TY - JOUR
T1 - Evaluation of multiple sclerosis disability outcome measures using pooled clinical trial data
AU - Goldman, Myla D.
AU - Larocca, Nicholas G.
AU - Rudick, Richard A.
AU - Hudson, Lynn D.
AU - Chin, Peter S.
AU - Francis, Gordon S.
AU - Jacobs, Adam
AU - Kapoor, Raj
AU - Matthews, Paul M.
AU - Mowry, Ellen M.
AU - Balcer, Laura J.
AU - Panzara, Michael
AU - Phillips, Glenn
AU - Uitdehaag, Bernard M.J.
AU - Cohen, Jeffrey A.
N1 - Funding Information:
MSOAC is funded through the National Multiple Sclerosis Society grant RG 4869-A-1 to the Critical Path Institute, supplemented by annual dues from industry sponsors.
Funding Information:
The Article Processing Charge was funded by the National Multiple Sclerosis Society.
Funding Information:
P.M.M. acknowledges support for activities related to this work from the NIHR Imperial Biomedical Research Centre.
Publisher Copyright:
© 2019 American Academy of Neurology.
PY - 2019/11/19
Y1 - 2019/11/19
N2 - 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.
AB - 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.
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U2 - 10.1212/WNL.0000000000008519
DO - 10.1212/WNL.0000000000008519
M3 - Article
C2 - 31641014
AN - SCOPUS:85075222702
SN - 0028-3878
VL - 93
SP - E1921-E1931
JO - Neurology
JF - Neurology
IS - 21
ER -