Brain, Vol. 122, No. 4, 641-647,
April 1999
© 1999 Oxford University Press
The natural history of multiple sclerosis: a geographically based study
6. Applications to planning and interpretation of clinical therapeutic trials in primary progressive multiple sclerosis
Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada
Correspondence to:
Dr G. C. Ebers, Department of Clinical Neurological Sciences, London Health Sciences Centre-University Campus, London, Ontario, Canada N6A 5A5 E-mail: gebers{at}lhsc.on.ca
The natural history of primary progressive multiple sclerosis (PP-multiple sclerosis) recently has been defined in a geographically based multiple sclerosis population. For a series of prognostically defined hypothetical entry criteria based upon current trends in presentation to the London Multiple Sclerosis Clinic, we determined the number of patients who would have been trial eligible. Using 23 year mean longitudinal natural history data, we identified the observed rate of deterioration for frequently used trial endpoints. Hypothetical entry criteria were based on the practical considerations which would attend the execution of clinical trials in progressive multiple sclerosis. We then developed a series of sample size tables giving the number of patients with PP-multiple sclerosis and the length of observation that would be required to detect a significant result (P = 0.05) for a 25, 50 and 75% decrease in the median time to progression with 80 or 90% power, with treatment efficacy based upon the ability to slow progression on the disability status score. It is expected that the considerations outlined here will prove useful for both trial design and interpretation of trials in PP-multiple sclerosis which will require multi-centre collaborative efforts.
primary progressive-multiple sclerosis; natural history; progression rate; treatment; clinical trials
DSS = disability status score; EDSS = extended disability status score; PP-multiple sclerosis = primary progressive multiple sclerosis
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Bosma, J. Kragt, L Brieva, Z Khaleeli, X Montalban, C. Polman, A. Thompson, M Tintore, and B. Uitdehaag The search for responsive clinical endpoints in primary progressive multiple sclerosis Multiple Sclerosis, June 1, 2009; 15(6): 715 - 720. [Abstract] [PDF]
|
|
|
|
|
|
H Butzkueven, J Chapman, E Cristiano, F Grand'Maison, M Hoffmann, G Izquierdo, D Jolley, L Kappos, T Leist, D Pohlau, et al. MSBase: an international, online registry and platform for collaborative outcomes research in multiple sclerosis Multiple Sclerosis, November 1, 2006; 12(6): 769 - 774. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Kremenchutzky, G. P. A. Rice, J. Baskerville, D. M. Wingerchuk, and G. C. Ebers The natural history of multiple sclerosis: a geographically based study 9: Observations on the progressive phase of the disease Brain, March 1, 2006; 129(3): 584 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S L Minden, D Frankel, L Hadden, J Perloff, K P Srinath, and D C Hoaglin The Sonya Slifka Longitudinal Multiple Sclerosis Study: methods and sample characteristics Multiple Sclerosis, February 1, 2006; 12(1): 24 - 38. [Abstract] [PDF]
|
|
|
|
 |
|
 J Oh, R G Henry, C Genain, S J Nelson, and D Pelletier Mechanisms of normal appearing corpus callosum injury related to pericallosal T1 lesions in multiple sclerosis using directional diffusion tensor and 1H MRS imaging J. Neurol. Neurosurg. Psychiatry, September 1, 2004; 75(9): 1281 - 1286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C Ebers Natural history of primary progressive multiple sclerosis Multiple Sclerosis, June 1, 2004; 10(1_suppl): S8 - S15. [Abstract] [PDF]
|
|
|
|
|
|
G. C Ebers Natural history of primary progressive multiple sclerosis Multiple Sclerosis, May 1, 2004; 10(3_suppl): S8 - S15. [Abstract] [PDF]
|
|
|
|
|
|
G. T. Ingle, V. L. Stevenson, D. H. Miller, and A. J. Thompson Primary progressive multiple sclerosis: a 5-year clinical and MR study Brain, November 1, 2003; 126(11): 2528 - 2536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G T Ingle, V L Stevenson, D H Miller, S M Leary, M Rovaris, F Barkhof, B Brochet, V Dousset, M Filippi, X Montalban, et al. Two-year follow-up study of primary and transitional progressive multiple sclerosis Multiple Sclerosis, April 1, 2002; 8(2): 108 - 114. [Abstract] [PDF]
|
|
|
|
|
|
X Montalban and A J Thompson Workshop on primary progressive multiple sclerosis: meeting summary Multiple Sclerosis, April 1, 2002; 8(2): 177 - 178. [PDF]
|
|
|
|
 |
|
 J. H. Noseworthy, C. Lucchinetti, M. Rodriguez, and B. G. Weinshenker Multiple Sclerosis N. Engl. J. Med., September 28, 2000; 343(13): 938 - 952. [Full Text] [PDF]
|
|
|
|
|
|
V L Stevenson, D H Miller, S M Leary, M Rovaris, F Barkhof, B Brochet, V Dousset, V Dousset, M Filippi, R Hintzen, et al. One year follow up study of primary and transitional progressive multiple sclerosis J. Neurol. Neurosurg. Psychiatry, June 1, 2000; 68(6): 713 - 718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Kremenchutzky, D Lee, G P A Rice, and G C Ebers Diagnostic brain MRI findings in primary progressive multiple sclerosis Multiple Sclerosis, April 1, 2000; 6(2): 81 - 85. [Abstract] [PDF]
|
|
|
|
|
|
G. C. Ebers, W. J. Koopman, W. Hader, A. D. Sadovnick, M. Kremenchutzky, P. Mandalfino, D. M. Wingerchuk, J. Baskerville, and G. P. A. Rice The natural history of multiple sclerosis: a geographically based study: 8: Familial multiple sclerosis Brain, March 1, 2000; 123(3): 641 - 649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kremenchutzky, D. Cottrell, G. Rice, W. Hader, J. Baskerville, W. Koopman, and G. C. Ebers The natural history of multiple sclerosis: a geographically based study: 7. Progressive-relapsing and relapsing-progressive multiple sclerosis: a re-evaluation Brain, October 1, 1999; 122(10): 1941 - 1950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Rudge The value of natural history studies of multiple sclerosis Brain, April 1, 1999; 122(4): 591 - 592. [Full Text] [PDF]
|
|
|
|
|
|
D. A. Cottrell, M. Kremenchutzky, G. P. A. Rice, W. J. Koopman, W. Hader, J. Baskerville, and G. C. Ebers The natural history of multiple sclerosis:a geographically based study: 5. The clinical features and natural history of primary progressive multiple sclerosis Brain, April 1, 1999; 122(4): 625 - 639. [Abstract] [Full Text] [PDF]
|
|