Evaluation of multiple sclerosis disability outcome measures using pooled clinical trial data.

Objective We report analyses of a pooled database by the Multiple Sclerosis Outcome Assessments Consortium to evaluate 4 proposed components of a multidimensional test battery. Methods Standardized data on 12,776 participants, comprising demographics, multiple sclerosis disease characteristics, Expanded Disability Status Scale (EDSS) score, performance measures, and Short Form–36 Physical Component Summary (SF-36 PCS), were pooled from control and treatment arms of 14 clinical trials. Analyses of Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), Low Contrast Letter Acuity (LCLA), and Symbol Digit Modalities Test (SDMT) included measurement properties; construct, convergent, and known group validity; and longitudinal performance of the measures individually and when combined into a multidimensional test battery relative to the EDSS and SF-36 to determine sensitivity and clinical meaningfulness. Results The performance measures had excellent test–retest reliability and showed expected differences between subgroups based on disease duration and EDSS level. Progression rates in detecting time to 3-month confirmed worsening were lower for T25FW and 9HPT compared to EDSS, while progression rates for LCLA and SDMT were similar to EDSS. When the 4 measures were analyzed as a multidimensional measure rather than as individual measures, progression on any one performance measure was more sensitive than the EDSS. Worsening on the performance measures analyzed individually or as a multidimensional test battery was associated with clinically meaningful SF-36 PCS score worsening, supporting clinical meaningfulness of designated performance test score worsening. Conclusion These results support the use of the 4 proposed performance measures, individually or combined into a multidimensional test battery as study outcome measures.