A system for determining maximum tolerated dose in clinical trial

Abstract

Toxicity study, especially in determining the maximum tolerated dose (MTD) in phase I clinical trial, is an important step in developing new life-saving drugs. In practice, toxicity levels may be categorised as binary grades, multiple grades, or in a more generalised case, continuous grades. In this study, we propose an overall MTD framework that includes all the aforementioned cases for a single toxicity outcome (response). The mechanism of determining MTD involves a function that is predetermined by user. Analytic properties of such a system are investigated and simulation studies are performed for various scenarios. The concept of the continual reassessment method (CRM) is also implied in the framework and Bayesian analysis, including Markov chain Monte Carlo (MCMC) methods are used in estimating the model parameters.