Use of the Multiple Sclerosis Functional Composite as an Outcome Measure in a Phase 3 Clinical Trial

Cohen, Jeffrey A.; Cutter, Gary; Fischer, Jill S.; Goodman, Andrew; Heidenreich, Fedor; Jak, Amy J.; Kniker, Judith E.; Kooijmans, Mariska; Lull, Julia M.; Sandrock, Alfred; Simon, Jack H.; Simonian, Nancy A.; Whitaker, John N.

doi:10.1001/archneur.58.6.961

Cited by 158 publications

(148 citation statements)

References 21 publications

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“…42 The primary outcome measure was change in the MS Functional Composite score (MSFC), an outcome measure that combines three domains: upper arm and hand function, cognition, and ambulation; it is expressed as a composite Z-score. 43 Two-year worsening in MSFC was reduced by 40.4% (P ϭ 0.033) in the treatment arm; this was attributable largely to preservation of upper extremity function as measured by the nine-hole peg test. There was a significant reduction in relapses, but no difference between groups in the progression of EDSS.…”

Section: Secondary Progressive Msmentioning

confidence: 87%

Interferon-β Treatment for Multiple Sclerosis

Bermel

Rudick

2007

Neurotherapeutics

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Summary:Multiple sclerosis (MS) is the leading nontraumatic cause of neurologic disability in young adults. Interferon-␤, approved for use in 1993, was the first treatment to modify the course and prognosis of the disease and remains a mainstay of MS treatment. Numerous large-scale clinical trials in early, active patient populations have established the clinical efficacy of interferon-␤ in reducing relapses and delaying disability progression. Although its mechanism of action remains incompletely understood, a reduction in active lesions seen on magnetic resonance imaging implies primary anti-inflammatory properties, a mechanism supported by basic immunologic research. Variation in individual patient responsiveness to interferon-␤ may be due to disease variability or differential induction of interferon-stimulated genes. The magnitude of the therapeutic effect appears to be similar among products, but the optimal dose, route, and frequency of administration of the drug remain uncertain.

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Section: Secondary Progressive Msmentioning

confidence: 87%

Interferon-β Treatment for Multiple Sclerosis

Bermel

Rudick

2007

Neurotherapeutics

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“…However, the individuals with MS achieved a significantly lower maximal heart rate (beats per minute) than the controls during the exercise test (p = 0.02), with a Cohen d effect size of 1.36 (which is considered large [10]). Despite not reaching statistical significance between groups, VO 2 peak and peak workload had large effect sizes (0.98 and 0.97, respectively) ( The mean between-leg Table 1.…”

Section: Whole Body Oxygen Uptakementioning

confidence: 93%

Lower-limb performance disparities: Implications for exercise prescription in multiple sclerosis

Larson

McCully²,

Larson³

et al. 2014

J Rehabil Res Dev

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Abstract-The purpose of this study was to examine unilateral lower-limb exercise tolerance during fixed-load cycling to quantify performance disparities of the legs. Eight individuals with relapsing-remitting multiple sclerosis (MS) and seven controls performed submaximal single-leg cycling. Individuals with MS performed significantly more work with the stronger leg than the weaker leg (stronger leg: 6.4 +/-1.7 kJ, weaker leg: 4.7 +/-2.5 kJ, p = 0.02). The control group displayed no statistical differences between limbs (p = 0.36). These results highlight a need for individualized exercise testing when prescribing training programs for those with MS.

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“…23 Before randomization, the 436 patients underwent three pre-baseline MSFC testing sessions. The MSFC had excellent intra-rater reliability, with an intraclass correlation coefficient of 0.90 for session three (final pre-baseline session) and session four (baseline session).…”

Section: Reliabilitymentioning

confidence: 99%

“…Several studies have demonstrated a moderately strong correlation between the MSFC and EDSS. 17,23,25 MRI measures, such as T1 and T2 lesion load, also correlate significantly with MSFC scores. 26 Additionally, one study found a moderately strong correlation between the MSFC and measures of brain atrophy in patients with relapsing-remitting MS Multiple Sclerosis Predictive criterion validity is the ability of an instrument to predict future disease status.…”

mentioning

confidence: 91%

“…Although these effects were evident initially, the MSFC scores stabilized by the fourth administration. 22,23 Practice effects were most apparent with the 9HPT, followed by the PASAT, whereas there were no practice effects for the 25FTW after the first administration. 24 Thus, it has been suggested that there should be one pre-baseline administration of the 25FTW, three pre-baseline administrations of the PASAT, and four pre-baseline administrations of the 9HPT to maximize efficiency.…”

mentioning

confidence: 96%

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Measuring Disability Progression with the Multiple Sclerosis Functional Composite

Krysko¹,

O’Connor²

2010

US Neurology

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The multiple sclerosis functional composite (MSFC) is a three-part quantitative objective measure of neurologic function, measuring leg (timed 25-foot walk [25FTW]), arm (nine-hole peg test [9HPT]), and cognitive (three-second paced auditory serial addition test [PASAT3]) function. The MSFC was developed to be a more sensitive measure of disability than the expanded disability status scale (EDSS) and has excellent reliability. Validity is supported by moderately strong correlations with EDSS, brain atrophy, and quality of life. Advantages of the MSFC include its continuous scale and inclusion of several disease dimensions. Limitations include practice effects, the lack of a visual function component, variations in reference populations, and limited understanding of clinically relevant MSFCz-score changes. MSFCz-score change has been used as a secondary end-point in MS trials, but EDSS progression remains the primary disability outcome. A new approach to MSFC data involves defining MSFC progression as worsening in an MSFC component by 15–20% over three months. With further study, this could be used as a primary disability outcome in future clinical trials.

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Use of the Multiple Sclerosis Functional Composite as an Outcome Measure in a Phase 3 Clinical Trial

Cited by 158 publications

References 21 publications

Interferon-β Treatment for Multiple Sclerosis

Interferon-β Treatment for Multiple Sclerosis

Lower-limb performance disparities: Implications for exercise prescription in multiple sclerosis

Measuring Disability Progression with the Multiple Sclerosis Functional Composite

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