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Abstract
Objective To investigate the reliability of clinical outcomes in secondary progressive multiple sclerosis (SPMS) trials, we compared the frequency of progression and improvement events on different clinical outcome measures in the placebo arms of 2 large randomized controlled trial (RCT) datasets.
Methods Using original trial data from the placebo arms of IMPACT (International MS Secondary Progressive Avonex Controlled Trial) and ASCEND (A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis), 2 large RCTs in SPMS, we compared disability progression and similarly defined improvement with and without 3- or 6-month confirmation on the outcome measures Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and their combinations.
Results In both datasets, the EDSS showed the highest rates of improvement over time, and the smallest difference between progression and improvement rates, followed by the T25FW and the 9HPT. For the T25FW and 9HPT, improvement rates were fairly stable over time and remained at below or around the 10% level. For the EDSS, improvement rates increased in parallel with disability progression rates.
Conclusions All investigated outcome measures in SPMS showed some evidence of random variation and measurement error, the T25FW and 9HPT less so than the more established outcome EDSS. Our findings are relevant for the design and critical appraisal of trials in SPMS.
Glossary
- 9HPT=
- 9-Hole Peg Test;
- ASCEND=
- A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis;
- EDSS=
- Expanded Disability Status Scale;
- IMPACT=
- International MS Secondary Progressive Avonex Controlled Trial;
- MS=
- multiple sclerosis;
- MSFC=
- Multiple Sclerosis Functional Composite;
- MSOAC=
- Multiple Sclerosis Outcome Assessment Consortium;
- PPMS=
- primary progressive multiple sclerosis;
- RCT=
- randomized controlled trial;
- RRMS=
- relapsing-remitting multiple sclerosis;
- SPMS=
- secondary progressive multiple sclerosis;
- T25FW=
- Timed 25-Foot Walk
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 12
- Received February 14, 2020.
- Accepted in final form August 6, 2020.
- © 2020 American Academy of Neurology
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