Specific power calculations for magnetic resonance imaging (MRI) in monitoring active relapsing-remitting multiple sclerosis (MS): implications for phase II therapeutic trials

Abstract

Inhomogeneous patient samples have been used in previous studies to determine the power of magnetic resonance imaging (MRI) for trial monitoring in multiple sclerosis (MS). These power-calculations might not be applicable to the active relapsing-remitting patient who is preferably included in trials. In order to reevaluate the power alculations for MRI in the monitoring of treatment in strictly relapsing-remitting MS and to compare the power of different trial designs we studied 12 relapsing-remitting MS patients prospectively for a median period of II months using monthly clinical assessments and gadolinium-enhanced MRI. A median number of two clinical relapses/patient occurred of which a median of one was treated with steroids. A median of 1.59 new lesions/scan/patient was detected (range 0–8). The total number of new active lesions correlated significantly with study period relapses (SRCC=0.72, P=0.023). Computer simulations using the bootstrap technique yielded mostly lower power values for a parallel groups design than in previous studies except for short follow-periods in larger samples. In this sample the open cross-over design was found to be between 20 and 40% more powerful. Results of power-calculations are clearly sample dependent implying that for treatment trial monitoring using MRI in relapsing-remitting MS conservative sample size estimates are to be used. In an active patient group open cross-over trial designs could be a very powerful alternative to parallel groups design.

Keywords

Multiple sclerosis magnetic resonance imaging trials computer simulations

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