Browsing by Subject "Correlated Data"

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    Bayesian hierarchical modeling for adaptive incorporation of historical information In clinical trials.
    (2010-08) Hobbs, Brian Paul
    Bayesian clinical trial designs offer the possibility of a substantially reduced sample size, increased statistical power, and reductions in cost and ethical hazard. However when prior and current information conflict, Bayesian methods can lead to higher than expected Type I error, as well as the possibility of a costlier and lengthier trial. We develop several models that allow for the commensurability of the information in the historical and current data to determine how much historical information is used. First, we propose methods for univariate Gaussian data and provide an example analysis of data from two successive colon cancer trials that illustrates a linear models extension of our adaptive borrowing approach. Next, we extend the general method to linear and linear mixed models as well as generalized linear and generalized linear mixed models. We also provide two more sample analyses using the colon cancer data. Finally, we consider the effective historical sample size of our adaptive method for the case when historical data is available only for the concurrent control arm, and propose "optimal" use of new patients in the current trial using an adaptive randomization scheme that is balanced with respect to the amount of incorporated historical information. The approach is then demonstrated using data from a trial comparing antiretroviral strategies in HIV-1-infected persons. Throughout the thesis we present simulation studies that compare frequentist operating characteristics and highlight the advantages of our adaptive borrowing methods.