Adaptive phase I-II clinical trial designs identifying optimal biological doses for targeted agents and immunotherapies

dc.contributor.authorZang, Yong
dc.contributor.authorGuo, Beibei
dc.contributor.authorQiu, Yingjie
dc.contributor.authorLiu, Hao
dc.contributor.authorOpyrchal, Mateusz
dc.contributor.authorLu, Xiongbin
dc.contributor.departmentBiostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
dc.date.accessioned2024-08-27T11:51:30Z
dc.date.available2024-08-27T11:51:30Z
dc.date.issued2024
dc.description.abstractTargeted agents and immunotherapies have revolutionized cancer treatment, offering promising options for various cancer types. Unlike traditional therapies the principle of "more is better" is not always applicable to these new therapies due to their unique biomedical mechanisms. As a result, various phase I-II clinical trial designs have been proposed to identify the optimal biological dose that maximizes the therapeutic effect of targeted therapies and immunotherapies by jointly monitoring both efficacy and toxicity outcomes. This review article examines several innovative phase I-II clinical trial designs that utilize accumulated efficacy and toxicity outcomes to adaptively determine doses for subsequent patients and identify the optimal biological dose, maximizing the overall therapeutic effect. Specifically, we highlight three categories of phase I-II designs: efficacy-driven, utility-based, and designs incorporating multiple efficacy endpoints. For each design, we review the dose-outcome model, the definition of the optimal biological dose, the dose-finding algorithm, and the software for trial implementation. To illustrate the concepts, we also present two real phase I-II trial examples utilizing the EffTox and ISO designs. Finally, we provide a classification tree to summarize the designs discussed in this article.
dc.eprint.versionAuthor's manuscript
dc.identifier.citationZang Y, Guo B, Qiu Y, Liu H, Opyrchal M, Lu X. Adaptive phase I-II clinical trial designs identifying optimal biological doses for targeted agents and immunotherapies. Clin Trials. 2024;21(3):298-307. doi:10.1177/17407745231220661
dc.identifier.urihttps://hdl.handle.net/1805/42977
dc.language.isoen_US
dc.publisherSage
dc.relation.isversionof10.1177/17407745231220661
dc.relation.journalClinical Trials
dc.rightsPublisher Policy
dc.sourcePMC
dc.subjectBayesian adaptive design
dc.subjectImmunotherapy
dc.subjectDose optimization
dc.subjectPhase I–II trial
dc.subjectTargeted agent
dc.titleAdaptive phase I-II clinical trial designs identifying optimal biological doses for targeted agents and immunotherapies
dc.typeArticle
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