Assessing time-by-covariate interactions in proportional hazards regression models using cubic spline functions

Stat Med. 1994 May 30;13(10):1045-62. doi: 10.1002/sim.4780131007.

Abstract

Proportional hazards (or Cox) regression is a popular method for modelling the effects of prognostic factors on survival. Use of cubic spline functions to model time-by-covariate interactions in Cox regression allows investigation of the shape of a possible covariate-time dependence without having to specify a specific functional form. Cubic spline functions allow one to graph such time-by-covariate interactions, to test formally for the proportional hazards assumption, and also to test for non-linearity of the time-by-covariate interaction. The functions can be fitted with existing software using relatively few parameters; the regression coefficients are estimated using standard maximum likelihood methods.

MeSH terms

  • Epidemiologic Methods
  • Humans
  • Leukemia / drug therapy
  • Leukemia / mortality
  • Prognosis
  • Proportional Hazards Models*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / therapy
  • Time Factors