title: Estimating covariate-adjusted log hazard ratios in randomized clinical trials using cox proportional hazards models and nonparametric randomization based analysis of covariance.
abstract: In the context of randomized clinical trials with time-to-event outcomes, estimates of covariate-adjusted log hazard ratios for comparing two treatments are obtained via nonparametric analysis of covariance by forcing the difference in means for covariables to zero. The method avoids the assumption of proportional hazards for each of the covariates, and it provides an adjusted analysis for the same population average treatment effect that the unadjusted analysis addresses. It is primarily useful in regulatory clinical trials that require analyses to be specified a priori. To illustrate, the method is applied to a study of lung disease with multivariate time-to-event outcomes.
authors: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN 37232-2158 USA. b.saville@vanderbilt.edu
authors: Benjamin R
authors: BR
authors: Saville
authors: Gary G
authors: GG
authors: Koch
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D011897:Random Allocation; D016032:Randomized Controlled Trials as Topic; D018709:Statistics, Nonparametric