{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T01:45:11Z","timestamp":1791769511019,"version":"4.3.4"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21lk0201702"],"award-info":[{"award-number":["JP21lk0201702"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceutical Statistics"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>When the number of patients is limited in clinical trials for rare diseases and pediatric developments, enrolling sufficient participants for confirmatory randomized clinical trials is difficult. Alternative trial designs using external controls have been proposed: augmented randomized clinical trials (ARCTs) and supplemented single\u2010arm trials (SSATs). In order to assess the favorable situations in which to implement each trial design, we propose to specify the sensitivity analysis for confounding at the planning phase, and call it \u201cpre\u2010sensitivity analysis.\u201d In addition, we assessed the probability that the pre\u2010sensitivity analysis would show a treatment effect, which we define as \u201cpower with confounders.\u201d A simulation was carried out across multiple cases, which considered the number of participants from external control data sources and the randomization ratio in an ARCT. The simulation indicated that allocating relatively more participants to the control arm in an ARCT could be considered when the available historical data are equal to or less than the number of concurrent trial participants. Conversely, when the available historical data are sufficient, allocating more participants to the test arm in an SSAT or ARCT could be considered.<\/jats:p>","DOI":"10.1002\/pst.70132","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T01:12:25Z","timestamp":1791767545000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Power With Confounders in Clinical Trials Using External Controls"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0125-6174","authenticated-orcid":false,"given":"Kentaro","family":"Kudo","sequence":"first","affiliation":[{"name":"Statistical and Quantitative Sciences, Data Sciences Institute, Research and Development, Takeda Pharmaceutical Company Ltd.  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9830-013X","authenticated-orcid":false,"given":"Tosiya","family":"Sato","sequence":"additional","affiliation":[{"name":"Institute of Statistical Mathematics  Tokyo Japan"},{"name":"Data Science and AI Innovation Research Promotion Center Shiga University  Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,11]]},"reference":[{"issue":"1","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s13023-020-1332-x","article-title":"A Roadmap to Using Historical Controls in Clinical Trials \u2010 By Drug Information Association Adaptive Design Scientific Working Group (DIA\u2010ADSWG)","volume":"15","author":"Ghadessi M.","year":"2020","journal-title":"Orphanet Journal of Rare Diseases"},{"issue":"7","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s40264-020-00944-1","article-title":"A Framework for Methodological Choice and Evidence Assessment for Studies Using External Comparators From Real\u2010World Data","volume":"43","author":"Gray C. M.","year":"2020","journal-title":"Drug Safety"},{"issue":"6","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1002\/pst.2120","article-title":"The Use of External Controls: To What Extent Can It Currently Be Recommended?","volume":"20","author":"Burger H. U.","year":"2021","journal-title":"Pharmaceutical Statistics"},{"key":"e_1_2_11_5_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.cct.2019.105856","article-title":"Hybrid Clinical Trials to Generate Real\u2010World Evidence: Design Considerations From a Sponsor's Perspective","volume":"94","author":"Zhu M.","year":"2020","journal-title":"Contemporary Clinical Trials"},{"issue":"3","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1097\/EDE.0000000000000457","article-title":"Sensitivity Analysis Without Assumptions","volume":"27","author":"Ding P.","year":"2016","journal-title":"Epidemiology"},{"key":"e_1_2_11_7_1","unstructured":"P.DingandT. J.VanderWeele \u201ceAppendix for \u2018Sensitivity Analysis Without Assumptions\u201daccess date Jun 27 2025 (2016) https:\/\/cdn\u2010links.lww.com\/permalink\/ede\/b\/ede_2016_02_29_ding_ede14\u2010700_sdc1.pdf."},{"issue":"1","key":"e_1_2_11_8_1","doi-asserted-by":"crossref","DOI":"10.1017\/cts.2023.635","article-title":"A Causal Roadmap for Generating High\u2010Quality Real\u2010World Evidence","volume":"7","author":"Dang L. E.","year":"2023","journal-title":"Journal of Clinical and Translational Science"},{"issue":"1","key":"e_1_2_11_9_1","doi-asserted-by":"crossref","DOI":"10.1017\/cts.2023.656","article-title":"Case Study of Semaglutide and Cardiovascular Outcomes: An Application of the Causal Roadmap to a Hybrid Design for Augmenting an RCT Control Arm With Real\u2010World Data","volume":"7","author":"Dang L. E.","year":"2023","journal-title":"Journal of Clinical and Translational Science"},{"issue":"22","key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"6124","DOI":"10.1158\/1078-0432.CCR-21-1471","article-title":"RE\u2010MIND: Comparing Tafasitamab + Lenalidomide (L\u2010MIND) With a Real\u2010World Lenalidomide Monotherapy Arm in Relapsed or Refractory Diffuse Large B\u2010Cell Lymphoma","volume":"27","author":"Zinzani P. L.","year":"2021","journal-title":"Clinical Cancer Research"},{"issue":"7","key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/S1470-2045(20)30225-4","article-title":"Tafasitamab Plus Lenalidomide in Relapsed or Refractory Diffuse Large B\u2010Cell Lymphoma (L\u2010MIND): A Multicentre, Prospective, Single\u2010Arm, Phase 2 Study","volume":"21","author":"Salles G.","year":"2020","journal-title":"Lancet Oncology"},{"key":"e_1_2_11_12_1","unstructured":"U.S. Food and Drug Administration. Center for Drug Evaluation and Research \u201cMulti\u2010Discipline Review: Application Number 761163Orig1s000\u201daccess date Jun 27 2025 (2020) https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2020\/761163Orig1s000MultidisciplineR.pdf."},{"issue":"4","key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/j.1469-1809.1955.tb01285.x","article-title":"The Estimation and Significance of the Logarithm of a Ratio of Frequencies","volume":"20","author":"Haldane J. B.","year":"1956","journal-title":"Annals of Human Genetics"},{"issue":"11","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1002\/sim.8086","article-title":"Using Simulation Studies to Evaluate Statistical Methods","volume":"38","author":"Morris T. P.","year":"2019","journal-title":"Statistics in Medicine"},{"key":"e_1_2_11_15_1","unstructured":"G.Kotecha D. E.Schwartz S.Ventz andL.Trippa \u201cLeveraging External Data in the Analysis of Randomized Controlled Trials: A Comparative Analysis \u201d arXivPreprint posted August 2024 accessed July 7 2026 arXiv:2408.13409 https:\/\/arxiv.org\/pdf\/2408.13409."},{"key":"e_1_2_11_16_1","unstructured":"K.Zhu R.Izem P.Yang et al. \u201cExternally Controlled Trials: A Review of Design and Borrowing Through a Causal Lens \u201d arXivPreprint posted May 2026 accessed July 7 2026. arXiv:2605.03282 https:\/\/arxiv.org\/pdf\/2605.03282."},{"key":"e_1_2_11_17_1","doi-asserted-by":"crossref","unstructured":"C.Liu M.Mayer K.Lactaoen L.Gomez G.Weissman andR.Hubbard \u201cAn E\u2010Value\u2013Informed Sensitivity Analysis Framework for Hybrid Controlled Trials \u201d medRxivPreprint posted March 6 2026 accessed July 7 2026 https:\/\/www.medrxiv.org\/content\/10.64898\/2026.03.05.26347653v1.full.pdf.","DOI":"10.64898\/2026.03.05.26347653"},{"key":"e_1_2_11_18_1","unstructured":"A.Gordon E.H\u00f8jbjerre\u2010Frandsen andA.Schuler \u201cA Non\u2010Parametric Sensitivity Analysis for Bounding Bias in Hybrid Control Trials \u201darXivPreprint posted November 20 2025 accessed July 7 2026 https:\/\/arxiv.org\/abs\/2507.18876v2."},{"issue":"4","key":"e_1_2_11_19_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7326\/M16-2607","article-title":"Sensitivity Analysis in Observational Research: Introducing the E\u2010Value","volume":"167","author":"VanderWeele T. J.","year":"2017","journal-title":"Annals of Internal Medicine"},{"issue":"2","key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.7326\/M18-2159","article-title":"Limitations and Misinterpretations of E\u2010Values for Sensitivity Analyses of Observational Studies","volume":"170","author":"Ioannidis J. P. A.","year":"2019","journal-title":"Annals of Internal Medicine"},{"issue":"2","key":"e_1_2_11_21_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1093\/ije\/dyac018","article-title":"Are E\u2010Values Too Optimistic or Too Pessimistic? Both and Neither!","volume":"51","author":"Sj\u00f6lander A.","year":"2022","journal-title":"International Journal of Epidemiology"}],"container-title":["Pharmaceutical Statistics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pst.70132","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pst.70132","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pst.70132","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T01:12:29Z","timestamp":1791767549000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pst.70132"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,11]]},"references-count":20,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1002\/pst.70132"],"URL":"https:\/\/doi.org\/10.1002\/pst.70132","archive":["Portico"],"relation":{},"ISSN":["1539-1604","1539-1612"],"issn-type":[{"value":"1539-1604","type":"print"},{"value":"1539-1612","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,11]]},"assertion":[{"value":"2025-07-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70132"}}