Developing, optimising and implementing a blended digital self-management tReatmEnt for FatigUe in multiplE scLerosis (REFUEL-MS)

Background: Multiple Sclerosis (MS) is an incurable, neurological disease typically diagnosed in young adults who are faced with a lifetime of relapsing and/or progressive disabling symptoms. Fatigue is the most prevalent symptom and has the largest impact on quality-of-life and early retirement from work. Fatigue in MS is more severe than fatigue in other long-term conditions (LTCs). Medications have little effect on MS-fatigue. Balance and mixed exercise interventions and cognitive-behavioural therapy (CBT) self-management for fatigue show moderate to large end-of-treatment effects. Work is needed to sustain treatment effects over time, including integrating effective treatments to provide patient choice and tailoring for different fatigue mechanisms. Implementing these treatments in NHS setting is key. In the UK, 90% of people with MS (pwMS) experience fatigue. Only 3% have been offered an exercise treatment and 6% a behavioural treatment. The aim of this programme is to draw together existing components of the most promising exercise and behavioural interventions into an individually-tailored physiotherapist/occupational therapist supported digital fatigue treatment (REFUEL-MS), that is clinically and cost-effective, and can be implemented routinely across NHS MS services. Methods: Aims will be met through interactive and iterative work packages (WPs). WP1 (months 1-18) Development of REFUEL-MS through refining a logic model, building the patient interface using co-design workshops and think-aloud methods with pwMS. Building health care professional (HCP) support package, platform and training through focus groups and think-aloud methods with HCPs. WP2 (in parallel with WP1) Addresses reach through focus groups (N=6) with formal/informal carers of pwMS and pwMS, and individual interviews (N=25-30) with under-served/seldom-heard pwMS. These data will feed into REFUEL-MS to ensure diversity and social care needs/support are addressed. WP3 (months 12-18) Optimises the functionality and acceptability of REFUEL-MS through mixed methods case-series with a diverse group of pwMS (N=15-20). WP4 (month 18-30) tests the feasibility of and refines the implementation plan through mixed-methods iterative case-series study in four diverse NHS services. WP5 (months 26-60) Hybrid-II stepped-wedge cluster randomised-controlled trial with internal pilot: 12 services randomised to 6 start times of REFUEL-MS delivery (3-months unexposed with treatment-as-usual data collected, 1 month for training of REFUEL-MS facilitators, 5 months exposed with REFUEL-MS delivery and data collection). 576 pwMS recruited (216 unexposed, 360 exposed). Primary effectiveness outcome: patient-level fatigue severity at 36-weeks post-baseline, primary implementation outcome: NoMAD. Treatment effects estimated using three-level linear mixed-effects models following the intention-to-treat principle (ITT). Cost-utility analysis relating the difference in total mean costs per phase to the difference in quality-adjusted life years. WP6 (months 60-66) To ensure sustainably, policy labs with key stakeholders to create a policy document on NHS scaling of REFUEL-MS and a business model for long-term sustainability. Workshops with other LTCs communities (patients and HCPs) to develop a template to adapt REFUEL-MS for other LTCs. Anticipated impact: Transformed standard fatigue care in MS including under-served/seldom-heard groups, implemented in 12-16 services, and scalable and sustainable in other MS NHS services in England. Longer-term impact includes: (1)Adapted and implemented REFUEL-MS for other LTCs, (2)Improved implementation and commissioning of evidence-based digital behavioural products.