title: Controlling Time-Dependent Confounding by Health Status and Frailty: Restriction Versus Statistical Adjustment.
abstract: Nonexperimental studies of preventive interventions are often biased because of the healthy-user effect and, in frail populations, because of confounding by functional status. Bias is evident when estimating influenza vaccine effectiveness, even after adjustment for claims-based indicators of illness. We explored bias reduction methods while estimating vaccine effectiveness in a cohort of adult hemodialysis patients. Using the United States Renal Data System and linked data from a commercial dialysis provider, we estimated vaccine effectiveness using a Cox proportional hazards marginal structural model of all-cause mortality before and during 3 influenza seasons in 2005/2006 through 2007/2008. To improve confounding control, we added frailty indicators to the model, measured time-varying confounders at different time intervals, and restricted the sample in multiple ways. Crude and baseline-adjusted marginal structural models remained strongly biased. Restricting to a healthier population removed some unmeasured confounding; however, this reduced the sample size, resulting in wide confidence intervals. We estimated an influenza vaccine effectiveness of 9% (hazard ratio = 0.91, 95% confidence interval: 0.72, 1.15) when bias was minimized through cohort restriction. In this study, the healthy-user bias could not be controlled through statistical adjustment; however, sample restriction reduced much of the bias.
authors: Leah J
authors: LJ
authors: McGrath
authors: Alan R
authors: AR
authors: Ellis
authors: M Alan
authors: MA
authors: Brookhart
mesh_terms: D000368:Aged; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006304:Health Status; D006801:Humans; D007252:Influenza Vaccines; D007676:Kidney Failure, Chronic; D008297:Male; D008875:Middle Aged; D009026:Mortality; D016016:Proportional Hazards Models
chemical_list: D007252:Influenza Vaccines
keywords: bias (epidemiology); confounding factors (epidemiology); influenza vaccines; renal dialysis