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GW4 Community Studying Fatigue in People with Multiple Long-term Conditions


Fatigue is a ubiquitous across multiple neurological and musculoskeletal conditions and is more severe in individuals with two or more long-term conditions, sometimes known as multimorbidity. The number of people living with multiple long-term conditions is increasing, and the presence of multiple long-term conditions poses a challenge to clinicians and patients as clinical guidelines (and the underpinning research) focus on single conditions. 

There is an urgent need to improve understanding and treatment of fatigue in individuals with multiple long-term conditions. At present, it is not clear which mechanistic pathways for fatigue are common across conditions and which are independent of the diagnostic label. Furthermore, it is not clear how fatigue presents across conditions, nor how best to define or measure fatigue across conditions. These factors critically impede the development and testing of targeted interventions for individuals with multiple long-term conditions.  

Our vision is to study fatigue regardless of associated diagnosis. Studying fatigue across multiple conditions, inclusive of multiple concurrent conditions, and at scale will allow us to identify mechanistic pathways that are common across conditions and identify ways in which conditions, or patients within a condition, cluster in their mechanistic pathways for fatigue.  It will also enable us to identify the core outcomes that are needed clinically, across conditions and inclusive of multiple concurrent conditions. 

We aim to build on the infrastructure and expertise that exists across GW4 to enable the development of targeted physical [non-pharmacological] interventions for fatigue across diagnostic labels and in individuals with multiple long-term conditions, and ultimately to enable the conduct efficient and novel clinical trials of these interventions. In this project we build the community, identify key strengths and uncertainties in this field, and take the first steps to generating the platform from which to achieve this goal.  


Project Summary

The GW4 fatigue community will identify and address the key uncertainties and define the key boundaries required to deliver the long-term aim of efficient clinical trials of mechanistically informed interventions for fatigue across clinical conditions and in multiple concurrent long-term conditions. 

A launch event will be held to create awareness of the collaboration and create a fatigue-focussed community of scholars. This will take the form of a symposium with invited speakers presenting cutting edge research on the topic of fatigue across conditions.

A systematic review will be conducted to synthesise existing evidence on mechanisms of fatigue in chronic health conditions and identify gaps in understanding to inform targeted studies.  

Three workshops will be held, each addressing a key uncertainty that must be resolved to progress towards developing mechanistically informed targeted interventions for fatigue. The target output of each workshop is a summary of key research questions that are priorities to address, and formation of collaborations and identification of best pathways to address these.  


Workshop 1 – Population & mechanisms: Scope current understanding of testable mechanisms underlying fatigue across multiple clinical populations and in the presence of multiple long-term conditions, and the expertise and resources available to study these within GW4   

 Workshop 2 – Outcomes: Explore what matters to people from diverse backgrounds living with fatigue multiple long-term conditions and identify how best to measure domains of importance.    

 Workshop 3 – Interventions and comparators: Identify promising interventions that target fatigue across conditions, and identifying if these map onto mechanisms 


The proposed activities will highlight strengths and synergies across GW4 that are not currently being exploited and engage members of the community. A summary of research priorities and potential pathways identified to address these priorities will be generated.   

University of Bath
University of Bristol
Cardiff University
University of Exeter