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

Autor:	Goldman MD; From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH., LaRocca NG; From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH., Rudick RA; From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH., Hudson LD; From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH., Chin PS; From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH., Francis GS; From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH., Jacobs A; From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH., Kapoor R; From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH., Matthews PM; From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH., Mowry EM; From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH., Balcer LJ; From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH., Panzara M; From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH., Phillips G; From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH., Uitdehaag BMJ; From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH., Cohen JA; From the University of Virginia (M.D.G.), Charlottesville; National Multiple Sclerosis Society (N.G.L.), New York, NY; Biogen (R.A.R., G.P.), Cambridge, MA; Critical Path Institute (L.D.H.), Tucson, AZ; Genentech (P.S.C.), South San Francisco, CA; Independent Neurology Clinical Development Consultant (G.S.F.); Premier Research (A.J.), Wokingham, UK; UCL Institute of Neurology (R.K.), London, UK; Imperial College London and UK Dementia Research Institute (P.M.M.); Johns Hopkins (E.M.M.), Baltimore, MD; New York University School of Medicine (L.J.B.), NY; Wave Life Sciences (M.P.), Cambridge, MA; VU University Medical Center (B.M.J.U.), Amsterdam, the Netherlands; and Cleveland Clinic (J.A.C.), OH. cohenj@ccf.org.
Jazyk:	angličtina
Zdroj:	Neurology [Neurology] 2019 Nov 19; Vol. 93 (21), pp. e1921-e1931. Date of Electronic Publication: 2019 Oct 22.
DOI:	10.1212/WNL.0000000000008519
Abstrakt:	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. (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Databáze:	MEDLINE
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