Evaluation of a home-based standing frame programme in people with progressive Multiple Sclerosis (SUMS): a pragmatic, multi-centre, randomised, controlled trial and cost-effectiveness analysis

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Data sharing. The SUMS study protocol and statistical analysis plan are publically available at https://www.plymouth.ac.uk/research/sums. Individual participant data that underlie the results will be made available (following de-identification) on a controlled access basis, subject to suitable data sharing agreements. Requests for data sharing should be made to the Chief Investigator (CI, Freeman) in the first instance. Requesters will be asked to complete an application form detailing specific requirements, rationale and proposed usage. Requests will be reviewed by the CI and study Sponsor who will consider the viability and suitability of the request and the credentials of the requester. Where access to requested data is granted, requesters will be asked to sign a data sharing agreement. Requested data will be made available, along with supporting documentation (e.g. data dictionary) on a secure server or via other secure data transfer method.Background: People severely impaired with progressive Multiple Sclerosis (MS) spend much of their day sitting, with very few options to improve motor function. In response, secondary physical and psychosocial complications can occur. Effective and feasible self-management strategies are needed to reduce sedentary behaviour and enhance motor function. We aimed to assess the clinical and cost-effectiveness of a homebased, self-managed, standing frame programme. Methods: A pragmatic, multi-centre (n=8, two regions in the United Kingdom), randomised controlled superiority trial of people with progressive MS and severe mobility impairment, with assessor-blinded outcome assessment using clinician and patient rated measures at baseline, 20 and 36 weeks. Following baseline assessment, participants were randomised (1:1) by computer-generated assignment to either a standing programme plus usual care or usual care alone. The intervention consisted of two home-based physiotherapy sessions (60 minutes each) to set up the standing programme, supported by 6 follow-up telephone calls (15-minutes/call). Participants were asked to stand for 30 minutes, 3 times weekly, over 20 weeks, with encouragement to continue in the longer term, although no further physiotherapy support was provided. The primary clinical outcome was motor function (Amended Motor Club Assessment, AMCA) at week 36, analysed in the intention-to-treat (ITT) population. A 9-point AMCA change was considered clinically meaningful a priori. Adverse events were collected by a daily pre-formatted patient diary throughout the 36 weeks. An economic evaluation established the resources required to provide the standing programme, estimated intervention costs, and conducted a cost-effectiveness analysis. Page 4 of 39 The trial registration is ISRCTN69614598. Findings: Between 16th September 2015 and 28th April 2017, 285 people with progressive MS were screened for eligibility and 140 were randomly assigned; 71 (intervention) and 69 (control). Of these, 122 completed the primary outcome (intervention = 61, control = 61) for the ITT analysis. Most people in the intervention group (66%) stood regularly over the 36 week trial period. Standing resulted in a significant increase in AMCA compared to usual care alone, with fully adjusted between-group difference in AMCA at 36 weeks of 4.7 points (95% confidence interval: 1.9 to 7.5). For the patient diarised adverse events (AEs), there was a disparity between the two groups in the frequency of short-term musculoskeletal pain (standing group = 486 of all 1188 AEs (41%); usual care group = 160 of all 736 AEs (21%)) which was potentially related to the intervention. The musculoskeletal pain lasted for over seven days in five people (standing group = 2; usual care group = 3. No serious AEs related to the study occurred. The additional quality-adjusted life-years (QALYs) in the standing programme group were 0.018, and the estimated incremental cost-per-QALY was approximately £14,700. Interpretation: The standing programme significantly increased motor function in people with severe progressive MS, although not to the degree that was considered a priori as clinically meaningful. This is one of the first physiotherapy interventions proven to be effective in this group of people. We have demonstrated that the programme is feasible as a home-based, self-managed intervention which could be routinely implemented in clinical practice in the United Kingdom.National Institute for Health Research (NIHR