title: Sensitivity analysis for missing outcomes in time-to-event data with covariate adjustment.
abstract: Covariate-adjusted sensitivity analyses is proposed for missing time-to-event outcomes. The method invokes multiple imputation (MI) for the missing failure times under a variety of specifications regarding the post-withdrawal tendency for having the event of interest. With a clinical trial example, we compared methods of covariance analyses for time-to-event data, i.e., the multivariable Cox proportional hazards (PH) model and nonparametric analysis of covariance, and then illustrated how to incorporate these methods into the proposed sensitivity analysis for covariate adjustment. The MI methods considered are Kaplan-Meier multiple imputation and covariate-adjusted and unadjusted PH multiple imputation. The assumptions, statistical issues, and features for these methods are discussed.
authors: a Merck Research Laboratories , North Wales , Pennsylvania , USA.
authors: Yue
authors: Y
authors: Zhao
authors: b Berry Consultants , Austin , Texas , USA.
authors: Benjamin R
authors: BR
authors: Saville
authors: c Biostatistics , University of North Carolina , Chapel Hill , North Carolina , USA.
authors: Haibo
authors: H
authors: Zhou
authors: c Biostatistics , University of North Carolina , Chapel Hill , North Carolina , USA.
authors: Gary G
authors: GG
authors: Koch
mesh_terms: D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D006801:Humans; D053208:Kaplan-Meier Estimate; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data*; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*
keywords: Covariate adjustment; multiple imputation; sensitivity analysis; time-to-event data
references: Stat Med. 2000 Apr 30;19(8):1039-58
references: 10790679
references: J Clin Psychiatry. 2003 Sep;64(9):1013-24
references: 14628976
references: Biometrics. 1969 Sep;25(3):489-504
references: 5824401
references: Biometrics. 1982 Sep;38(3):563-95
references: 6756493
references: J Biopharm Stat. 2014;24(2):229-53
references: 24605967
references: Control Clin Trials. 1998 Jun;19(3):249-56
references: 9620808
references: Stat Med. 1998 Aug 15-30;17(15-16):1863-92
references: 9749453
references: Stat Med. 2008 Dec 10;27(28):5850-60
references: 18759373
references: J Biopharm Stat. 2013 Mar 11;23(2):477-90
references: 23437952
references: Stat Med. 1991 Apr;10(4):585-98
references: 2057657