Power Calculations for Preclinical Studies Using a K-Sample Rank Test and the Lehmann Alternative Hypothesis

Power calculations in a small sample comparative study, with a continuous outcome measure, are typically undertaken using the asymptotic distribution of the test statistic. When the sample size is small, this asymptotic result can be a poor approximation. An alternative approach, using a rank based test statistic, is an exact power calculation. When the number of groups is greater than two, the number of calculations required to perform an exact power calculation is prohibitive. To reduce the computational burden, a Monte Carlo resampling procedure is used to approximate the exact power function of a k-sample rank test statistic under the family of Lehmann alternative hypotheses. The motivating example for this approach is the design of animal studies, where the number of animals per group is typically small.

Survival Analysis with Large Dimensional Covariates: An Application in Microarray Studies

Use of microarray technology often leads to high-dimensional and low- sample size data settings. Over the past several years, a variety of novel approaches have been proposed for variable selection in this context. However, only a small number of these have been adapted for time-to-event data where censoring is present. Among standard variable selection methods shown both to have good predictive accuracy and to be computationally efficient is the elastic net penalization approach. In this paper, adaptation of the elastic net approach is presented for variable selection both under the Cox proportional hazards model and under an accelerated failure time (AFT) model. Assessment of the two methods is conducted through simulation studies and through analysis of microarray data obtained from a set of patients with diffuse large B-cell lymphoma where time to survival is of interest. The approaches are shown to match or exceed the predictive performance of a Cox-based and an AFT-based variable selection method. The methods are moreover shown to be much more computationally efficient than their respective Cox- and AFT- based counterparts.