SEMIPARAMETRIC AND NONPARAMETRIC METHODS FOR THE ANALYSIS OF REPEATED MEASUREMENTS WITH APPLICATIONS TO CLINICAL-TRIALS

Techniques applicable for the analysis of longitudinal data when the response variable is non-normal are not nearly as comprehensive as for normally-distributed outcomes. However, there have been several recent developments. Semi-parametric and non-parametric methodology for the analysis of repeated measurements is reviewed. The commonly encountered design in which, for each subject, one assesses a univariate response variable at multiple fixed time points, is considered. The types of outcomes considered include binary, ordered categorical, and continuous (but extremely non-normal) response variables. All of the methods considered allow for incomplete data due to the occurrence of missing observations. In addition, discrete and/or continuous covariates, which may be time-dependent, are accommodated by some of the approaches. The methods are demonstrated using data from three clinical trials.