Faculty, Staff and Student Publications

Language

English

Publication Date

1-1-2025

Journal

Statistics in Biopharmaceutical Research

DOI

10.1080/19466315.2024.2370403

PMID

40321359

PMCID

PMC12046385

PubMedCentral® Posted Date

1-1-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Drug combinations are increasingly utilized in cancer treatment to enhance drug effectiveness through synergistic therapeutic effects. However, determining the optimal biological dose combination (OBDC) in small-scale drug combination trials presents challenges due to the increased complexity of the dose space. To effectively optimize the dose combination of combined drugs, we propose a model-assisted design by extending the single-agent Bayesian optimal interval phase I/II (BOIN12) design. Our approach incorporates a utility function to balance the trade-off between risk and benefit and directly models the utility of each dose by constructing a quasi-beta-binomial model. A key advantage of our design is the simplification of decision-making during interim periods by considering all possible outcomes and pre-including the decision rule in the protocol. Additionally, we present a time-to-event (TITE) version of our design, employing an approximate likelihood approach to mitigate potential late-onset effects. We demonstrate that our proposed design exhibits robust and desirable operating characteristics across various scenarios through extensive simulation studies.

Keywords

Dose optimization, Drug combination, Risk-benefit trade-off, Bayesian adaptive design, Model-assisted design

Published Open-Access

yes

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