TY - JOUR
T1 - Marginal structural cox models for estimating the association between β-interferon exposure and disease progression in a multiple sclerosis cohort
AU - Karim, Mohammad Ehsanul
AU - Gustafson, Paul
AU - Petkau, John
AU - Zhao, Yinshan
AU - Shirani, Afsaneh
AU - Kingwell, Elaine
AU - Evans, Charity
AU - Van Der Kop, Mia
AU - Oger, Joel
AU - Tremlett, Helen
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/7/15
Y1 - 2014/7/15
N2 - Longitudinal observational data are required to assess the association between exposure to β-interferon medications and disease progression among relapsing-remitting multiple sclerosis (MS) patients in the real-world clinical practice setting. Marginal structural Cox models (MSCMs) can provide distinct advantages over traditional approaches by allowing adjustment for time-varying confounders such as MS relapses, as well as baseline characteristics, through the use of inverse probability weighting. We assessed the suitability of MSCMs to analyze data from a large cohort of 1,697 relapsing-remitting MS patients in British Columbia, Canada (1995-2008). In the context of this observational study, which spanned more than a decade and involved patients with a chronic yet fluctuating disease, the recently proposed normalized stabilized weights were found to be the most appropriate choice of weights. Using this model, no association between β-interferon exposure and the hazard of disability progression was found (hazard ratio = 1.36, 95% confidence interval: 0.95, 1.94). For sensitivity analyses, truncated normalized unstabilized weights were used in additional MSCMs and to construct inverse probability weight-adjusted survival curves; the findings did not change. Additionally, qualitatively similar conclusions from approximation approaches to the weighted Cox model (i.e., MSCM) extend confidence in the findings.
AB - Longitudinal observational data are required to assess the association between exposure to β-interferon medications and disease progression among relapsing-remitting multiple sclerosis (MS) patients in the real-world clinical practice setting. Marginal structural Cox models (MSCMs) can provide distinct advantages over traditional approaches by allowing adjustment for time-varying confounders such as MS relapses, as well as baseline characteristics, through the use of inverse probability weighting. We assessed the suitability of MSCMs to analyze data from a large cohort of 1,697 relapsing-remitting MS patients in British Columbia, Canada (1995-2008). In the context of this observational study, which spanned more than a decade and involved patients with a chronic yet fluctuating disease, the recently proposed normalized stabilized weights were found to be the most appropriate choice of weights. Using this model, no association between β-interferon exposure and the hazard of disability progression was found (hazard ratio = 1.36, 95% confidence interval: 0.95, 1.94). For sensitivity analyses, truncated normalized unstabilized weights were used in additional MSCMs and to construct inverse probability weight-adjusted survival curves; the findings did not change. Additionally, qualitatively similar conclusions from approximation approaches to the weighted Cox model (i.e., MSCM) extend confidence in the findings.
KW - bias (epidemiology)
KW - causality
KW - confounding factors (epidemiology)
KW - epidemiologic methods
KW - inverse probability weighting
KW - marginal structural Cox model
KW - multiple sclerosis
KW - survival analysis
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U2 - 10.1093/aje/kwu125
DO - 10.1093/aje/kwu125
M3 - Article
C2 - 24939980
AN - SCOPUS:84904018610
VL - 180
SP - 160
EP - 171
JO - American Journal of Epidemiology
JF - American Journal of Epidemiology
SN - 0002-9262
IS - 2
ER -