Mixed model analysis of censored longitudinal data with flexible random-effects density

Biostatistics. 2012 Jan;13(1):61-73. doi: 10.1093/biostatistics/kxr026. Epub 2011 Sep 13.


Mixed models are commonly used to represent longitudinal or repeated measures data. An additional complication arises when the response is censored, for example, due to limits of quantification of the assay used. While Gaussian random effects are routinely assumed, little work has characterized the consequences of misspecifying the random-effects distribution nor has a more flexible distribution been studied for censored longitudinal data. We show that, in general, maximum likelihood estimators will not be consistent when the random-effects density is misspecified, and the effect of misspecification is likely to be greatest when the true random-effects density deviates substantially from normality and the number of noncensored observations on each subject is small. We develop a mixed model framework for censored longitudinal data in which the random effects are represented by the flexible seminonparametric density and show how to obtain estimates in SAS procedure NLMIXED. Simulations show that this approach can lead to reduction in bias and increase in efficiency relative to assuming Gaussian random effects. The methods are demonstrated on data from a study of hepatitis C virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antiviral Agents / therapeutic use
  • Bias
  • Biostatistics
  • Data Interpretation, Statistical
  • Hepatitis C / drug therapy
  • Hepatitis C / virology
  • Humans
  • Interferon-alpha / therapeutic use
  • Linear Models
  • Longitudinal Studies
  • Models, Statistical*
  • Statistics, Nonparametric
  • Viral Load / drug effects


  • Antiviral Agents
  • Interferon-alpha