The Gaussian approximation for multi-color generalized Friedman’s urn model

The generalized Friedman’s urn model is a popular urn model which is widely used in many disciplines.In particular,it is extensively used in treatment allocation schemes in clinical trials.In this paper,we show that both the urn composition process and the allocation proportion process can be approximated by a multi-dimensional Gaussian process almost surely for a multi-color generalized Friedman’s urn model with both homogeneous and non-homogeneous generating matrices.The Gaussian process is a solution of a stochastic differential equation.This Gaussian approximation is important for the understanding of the behavior of the urn process and is also useful for statistical inferences.As an application,we obtain the asymptotic properties including the asymptotic normality and the law of the iterated logarithm for a multi-color generalized Friedman's urn model as well as the randomized-play-the-winner rule as a special case.

Bayesian doubly adaptive randomization in clinical trials

Bayesian adaptive randomization has attracted increasingly attention in the literature and has been implemented in many phase II clinical trials. Doubly adaptive biased coin design(DBCD) is a superior choice in response-adaptive designs owing to its promising properties. In this paper, we propose a randomized design by combining Bayesian adaptive randomization with doubly adaptive biased coin design. By selecting a fixed tuning parameter, the proposed randomization procedure can target an explicit allocation proportion, and assign more patients to the better treatment simultaneously. Moreover, the proposed randomization is efficient to detect treatment differences. We illustrate the proposed design by its applications to both discrete and continuous responses, and evaluate its operating features through simulation studies.

Covariate-adaptive designs with missing covariates in clinical trials

Many covariate-adaptive randomization procedures have been proposed and implemented to balance important covariates in clinical trials. These methods are usually based on fully observed covariates. In practice,the covariates of a patient are often partially missing. We propose a novel covariate-adaptive design to deal with missing covariates and study its properties. For the proposed design, we show that as the number of patients increases, the overall imbalance, observed margin imbalance and fully observed stratum imbalance are bounded in probability. Under certain covariate-dependent missing mechanism, the proposed design can balance missing covariates as if the covariates are observed. Finally, we explore our methods and theoretical findings through simulations.