Surrogate endpoints for EDSS worsening in multiple sclerosis. A meta-analytic approach.
Summary
The aim of this study is to evaluate the effect of clinical and MRI markers to predict the effect of a new treatment in a clinical trial. The authors studied 10,009 people with multiple sclerosis (MS) involved in 19 clinical trials. They found a significant correlation between EDSS worsening and MRI lesions. They concluded supporting the use of these markers in MS clinical trials. Sormani MP, Bonzano L, Roccatagliata L, Mancardi GL, Uccelli A, Bruzzi P. Neurology. 2010 Jun 23
Details
The onjective of this work was 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.
A pooled analysis was employed using 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. Data was extracted 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.
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.
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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