SFU: Surface-Free Utility-Based Design for Dose Optimization in Cancer Drug Combination Trials

Precision oncology has demonstrated the potential of drug combinations in effectively enhancing anti-tumor efficiency and controlling disease progression. Nonetheless, dose optimization in early-phase drug combination trials presents various challenges and is considerably more complex than single-ag...

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Bibliographic Details
Published in:Statistics in biosciences 2024-12, Vol.16 (3), p.854-881
Main Authors: Zhang, Jingyi, Wages, Nolan A., Lin, Ruitao
Format: Article
Language:English
Subjects:
Biostatistics
Chemotherapy
Design optimization
Drug development
Drug dosages
Effectiveness
Health Sciences
Mathematics and Statistics
Medicine
Optimization
Original Paper
Precision medicine
Statistics
Statistics for Life Sciences
Theoretical Ecology/Statistics
Toxicity
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Summary:Precision oncology has demonstrated the potential of drug combinations in effectively enhancing anti-tumor efficiency and controlling disease progression. Nonetheless, dose optimization in early-phase drug combination trials presents various challenges and is considerably more complex than single-agent dose optimization. To address this, we propose a surface-free design for exploring the optimal doses of combination therapy within the phase I–II framework. Rather than relying on parametric models to define the shape of toxicity and efficacy surfaces, our approach centers on characterizing dose-toxicity and dose-efficacy relationships between adjacent dose combinations using surface-free models. The proposed design encompasses a run-in phase, facilitating a swift exploration of the dose space, followed by a main phase where the dose-finding rule relies on the proposed surface-free model. Through extensive simulation studies, we have thoroughly examined the operating characteristics of this innovative design. The results demonstrate that our method exhibits desirable operating characteristics across a wide range of dose-toxicity and dose-efficacy relationships.
ISSN:1867-1764
1867-1772
DOI:10.1007/s12561-024-09424-x