The timed 25-foot walk (T25FW) is the most common standalone measure of ambulation in the management of patients with MS and in clinical research, explains Anissa Kalinowski, MBA, MSc. “Based on existing research, the T25FW demonstrates strong content validity, criterion validity, construct validity, responsiveness, and clinical meaningfulness,” Kalinowski says. “However, prior research has not established the test’s predictive validity and has not explored the test in a treatment-naïve population. Furthermore, in-depth patient-level analysis for the T25FW has not been reported for a large heterogeneous cohort of patients with MS.”

For a paper published in Multiple Sclerosis Journal, Kalinowski and colleagues evaluated T25FW performance and factors associated with its change in the Multiple Sclerosis Outcome Assessments Consortium (MSOAC) Placebo Database.  “A need existed for sensitive outcome measures in MS research and clinical trials,” Kalinowski says. “Additionally, there was a need for better data for monitoring patients in clinical practice. The T25FW has been in use for more than 25 years and yet is rarely used as a primary outcome in trials. This is due, in part, to regulators viewing the Expanded Disability Status Scale (EDSS) as a more meaningful clinical outcome. However, our research shows that, as a biomarker, the T25FW is an indicator of EDSS worsening and may pick up changes before the EDSS is measured by a clinician.”

Walking Speed an Earlier Disability Marker Than EDSS

The researchers utilized a meta-database of trials sponsored by the National MS Society and a repository of trials supported by pharmaceutical company trials and National Institute of Health (NIH) trials curated at the Critical Path Institute (C-PATH). “This allowed us access to more data than would be available from any one trial and provided a broader range of disability levels across a wide range of trials,” Kalinowski explains. “More specifically, we obtained placebo group data for 2,465 patients from nine trials and were able to examine changes within and between individuals, with data available for an average of 1-3 years.”

The study team found that the T25FW has excellent features as an outcome measure, with high test-retest reliability, and is sensitive to clinical change, indicating that it has merit as a standalone measure in MS trials. “We found that walking speed is often an earlier marker of disability worsening than EDSS,” Kalinowski says.

The investigators also confirmed and validated for the timed walk what was known about EDSS—that age, male sex, and MS disease type present the same risk factors for worsening. “This supports confirmation that the T25FW is a biomarker for future EDSS disability worsening and that it, in and of itself, may be an outcome measure that should be evaluated clinically,” adds Kalinowski (Table).

 T25FW Can Enrich Existing Data

Clinicians may benefit from using the T25FW in clinical practice, as it might serve as a relevant indicator of both current and future disability, while being easier to implement than EDSS, according to Kalinowski. “Neurologists who are not using the timed walk as standard practice may consider adopting this simple measure into their neurologic assessments,” she suggests. “In addition, an observation of a greater than 20% change over time in the T25FW can enrich the data that neurologists have on hand to evaluate disease progression and therapy selection at an earlier time point.”

Kalinowski and colleagues would like to see future research pursue a better understanding of the discordance between the progression on the timed walk versus EDSS. “Is this due to measurement error or are the data telling us something about mechanisms of actions of treatments or the ways in which the disease is impacting an individual?” she asks rhetorically. “Future studies should also explore aspects of the T25FW in patients with truly minimal disease. In addition, the clinical sensitivity of the 20% cutoff could be re-examined to optimize use of the measure in clinical trials.”

 

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