title: Marginal structural Cox models for estimating the association between β-interferon exposure and disease progression in a multiple sclerosis cohort.
abstract: 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.
authors.forename: Mohammad Ehsanul
authors.initials: ME
authors.lastname: Karim
authors.forename: Paul
authors.initials: P
authors.lastname: Gustafson
authors.forename: John
authors.initials: J
authors.lastname: Petkau
authors.forename: Yinshan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Shirani
authors.forename: Elaine
authors.initials: E
authors.lastname: Kingwell
authors.forename: Charity
authors.initials: C
authors.lastname: Evans
authors.forename: Mia
authors.initials: M
authors.lastname: van der Kop
authors.forename: Joel
authors.initials: J
authors.lastname: Oger
authors.forename: Helen
authors.initials: H
authors.lastname: Tremlett
mesh_terms: D001955:British Columbia; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D018450:Disease Progression; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000503:physiopathology; D011336:Probability; D016016:Proportional Hazards Models; D016019:Survival Analysis
chemical_list: D007155:Immunologic Factors; D016899:Interferon-beta
keywords: bias (epidemiology); causality; confounding factors (epidemiology); epidemiologic methods; inverse probability weighting; marginal structural Cox model; multiple sclerosis; survival analysis