The Total i3+3 (Ti3+3) Design for Assessing Multiple Types and Grades of Toxicity in Phase I Trials

Liu, Meizi; Ji, Yuan; Lin, Ji

doi:10.51387/22-NEJSDS7

The New England Journal of Statistics in Data Science

The Total i3+3 (Ti3+3) Design for Assessing Multiple Types and Grades of Toxicity in Phase I Trials

Volume 2, Issue 1 (2024), pp. 72–85

Meizi Liu Yuan Ji Ji Lin

https://doi.org/10.51387/22-NEJSDS7

Pub. online: 4 October 2022 Type: Cancer Research

Open Access

Published
4 October 2022

Abstract

Phase I trials investigate the toxicity profile of a new treatment and identify the maximum tolerated dose for further evaluation. Most phase I trials use a binary dose-limiting toxicity endpoint to summarize the toxicity profile of a dose. In reality, reported toxicity information is much more abundant, including various types and grades of adverse events. Building upon the i3+3 design (Liu et al., 2020), we propose the Ti3+3 design, in which the letter “T” represents “total” toxicity. The proposed design takes into account multiple toxicity types and grades by computing the toxicity burden at each dose. The Ti3+3 design aims to achieve desirable operating characteristics using a simple statistics framework that utilizes“toxicity burden interval” (TBI). Simulation results show that Ti3+3 demonstrates comparable performance with existing more complex designs.

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Keywords

Interval design Multiple toxicity grades Rule-based design Toxicity burden

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