arXiv subjects

Philip He

Publications and source records attributed to Philip He.

3 recordsLinked to original sources

arXiv2026

BOIN Designs for Dose Escalation With Selected Dose Combinations in Oncology Phase I Trials

In phase I dose escalation studies for dual-agent combinations, at least one drug often has an established monotherapy dose. Consequently, substantial prior clinical safety data often exist for one or more monotherapies, allowing the study to focus on a subset of selected dose combinations rather than exhaustively evaluating all possible dose combinations for two agents. The Bayesian Optimal Interval (BOIN) design framework is widely recognized for its robust performance and ease of implementation; however, the BOIN for combination design, abbreviated as BOIN-C in this paper, was originally developed to evaluate full combinations and may not be directly applicable for the subset of selected combinations. In this paper, we propose three extensions to the BOIN-C design to address scenarios involving selected dose combinations: (a) BOIN-CS: a generalized BOIN-C design to accommodate any subset of dose combinations. (b) BOIN-CE: Exploration of new off-diagonal dose combinations when de-escalating. This option provides additional opportunities to treat patients with dose combinations that have not been administered. (c) BOIN-CB: Bayesian logistic regression model (BLRM)-guided BOIN design, which uses the BLRM model to break the tie when two dose combinations have an equal posterior probability of being selected. This can be useful when the dose-toxicity relationship is expected to be reasonably aligned with a logistic relationship. These study design options are motivated by practical considerations, and their operating characteristics are evaluated through extensive simulations under various scenarios, demonstrating satisfactory performance.

stat.ME↗

arXiv2024

A Bayesian Hybrid Design with Borrowing from Historical Study

In early phase drug development of combination therapy, the primary objective is to preliminarily assess whether there is additive activity from a novel agent when combined with an established monotherapy. Due to potential feasibility issues for conducting a large randomized study, uncontrolled single-arm trials have been the mainstream approach in cancer clinical trials. However, such trials often present significant challenges in deciding whether to proceed to the next phase of development due to the lack of randomization in traditional two-arm trials. A hybrid design, leveraging data from a completed historical clinical study of the monotherapy, offers a valuable option to enhance study efficiency and improve informed decision-making. Compared to traditional single-arm designs, the hybrid design may significantly enhance power by borrowing external information, enabling a more robust assessment of activity. The primary challenge of hybrid design lies in handling information borrowing. We introduce a Bayesian dynamic power prior (DPP) framework with three components of controlling amount of dynamic borrowing. The framework offers flexible study design options with explicit interpretation of borrowing, allowing customization according to specific needs. Furthermore, the posterior distribution in the proposed framework has a closed form, offering significant advantages in computational efficiency. The proposed framework's utility is demonstrated through simulations and a case study.

stat.ME↗

arXiv2023

A Bayesian Basket Trial Design Using Local Power Prior

In recent years, basket trials, which allow the evaluation of an experimental therapy across multiple tumor types within a single protocol, have gained prominence in early-phase oncology development. Unlike traditional trials, which evaluate each tumor type separately and often face challenges with limited sample sizes, basket trials offer the advantage of borrowing information across various tumor types to enhance statistical power. However, a key challenge in designing basket trials is determining the appropriate extent of information borrowing while maintaining an acceptable type I error rate control. In this paper, we propose a novel 3-component local power prior (local-PP) framework that introduces a dynamic and flexible approach to information borrowing. The framework consists of three components: global borrowing control, pairwise similarity assessments, and a borrowing threshold, allowing for tailored and interpretable borrowing across heterogeneous tumor types. Unlike many existing Bayesian methods that rely on computationally intensive Markov chain Monte Carlo (MCMC) sampling, the proposed approach provides a closed-form solution, significantly reducing computation time in large-scale simulations for evaluating operating characteristics. Extensive simulations demonstrate that the proposed local-PP framework performs comparably to more complex methods while significantly shortening computation time.

stat.AP↗