BE-BOIN: A Dose Optimization Design Accommodating Backfill and Late-Onset Toxicity
4 affiliations
- 1Eli Lilly and Company, Indianapolis, IN USA
- 2Department of Biostatistics and Data Science, The University of Texas Health Science Center, Houston, TX USA
- 3Astellas Pharma Global Development Inc., Northbrook, IL USA
- 4Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX USA
Abstract
The US Food and Drug Administration (FDA) launched Project Optimus and issued guidance to reform dose-finding and selection trials, shifting the paradigm from identifying the maximum tolerated dose (MTD) to determining the optimal biological dose (OBD), which optimizes the risk and benefit of treatments. The FDA’s guidance emphasizes the importance of collecting sufficient toxicity and efficacy data across multiple doses and considering late-onset cumulative toxicity that often results in tolerability issues. To address these challenges, we propose the BE-BOIN (Backfill time-to-Event Bayesian Optimal INterval) design, which allows backfilling patients into safe and effective doses during dose escalation and accommodates late-onset toxicities. BE-BOIN enables the collection of additional safety and efficacy data to enhance the accuracy and reliability of OBD selection and supports real-time dose decisions for new patients. Our simulation studies show that BE-BOIN accurately identifies the MTD and OBD while significantly reducing trial duration.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s43441-026-00994-0.
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BibTeX
@article{chen2026beboin,
title = {{BE-BOIN: A Dose Optimization Design Accommodating Backfill and Late-Onset Toxicity}},
author = {Kai Chen and Yixuan Zhao and Kentaro Takeda and Ying Yuan},
journal = {Therapeutic Innovation \& Regulatory Science},
year = {2026},
month = aug,
doi = {10.1007/s43441-026-00994-0},
url = {https://doi.org/10.1007/s43441-026-00994-0},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - BE-BOIN: A Dose Optimization Design Accommodating Backfill and Late-Onset Toxicity
AU - Kai Chen
AU - Yixuan Zhao
AU - Kentaro Takeda
AU - Ying Yuan
PY - 2026
DA - 2026/08/10
JO - Therapeutic Innovation & Regulatory Science
DO - 10.1007/s43441-026-00994-0
UR - https://doi.org/10.1007/s43441-026-00994-0
AB - The US Food and Drug Administration (FDA) launched Project Optimus and issued guidance to reform dose-finding and selection trials, shifting the paradigm from identifying the maximum tolerated dose (MTD) to determining the optimal biological dose (OBD), which optimizes the risk and benefit of treatments. The FDA’s guidance emphasizes the importance of collecting sufficient toxicity and efficacy data across multiple doses and considering late-onset cumulative toxicity that often results in tolerability issues. To address these challenges, we propose the BE-BOIN (Backfill time-to-Event Bayesian Optimal INterval) design, which allows backfilling patients into safe and effective doses during dose escalation and accommodates late-onset toxicities. BE-BOIN enables the collection of additional safety and efficacy data to enhance the accuracy and reliability of OBD selection and supports real-time dose decisions for new patients. Our simulation studies show that BE-BOIN accurately identifies the MTD and OBD while significantly reducing trial duration. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s43441-026-00994-0.
SN - 2168-4790
SN - 2168-4804
ER -