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 language | English |
|---|---|
| Pages (from-to) | 13-21 |
| Number of pages | 9 |
| Journal | Nature Reviews Neurology |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2012 |
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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 journal › Article
}
TY - JOUR
T1 - MRI monitoring of immunomodulation in relapse-onset multiple sclerosis trials
AU - Barkhof, Frederik
AU - Simon, Jack H.
AU - Fazekas, Franz
AU - Rovaris, Marco
AU - Kappos, Ludwig
AU - De Stefano, Nicola
AU - Polman, Chris H.
AU - Petkau, John
AU - Radue, Ernst W.
AU - Sormani, Maria P.
AU - Li, David K.
AU - O'Connor, Paul
AU - Montalban, Xavier
AU - Miller, David H.
AU - Filippi, Massimo
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
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U2 - 10.1038/nrneurol.2011.190
DO - 10.1038/nrneurol.2011.190
M3 - Article
C2 - 22143362
AN - SCOPUS:84655162283
VL - 8
SP - 13
EP - 21
JO - Nature Reviews Neurology
JF - Nature Reviews Neurology
SN - 1759-4758
IS - 1
ER -