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Activity Number: 359 - Contributed Poster Presentations: Biopharmacutical Section
Type: Contributed
Date/Time: Tuesday, July 31, 2018 : 10:30 AM to 12:20 PM
Sponsor: Biopharmaceutical Section
Abstract #330429
Title: The Modified Toxicity Probability Interval Design with Consideration of Late Onset Toxicities
Author(s): Xiaohui Huang* and Guan Xing
Companies: Gilead Sciences and Gilead Sciences
Keywords: mTPI; Late Oneset Toxicities; dose escalation design

The modified toxicity probability interval (mTPI) design (Ji, et al 2010) is recognized as a reliable model-based method to identify a maximum tolerated dose (MTD) in early phase dose-escalation trials. In the mTPI design, each enrolled subject is followed for a finite period of time based on predictions of when toxicity may occur. Dose escalation decisions are made when toxicity outcomes of a cohort during the follow-up period are observed, and late-onset toxicities are not incorporated in the decisions. Motivated by the time-to-event continual reassessment method proposed by Cheung and Chappell (2000), we extend the standard mTPI design by applying a weighted binomial likelihood in estimating the probability of toxicity at situations with late-onset toxicity concerns. We examine operating characteristics of the time-to-event mTPI design compared with the standard method through simulation studies. Time to toxicity is modeled with multiple distribution models to capture different patterns of toxicity times. Impacts of toxicity time models and the observation period relative to subject admission rate on performance of the proposed design are discussed.

Authors who are presenting talks have a * after their name.

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