported trial HR (HR 0.91; 95% CI: 0.56, 1.49). This analysis demonstrates the feasibility and applicability of leveraging RWD in clinical trial design to supplement clinical trial control arms.<\/jats:p>","DOI":"10.1002\/cpt.3528","type":"journal-article","created":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T00:53:57Z","timestamp":1734742437000},"page":"1021-1029","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Investigational Use of Real\u2010World Data as a Hybrid Control in Pancreatic Ductal Adenocarcinoma From the Randomized Phase Ib\/<scp>II MORPHEUS<\/scp> Trial"],"prefix":"10.1002","volume":"117","author":[{"given":"Andrew H.","family":"Ko","sequence":"first","affiliation":[{"name":"University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do\u2010Youn","family":"Oh","sequence":"additional","affiliation":[{"name":"Seoul National University Hospital, Cancer Research Institute Seoul National University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9149-2320","authenticated-orcid":false,"given":"Janet","family":"Lau","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  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