Joint inference for nonlinear mixed-effects models and time to event at the presence of missing data

Biostatistics. 2008 Apr;9(2):308-20. doi: 10.1093/biostatistics/kxm029. Epub 2007 Aug 29.

Abstract

In many longitudinal studies, the individual characteristics associated with the repeated measures may be possible covariates of the time to an event of interest, and thus, it is desirable to model the time-to-event process and the longitudinal process jointly. Statistical analyses may be further complicated in such studies with missing data such as informative dropouts. This article considers a nonlinear mixed-effects model for the longitudinal process and the Cox proportional hazards model for the time-to-event process. We provide a method for simultaneous likelihood inference on the 2 models and allow for nonignorable data missing. The approach is illustrated with a recent AIDS study by jointly modeling HIV viral dynamics and time to viral rebound.

Publication types

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

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy
  • Acquired Immunodeficiency Syndrome / epidemiology*
  • Anti-HIV Agents / therapeutic use
  • Biometry / methods
  • Disease Progression
  • HIV / pathogenicity
  • Humans
  • Likelihood Functions
  • Longitudinal Studies*
  • Nonlinear Dynamics*
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Reference Values
  • Research Design* / statistics & numerical data
  • Time*
  • Treatment Outcome
  • Viral Load / statistics & numerical data

Substances

  • Anti-HIV Agents