MRI monitoring of immunomodulation in relapse-onset multiple sclerosis trials

Frederik Barkhof, Jack H. Simon, Franz Fazekas, Marco Rovaris, Ludwig Kappos, Nicola De Stefano, Chris H. Polman, John Petkau, Ernst W. Radue, Maria P. Sormani, David K. Li, Paul O'Connor, Xavier Montalban, David H. Miller, Massimo Filippi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)13-21
Number of pages9
JournalNature Reviews Neurology
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 2012

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Immunomodulation
Multiple Sclerosis
Outcome Assessment (Health Care)
Recurrence
Placebos
Safety
Controlled Clinical Trials
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

MRI monitoring of immunomodulation in relapse-onset multiple sclerosis trials. / Barkhof, Frederik; Simon, Jack H.; Fazekas, Franz; Rovaris, Marco; Kappos, Ludwig; De Stefano, Nicola; Polman, Chris H.; Petkau, John; Radue, Ernst W.; Sormani, Maria P.; Li, David K.; O'Connor, Paul; Montalban, Xavier; Miller, David H.; Filippi, Massimo.

In: Nature Reviews Neurology, Vol. 8, No. 1, 01.2012, p. 13-21.

Research output: Contribution to journalArticle

Barkhof, F, Simon, JH, Fazekas, F, Rovaris, M, Kappos, L, De Stefano, N, Polman, CH, Petkau, J, Radue, EW, Sormani, MP, Li, DK, O'Connor, P, Montalban, X, Miller, DH & Filippi, M 2012, 'MRI monitoring of immunomodulation in relapse-onset multiple sclerosis trials', Nature Reviews Neurology, vol. 8, no. 1, pp. 13-21. https://doi.org/10.1038/nrneurol.2011.190
Barkhof, Frederik ; Simon, Jack H. ; Fazekas, Franz ; Rovaris, Marco ; Kappos, Ludwig ; De Stefano, Nicola ; Polman, Chris H. ; Petkau, John ; Radue, Ernst W. ; Sormani, Maria P. ; Li, David K. ; O'Connor, Paul ; Montalban, Xavier ; Miller, David H. ; Filippi, Massimo. / MRI monitoring of immunomodulation in relapse-onset multiple sclerosis trials. In: Nature Reviews Neurology. 2012 ; Vol. 8, No. 1. pp. 13-21.
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