A mixture model using likelihood‐based and Bayesian approaches for identifying responders and non‐responders in longitudinal clinical trials

A longitudinal mixture model for classifying patients into responders and non‐responders is established using both likelihood‐based and Bayesian approaches. The model takes into consideration responders in the control group. Therefore, it is especially useful in situations where the placebo response is strong, or in equivalence trials where the drug in development is compared with a standard treatment. Under our model, a treatment shows evidence of being effective if it increases the proportion of responders or increases the response rate among responders in the treated group compared with the control group. Therefore, the model has flexibility to accommodate different situations. The proposed method is illustrated using simulation and a depression clinical trial dataset for the likelihood‐based approach, and the same depression clinical trial dataset for the Bayesian approach. The likelihood‐based and Bayesian approaches generated consistent results for the depression trial data. In both the placebo group and the treated group, patients are classified into two components with distinct response rate. The proportion of responders is shown to be significantly higher in the treated group compared with the control group, suggesting the treatment paroxetine is effective. Copyright © 2014 John Wiley & Sons, Ltd.     

A monte carlo study of variable selection and inferences in a two stage random coefficient linear regression model with unbalanced data

A growth curve analysis is often applied to estimate patterns of changes in a given characteristic of different individuals. It is also used to find out if the variations in the growth rates among individuals are due to effects of certain covariates. In this paper, a random coefficient linear regression model, as a special case of the growth curve analysis, is generalized to accommodate the situation where the set of influential covariates is not known a priori. Two different approaches for seleaing influential covariates (a weighted stepwise selection procedure and a modified version of Rao and Wu’s selection criterion) for the random slope coefficient of a linear regression model with unbalanced data are proposed. Performances of these methods are evaluated by means of Monte-Carlo simulation. In addition, several methods (Maximum Likelihood, Restricted Maximum Likelihood, Pseudo Maximum Likelihood and Method of Moments) for estimating the parameters of the selected model are compared Proposed variable selection schemes and estimators are appliedtotheactualindustrial problem which motivated this investigation.