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Surrogate endpoints for EDSS worsening in multiple sclerosis. A meta-analytic approach.

Abstract

OBJECTIVE
To evaluate whether the effects on potential surrogate endpoints, such as MRI markers and relapses, observed in trials of experimental treatments are able to predict the effects of these treatments on disability progression as defined in relapsing-remitting multiple sclerosis (RRMS) trials.
METHODS
We used a pooled analysis of all the published randomized controlled clinical trials in RRMS reporting data on Expanded Disability Status Scale (EDSS) worsening and relapses or MRI lesions or both. We extracted data on relapses, MRI lesions, and the proportion of progressing patients. A regression analysis weighted on trial size and duration was performed to study the relationship between the treatment effect observed in each trial on relapses and MRI lesions and the observed treatment effect on EDSS worsening.
RESULTS
A set of 19 randomized double-blind controlled trials in RRMS were identified, for a total of 44 arms, 25 contrasts, and 10,009 patients. A significant correlation was found between the effect of treatments on relapses and the effect of treatments on EDSS worsening: the adjusted R(2) value of the weighted regression was 0.71. The correlation between the treatment effect on MRI lesions and EDSS worsening was slightly weaker (R(2) = 0.57) but significant.
CONCLUSIONS
These findings support the use of commonly used surrogate markers of EDSS worsening as endpoints in multiple sclerosis clinical trials. Further research is warranted to validate surrogate endpoints at the individual level rather than at the trial level, to draw important conclusions in the management of the individual patient.

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    • Authors

    Sormani MP, Bonzano L, Roccatagliata L, Mancardi GL, Uccelli A, Bruzzi P

    Institution

    Department of Health Sciences, Via Pastore 1, Genoa, Italy. mariapia.sormani@unige.it

    Source

    Neurology 75:4 2010 Jul 27 pg 302-9

    MeSH

    Disability Evaluation
    Humans
    Magnetic Resonance Imaging
    Multiple Sclerosis, Relapsing-Remitting
    Predictive Value of Tests
    Sensitivity and Specificity

    Pub Type(s)

    Journal Article
    Meta-Analysis

    Language

    eng

    PubMed ID

    20574036