Abstract

Traditional clinical trials have been inefficient in their methods of dose finding and dose allocation. In this paper a four-parameter logistic equation is used to model the outcome of Bernoulli-response clinical trials. A Bayesian adaptive design is used to fit the logistic equation to the dose-response curve of Phase II and Phase III clinical trials. Because of inherent restrictions in the logistic model, symmetric candidate densities cannot be used, thereby creating asymmetric jumping rules inside the Markov chain Monte Carlo algorithm. An order restricted Metropolis-Hastings algorithm is implemented to account for these limitations. Modeling clinical trials in a Bayesian framework allows the experiment to be adaptive. In this adaptive design batches of subjects are assigned to doses based on the posterior probability of success for each dose, thereby increasing the probability of receiving advantageous doses. Good posterior fitting is demonstrated for typical dose-response curves and the Bayesian design is shown to properly stop drug trials for clinical futility or clinical success. In this paper we demonstrate that an adaptive Bayesian approach to dose-response studies increases both the statistical and medicinal effectiveness of clinical research.

Degree

MS

College and Department

Physical and Mathematical Sciences; Statistics

Rights

http://lib.byu.edu/about/copyright/

Date Submitted

2007-08-06

Document Type

Thesis

Handle

http://hdl.lib.byu.edu/1877/etd2065

Keywords

adaptive, clinical trial, Bayesian, Metropolis-Hastings, logistic model, simulation

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