Magnetic resonance imaging as a surrogate outcome for multiple sclerosis relapses
- 1 July 2008
- journal article
- research article
- Published by SAGE Publications in Multiple Sclerosis Journal
- Vol. 14 (6), 770-778
- https://doi.org/10.1177/1352458507088104
Abstract
Background Magnetic resonance imaging (MRI) of lesions in the brain may be the best current candidate for a surrogate biological marker of clinical outcomes in relapsing remitting multiple sclerosis (MS), based on its role as an objective indicator of disease pathology. No biological surrogate marker has yet been validated for MS clinical outcomes. Objective The objective of this study was to use a multi-phased study to determine if a valid surrogate relationship could be demonstrated between counts of contrast enhancing lesions (CELs) and occurrence of relapses in MS. Methods We examined correlations for the concurrent and predictive relationship between CELs over 6 months and MS relapses over the same 6 months and an additional 6 months (total: 12 months), using available data on untreated patients from a large clinical trial and natural history database. Results Concurrent and predictive correlations were inadequate to justify continuation of this study to the planned additional phases required to demonstrate a surrogate relationship between CELs and MS relapses. Conclusions Confidence intervals for correlations between CELs and MS relapses exclude the possibility that CELs can be a good surrogate for relapses over the time scales we investigated. Further exploration of surrogacy between MRI measures and MS clinical outcomes may require improved datasets, the development of MRI techniques that couple better to clinical disease, and the ability to test a wide range of imaging- and clinically-based hypotheses for surrogacy.This publication has 26 references indexed in Scilit:
- Magnetization transfer MRI metrics predict the accumulation of disability 8 years later in patients with multiple sclerosisBrain, 2006
- A Randomized, Placebo-Controlled Trial of Natalizumab for Relapsing Multiple SclerosisThe New England Journal of Medicine, 2006
- Why Most Published Research Findings Are FalsePLoS Medicine, 2005
- Surrogate Endpoints And FDA’s Accelerated Approval ProcessHealth Affairs, 2005
- MRI metrics as surrogate endpoints for EDSS progression in SPMS patients treated with IFN β-1bNeurology, 2003
- A Controlled Trial of Natalizumab for Relapsing Multiple SclerosisThe New England Journal of Medicine, 2003
- European/Canadian multicenter, double‐blind, randomized, placebo‐controlled study of the effects of glatiramer acetate on magnetic resonance imaging–measured disease activity and burden in patients with relapsing multiple sclerosisAnnals of Neurology, 2001
- Intramuscular interferon beta‐1a for disease progression in relapsing multiple sclerosisAnnals of Neurology, 1996
- Copolymer 1 reduces relapse rate and improves disability in relapsing‐remitting multiple sclerosisNeurology, 1995
- Surrogate endpoints in clinical trials: Definition and operational criteriaStatistics in Medicine, 1989