Background
In multi-site HIV observational cohorts, clustering of observations often occur within sites. Ignoring clustering may lead to “Simpson's paradox” (SP) where the trend observed in the aggregated data is reversed when the groups are separated. This study aimed to investigate the SP in an Asian HIV cohort and the effects of site-level adjustment through various Cox-regression models.
Methods
Survival time from combination antiretroviral therapy (cART) initiation was analysed using four Cox models: (i) no site adjustment; (ii) site as a fixed effect; (iii) stratification through site; and (iv) shared frailty on site.
Results
A total of 6454 patients were included from 23 sites in Asia. SP was evident in the year of cART initiation variable. Model (i) shows the hazard ratio (HR) for years 2010-2014 was higher than the HR for 2006-2009, compared to 2003-2005 (HR = 0.68 vs 0.61). Models (ii)-(iv) consistently implied greater improvement in survival for those who initiated in 2010-2014 than 2006-2009 contrasting findings from Model (i). The effects of other significant covariates on survival were similar across four models.
Conclusions
Ignoring site can lead to SP causing reversal of treatment effects. Greater emphasis should be made to include site in survival models when possible.
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