The use of magnetic resonance imaging in multiple sclerosis treatment trials: power calculations for annual lesion lend measurement

Phase III definitive treatment trials of new multiple sclerosis (MS) therap ies now routinely incorporate an annual magnetic resonance imaging protocol , with change in T2-weighted brain lesion load providing an important outco me measure. To date the accepted strategy has been to perform a core imagin g protocol on all patients in such studies. The aim of this study was to pr ovide power calculations based on this MRI endpoint. Serial MRI data from 1 28 patients with either relapsing remitting (RR) or secondary progressive ( SP) MS were used to calculate sample size requirements using a repeated mea sures analysis of variance design. We provide sample size calculations base d on various follow-up intervals and effect sizes. Sample sizes for the SPM S cohort were substantially larger than for the RRMS group, reflecting the greater variance in lesion load changes between patients in the SPMS group. With a follow-up of 3 years, we estimate that only 12 and 33 patients per arm are needed to show stabilisation of MRI lesion load in the RRMS and SPM S groups, respectively. Our results suggest that ongoing phase III treatmen t trials are more than adequately powered to detect even subtle treatment e ffects, and indicate that incorporating measurements from longer follow-up durations increases power substantially. We conclude that an annual imaging protocol provides a robust and powerful tool for assessing effects on the radiological appearance of the disease process.