The Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR)--Critical review facing the 20 anniversary.

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.