2024/08/30 by Yunlong Yang, Yang, Yunlong, Ying Yuan +1
Decision Sciences · #FOS: Computer and information sciences #Methodology (stat.ME) #Optimal Experimental Design Methods
paper · pdf · doi:10.48550/arxiv.2408.17392
openalex publication_date 2024/08/30 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
The primary objective of Phase I oncology trials is to assess the safety and tolerability of novel therapeutics. Conventional dose escalation methods identify the maximum tolerated dose (MTD) based on dose-limiting toxicity (DLT). However, as cancer therapies have evolved from chemotherapy to targeted therapies, these traditional methods have become problematic. Many targeted therapies rarely produce DLT and are administered over multiple cycles, potentially resulting in the accumulation of lower-grade toxicities, which can lead to intolerance, such as dose reduction or interruption. To address this issue, we proposed dual-criterion designs that find the MTD based on both DLT and non-DLT-caused intolerance. We considered the model-based design and model-assisted design that allow real-time decision-making in the presence of pending data due to long event assessment windows. Compared to DLT-based methods, our approaches exhibit superior operating characteristics when intolerance is the primary driver for determining the MTD and comparable operating characteristics when DLT is the primary driver.