title: MRI monitoring of immunomodulation in relapse-onset multiple sclerosis trials.
abstract: Over the past 15 years, MRI lesion activity has become the accepted surrogate primary outcome measure in proof-of-concept placebo-controlled clinical trials of new immunomodulating therapies in relapse-onset multiple sclerosis (MS). In parallel, the number of patients that are available for the placebo arm of trials has declined, and more-aggressive drugs are being developed. A critical review is warranted to ensure efficient MRI--and patient--resource utilization. Recently, an international panel reviewed the methodology for efficient use of MRI-monitored trials in relapse-onset MS. In this article, we provide up-to-date recommendations for scan acquisition, image analysis, outcome-measure definition and standards of reporting. Factors to consider for optimizing trial design, such as outcome measure selection and the unique requirements of phase II and phase III trials, including active-comparator studies, are outlined. Finally, we address safety considerations in the use of MRI in MS trials, and the safety-related responsibilities of the various parties involved in conducting such trials.
authors.affiliation: VU University Medical Centre, Amsterdam, The Netherlands. f.barkhof@vumc.nl
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Jack H
authors.initials: JH
authors.lastname: Simon
authors.forename: Franz
authors.initials: F
authors.lastname: Fazekas
authors.forename: Marco
authors.initials: M
authors.lastname: Rovaris
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.forename: Nicola
authors.initials: N
authors.lastname: de Stefano
authors.forename: Chris H
authors.initials: CH
authors.lastname: Polman
authors.forename: John
authors.initials: J
authors.lastname: Petkau
authors.forename: Ernst W
authors.initials: EW
authors.lastname: Radue
authors.forename: Maria P
authors.initials: MP
authors.lastname: Sormani
authors.forename: David K
authors.initials: DK
authors.lastname: Li
authors.forename: Paul
authors.initials: P
authors.lastname: O'Connor
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.forename: David H
authors.initials: DH
authors.lastname: Miller
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D002986:Clinical Trials as Topic; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D056747:Immunomodulation; D008279:Magnetic Resonance Imaging; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology*; D012107:Research Design