Interim analysis of clinical trials based on urn models

Abstract

AbstractClinical trials usually involve efficient and ethical objectives such as maximizing the power and minimizing the total failure number. Interim analysis is now a standard technique in practice to achieve these objectives. Randomized urn models have been extensively studied in the literature. In this paper, we propose to perform interim analysis on clinical trials based on urn models and study its properties. We show that the urn composition, allocation of patients and parameter estimators can be approximated by a joint Gaussian process. Consequently, sequential test statistics of the proposed procedure converge to a Brownian motion in distribution and the sequential test statistics asymptotically satisfy the canonical joint distribution defined in Jennison & Turnbull (Jennison & Turnbull 2000. Group Sequential Methods with Applications to Clinical Trials, Chapman and Hall/CRC). These results provide a solid foundation and open a door to perform the interim analysis on randomized clinical trials with urn models in practice. Furthermore, we demonstrate our proposal through examples and simulations by applying sequential monitoring and stochastic curtailment techniques. The Canadian Journal of Statistics 40: 550–568; 2012 © 2012 Statistical Society of Canada