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2016 ; 16
(1
): 148
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A comparison of time dependent Cox regression, pooled logistic regression and
cross sectional pooling with simulations and an application to the Framingham
Heart Study
#MMPMID27809784
Ngwa JS
; Cabral HJ
; Cheng DM
; Pencina MJ
; Gagnon DR
; LaValley MP
; Cupples LA
BMC Med Res Methodol
2016[Nov]; 16
(1
): 148
PMID27809784
show ga
BACKGROUND: Typical survival studies follow individuals to an event and measure
explanatory variables for that event, sometimes repeatedly over the course of
follow up. The Cox regression model has been used widely in the analyses of time
to diagnosis or death from disease. The associations between the survival outcome
and time dependent measures may be biased unless they are modeled appropriately.
METHODS: In this paper we explore the Time Dependent Cox Regression Model (TDCM),
which quantifies the effect of repeated measures of covariates in the analysis of
time to event data. This model is commonly used in biomedical research but
sometimes does not explicitly adjust for the times at which time dependent
explanatory variables are measured. This approach can yield different estimates
of association compared to a model that adjusts for these times. In order to
address the question of how different these estimates are from a statistical
perspective, we compare the TDCM to Pooled Logistic Regression (PLR) and Cross
Sectional Pooling (CSP), considering models that adjust and do not adjust for
time in PLR and CSP. RESULTS: In a series of simulations we found that time
adjusted CSP provided identical results to the TDCM while the PLR showed larger
parameter estimates compared to the time adjusted CSP and the TDCM in scenarios
with high event rates. We also observed upwardly biased estimates in the
unadjusted CSP and unadjusted PLR methods. The time adjusted PLR had a positive
bias in the time dependent Age effect with reduced bias when the event rate is
low. The PLR methods showed a negative bias in the Sex effect, a subject level
covariate, when compared to the other methods. The Cox models yielded reliable
estimates for the Sex effect in all scenarios considered. CONCLUSIONS: We
conclude that survival analyses that explicitly account in the statistical model
for the times at which time dependent covariates are measured provide more
reliable estimates compared to unadjusted analyses. We present results from the
Framingham Heart Study in which lipid measurements and myocardial infarction data
events were collected over a period of 26 years.