Nonparametric Methods for Stratified Two-Sample Designs with Application to Multiclinic Trials

Abstract

Abstract Motivated by some problems arising from multiclinic trials, we consider stratified two-sample designs. Nonparametric effects are defined and nonparametric hypotheses are formulated in a design where treatment, centers (strata), and interactions are assumed to be fixed factors. The interpretation of the nonparametric effects and hypotheses is analyzed in two classes of semiparametric models: the linear models and models with Lehmann alternatives. The case where centers and interactions are assumed to be random factors, the so-called mixed model, is also considered. Nonparametric effects and hypotheses are defined for general models, and their properties are analyzed in corresponding linear models and in models with Lehmann alternatives. The nonparametric effects are estimated by linear rank statistics where the ranks over all centers are used. The mixed model for repeated (baseline and endpoint) observations is briefly considered, and rank procedures are also proposed for this model. All procedure...