Hierarchical proportional hazards regression models for highly stratified data

Bradley P. Carlin, James S Hodges

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

In clinical trials conducted over several data collection centers, the most common statistically defensible analytic method, a stratified Cox model analysis, suffers from two important defects. First, identification of units that are outlying with respect to the baseline hazard is awkward since this hazard is implicit (rather than explicit) in the Cox partial likelihood. Second (and more seriously), identification of modest treatment effects is often difficult since the model fails to acknowledge any similarity across the strata. We consider a number of hierarchical modeling approaches that preserve the integrity of the stratified design while offering a middle ground between traditional stratified and unstratified analyses. We investigate both fully parametric (Weibull) and semiparametric models, the latter based not on the Cox model but on an extension of an idea by Gelfand and Mallick (1995, Biometrics 51, 843-852), which models the integrated baseline hazard as a mixture of monotone functions. We illustrate the methods using data from a recent multicenter AIDS clinical trial, comparing their ease of use, interpretation, and degree of robustness with respect to estimates of both the unit-specific baseline hazards and the treatment effect.

Original languageEnglish (US)
Pages (from-to)1162-1170
Number of pages9
JournalBiometrics
Volume55
Issue number4
DOIs
StatePublished - Dec 1999

Keywords

  • Baseline hazard function
  • Bayesian methods
  • Cox model
  • Markov chain Monte Carlo
  • Partial likelihood

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