MRI metrics as surrogate markers for clinical relapse rate in relapsing-remitting MS patients.

Abstract

To formally validate metrics derived from conventional MRI as surrogate endpoints for relapse rate in MS. Although metrics derived from MRI are used widely in clinical trials of MS, a formal statistical validation of MRI metrics as surrogate endpoints for clinical outcome in MS is lacking. A validation procedure was applied to clinical and MRI data collected in the context of a randomized, double-blind, placebo-controlled trial of glatiramer acetate in patients with relapsing-remitting MS. The four Prentice operational criteria were applied to assess surrogacy for the number of new enhancing lesions, the percentage change of T2 lesion volume, and a composite MRI score based on these two metrics. The results of this analysis show that all three MRI measures considered by the authors had a behavior compatible with the Prentice criteria for valid surrogates. The composite MRI score correlated with relapses and accounted for much of the treatment effect on relapse rate. This preliminary study suggests that conventional MRI metrics might serve as valid surrogate endpoints in MS trials with glatiramer acetate or treatments thought to have a similar mode of action.