Novel ways to assess MS

Until recently, MS clinical trial endpoints have focused primarily upon measures of disease activity instead of patient-reported outcome measures (PROMs). There is a growing desire, especially from regulatory authorities, to include endpoints measuring disease activity as seen from the patient’s perspective.

MS performance test

The Multiple Sclerosis Performance Test (MSPT) is a novel, iPad®-based disability assessment tool that resembles the Multiple Sclerosis Functional Composite (MSFC) [1,2]. It includes a computer-adapted version of Neuro-QoL, and 4 self-administered neuroperformance tests, providing measurements of walking speed, manual dexterity, low contrast visual acuity, and cognitive processing speed.

Convergent validity studies comparing the MSPT and MSFC subtests have been published [3] or are under editorial review. MSPT is being used as part of the international MS-PATHS network of MS centres, where over 40,000 MSPT assessments have already been conducted to date. Normative databases are commonly used in neuropsychology because performance on cognitive tests can be influenced by demographic variables, such as age, education, and sex. Demographics may also influence tests designed to measure vision and motor function.
Dr Megan Sokolowski (Cleveland Clinic, OH, USA), analysed a demographically stratified normative database of healthy individuals (n=517) who self-administered the 4 MSPT neuroperformance modules [4]. Age was a significant (P<0.05) predictor for all MSPT modules: Walking Speed Test (WST), Manual Dexterity Test (MDT), Contrast Sensitivity Test (CST), and Processing Speed Test (PST). Compared to raw scores, adjusted z-scores correct for differences in performance due to demographic variables, thereby allowing a more accurate representation of the impact of MS on cognitive, visual, and motor neuroperformance. Adjusted z-scores align performance on all the neuroperformance measures to the same scale and allow for the development of meaningful cut-scores for clinical interpretation [4].

Advancing walking measurement

According to Prof. Jeremy Hobart (University of Plymouth, United Kingdom), who presented a study evaluating PROMs [5], there are strong clinical, scientific, and regulatory justifications for advancing the currently available MS walking PROMs. “We believe that these instruments have strong conceptual underpinnings: concept of interest and context of use. We used a hypothesis-testing psychometric approach rather than modelling approach, to determine the strength of the concept. We believe that it meets requirements for clinical trials and provides a more comprehensive assessment of MS walking than existing scales. It was demonstrated to be conceptually and empirically superior to MS walking scale (MSWS)-12. Finally, we can compare two instruments, i.e. MSWS-32 and MSWS-12 scores, on exactly the same metric.”

Remotely monitored ambulatory activity

Another proposed outcome measure for clinical trials is remote ambulatory activity monitoring. A prospective, longitudinal, observational cohort study has already validated this instrument [6]. Step-count monitoring is also an exploratory endpoint (average daily step count from the first 30 days; STEPS) of SPI2, a phase 3 trial investigating the efficacy and safety of high-dose, pharmaceutical-grade biotin (MD1003) in patients with inactive primary and secondary progressive MS.

In this study, STEPS correlated to clinical measures of ambulation (EDSS, timed 25-foot walk), cognitive function (Symbol Digit Modalities test), brain and spinal cord MRI atrophy metrics, and quality of life. Dr Valerie Block (University of California San Francisco, CA, USA) stated that these data support the study of STEPS as an exploratory outcome measure in clinical trials for progressive MS [7]. She thinks that remote gait monitoring via Fitbit could become a surrogate for MS disability in clinical trials. Longitudinal analysis of STEPS in the SPI2 study is on-going; results will be presented next year.

1. Rudick RA, et al. J Vis Exp. 2014;:e51318.
2. Rhodes JK, et al. Adv Ther. 2019;36:1741-1755.
3. Rao SM, et al. Mult Scler. 2017;23:1929-1937.
4. Sokolowski M, et al. ECTRIMS 2019, abstract 215.
5. Hobart J, Burke L. ECTRIMS 2019, abstract 216.
6. Block VJ, et al. JAMA Netw Open. 2019;2:e190570.
7. Block V, et al. ECTRIMS 2019, abstract 217.

 



Posted on 8 November, 201922 March, 2021