Journal
AMERICAN JOURNAL OF EPIDEMIOLOGY
Volume 180, Issue 2, Pages 160-171Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/aje/kwu125
Keywords
bias (epidemiology); causality; confounding factors (epidemiology); epidemiologic methods; inverse probability weighting; marginal structural Cox model; multiple sclerosis; survival analysis
Categories
Funding
- Multiple Sclerosis (MS) Society of Canada (Toronto, Ontario, Canada)
- National MS Society (New York, New York) [RG 4202-A-2]
- Canadian Institutes of Health Research (CIHR) (Ottawa, Ontario, Canada) [MOP-93646]
- Natural Sciences and Engineering Research Council of Canada (Ottawa, Ontario, Canada)
- CIHR [MOP-93646]
- National MS Society [RG 4202-A-2]
- Natural Sciences and Engineering Research Council of Canada
- MS Society of Canada
- Michael Smith Foundation for Health Research (Vancouver, British Columbia, Canada)
- Michael Smith Foundation for Health Research
- CIHR Doctoral Award-Doctoral Foreign Study Award
- CIHR Strategy for Patient-Oriented Research
- CIHR HIV/AIDS Research Initiative
- Christopher Foundation (Vancouver, British Columbia, Canada)
- University of British Columbia (Vancouver, British Columbia, Canada)
- Canada Research Chair Program
- MS Society of Canada Don Paty Career Development Award
- Michael Smith Foundation for Health Research Scholar
- MS Trust (Letchworth, United Kingdom)
- Pacific Institute for the Mathematical Sciences (Vancouver, British Columbia, Canada)
- Bayer AG (Leverkusen, Germany)
- BTG International Ltd. (London, United Kingdom)
- EMD Serono, Inc. (Mississauga, Ontario, Canada)
- Merck Serono (Darmstadt, Germany)
- Myelin Repair Foundation (Saratoga, California)
- Novartis International AG (Basel, Switzerland)
- endMS Research and Training Network
- European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (Basel, Switzerland)
- Consortium of MS Centers (Hackensack, New Jersey)
- International Society for Pharmacoepidemiology (Bethesda, Maryland)
- Bayer
- ECTRIMS
- Sanofi-Aventis (Bridgewater, New Jersey)
- Biogen Idec (Cambridge, Massachusetts)
- BioMS Medical Corporation (Edmonton, Alberta, Canada)
- Corixa Corporation (Marietta, Pennsylvania)
- Genentech (South San Francisco, California)
- Novartis
- EMD Serono
- Talecris Biotherapeutics (Research Triangle Park, North Carolina)
- Teva Neuroscience, Inc. (Kansas City, Missouri)
- Biogen Idec.
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Longitudinal observational data are required to assess the association between exposure to beta-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 beta-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.
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