title: A sequential stratification method for estimating the effect of a time-dependent experimental treatment in observational studies.
abstract: Survival analysis is often used to compare experimental and conventional treatments. In observational studies, the therapy may change during follow-up and such crossovers can be summarized by time-dependent covariates. Given the ever-increasing donor organ shortage, higher-risk kidneys from expanded criterion donors (ECD) are being transplanted. Transplant candidates can choose whether to accept an ECD organ (experimental therapy), or to remain on dialysis and wait for a possible non-ECD transplant later (conventional therapy). A three-group time-dependent analysis of such data involves estimating parameters corresponding to two time-dependent indicator covariates representing ECD transplant and non-ECD transplant, each compared to remaining on dialysis on the waitlist. However, the ECD hazard ratio estimated by this time-dependent analysis fails to account for the fact that patients who forego an ECD transplant are not destined to remain on dialysis forever, but could subsequently receive a non-ECD transplant. We propose a novel method of estimating the survival benefit of ECD transplantation relative to conventional therapy (waitlist with possible subsequent non-ECD transplant). Compared to the time-dependent analysis, the proposed method more accurately characterizes the data structure and yields a more direct estimate of the relative outcome with an ECD transplant.
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109-2029, USA. deschau@umich.edu
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Schaubel
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolfe
authors.forename: Friedrich K
authors.initials: FK
authors.lastname: Port
mesh_terms: D001699:Biometry / Q000379:methods*; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D006801:Humans; D007676:Kidney Failure, Chronic / Q000401:mortality / Q000601:surgery / Q000628:therapy; D016030:Kidney Transplantation; D016016:Proportional Hazards Models; D017582:Renal Replacement Therapy; D016019:Survival Analysis; D013997:Time Factors