. 2019 Nov 19;93(21):e1921-e1931.

doi: 10.1212/WNL.0000000000008519. Epub 2019 Oct 22.

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

Myla D Goldman¹, Nicholas G LaRocca¹, Richard A Rudick¹, Lynn D Hudson¹, Peter S Chin¹, Gordon S Francis¹, Adam Jacobs¹, Raj Kapoor¹, Paul M Matthews¹, Ellen M Mowry¹, Laura J Balcer¹, Michael Panzara¹, Glenn Phillips¹, Bernard M J Uitdehaag¹, Jeffrey A Cohen²; Multiple Sclerosis Outcome Assessments Consortium

Collaborators, Affiliations

Collaborators

Multiple Sclerosis Outcome Assessments Consortium:
Jane Haley, Steven Greenberg, Thomas Marshall, Xiaolan Ye, Andrew Blight, Matthew Sidovar, Craig Sherburne, Christina Casteris, Bjorn Sperling, Gilbert O'Neill, Glenn Phillips, Ih Chang, Jacob Elkins, John Richert, Richard Rudick, Tanuja Chitnis, Jesse Cedarbaum, Sanjay Keswani, Daniel Ontaneda, Deborah Miller, Jeffrey Cohen, Robert Bermel, June Halper, Gordon Francis, William Anthony, Alicia West, Bess LeRoy, Bob Stafford, Ann Robbins, Lynn Hudson, Stephen Coons, Emily Hartley, Gary Lundstrom, Jon Neville, Geoffrey Dunbar, Tanya Fischer, Thorsten Eickenhorst, Maria Isaac, Kathy Smith, David Margolin, Irina Antonijevic, Jeff Palmer, Michael Panzara, Phillipe Truffinet, Jennifer Panagoulias, Stephen Lake, Maria Davy, Paul Thompson, Paul Matthews, Gill Webster, Simon Wilkinson, Giampaolo Brichetto, Paola Zaratin, Ellen Mowry, Kathryn Fitzgerald, Peter Calabresi, John DeLuca, Lauren Strober, Nancy Chiaravalloti, Nancy Mayo, Wendy Kaye, Fred Lublin, Aaron Miller, Ursula Utz, Nicholas LaRocca, Timothy Coetzee, Weyman Johnson, Karen Lee, Susan Kohlhass, Laura Balcer, David Leppert, Frank Dahlke, Paul McGuire, Richard Meibach, Jerry Weaver, Jeremy Hobart, Adam Jacobs, Shari Medendorp, Algirdas Kakarieka, Bruno Musch, Donna Masterman, Peter Chin, Giancarlo Comi, Ralph Benedict, Lauren Krupp, Joshua Steinerman, Matthew Davis, Volker Knappertz, Elizabeth Morrison, Raj Kapoor, Myla Goldman, Gary Cutter, Maria Pia Sormani, Peter Fey, Rob Motl, Brenda Banwell, Andrew Goodman, Jerry Wolinsky, Dagmar Amtmann, Bernard Uitdehaag, Robert Naismith

Affiliations

¹ 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.
² 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.

PMID: 31641014
PMCID: PMC6885577
DOI: 10.1212/WNL.0000000000008519

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

Myla D Goldman et al. Neurology. 2019.

. 2019 Nov 19;93(21):e1921-e1931.

doi: 10.1212/WNL.0000000000008519. Epub 2019 Oct 22.

Authors

Collaborators

Multiple Sclerosis Outcome Assessments Consortium:
Jane Haley, Steven Greenberg, Thomas Marshall, Xiaolan Ye, Andrew Blight, Matthew Sidovar, Craig Sherburne, Christina Casteris, Bjorn Sperling, Gilbert O'Neill, Glenn Phillips, Ih Chang, Jacob Elkins, John Richert, Richard Rudick, Tanuja Chitnis, Jesse Cedarbaum, Sanjay Keswani, Daniel Ontaneda, Deborah Miller, Jeffrey Cohen, Robert Bermel, June Halper, Gordon Francis, William Anthony, Alicia West, Bess LeRoy, Bob Stafford, Ann Robbins, Lynn Hudson, Stephen Coons, Emily Hartley, Gary Lundstrom, Jon Neville, Geoffrey Dunbar, Tanya Fischer, Thorsten Eickenhorst, Maria Isaac, Kathy Smith, David Margolin, Irina Antonijevic, Jeff Palmer, Michael Panzara, Phillipe Truffinet, Jennifer Panagoulias, Stephen Lake, Maria Davy, Paul Thompson, Paul Matthews, Gill Webster, Simon Wilkinson, Giampaolo Brichetto, Paola Zaratin, Ellen Mowry, Kathryn Fitzgerald, Peter Calabresi, John DeLuca, Lauren Strober, Nancy Chiaravalloti, Nancy Mayo, Wendy Kaye, Fred Lublin, Aaron Miller, Ursula Utz, Nicholas LaRocca, Timothy Coetzee, Weyman Johnson, Karen Lee, Susan Kohlhass, Laura Balcer, David Leppert, Frank Dahlke, Paul McGuire, Richard Meibach, Jerry Weaver, Jeremy Hobart, Adam Jacobs, Shari Medendorp, Algirdas Kakarieka, Bruno Musch, Donna Masterman, Peter Chin, Giancarlo Comi, Ralph Benedict, Lauren Krupp, Joshua Steinerman, Matthew Davis, Volker Knappertz, Elizabeth Morrison, Raj Kapoor, Myla Goldman, Gary Cutter, Maria Pia Sormani, Peter Fey, Rob Motl, Brenda Banwell, Andrew Goodman, Jerry Wolinsky, Dagmar Amtmann, Bernard Uitdehaag, Robert Naismith

Affiliations

¹ 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.
² 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.

PMID: 31641014
PMCID: PMC6885577
DOI: 10.1212/WNL.0000000000008519

Erratum in

Evaluation of Multiple Sclerosis Disability Outcome Measures Using Pooled Clinical Trial Data.
[No authors listed] [No authors listed] Neurology. 2021 Mar 9;96(10):504-505. doi: 10.1212/WNL.0000000000011677. Epub 2021 Feb 12. Neurology. 2021. PMID: 33579759 Free PMC article. No abstract available.

Abstract

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.

PubMed Disclaimer

Figures

**Figure 1. Distribution of performance measure scores at baseline**
(A) Timed 25-Foot Walk (T25FW) (seconds). (B) 9-Hole Peg Test (9HPT) (seconds). (C) Low Contrast Letter Acuity (LCLA) with 2.5% contrast (number correct). (D) Symbol Digit Modalities Test (SDMT) (number correct).

**Figure 2. Kaplan-Meier graphs of time to 3-month confirmed disability worsening on performance measures compared to Expanded Disability Status Scale**
(A) Timed 25-Foot Walk (T25FW). (B) 9-Hole Peg Test (9HPT). (C) Low Contrast Letter Acuity (LCLA) with 2.5% contrast. (D) Symbol Digit Modalities Test (SDMT). (E) Any 1 or any 2 performance measures.

See this image and copyright information in PMC

Comment in

Measuring disability in multiple sclerosis: Walking plus much more.
Sormani MP, Naismith RT. Sormani MP, et al. Neurology. 2019 Nov 19;93(21):919-920. doi: 10.1212/WNL.0000000000008515. Epub 2019 Oct 22. Neurology. 2019. PMID: 31641015 No abstract available.

References

1. Whitaker JN, McFarland HF, Rudge P, Reingold SC. Outcomes assessment in multiple sclerosis clinical trials: a critical analysis. Mult Scler 1995;1:37–47. - PubMed
1. Rudick R, Antel J, Confavreux C, et al. . Clinical outcomes assessment in multiple sclerosis. Ann Neurol 1996;40:469–479. - PubMed
1. Rudick R, Antel J, Confavreux C, et al. . Recommendations from the National Multiple Sclerosis Society clinical outcomes assessment task force. Ann Neurol 1997;42:379–382. - PubMed
1. Schwid SR, Goodman AD, McDermott MP, Bever CF, Cook SD. Quantitative functional measures in MS: what is a reliable change? Neurology 2002;58:1294–1296. - PubMed
1. Kragt J, Van der Linden F, Nielsen J, Uitdehagg B, Polman C. Clinical impact of 20% worsening on Timed 25-Foot Walk and 9-Hole Peg Test in multiple sclerosis. Mult Scler 2006;12:594–598. - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Erratum in

Abstract

Figures

Comment in

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical