title: 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-calculations 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 12 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.
authors.affiliation: Dutch MR centre for MS research, Academic Hospital Vrije Universiteit, Amsterdam.
authors.forename: L
authors.initials: L
authors.lastname: Truyen
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
authors.forename: M
authors.initials: M
authors.lastname: Tas
authors.forename: M A
authors.initials: MA
authors.lastname: Van Walderveen
authors.forename: S T
authors.initials: ST
authors.lastname: Frequin
authors.forename: O R
authors.initials: OR
authors.lastname: Hommes
authors.forename: J J
authors.initials: JJ
authors.lastname: Nauta
authors.forename: C H
authors.initials: CH
authors.lastname: Polman
authors.forename: J
authors.initials: J
authors.lastname: Valk
mesh_terms: D000328:Adult; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000503:physiopathology*; D012008:Recurrence; D012107:Research Design