- •SLCMSR challenged established outcome parameters in MS.
- •Sustained increase of EDSS appeared to be an invalid outcome for clinical trials.
- •SLCMSR contributed to the development of new outcomes such as real-world walking speed.
- •A tool was constructed to provide individual prognostic estimates based on a matching algorithm.
The SLCMSR was formed as an international Multiple Sclerosis Trials, Research and Resource Center to identify clinical MRI and other predictors of the course of multiple sclerosis (MS) based on a large database of natural history and clinical trial data. Using an elaborate validation concept several key findings were published, challenging established outcome parameters and their assessment in MS such as disability ratings with Expanded Disability Status Scale (EDSS), relapses and MRI endpoints. Sustained increase of EDSS appeared to be an invalid outcome for 2–3 year clinical trials at least in patients with relapsing-remitting MS. The number of gadolinium-enhancing lesions and T2-lesion load on MRI were shown not to have a meaningful additional predictive value for the disease course. These issues risen some 15 years ago had triggered controversial discussions which have also been noticed by regulatory authorities and they all have not been resolved. In addition the SLCMSR contributed to the development of new outcomes such as real-world walking speed as an attractive, ecologically valid tool based on a wearable device. A so-called evidence-based-decision-support tool was constructed to provide individual prognostic estimates based on a matching algorithm to a given database. This paper condensates the findings of 20 years of critical MS research.
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- Day-to-day variability of maximum walking distance in MS patients can mislead to relevant changes in the Expanded Disability Status Scale (EDSS): average walking speed is a more constant parameter.Mult. Scler. 2001; 7: 105-109
- Predicting Gadolinium enhancement status in MS patients eligible for randomized clinical trials.Neurology. 2005; 65: 1447-1454
- MRI - the perfect surrogate marker for multiple sclerosis?.Nat. Rev. Neurol. 2009; 5: 182-183
- Blood neurofilament light: a critical review of its application to neurologic disease.Ann. Clin. Transl. Neurol. 2020; 7: 2508-2523
- Expanded disability status scale progression assessment heterogeneity in multiple sclerosis according to geographical areas.Ann. Neurol. 2018; 84: 621-625
- Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process.Brain. 2003; 126: 770-782
- Silent progression in disease activity-free relapsing multiple sclerosis.Ann. Neurol. 2019; 85: 653-666
- Generating Evidence from Historical Data Using Robust Prognostic Matching: experience from Multiple Sclerosis.in: Schüler P. Buckley B. Re-Engineering Clinical Trials: Best Practices For Streamlining the Development Process E- p. Elsevier, Oxford2014: 177-185
Daumer M., Lederer C., et al., Briefing Book for the EMA Qualification of novel methodologies for drug development, 01-February- 2017, https://www.fda.gov/drugs/clinical-outcome-assessment-coa-qualification-program/ddt-coa-000106-actibeltr-multiple-sclerosis.
- Similarities and differences between two major MS natural history studies.Mult. Scler. 2010; 16 (S209)
- MRI as an outcome in multiple sclerosis clinical trials.Neurology. 2007; 72: 705-711
- Reducing the probability of false positive research findings by pre-publication validation – Experience with a large multiple sclerosis database.BMC Med. Res Methodol. 2008; 8: 18https://doi.org/10.1186/1471-2288-8-18
- Survival, and time to an advanced disease state or progression, of untreated patients with moderately severe multiple sclerosis in a multicenter observational database: relevance for design of a clinical trial for high dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation.Mult. Scler. 2006; 12: 174-179
- Disability as an outcome in MS clinical trials.Neurology. 2008; 71: 624-631
- A Web-based tool for personalized prediction of long-term disease course in patients with multiple sclerosis.Eur. J. Neurol. 2013; 20 (2013): 1107-1109
- Prognostic risk estimates of patients with multiple sclerosis and their physicians: comparison to an online analytical risk counseling tool.PLoS ONE. 2013; 17 (8): e59042
- Predictors of relapse rate in MS clinical trials.Neurology. 2005; 13 (65): 1769-1773
- Why most published research findings are false.PLoS Med. 2005; 2: e124https://doi.org/10.1371/journal.pmed.0020124
- MSBase Study Group. Predictors of long-term disability accrual in relapse-onset multiple sclerosis.Ann. Neurol. 2016; 80: 89-100
- Long-term prognostic counselling in people with multiple sclerosis using an online analytical processing tool.Mult. Scler. 2021; 27: 1442-1450
- NIH issues a seismic mandate: share data publicly.Nature. 2022; 602: 558-559
- MRI T2 lesion burden in multiple sclerosis: a plateauing relationship with clinical disability.Neurology. 2006; 66: 1384-1389
- Risk factors for occurrence of a second clinical event in patients with a clinically isolated syndrome at high risk.Meeting Am. Acad. Neurol. Chicago. 2008; (12.-19.4)
- Onset of secondary progressive phase and long-term evolution of multiple sclerosis.J. Neurol. Neurosurg. Psych. 2014; 85: 67-75
- Age and disability accumulation in multiple sclerosis.Neurology. 2011; 77: 1246-1252
- The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability.Brain. 2010; 133: 1914-1929
- Development and validation of a new method to measure walking speed in free-living environments using the actibelt1 platform.PLoS ONE. 2011; 6 (doi: 10. 1371/journal.pone.0023080): e23080
- Fampridine and real-life walking in multiple sclerosis: low predictive value of clinical test for habitual short-term changes.J. Neurol. Sci. 2016; 368: 318-325
- Eological validity of walking capacity tests in multiple sclerosis.PLoS ONE. 2015; 10e0123822https://doi.org/10.1371/journal.pone.0123822
- Validating predictors of disease progression in a large cohort of primary-progressive multiple sclerosis based on a systematic literature review.PLoS ONE. 2014; 9: e92761https://doi.org/10.1371/journal.pone.0092761
- Placebo cohorts in phase-3 MS treatment trials - predictors for on-trial disease activity 1990-2010 based on a meta-analysis and individual case data.PLoS ONE. 2012; 7: e50347https://doi.org/10.1371/journal.pone.0050347
- Impact of multiple sclerosis relapses on progression diminishes with time.Neurology. 2009; 73: 1616-1623
- The long-term outcomes of CIS patients in the Barcelona inception cohort: looking back to recognize aggressive MS.Mult. Scler. 2020; 26: 1658-1669
- Considerations for development of an evidence dossier to support the use of mobile sensor technology for clinical outcome assessments in clinical trials.Contemp. Clin. Trials. 2020; 91105962https://doi.org/10.1016/j.cct.2020.105962
- 2021 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis.Lancet Neurol. 2021; 20: 653-670
- Relapses and subsequent worsening of disability in relapsing-remitting multiple sclerosis.Neurology. 2006; 67: 804-808
Published online: May 16, 2022
Accepted: May 13, 2022
Received in revised form: March 31, 2022
Received: January 9, 2022
© 2022 Published by Elsevier B.V.