Accepted for Publication: November 22, 2013.
Published Online: January 20, 2014. doi:10.1001/jamaneurol.2013.5993.
Study concept and design: Ascherio, Munger, Polman, Freedman, Montalban, Pleimes, Sandbrink, Pohl.
Acquisition of data: Ascherio, Polman, Barkhof, Pleimes, Sandbrink, Pohl.
Analysis and interpretation of data: Ascherio, Munger, White, Köchert, Simon, Freedman, Hartung, Miller, Edan, Barkhof, Pleimes, Radü, Sandbrink, Kappos, Pohl.
Drafting of the manuscript: Ascherio.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Ascherio, Munger, White, Köchert, Pleimes.
Obtained funding: Ascherio, Munger, Polman, Sandbrink.
Administrative, technical, and material support: Freedman, Hartung, Pleimes, Kappos.
Study supervision: Ascherio, Polman, Edan, Barkhof, Sandbrink, Kappos.
Conflict of Interest Disclosures: Dr Ascherio has received honoraria for speaking at scientific symposia by Roche, Sanofi-Aventis, Serono, and Almirall. Mr White has served as a consultant for and received financial compensation from Bayer Schering Pharma. Dr Köchert is a statistical consultant paid by Bayer Pharma AG. Dr Polman has received personal compensation from Biogen Idec, Bayer Schering Pharma AG, Teva Pharmaceutical Industries, Merck Serono, Novartis Pharmaceutical Corp, GlaxoSmithKline, Actelion Pharmaceuticals Ltd, UCB, and Roche for consulting services. The VU University Medical Center received financial support for research activities from Bayer Schering, Biogen Idec, Merck Serono, Teva, Novartis, GlaxoSmithKline, and Roche. Dr Freedman has received personal compensation and research support from Teva Pharmaceutical Industries, Merck Serono, Bayer Schering Pharma AG, Biogen-Dompé, and Genmab. Dr Hartung has received honoraria for consulting and speaking at symposia from Bayer Schering Pharma, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Teva, and Sanofi-Aventis, with approval by the rector of Heinrich-Heine University. Dr Miller has received honoraria and compensation through payments to University College London Institute of Neurology for advisory committee and/or consultancy advice in multiple sclerosis studies from Biogen Idec, GlaxoSmithKline, and Bayer Schering, as well as for work as editor of the Journal of Neurology. Dr Miller has received research grant support through the University College London Institute of Neurology for performing central magnetic resonance imaging analysis of multiple sclerosis trials from GlaxoSmithKline, Biogen Idec, and Novartis. Dr Montalban has received speaking honoraria and travel expenses for scientific meetings and has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past with Bayer, Biogen Idec, EMD, Genentech, Genzyme, Merck Serono, Neurotec, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall. Dr Edan has received honoraria for lectures or consulting from Biogen Idec, Merck Serono, and Sanofi-Aventis and received personal compensation for serving on the BENEFIT scientific advisory board and for speaking from Bayer Schering Pharma AG. Dr Edan has also received research support from Serono through a grant to University Hospital to support a research program on magnetic resonance imaging in multiple sclerosis and from Teva through a grant to support a research program on anti-IBF neutralizing antibodies. Dr Barkhof has received compensation for consultancy from Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Genzyme, Roche, and Teva, as well as has received research support from the Dutch Foundation for MS Research (a nongovernmental organization). Dr Pleimes is a salaried employee of Bayer Pharma AG/Bayer HealthCare Pharmaceuticals. Dr Pleimes owns stock in Bayer AG, the owner of Bayer Pharma AG/Bayer HealthCare Pharmaceuticals. Dr Radü has received honoraria for serving as a speaker at scientific meetings and a consultant for Novartis, Biogen Idec, Merck Serono, and Bayer Schering. He has received financial support for research activities from Actelion, Basilea Pharmaceutica Ltd, Biogen Idec, Merck Serono, and Novartis. Dr Sandbrink is a salaried employee of Bayer Pharma AG/Bayer HealthCare Pharmaceuticals. Dr Sandbrink owns stock in Bayer AG, the owner of Bayer Pharma AG/Bayer HealthCare Pharmaceuticals. Dr Kappos has lectured at medical conferences or in public and received honoraria, which have been exclusively used for funding research for his department. Research and the clinical operations (nursing and patient care services) of the MS Center in Basel have been supported by nonrestricted grants from Acorda Therapeutics Inc, Actelion Pharmaceuticals Ltd, Allozyne, BaroFold, Bayer HealthCare Pharmaceuticals, Bayer Schering Pharma, Bayhill, Biogen Idec, Boehringer Ingelheim, Eisai Inc, Elan, Genmab, GlaxoSmithKline, Merck Serono, MediciNova, Novartis, Sanofi-Aventis, Santhera Pharmaceuticals, Shire Plc, Roche, Teva, UCB, and Wyeth, as well as by grants from the Swiss MS Society, the Swiss National Research Foundation, the European Union, the Gianni Rubatto Foundation, Novartis, and Roche Research Foundations. Dr Pohl is a salaried employee of Bayer Pharma AG/Bayer HealthCare Pharmaceuticals. Dr Pohl owns stock in Bayer AG, the owner of Bayer Pharma AG/Bayer HealthCare Pharmaceuticals. No other disclosures were reported.
Funding/Support: This study was supported by the National Institute of Neurological Diseases and Stroke and the National Multiple Sclerosis Society. The BENEFIT study was sponsored by Bayer.
Role of the Sponsor: The funding agencies had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We acknowledge the BENEFIT participants, Robert Ristuccia, PhD, for technical support, and Leslie Unger, BA, for administrative support. Dr Ristuccia is the medical director of Precept Medical Communications and did not receive compensation from a funding sponsor for his contribution. Ms Unger is with the Harvard School of Public Health; part of her institutional salary was covered by the National Institutes of Health grant that supported this research.