Online Program Home
My Program

Abstract Details

Activity Number: 115 - Novel Statistical Methods for Emerging Problems in Modern Clinical Trials and Drug Development
Type: Topic Contributed
Date/Time: Monday, July 29, 2019 : 8:30 AM to 10:20 AM
Sponsor: Biopharmaceutical Section
Abstract #306497 Presentation
Title: A Unified Framework for Time-To-Toxicity Dose-Finding Designs in Immune and Non-Immune Clinical Trials
Author(s): Yuan Ji* and Tianjian Zhou
Companies: The University of Chicago and The University of Chicago
Keywords: Clinical Trials; Late-onset toxicity; Maximum tolerated dose; Missing data; Survival Analysis; Bayesian inference

In dose-finding trials, it is desirable to make dose assignment decisions in real time in the presence of pending toxicity outcomes, especially when patient accrual is fast or the dose limiting toxicity is of late-onset. Several time-to-event designs have been proposed for this purpose by utilizing the follow-up time information. We present a unified statistical framework for time-to-event designs to reveal the connection among the existing methods. The general idea is to treat the pending outcomes as censored observations or missing data and proceed with inference by modeling the time-to-toxicity. The frame- work opens the door to new designs, including a class of designs based on probabilistic rules of dose-finding decisions. To facilitate the use of time-to-event designs in practice, we introduce efficient computational algorithms and review common practical considerations such as safety rules and suspension rules. Large sample convergence properties of interval-based time-to-event designs are studied in theory. Finally, the operating characteristics of several designs are evaluated and compared through computer simulations.

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

Back to the full JSM 2019 program