A semiparametric Cox-Aalen transformation model with censored data

Biometrics. 2023 Dec;79(4):3111-3125. doi: 10.1111/biom.13895. Epub 2023 Jul 4.

Abstract

We propose a broad class of so-called Cox-Aalen transformation models that incorporate both multiplicative and additive covariate effects on the baseline hazard function within a transformation. The proposed models provide a highly flexible and versatile class of semiparametric models that include the transformation models and the Cox-Aalen model as special cases. Specifically, it extends the transformation models by allowing potentially time-dependent covariates to work additively on the baseline hazard and extends the Cox-Aalen model through a predetermined transformation function. We propose an estimating equation approach and devise an expectation-solving (ES) algorithm that involves fast and robust calculations. The resulting estimator is shown to be consistent and asymptotically normal via modern empirical process techniques. The ES algorithm yields a computationally simple method for estimating the variance of both parametric and nonparametric estimators. Finally, we demonstrate the performance of our procedures through extensive simulation studies and applications in two randomized, placebo-controlled human immunodeficiency virus (HIV) prevention efficacy trials. The data example shows the utility of the proposed Cox-Aalen transformation models in enhancing statistical power for discovering covariate effects.

Keywords: Cox-Aalen model; ES algorithm; estimating equations; time-dependent covariates; transformation models.

Publication types

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

MeSH terms

  • Algorithms*
  • Computer Simulation
  • Humans
  • Models, Statistical
  • Proportional Hazards Models
  • Research Design*