The i3+3 Design for Phase I Clinical Trials

Liu, Meizi; Wang, Sue-Jane; Ji, Yuan

doi:10.48550/arxiv.1901.01303

Cited by 1 publication

(2 citation statements)

References 13 publications

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“…The PoD-TPI design is built upon the mTPI-2 design. Nevertheless, the proposed strategy can be applied to other model-free or model-assisted designs such as 3+3 (Storer, 1989), BOIN (Liu and Yuan, 2015), keyboard (Yan et al, 2017) or i3+3 (Liu et al, 2019). It suffices to change the deterministic decision function A according to the specific design.…”

Section: Discussionmentioning

confidence: 99%

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PoD-TPI: Probability-of-Decision Toxicity Probability Interval Design to Accelerate Phase I Trials

Zhou

Guo

2019

Stat Biosci

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Cohort-based enrollment can slow down dose-finding trials since the outcomes of the previous cohort must be fully evaluated before the next cohort can be enrolled. This results in frequent suspension of patient enrollment. The issue is exacerbated in recent immune oncology trials where toxicity outcomes can take a long time to observe. We propose a novel phase I design, the probability-of-decision toxicity probability interval (PoD-TPI) design, to accelerate phase I trials. PoD-TPI enables dose assignment in real time in the presence of pending toxicity outcomes. With uncertain outcomes, the dose assignment decisions are treated as a random variable, and we calculate the posterior distribution of the decisions. The posterior distribution reflects the variability in the pending outcomes and allows a direct and intuitive evaluation of the confidence of all possible decisions. Optimal decisions are calculated based on 0-1 loss, and extra safety rules are constructed to enforce sufficient protection from exposing patients to risky doses. A new and useful feature of PoD-TPI is that it allows investigators and regulators to balance the trade-off between enrollment speed and making risky decisions by tuning a pair of intuitive design parameters. Through numerical studies, we evaluate the operating characteristics of PoD-TPI and demonstrate that PoD-TPI shortens trial duration and maintains trial safety and efficiency compared to existing time-to-event designs.

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Section: Discussionmentioning

confidence: 99%

“…Simpler model-assisted designs like the cumulative cohort design (CCD, Ivanova et al, 2007) and the Bayesian optimal interval design (BOIN, Liu and Yuan, 2015) also uses intervals as the basis for decision making. The latest i3+3 design (Liu et al, 2019) is again based on interval rules, but without a model.…”

Section: Introductionmentioning

confidence: 99%