Improved utility with adaptive penalties in dose-optimization trials

Improved utility with adaptive penalties in dose-optimization trials | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Improved utility with adaptive penalties in dose-optimization trials Weijia Zhang, Jingyi Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8852216/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background: The objective of Phase I/II dose-finding design is to determine the Optimal Biological Dose(OBD) that is acceptably safe and demonstrates sufficient anti-tumor activity by maximizing a pre-specified utility function that balances safety and efficacy. In oncology, treatment is typically delivered over multiple cycles, which complicates OBD identification, moreover, achieving higher anti-tumor activity requires toxicity that is under control. Method: To address this challenge, we propose and evaluate the improved utility with pre-specified weights and adaptive penalties methods to regulate toxicity according to doses. Results: This approach enables the dynamic optimal dose that could be recommended based on trade-off between safety and efficacy. Conclusions: The simulation studies demonstrate that the proposed model outperforms the simply utility method across several performance metrics. Utility Adaptive penalties Toxicity-efficacy Dose-optimization trial Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 24 Apr, 2026 Reviewers agreed at journal 15 Apr, 2026 Reviewers invited by journal 15 Apr, 2026 Editor assigned by journal 28 Feb, 2026 Editor invited by journal 25 Feb, 2026 Submission checks completed at journal 25 Feb, 2026 First submitted to journal 25 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8852216","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":626552354,"identity":"c91d2c76-da82-4dd0-91c2-f7b25eb037a3","order_by":0,"name":"Weijia Zhang","email":"","orcid":"","institution":"Hubei University of Automotive Technology","correspondingAuthor":false,"prefix":"","firstName":"Weijia","middleName":"","lastName":"Zhang","suffix":""},{"id":626552355,"identity":"90ead03e-d4d4-4e82-b4c1-e40257e197f9","order_by":1,"name":"Jingyi Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIiWNgGAWjYJCCAyDCgIGB+eGHCgk5eVK0sBlLnLEwNmwg1iqgFgYJ3raKRIgJeIA5e+/Dgz/+2MkDGQcMJOdJJDA2MD98dAOPFsue4waHeduSDXf2nEt4ULhNIo8d6EDjHHzuuZHGcBhocILBjRwDA8ltEsWMDTxs0ni13H/GAHRYfYLB/TcGErxzJBIbDhDScoONAajmMNAWHqCWBmK0nAE6jLftuOGGMzlmxhLHJIwNmwn55fgx5o8//lTLGxw/Y/zwQ02dnDx788PH+LRgAcykKR8Fo2AUjIJRgAUAAG9rTI1SgSE9AAAAAElFTkSuQmCC","orcid":"","institution":"Imperial College London","correspondingAuthor":true,"prefix":"","firstName":"Jingyi","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2026-02-11 13:23:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8852216/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8852216/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107704518,"identity":"41e5897c-aa9f-4a87-ae5d-3a28cc84e4bd","added_by":"auto","created_at":"2026-04-24 08:45:54","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":247782,"visible":true,"origin":"","legend":"","description":"","filename":"main.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8852216/v1_covered_ad5991d1-b740-49d3-a208-055c93351508.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Improved utility with adaptive penalties in dose-optimization trials","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-medical-research-methodology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmrm","sideBox":"Learn more about [BMC Medical Research Methodology](http://bmcmedresmethodol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmrm/default.aspx","title":"BMC Medical Research Methodology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Utility, Adaptive penalties, Toxicity-efficacy, Dose-optimization trial","lastPublishedDoi":"10.21203/rs.3.rs-8852216/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8852216/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: The objective of Phase I/II dose-finding design is to determine the Optimal Biological Dose(OBD) that is acceptably safe and demonstrates sufficient anti-tumor activity by maximizing a pre-specified utility function that balances safety and efficacy. 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