Table 1.
Questionnaires and clinical tools used to assess walking abilitya
| Instrument | Number of items/tasks | Score rangeb | Established clinically important change | Threshold used in ENHANCE | Description | Completion dates |
|---|---|---|---|---|---|---|
| MSWS-12 | 12 | 100–0 | Reduction from baseline score of 6.9 (group comparison) or 8.0 (individual-level comparison) points [14] | Mean 8-point reduction from baseline over 24 weeks | A reliable and accepted self-reported disease-specific measure of mobility limitations owing to MS during the preceding 2 weeks. The 12 questions ask about different aspects of walking: ability and speed of walk; ability to run; ability to climb and descend stairs; balance and smoothness of gait; and support, effort, and concentration required. Participants rate limitations of their mobility due to MS on a Likert 5-point scale (from 1 = not at all to 5 = extremely). Total score ranges from 1 to 60 and is transformed to a scale of 0–100. A higher MSWS-12 score represents poorer walking ability [10, 14, 16] | Screening, day 1 (before randomization), at weeks 2, 4, 8, 12, 16, 20, and 24 (end of treatment), and 26 (follow-up), or at early termination |
| TUG speed | 1 | Continuous | ≥ 15% mean improvement in TUG speed (see Sect. 2.3) | Mean 15% increase in TUG speed | Objective measure of dynamic balance and mobility [19], which has demonstrated high reliability in individuals with MS; not recommended to predict falls. TUG measures the speed of individuals to move from a seated position to stand up, walk 3 m, turn, walk 3 m [21]. In ENHANCE, TUG (ft/s) was performed at the same time (± 3 h) and with the same footwear and walking aids (if required) during each visit to avoid variation. Further research on thresholds of clinically important change for TUG speed is required [23] | Screening, day 1 (before randomization), at weeks 2, 4, 8, 12, 16, 20, and 24 (end of treatment), and 26 (follow-up) |
| MSIS-29 | Psychometrically designed and self-reported disease-specific measure of the impact of MS on physical and psychological health. The MSIS-29 PHYS score is calculated by summing the 20 items and transforming the score to a scale of 0 (no impact of MS) to 100 (extreme impact of MS) [41] | Screening, day 1 (before randomization), at weeks 2, 4, 8, 12, 16, 20, and 24 (end of treatment) | ||||
| PHYS | 20 | 100–0 | ≥ 7.5–8.0 [17, 42] | |||
| PSYCH | 9 | |||||
| BBS | 14 | 0–56 | Falls were frequent with scores > 45d | Objective measure of static and dynamic balance, which has demonstrated validity and high test–retest reliability in individuals with MS but possible ceiling effects and variability, with good specificity but low sensitivity. Each task is scored from 0 (unable to perform) to 4 (able to perform independently). A higher BBS score represents better balance; recommended to predict multiple falls once a fall has occurred [20, 21, 43–46] | Screening, day 1 (before randomization), at weeks 2, 12, and 24 (end of treatment) | |
| ABILHAND | 56e | 0–100 | TBC for individuals with MS. 0.47–1.89 logits in patients with rheumatoid arthritis [47], and 0.26–0.35 logits in patients with stroke [48] | Self-reported measure of manual ability to manage daily activities among chronic stroke patients. Participants estimate the ease or difficulty of performing each upper limb activity using a 3-level response scale: impossible (0), difficult (1), and easy (2). A higher ABILHAND score represents better manual ability [48, 49] | Day 1 (before randomization), at weeks 2, 8, and 20 | |
BBS Berg Balance Scale, MS multiple sclerosis, MSIS-29 Multiple Sclerosis Impact Scale, MSWS-12 12-item Multiple Sclerosis Walking Scale, PHYS Physical Impact subscale, PR prolonged-release, PSYCH Psychological Impact Subscale, TBC to be confirmed, TUG Timed Up and GO
aWhen multiple assessments were scheduled at a given visit, they were performed in the following order: MSWS-12, TUG, BBS, MSIS-29, and ABILHAND (followed by any other assessments)
bScore ranges are provided as worst score—optimal functioning score
cNot included as a secondary endpoint
dAmong older individuals dependent in activities of daily living and living in residential care facilities
eWe used the original pool of 56 items (to maximize measurement range and precision) [18] with the 3-category response format [49] that proved to work in stroke