The MSOAC approach to developing performance outcomes to measure and monitor multiple sclerosis disability

Abstract

Background:The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability.Objectives:(1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials.Methods:(1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials.Conclusion:Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC standard for MS (http://www.cdisc.org/therapeutic#MS) was published, allowing pooling of clinical trial data. MSOAC member organizations contributed clinical data from 16 trials, including 14,370 subjects. Data from placebo-arm subjects are available to qualified researchers. This integrated, standardized dataset is being analyzed to support qualification of disability endpoints by regulatory agencies.

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

“…21 Other studies in patients with secondary progressive multiple sclerosis have used composite outcome measurements and reported differences in outcomes assessing upper limb versus lowerlimb function, 11,24 highlighting the importance of using sensitive measures of disease worsening in secondary progressive multiple sclerosis trials that include key domains of function in addition to ambulation. 25 In part 1 of this study, we observed an apparent beneficial effect of natalizumab on limb function but not on measures of ambulation. Although this difference could be explained by different treatment effects on neural systems serving different functions, the findings are also consistent with the possibility that the benefits of stopping inflammation from further damaging the CNS manifest after a delay that is shorter in pathways with shorter axons than in pathways with longer axons.…”

Novel MS vital sign: multi‐sensor captures upper and lower limb dysfunction

“…In addition to the benefits of this new vital sign for clinical care, there is a high demand for improved outcome measures in MS for clinical trials. 10 The limitations of the gold standard EDSS exam have been well described elsewhere 11,12 but include interrater variability and insensitivity to change over the short term. The strong dependence of the scale on ambulatory status means for a patient using a cane (EDSS 6.0) even if she had worsening of her dominant upper limb function, her official outcome in a trial would be "stable" as long as she continued to use a cane and did not start using a walker (EDSS 6.5).…”

Expanded disability status scale progression assessment heterogeneity in multiple sclerosis according to geographical areas

“…The results of this study, reflecting a large dataset of >1,700 patients from 3 clinical trials, enrolled according to the same inclusion criteria and followed for 2 years under placebo, call for harmonization procedures for MS patients’ clinical assessment. Large efforts have been devoted to defining composite outcomes to improve the clinical assessment of MS patients; the MSFC, incorporating 3 functional measures, reflecting cognition, ambulation, and upper limb function, is an example of such an effort. However, these attempts to create new measures were mainly focused on increasing the sensitivity of the outcome and its ability to better assess multiple disease aspects.…”