{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:24:58Z","timestamp":1789017898344,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>As single\u2010arm trials (SATs) are increasingly used in pharmaceutical research, the validity of such study designs needs to be critically assessed. We characterize the feasibility of supplementing SATs with real\u2010world data (RWD)\u2010derived external control arms by determining the proportion of SATs on breast cancer and amyotrophic lateral sclerosis (ALS) for which an external control arm based on RWD can be constructed. The main outcome measure is the number and percentage of trials for which all important eligibility criteria and at least one primary endpoint could be identified in one of five German RWD sources. We surveyed all SATs concerning breast cancer or ALS treatment registered in the European Union\u2019s clinical trial registers between 2004 and 2023. Ten out of 379 breast cancer SATs and 2 of 11 ALS SATs could feasibly be supplemented with RWD\u2010derived external control arms, if all important eligibility criteria and a primary endpoint have to be identifiable in the RWD source. Ninety\u2010three breast cancer trials had at least one outcome ascertainable in a RWD source, and 35 trials had all important eligibility criteria recorded in a RWD source. Nine ALS trials had at least one primary endpoint ascertainable in RWD sources, and 2 had all important eligibility criteria recorded in a RWD source. Our study shows that SATs with RWD\u2010derived external control arms will rarely be suitable to establish treatment effects of medicines in the current setting for the investigated phenotypes and that SATs should be designed with limitations of the source of external controls in mind.<\/jats:p>","DOI":"10.1002\/cpt.3684","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T11:09:11Z","timestamp":1744801751000},"page":"1443-1450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Supplementing Single\u2010Arm Trials with External Control Arms\u2014Evaluation of German Real\u2010World Data"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9509-0342","authenticated-orcid":false,"given":"Martin","family":"Russek","sequence":"first","affiliation":[{"name":"Research Division, Pharmacoepidemiology Federal Institute for Drugs and Medical Devices (BfArM)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1682-7913","authenticated-orcid":false,"given":"Jonas","family":"Peltner","sequence":"additional","affiliation":[{"name":"Pharmacoepidemiology in Neurodegenerative Disorders German Center for Neurodegenerative Diseases (DZNE)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4828-6058","authenticated-orcid":false,"given":"Britta","family":"Haenisch","sequence":"additional","affiliation":[{"name":"Research Division, Pharmacoepidemiology Federal Institute for Drugs and Medical Devices (BfArM)  Bonn Germany"},{"name":"Pharmacoepidemiology in Neurodegenerative Disorders German Center for Neurodegenerative Diseases (DZNE)  Bonn Germany"},{"name":"University of Bonn Center for Translational Medicine  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1177\/2168479015580383"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43441-024-00693-8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12961-025-01287-y"},{"key":"e_1_2_10_4_1","unstructured":"EudraCT Public website \u2013 Home page<https:\/\/eudract.ema.europa.eu\/>. 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