Dataset Information

Clinically meaningful performance benchmarks in MS: timed 25-foot walk and the real world.

ABSTRACT:

Objective

Identify and validate clinically meaningful Timed 25-Foot Walk (T25FW) performance benchmarks in individuals living with multiple sclerosis (MS).

Methods

Cross-sectional study of 159 MS patients first identified candidate T25FW benchmarks. To characterize the clinical meaningfulness of T25FW benchmarks, we ascertained their relationships to real-life anchors, functional independence, and physiologic measurements of gait and disease progression. Candidate T25FW benchmarks were then prospectively validated in 95 subjects using 13 measures of ambulation and cognition, patient-reported outcomes, and optical coherence tomography.

Results

T25FW of 6 to 7.99 seconds was associated with a change in occupation due to MS, occupational disability, walking with a cane, and needing "some help" with instrumental activities of daily living; T25FW ?8 seconds was associated with collecting Supplemental Security Income and government health care, walking with a walker, and inability to do instrumental activities of daily living. During prospective benchmark validation, we trichotomized data by T25FW benchmarks (<6 seconds, 6-7.99 seconds, and ?8 seconds) and found group main effects on 12 of 13 objective and subjective measures (p < 0.05).

Conclusions

Using a cross-sectional design, we identified 2 clinically meaningful T25FW benchmarks of ?6 seconds (6-7.99) and ?8 seconds. Longitudinal and larger studies are needed to confirm the clinical utility and relevance of these proposed T25FW benchmarks and to parse out whether there are additional benchmarks in the lower (<6 seconds) and higher (>10 seconds) ranges of performance.

SUBMITTER: Goldman MD

PROVIDER: S-EPMC3821712 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Publications

Clinically meaningful performance benchmarks in MS: timed 25-foot walk and the real world.

Goldman Myla D MD Motl Robert W RW Scagnelli John J Pula John H JH Sosnoff Jacob J JJ Cadavid Diego D

Neurology 20131030 21

<h4>Objective</h4>Identify and validate clinically meaningful Timed 25-Foot Walk (T25FW) performance benchmarks in individuals living with multiple sclerosis (MS).<h4>Methods</h4>Cross-sectional study of 159 MS patients first identified candidate T25FW benchmarks. To characterize the clinical meaningfulness of T25FW benchmarks, we ascertained their relationships to real-life anchors, functional independence, and physiologic measurements of gait and disease progression. Candidate T25FW benchmarks ...[more]

PMID: 24174581

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Project description:Background and objectivesClinical trials in relapsing-remitting multiple sclerosis (RRMS) usually use the Expanded Disability Status Scale (EDSS) as their primary disability outcome measure, while the more recently developed outcomes timed 25-ft walk (T25FW) and 9-hole peg test (NHPT) may be more useful and patient relevant. The objective of this work was to compare the EDSS to the T25FW and NHPT in a large RRMS randomized controlled trial (RCT) dataset.MethodsWe used the dataset from Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis (CombiRx) (clinicaltrials.gov identifier NCT00211887), a large phase 3 RCT, to compare the EDSS to the alternative outcomes T25FW and NHPT. We investigated disability worsening vs similarly defined improvement, unconfirmed vs confirmed and sustained disability change, and the presentation methods cumulative Kaplan-Meier survival curves vs cross-sectional disability worsening.ResultsCombiRx included 1,008 participants. A comparison of confirmed and sustained worsening events showed that, throughout the trial, there were substantially fewer sustained than confirmed events, with a positive predictive value of confirmed for sustained worsening at 24 months of 0.73 for the EDSS, 0.73 for the T25FW, and 0.8 for the NHPT. More concerning were the findings that worsening on the EDSS occurred as frequently as similarly defined improvement throughout the 3 years of follow-up and that improvement rates increased in parallel with worsening rates. The T25FW showed low improvement rates of <10% throughout the trial. We also found that Kaplan-Meier survival analysis, the standard presentation and analysis method in modern RRMS trials, yields exaggerated estimates of disability worsening. With the Kaplan-Meier method, the proportion of patients with worsening events steadily increases until it reaches several-fold the number of events seen with more conservative analysis methods. For 3-month confirmed disability worsening up to 36 months, the Kaplan-Meier method yields 2.6-fold higher estimates for the EDSS, 2.9-fold higher estimates for the T25FW, and 5.1-fold higher estimates for the NHPT compared to a more conservative presentation of the same data.DiscussionOur analyses raise concerns about using the EDSS as the standard disability outcome in RRMS trials and suggest that the T25FW may be a more useful measure. These findings are relevant for the design and critical appraisal of RCTs.

Project description:A dataset range of isocenter congruency verification tests have been examined from a statistical perspective for the purpose of establishing tolerance levels that are meaningful, based on the fundamental limitation of linear accelerator isocentricity and the demands of a high-precision stereotactic radiosurgery program. Using a laser-defined isocenter, a total of 149 individual isocenter congruency tests were examined with recorded values for ideal spatial corrections to the isocenter test tool. These spatial corrections were determined from radiation exposures recorded on an electronic portal imaging device (EPID) at various gantry, collimator, and treatment couch combinations. The limitations of establishing an ideal isocenter were quantified from each variable which contributed to uncertainty in isocenter definition. Individual contributors to uncertainty, specifically, daily positioning setup errors, gantry sag, multileaf collimator (MLC) offset, and couch walkout, were isolated from isocenter congruency measurements to determine a clinically meaningful isocenter measurement. Variations in positioning of the test tool constituted, on average, 0.38 mm magnitude of correction. Gantry sag and MLC offset contributed 0.4 and 0.16 mm, respectively. Couch walkout had an average degrading effect to isocenter of 0.72 mm. Considering the magnitude of uncertainty contributed by each uncertainty variable and the nature of their combination, an appropriate schedule action and immediate action level were determined for use in analyzing daily isocenter congruency test results in a stereotactic radiosurgery (SRS) program. The recommendations of this study for this linear accelerator include a schedule action level of 1.25 mm and an immediate action level of 1.50mm, requiring prompt correction response from clinical medical physicists before SRS or stereotactic body radiosurgery (SBRT) is administered. These absolute values were derived from considering relative data from a specific linear accelerator and, therefore, represent a means by which a numerical quantity can be used as a test threshold with relative specificity to a particular linear accelerator.

Dataset Information

Clinically meaningful performance benchmarks in MS: timed 25-foot walk and the real world.

Objective

Methods

Results

Conclusions

Publications

Clinically meaningful performance benchmarks in MS: timed 25-foot walk and the real world.

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