Target toxicity design for phase I dose-finding

Abstract

We propose a new two-/three-stage dose-finding design called Target Toxicity (TT) for phase I clinical trials, where we link the decision rules in the dose-finding process with the conclusions from a hypothesis test. The power to detect excessive toxicity is also given. This solves the problem of why the minimal number of patients is needed for the selected dose level. Our method provides a statistical explanation of traditional ‘3+3’ design using frequentist framework. The proposed method is very flexible and it incorporates other interval-based decision rules through different parameter settings. We provide the decision tables to guide investigators when to decrease, increase or repeat a dose for next cohort of subjects. Simulation experiments were conducted to compare the performance of the proposed method with other dose-finding designs. A free open source R package tsdf is available on CRAN. It is dedicated to deriving two-/three-stage design decision tables and perform dose-finding simulations.

Keywords

• group-sequential-like designs
• dose-finding
• phase i
• mtd
• recommended phase ii doses
• power