Title: What is the evidence for interventions used to manage sleep disturbances in people with fibromyalgia? A comprehensive evidence synthesis to inform clinical practice and future research
Funder: Chief Scientist Office, Scotland

Abstract: Fibromyalgia is a common long-term condition, characterised by persistent pain all over the body, sleep disturbance and fatigue. It affects 1 in 20 adults in the UK. There is no cure for fibromyalgia but there are several treatments that relieve some of the symptoms and make the condition easier to live with. Sleep problems, such as difficulties falling asleep, frequent awakenings and unrefreshed sleep are reported by almost all people with fibromyalgia. Current treatments for improving sleep problems include medications such as amitriptyline, and non-drug interventions such as exercise, massage, cognitive behavioural therapy, dietary and lifestyle modifications, and complementary and alternative therapies (e.g. acupuncture). The scientific literature on approaches to treat sleep problems in people with fibromyalgia is confusing and difficult to interpret. There is uncertainty about which interventions are most effective in improving sleep and which require further evaluation in future clinical studies. _x000D_ _x000D_ In this study we will combine information from studies across the world that have evaluated the benefits, harms and acceptability of both drug and non-drug therapies for helping people with sleep problems due to fibromyalgia. _x000D_ _x000D_ The team responsible for running this project include a patient who lives with fibromyalgia alongside experienced health professionals and researchers who have worked in the field of fibromyalgia or who are experts in sleep, physical therapy and research methods. We will develop sound strategies to identify all relevant studies that have been published. We will extract information on the effects and safety of treatments for fibromyalgia-related sleep problems from the identified studies and use mathematical methods to analyse these data. In our primary analysis, we will compare different treatments. We will also consider the characteristics of the tools used to measure sleep outcomes in people with fibromyalgia and incorporate information on the personal experiences and expectations of treatments gathered from those who experience sleep problems because of fibromyalgia. _x000D_ _x000D_ Patient and public involvement (PPI)_x000D_ This research plan was developed in partnership with a patient who is experiencing sleep problems due to fibromyalgia. She will be part of our project team and will attend all project meetings. We will also set up an Advisory Group comprised of national and international experts in the field and lay people living with fibromyalgia. The lay people within the Group will help to ensure that our project captures what matters most to those who experience sleep problems due to fibromyalgia and will provide advice on the best way to report our findings to the public and policy makers. _x000D_ _x000D_ Dissemination_x000D_ Findings of this research will provide important information on the treatment of fibromyalgia-related sleep problems. We will develop a dissemination plan with our patient partner and Advisory Group. We intend to share our findings with NHS healthcare professionals, patients, policymakers and the public. We will make our findings available on social media including Twitter, present them at national and international clinical meetings and publish them in mainstream medical journals. We will also contact relevant charities and healthcare organisations and will disseminate our findings through their channels to reach wider audiences.

Lay abstract: Research question: What is the evidence for interventions used to manage sleep disturbances in people with fibromyalgia? A comprehensive evidence synthesis to inform clinical practice and future research._x000D_ _x000D_ Background: In people with fibromyalgia, sleep disturbance is one of the most common reported symptoms and an adverse prognostic factor. The James Lind Alliance Priority Setting Partnerships has identified the need to determine which interventions are more effective for the management of fibromyalgia-related sleep problems as one of their top priorities._x000D_ _x000D_ Aims and objectives: Synthesis of quantitative and qualitative evidence and patient-reported outcome measures (PROMs) analysis to inform management of fibromyalgia-related sleep problems._x000D_ _x000D_ Search strategy: Major electronic databases (MEDLINE, Embase, Science Citation Index, CINAHL, AMED, CDSR, CENTRAL, APA PsycInfo, DARE, the NIHR Journals Library) with no language or publication date restrictions and ongoing studies registries._x000D_ _x000D_ Research strategy: Choice of primary and secondary outcomes will be agreed upon by the project Advisory Group. These may include measures of sleep, activities of daily living, adverse events and quality of life. Data selection and extraction will be performed independently by two reviewers. For the quantitative evidence synthesis, network meta-analysis (NMA) will be performed to compare interventions that have not been directly compared in clinical trials and analyse results of direct and indirect comparisons collectively. A Bayesian framework will be used, in accord with NICE Decision Support Unit guidance. Component NMAs will be used when appropriate. The GRADE approach for NMA will be used to rate the quality of direct and indirect effect estimates. A recently published systematic review of qualitative evidence assessing the experience of people with fibromyalgia-related sleep problems will be updated and the quality of its evidence assessed using GRADE-CERQual. Content analysis of PROMs of sleep quality in people with fibromyalgia will be performed. Using an interpretive approach, outputs from quantitative, qualitative and PROMs analyses will be synthesised to draw overall conclusions._x000D_ _x000D_ Project timelines: Month 1-3: Protocol development and registration, consolidation of Advisory Group, literature searches; Month 4-11: Quantitative evidence synthesis, update of a recent qualitative systematic review, PROMs analysis, integration of findings/mixed-methods synthesis, writing up. Month 12: Final report, manuscripts preparation, dissemination activities._x000D_ _x000D_ Anticipated impact and dissemination: Evidence to inform clinical practice and future research; enhanced quality of life for people with fibromyalgia-related sleep problems. Thorough dissemination strategies will be developed in discussion with the Advisory Group and our PPI co-applicant and targeted to different audiences. Outputs will include academic publications and presentations, methodological papers and appropriate summaries for patients, the public, policymakers and health professionals including infographics, podcasts, and tweets. Contacts with relevant PPI and social media groups will be established to facilitate access to our findings by people with fibromyalgia, carers and their families. Existing links with relevant charities, healthcare and professional organisations will be leveraged to cascade our findings to patients, healthcare professionals, policymakers and the public.

Research activity codes: 6.1 PHARMACEUTICALS;6.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.7 PHYSICAL;6.8 COMPLEMENTARY
Health categories: MUSCULOSKELETAL