Disease progression, or gradual worsening, experienced by people who have multiple sclerosis usually occurs over many years, and it is difficult to track with the standard clinical measurement scales used by doctors to assess disease activity. An international meeting was convened to determine how to improve clinical measures so that MS progression can be better tracked, especially during clinical trials of experimental therapies aimed at stopping progression. Better ways of measuring changes in disability will help to speed the development of new therapies for MS, in particular for progressive forms of the disease.
The meeting was organized by the International Advisory Committee on Clinical Trials in MS, an international group of MS experts jointly sponsored by the National MS Society and the European Committee for Treatment and Research in MS (ECTRIMS).* A summary of this meeting has now been published in Lancet Neurology (2012 May;11(5):467-476). The Society is responding to the group’s recommendations, and sponsoring a collaborative effort to revise one clinical measure for primary use as a means of measuring disability in MS studies.
The Meeting: The “International Conference on Disability Outcomes in MS” was held in Washington, D.C. in 2011. Over 70 experts in MS and clinical trial design from around the world – including academic physicians and scientists, representatives of companies pursuing new therapies in MS and regulators from the U.S., Europe and Canada – gathered to discuss the measures currently used to measure MS disability, including the Expanded Disability Status Scale (EDSS), and the MS Functional Composite (MSFC). They agreed that these measures do not adequately measure the changes in MS progression that occur over time, or the patients’ own perceptions of their health and quality of life.
The group reviewed disability rating methods that show promise but require more study, such as “composite” endpoints that combine several measures, and innovative tools such as smart phones and other instruments that may offer better ways of tracking a person’s mobility.
Imaging, such as sophisticated MRI techniques used to examine changes in MS in the brain and spinal cord, and techniques to assess changes in the visual system over time (such as optical coherence tomography, OCT), were also discussed in terms of their abilities to objectively track signs of disease progression.
Meeting participants also reviewed a variety of “patient reported outcomes” being explored in MS clinical trials. These are surveys of clinical trial participants’ perspectives of their own health status and response to therapies, and are increasingly incorporated into clinical trials in MS and many other disorders. These subjective measures can add a dimension of clinical relevance to the objective measurements used by physicians to assess disability and the effectiveness of therapies.
The attendees made recommendations for improving upon current measures. In the case of the EDSS, they recommended developing a standard interview script so that all clinicians would administer this scale similarly, and simplifying the complex scoring rules. In the case of the MSFC, the group recommended that the MSFC could be improved by the addition of a test that measures change in visual function over time, by replacing the currently used method of assessing cognitive function, and by developing alternative scoring methods.
Following the meeting, these recommendations were discussed by the National MS Society’s senior research advisors, who concluded that the Society should sponsor an effort to revise the MSFC. The advisors appointed an interdisciplinary group of people with expertise in the clinical trials arena, from academia, industry, regulatory agencies and patient advocacy groups. This team is shepherding the process of revising the MSFC scale for use as a primary disability outcome in MS clinical trials.
The goal is to speed clinical trials of promising therapies aimed at stopping progression or restoring function. “We can’t afford to wait years to determine whether a therapy is working against MS progression,” noted Timothy Coetzee, PhD, Chief Research Officer of the Society.
*Additional support for the meeting was provided by the Americas Committee for Treatment and Research in MS, MS International Federation, MS Society of Canada, Bayer Healthcare Pharmaceuticals, Inc., Biogen Idec, Inc., F Hoffmann-LaRoche Ltd., Genzyme Corporation, Novartis Corporation, Sanofi-Aventis SA, and Teva Pharmaceutical Industries Ltd.