A Sequential Stratification Method for Estimating the Effect of a Time-Dependent Experimental Treatment in Observational Studies
Article first published online: 27 FEB 2006
Volume 62, Issue 3, pages 910–917, September 2006
How to Cite
Schaubel, D. E., Wolfe, R. A. and Port, F. K. (2006), A Sequential Stratification Method for Estimating the Effect of a Time-Dependent Experimental Treatment in Observational Studies. Biometrics, 62: 910–917. doi: 10.1111/j.1541-0420.2006.00527.x
- Issue published online: 27 FEB 2006
- Article first published online: 27 FEB 2006
- Received August 2004. Revised October 2005. Accepted October 2005.
- Cohort study;
- Failure time data;
- Proportional hazards model;
- Risk set;
- Survival analysis
Summary 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.