short-term relapse quantitation as a fully surrogate endpoint for long-term sustained progression of disability in rrms patients treated with natalizumab短期复发定量作为长期持续发展的全面代理端点名rrms natalizumab患者的残疾.pdfVIP

Hindawi Publishing Corporation Neurology Research International Volume 2011, Article ID 195831, 6 pages doi:10.1155/2011/195831 Research Article Short-Term Relapse Quantitation as a Fully Surrogate Endpoint for Long-Term Sustained Progression of Disability in RRMS Patients Treated with Natalizumab Y. C. Wang,1 A. Sandrock,2 J. R. Richert,2 L. Meyerson,1 and X. Miao3 1 Department of Biometrics, Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA 2 Neurology Clinical Development, Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA 3 Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA Correspondence should be addressed to Y. C. Wang, ycwang us@ Received 2 May 2011; Revised 17 November 2011; Accepted 19 November 2011 Academic Editor: Mamede de Carvalho Copyright © 2011 Y. C. Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Time to sustained worsening in the expanded disability status scale as the standard for evaluating the accumulation of disability has been used as a measure of clinical efficacy in many relapsing-remitting multiple sclerosis (RRMS) clinical trials. However, this measurement usually requires a large sample and long-term study to demonstrate the treatment effect. Annualized relapse rate or time to first relapse is also widely used as alternative measurements of clinical efficacy. A formal statistical validation of short-term relapse activity as a surrogate endpoint for long-term sustained progression of disability could potentially permit smaller, shorter, and less expensive clinical trials in RRMS. Four statistical validation/evaluation appro