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Comparison Between Simultaneous and Sequential Utilization of Safety and Efficacy for Optimal Dose Determination in Bayesian Model-Assisted Designs

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Abstract

It has become quite common in recent early oncology trials to include both the dose-finding and the dose-expansion parts within the same study. This shift can be viewed as a seamless way of conducting the trials to obtain information on safety and efficacy hence identifying an optimal dose (OD) rather than just the maximum tolerated dose (MTD). One approach is to conduct a dose-finding part based solely on toxicity outcomes, followed by a dose expansion part to evaluate efficacy outcomes. Another approach employs only the dose-finding part, where the dose-finding decisions are made utilizing both the efficacy and toxicity outcomes of those enrolled patients. In this paper, we compared the two approaches through simulation studies under various realistic settings. The percentage of correct ODs selection, the average number of patients allocated to the ODs, and the average trial duration are reported in choosing the appropriate designs for their early-stage dose-finding trials, including expansion cohorts.

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Data Availability

R shiny app available on https://www.trialdesign.org/ for BOIN12 and TITE-BOIN12 design; SAS code for BOIN-ET and TITE-BOIN-ET and R code for BOIN + BOP2 and TITE-BOIN + BOP2 available upon request.

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Authors and Affiliations

  1. Biostatistics, Data Science, Astellas Pharma Inc, 1 Astellas Way, N3.272.A, Northbrook, IL, 60062, USA

    Ran Li, Kentaro Takeda & Alan Rong

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  1. Ran Li
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  2. Kentaro Takeda
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  3. Alan Rong
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Contributions

RL: Substantial Contribution to the concept, design, conduction of the work. Drafting the work and revising it. KT: Substantial Contribution to the design, conduction of the work. Revising the draft Critically for important intellectual content AR: Revising the draft critically for important intellectual contents.

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Correspondence to Ran Li.

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Li, R., Takeda, K. & Rong, A. Comparison Between Simultaneous and Sequential Utilization of Safety and Efficacy for Optimal Dose Determination in Bayesian Model-Assisted Designs. Ther Innov Regul Sci 57, 728–736 (2023). https://doi.org/10.1007/s43441-023-00517-1

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