Practical Model-Based Dose Finding in Early-Phase Clinical Trials

Practical model-based dose finding in early-phase clinical trials: optimizing tissue plasminogen activator dose for treatment of ischemic stroke in children.

BACKGROUND AND PURPOSE A safe and effective tissue plasminogen activator (tPA) dose for childhood stroke has not been established. This article describes a Bayesian outcome-adaptive method for determining the best dose of an experimental agent and explains how this method was used to design a dose-finding trial for tPA in childhood. METHODS The method assigns doses to successive cohorts of pa...

Dose-finding Designs for Phase Ii Clinical Trials

Adaptive dose insertion in early phase clinical trials.

BACKGROUND AND PURPOSE We propose to adaptively insert new doses during the course of a dose-finding trial when none of the prespecified doses in the trial are acceptable, for example, have tolerable toxicity. METHODS Our procedure uses an activation rule to determine whether a new dose is needed and an inverse dose-response algorithm to estimate new doses to be inserted into the trial. RES...

Bayesian Dose Finding in Phase I Clinical Trials Based on a New Statistical Framework

Phase I clinical trials aim to find the maximum tolerated dose of an experimental drug. We consider dose escalation, de-escalation, or staying at the current dose as three different stochastic moves over the lattice of a sequence of prespecified dose levels. Each move is chosen by minimizing an expected penalty that determines the dose level for treating the next cohort of patients. We develop ...

Dose-finding in phase I clinical trials based on toxicity probability intervals.

BACKGROUND Most phase I clinical trials conducted at the M. D. Anderson Cancer Center use the algorithmic 3 + 3 design, despite the availability of more advanced model-based designs such as the continual reassessment method. PURPOSE Through simple statistical modeling and computing, we develop a dose-finding design that can be easily understood and implemented by non-statisticians. METHODS ...