A sequential stratification method for estimating the effect of a time-dependent experimental treatment in observational studies

Biometrics. 2006 Sep;62(3):910-7. doi: 10.1111/j.1541-0420.2006.00527.x.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biometry / methods*
  • Cross-Over Studies
  • Data Interpretation, Statistical
  • Humans
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / surgery
  • Kidney Failure, Chronic / therapy
  • Kidney Transplantation
  • Proportional Hazards Models
  • Renal Replacement Therapy
  • Survival Analysis
  • Time Factors