The Multiple Sclerosis Functional Composite: a new clinical outcome measure for multiple sclerosis trials

2002 ◽  
Vol 8 (5) ◽  
pp. 359-365 ◽  
Author(s):  
R A Rudick ◽  
G Cutter ◽  
S Reingold
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Cognitive Function ◽  
Clinical Outcome ◽  
Outcome Measures ◽  
Standard Therapy ◽  
Outcome Measure ◽  
Task Force ◽  
Multiple Sclerosis Functional Composite ◽  
Clinical Outcome Measure

With the advent and widespread use of partially effective disease modifying drug therapies for multiple sclerosis (MS), future clinical trials will undoubtedly test experimental interventions against standard therapy, or will test combinations of drugs against standard therapy. In either case, incremental progress in slowing disability progression in future MS clinical trials will require much larger sample sizes, more sensitive outcome measures, or a combination of the two. Because improved clinical outcome methods would likely accelerate progress in MS therapeutics, the National Multiple Sclerosis Society (NMSS) convened an international task force in 1994 to recommend improved clinical outcome measures. As the result of a two-year process of discussion and data analysis, the task force recommended the Multiple Sclerosis Functional Composite (MSFC) as a new clinical outcome measure for future MS trials. MSFC consists of timed tests of walking, arm function, and cognitive function, expressed as a single score along a continuous scale. The task force recommended that MSFC be included in future MS trials, and recommended a series of validation studies. Subsequent studies have provided evidence that MSFC correlates moderately with Expanded Disability Status Scale (EDSS), and that correlation is driven by strong correlations with the ambulatory function component; arm function and cognitive function correlate at lower levels with EDSS. The MSFC correlates better than EDSS with magnetic resonance imaging (MRI) variables, including brain atrophy, and shows significant correlation with patient-reported disease-related quality of life (QOL). MSFC and short-term change in MSFC correlate with future clinical and MRI status, and the strength of the correlations compares favorably with well-known cardiovascular risk factors. The studies in aggregate indicate that MSFC and MSFC change are clinically meaningful, and that MSFC has substantial advantages over alternative clinical outcome measures for MS clinical trials.

Revisiting The Multiple Sclerosis Functional Composite: proceedings from the National Multiple Sclerosis Society (NMSS) Task Force on Clinical Disability Measures

2012 ◽  
Vol 18 (8) ◽  
pp. 1074-1080 ◽  
Author(s):  
D Ontaneda ◽  
N LaRocca ◽  
T Coetzee ◽  
RA Rudick
Keyword(s):  
Multiple Sclerosis ◽  
Outcome Measure ◽  
Task Force ◽  
Critical Path ◽  
Washington Dc ◽  
Functional Composite ◽  
Multiple Sclerosis Functional Composite ◽  
Score Method ◽  
National Multiple Sclerosis Society ◽  
Disability Outcome

This article describes proceedings from a meeting of the National Multiple Sclerosis Society (NMSS) Task Force on Clinical Disability Measures (the TF). The TF was appointed by the NMSS Research Programs Advisory Committee with the goal of pooling and analyzing existing datasets to explore the utility of novel disability outcome measures based on the Multiple Sclerosis Functional Composite (MSFC) approach. The TF seeks to determine the suitability of the MSFC approach as a primary clinical outcome measure for registration trials in MS. The TF met in Washington, DC, Dec. 14 and 15, 2011, and provided unanimous support for a collaborative approach involving representatives from academic medicine, the pharmaceutical industry, regulatory agencies, the NMSS and the Critical Path Institute. There was also unanimous agreement that analysis of existing datasets would be useful in making progress toward the objective. The TF placed high value on determining the clinical meaning of individual component measures for the MSFC, and in establishing optimal analysis methods for MSFC so that scores would be more interpretable than the originally recommended z-score method. The background for a collaborative project aimed at developing an improved disability outcome measure is described in this paper.

The Multiple Sclerosis Functional Composite measure (MSFC): an integrated approach to MS clinical outcome assessment

1999 ◽  
Vol 5 (4) ◽  
pp. 244-250 ◽  
Author(s):  
J S Fischer ◽  
R A Rudick ◽  
G R Cutter ◽  
S C Reingold ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Function ◽  
Clinical Outcome ◽  
Outcome Assessment ◽  
Task Force ◽  
Hand Function ◽  
Integrated Approach ◽  
Functional Composite ◽  
Assessment Task ◽  
Functional Outcome Measures

Clinical outcome assessment in Multiple Sclerosis (MS) is challenging due to the diversity and fluctuating nature of MS symptoms. Traditional clinical scales such as the EDSS are inadequate in their assessment of key clinical dimensions of MS (e.g., cognitive function), and they have psychometric limitations as well. Based on analyses of pooled data from natural history studies and from placebo groups in clinical trials, the National MS Society's Clinical Outcomes Assessment Task Force recently proposed a new multidimensional clinical outcome measure, the MS Functional Composite (MSFC). The MSFC comprises quantitative functional measures of three key clinical dimensions of MS: leg function/ambulation, arm/hand function, and cognitive function. Scores on component measures are converted to standard scores (z-scores), which are averaged to form a single MSFC score. Preliminary analyses confirm that: (1) the three clinical dimensions of the MSFC are relatively independent; (2) the MSFC is sensitive to clinical changes over 1- and 2-year intervals; and (3) the MSFC has acceptable criterion validity (i.e., predicts both concurrent and subsequent EDSS change). The advantages and potential limitations of incorporating quantitative functional outcome measures such as the MSFC into collaborative databases are discussed.

scholarly journals Clinical outcome measures for progressive MS trials

2017 ◽  
Vol 23 (12) ◽  
pp. 1627-1635 ◽  
Author(s):  
Daniel Ontaneda ◽  
Jeffrey A Cohen ◽  
Maria Pia Amato
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Clinical Outcome ◽  
Outcome Measures ◽  
Treatment Options ◽  
Unmet Need ◽  
Screening Tests ◽  
Future Research ◽  
Neuroprotective Effects ◽  
Patient Reported

Treatment options for progressive multiple sclerosis remain the main unmet need of the field. As the understanding of multiple sclerosis (MS) pathogenesis improves, new pathways and molecules will be tested for potential reparative, remyelinating, or neuroprotective effects. The clinical outcomes used will determine successful demonstration of beneficial treatment effects to regulatory agencies, clinicians, and persons with MS. This review focuses on clinical outcome measures including the Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, and novel composite measures of disability. The paper also covers cognitive outcomes and screening tests for use in clinical trials. The growing importance of patient-reported outcomes and their suitability for clinical trials is also presented. The review aims to create consensus in regard to these topics and suggestions for future research.

Digital Technology in Clinical Trials for Multiple Sclerosis: a systematic review. (Preprint)

2020 ◽  
Author(s):  
Marcello De Angelis ◽  
Luigi Lavorgna ◽  
Antonio Carotenuto ◽  
Martina Petruzzo ◽  
Roberta Lanzillo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Outcome Measures ◽  
Digital Technology ◽  
Clinical Trial Design ◽  
Motor Rehabilitation ◽  
Robot Assisted ◽  
Future Directions ◽  
Treatment Side Effects

BACKGROUND Clinical trials in multiple sclerosis (MS) have leveraged the use of digital technology to overcome limitations in treatment and disease monitoring. OBJECTIVE To review the use of digital technology in concluded and ongoing MS clinical trials. METHODS In March 2020, we searched for “multiple sclerosis” and “trial” on pubmed.gov and clinicaltrials.gov using “app”, “digital”, “electronic”, “internet” and “mobile” as additional search words, separately. Overall, we included thirty-five studies. RESULTS Digital technology is part of clinical trial interventions to deliver psychotherapy and motor rehabilitation, with exergames, e-training, and robot-assisted exercises. Also, digital technology has become increasingly used to standardise previously existing outcome measures, with automatic acquisitions, reduced inconsistencies, and improved detection of symptoms. Some trials have been developing new patient-centred outcome measures for the detection of symptoms and of treatment side effects and adherence. CONCLUSIONS We will discuss how digital technology has been changing MS clinical trial design, and possible future directions for MS and neurology research.

scholarly journals Development of a Retinopathy of Prematurity Activity Scale and Clinical Outcome Measures for Use in Clinical Trials

2019 ◽  
Vol 137 (3) ◽  
pp. 305 ◽  
Author(s):  
Lois E. H. Smith ◽  
Ann Hellström ◽  
Andreas Stahl ◽  
Alistair Fielder ◽  
Wiley Chambers ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Outcome ◽  
Outcome Measures ◽  
Retinopathy Of Prematurity ◽  
Activity Scale

Disease progression in multiple sclerosis: combining physicians’ and patients’ perspectives?

2010 ◽  
Vol 17 (2) ◽  
pp. 234-240 ◽  
Author(s):  
JJ Kragt ◽  
JM Nielsen ◽  
FAH van der Linden ◽  
CH Polman ◽  
BMJ Uitdehaag
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcome ◽  
Disease Progression ◽  
Outcome Measures ◽  
Added Value ◽  
Impact Scale ◽  
Disability Status ◽  
The Impact ◽  
Nine Hole Peg Test ◽  
Combine Outcome

Background: To assess disease progression in multiple sclerosis (MS) several outcome measures are available. The interrelation of changes on different scales has not been studied extensively and the concept of combining scales has only recently been introduced in MS. Objective: To explore combining different clinical outcome measures in the evaluation of disease progression in MS. Methods: In 553 patients we studied the presence of relevant changes according to standard definitions on the Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test (9HPT), Timed 25-Foot Walk (T25FW) and the Multiple Sclerosis Impact Scale (MSIS-29). We examined ‘exclusive worsening’ (worsening on one measure while not worsening on any other measure) and ‘opposing changes’ (worsening on one measure while improving on another measure). Finally, we investigated the impact of combining assessments. Results: Based on the EDSS alone, 140 patients progressed. However, almost twice as many (275) showed worsening on any of the clinical outcome measures. Exclusive worsening was observed in 37 patients on the EDSS, 13 on the 9HPT, 39 on the T25FW and 44 on the MSIS physical. Of all worsened patients 76 (28%) showed opposing changes, a phenomenon predominantly observed when combining physician-based and patient-derived outcome measures. Conclusion: When assessing disease progression in MS, sensitivity to change can be increased by combining different outcome measures. The added value is especially present when combining measures from different perspectives. However, further research is needed to evaluate the optimal way to combine outcome measures before implementing this strategy in clinical studies.

scholarly journals The added value of cognition-targeted exercise versus symptom-targeted exercise for multiple sclerosis fatigue: A randomized controlled pilot trial

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0258752
Author(s):  
Azza Alketbi ◽  
Salah Basit ◽  
Nouran Hamza ◽  
Lori M. Walton ◽  
Ibrahim M. Moustafa
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcome ◽  
Outcome Measures ◽  
Recruitment Rate ◽  
Control Group ◽  
Entire Study ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Intervention Protocol

Background Fatigue is considered one of the most common symptoms of multiple sclerosis (MS) and lacks a current standardized treatment. Therefore, the aim of this study was to examine the feasibility and effectiveness of a cognition-targeted exercise versus symptom-targeted exercise for MS fatigue. Methods In this Pilot, parallel-group, randomized controlled trial, sixty participants with multiple sclerosis, were randomly assigned to either a Cognition-Targeted Exercise (CTE) (N = 30, mean age 41) or a Symptom-Targeted Exercise (STE) (N = 30, mean age 42). The participants in the experimental group received eight, 50-minute sessions of weekly Cognitive Behavior Therapy (CBT) in addition to a CTE Program; whereas, participants in the control group received eight, 50-minute sessions of weekly CBT in addition to the standardized physiotherapy program (STE Program). Feasibility was assessed through recruitment rate, participant retention, adherence and safety, in addition to clinical outcome measures, including: (1) Modified Fatigue Impact Scale (MFIS), (2) Work and Social Adjustment Scale (WSAS), (3) Hospital Anxiety and Depression Scale (HADS), and Perceived Stress Scale (PSS). All outcome measures were assessed at baseline (pretreatment), following completion of the eight visit intervention protocol, and at 3-months follow-up. Results The recruitment rate was 60% and 93% of participants completed the entire study. The recruited participants complied with 98% of the required visits. No adverse events were recorded. A Generalized Estimation Equation Model revealed a significant difference over time as an interaction term during the post and follow up visit for all clinical outcome measures (p < .001). Conclusion The addition of CTE to CBT exhibited positive and more lasting influence on MS fatigue outcomes compared to Symptom-Targeted Exercise (STE). Feasibility and efficacy data from this pilot study provide support for a full-scale RCT of CTE as an integral component of Multiple Sclerosis fatigue management.

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