title: Robust covariate-adjusted log-rank statistics and corresponding sample size formula for recurrent events data.
abstract: Recurrent events data are frequently encountered in clinical trials. This article develops robust covariate-adjusted log-rank statistics applied to recurrent events data with arbitrary numbers of events under independent censoring and the corresponding sample size formula. The proposed log-rank tests are robust with respect to different data-generating processes and are adjusted for predictive covariates. It reduces to the Kong and Slud (1997, Biometrika 84, 847-862) setting in the case of a single event. The sample size formula is derived based on the asymptotic normality of the covariate-adjusted log-rank statistics under certain local alternatives and a working model for baseline covariates in the recurrent event data context. When the effect size is small and the baseline covariates do not contain significant information about event times, it reduces to the same form as that of Schoenfeld (1983, Biometrics 39, 499-503) for cases of a single event or independent event times within a subject. We carry out simulations to study the control of type I error and the comparison of powers between several methods in finite samples. The proposed sample size formula is illustrated using data from an rhDNase study.
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, North Carolina 27599-7420, U.S.A.
authors.forename: Rui
authors.initials: R
authors.lastname: Song
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, North Carolina 27599-7420, U.S.A.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kosorok
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, North Carolina 27599-7420, U.S.A.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Cai
mesh_terms: D000704:Analysis of Variance; D001699:Biometry / Q000379:methods*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003550:Cystic Fibrosis / Q000188:drug therapy; D003627:Data Interpretation, Statistical; D003850:Deoxyribonuclease I / Q000627:therapeutic use; D006801:Humans; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D011994:Recombinant Proteins / Q000627:therapeutic use; D018401:Sample Size; D016019:Survival Analysis
chemical_list: D011994:Recombinant Proteins; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I