Multiple Sclerosis-Simvastatin Trial 2

The initial disability progression event is finalised as positive if disability is sustained and confirmed ≥6* months later. Progression of disability defined as an increase of at least 1 point if EDSS baseline score <6, or an increase of 0.5 point if baseline EDSS score is ≥6.

MSWS-12v2 is a12 item patient report measure on the impact of MS on the individual's walking ability over the previous 2 weeks. Each item will be summed to generate a total score and transformed to a scale with a range of 0 to 100 with high scores indicating greater impact on walking.

MS Impact Scale-29 version 2 (MSIS-29v2) - A psychometrically validated patient-reported outcome measure increasingly used for measuring the impact of MS on people's lives. The 29-item scale assesses the impact of MS on people's health related quality of life in terms of their physical and psychological well-being over the previous 2 weeks.

To estimate the incremental cost and cost-effectiveness of simvastatin versus standard care for the trial period and for the lifetime horizon using the Client Client Services Receipt Inventory Form.

mRS is used to evaluate the degree of disability in daily activities of those with neurological disability.

Sloan chart testing is a reliable, quantitative, and clinically practical measure of visual function that will be administered by trained assessors. The chart consists of rows of grey letters on a white background. Letters are displayed in decreasing order from the top of the chart to the bottom. Testing will be conducted at three different contrast levels (100%, 2.5% and 1.25%). The chart will be scored based on the number of letters correctly identified out of 60.

EQ-5D 5L is a 5 item questionnaire (assessing - mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and visual analogue scale (VAS) enables calculation of quality adjusted life years (QALY) to enable health economic analyses to be performed. Each dimension assessed has 5 response scales to select from: no problems, slight problems, moderate problems, severe problems, and extreme problems

A Modified Multiple Sclerosis Functional Composite (MSFC) score comprised of 3 components (T25FW, 9HPT, SDMT). The Symbol digit modalities test (SDMT) will replace the Paced Auditory Serial Addition Test (PASAT), one of the three components in the Standard MSFC.

BICAMS is a composite cognitive assessment tool comprising of the three components : Symbol Digit Modalities Test (SDMT) , California Verbal Learning Test-II (CVLT-II) and Brief visuospatial memory test- Revised (BVMT-R)

SDMT is a brief measure of cognitive processing speed. It measures information processing speed for visually presented stimuli, but is self-paced, with at least equal reliability and sensitivity to the presence of worsening cognitive impairment.

A questionnaire measuring the severity of physical and mental fatigue. The total score range is minimum of 0 and maximum of 33.

For the subscales, physical fatigue score has a minimum of 0 and maximum of 21. The Mental fatigue score has a minimum of 0 and maximum of 12.

The CSRI is a questionnaire that collects information on service utilisation, income, accommodation and other cost-related variables. Its primary purpose is to allow resource use patterns in each of the two arms to be described, and support costs to be estimated for health economics purposes.

T25-FW is a quantitative mobility and leg function performance test based on a timed 25-foot walk

A relapse will be defined as new or worsening neurological symptom(s) in the absence of fever, lasting for more than 24 hours, and have been preceded by a period of clinical stability of at least 30 days, with no other explanation than MS.

A secondary composite progression outcome measure defined as one or more of: ≥20% increase in time taken to complete the 25 Foot Walk (T25FW); or ≥20% increase in time to complete 9 Hole Peg Test (9HPT); or increase in EDSS (0.5 point increase if baseline ≥6 /1.0 point increase if baseline <6). The initial disability progression event will be finalised as positive if it is sustained and confirmed ≥6 months later*. The time to event analysis will be from randomisation until date of the initial disability progression (if subsequently confirmed)

The 9HPT is a brief, standardized, quantitative test of upper extremity function. Participants are instructed to pick up 9 pegs, one at a time, as quickly as possible and are required to insert them into 9 empty peg holes. Once all nine pegs have been inserted, the participant should immediately remove the pegs, one at a time. The total time taken to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand. The two trials for each hand are averaged.