scholarly journals Upper cervical cord area in early relapsing-remitting multiple sclerosis: Cross-sectional study of factors influencing cord size

2006 ◽  
Vol 23 (4) ◽  
pp. 473-476 ◽  
Author(s):  
Waqar Rashid ◽  
Gerard R. Davies ◽  
Declan T. Chard ◽  
Colette M. Griffin ◽  
Dan R. Altmann ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cross Sectional Study ◽  
Cervical Cord ◽  
Sectional Study ◽  
Cross Sectional ◽  
Factors Influencing ◽  
Relapsing Remitting ◽  
Upper Cervical ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Comparison of the EDSS, Timed 25-Foot Walk, and the 9-Hole Peg Test as Clinical Trial Outcomes in Relapsing-Remitting Multiple Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012690
Author(s):  
Marcus W. Koch ◽  
Jop P. Mostert ◽  
Jerry S. Wolinsky ◽  
Fred D. Lublin ◽  
Bernard Uitdehaag ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Controlled Trial ◽  
Cross Sectional ◽  
Link Type ◽  
Kaplan Meier ◽  
Relapsing Remitting ◽  
Disability Outcome ◽  
Remitting Multiple Sclerosis ◽  
Presentation Methods ◽  
Relapsing Remitting Multiple Sclerosis

Background:Clinical trials in relapsing-remitting multiple sclerosis (RRMS) usually use the Expanded Disability Status Scale (EDSS) as their primary disability outcome measure, while the more recently developed outcomes timed 25 foot walk (T25FW) and nine hole peg test (NHPT) may be more useful and patient-relevant.Objective:To compare the EDSS to the T25FW and NHPT in a large RRMS randomized controlled trial (RCT) dataset.Methods:We used the dataset from CombiRx (clinicaltrials.gov identifier NCT00211887), a large phase 3 RCT, to compare the EDSS to the alternative outcomes T25FW and NHPT. We investigated disability worsening versus similarly defined improvement, unconfirmed versus confirmed and sustained disability change, and the presentation methods cumulative Kaplan-Meier survival curves versus cross-sectional disability worsening.Results:CombiRx included 1,008 participants. A comparison of confirmed versus sustained worsening events showed that throughout the trial, there were substantially fewer sustained than confirmed events, with a positive predictive value of confirmed for sustained worsening at 24 months of 0.73 for the EDSS, 0.73 for the T25FW, and 0.8 for the NHPT. More concerning was the finding that worsening on the EDSS occurred as frequently as similarly defined improvement throughout the three years of follow up, and that improvement rates increased in parallel with worsening rates. The T25FW showed low improvement rates of below 10% throughout the trial. We also found that Kaplan-Meier survival analysis, the standard presentation and analysis method in modern RRMS trials, yields exaggerated estimates of disability worsening. Using the Kaplan-Meier method, the proportion of patients with worsening events steadily increases, until it reaches several fold the number of events seen with more conservative analysis methods. For 3 month CDW at 36 months the ‘Kaplan-Meier’ method yields 2.6 fold higher estimates for the EDSS, 2.9 fold higher estimates for the T25FW and 5.1 fold higher estimates for the NHPT compared to a more conservative presentation of the same data.Discussion:Our analyses raise concerns about using the EDSS as the standard disability outcome in RRMS trials, and suggest that the T25FW may be a more useful measure. These findings are relevant for the design and critical appraisal of RCTs.

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