The fatigue enigma: towards an integrative theoretical framework across clinical conditions

Background: Fatigue is a complex phenomenon that presents persistent challenges for research and clinical care across multiple conditions. Objective: To explore development of an integrative theoretical framework linking lived experience, underlying mechanisms, and the design and evaluation of interventions. Methods: We conducted systematic scoping reviews to identify (i) systematic and narrative reviews of mechanisms or pathways of fatigue across clinical conditions, and (ii) systematic reviews and recent randomised controlled trials of interventions addressing fatigue. These reviews informed four consensus workshops with researchers, clinicians, and individuals with lived experience of fatigue that examined: (1) the meaning and evaluation of fatigue across conditions; (2) mechanisms and pathways; (3) evidence for outcomes and novel interventions; and (4) consensus development and program theory generation. Key findings: We present a summary of the discussions across the workshops and highlight the challenges that remain in evaluating the utility of an integrative theoretical framework. Substantial conceptual ambiguity was identified in how
fatigue is defined and how mechanisms, pathways, and interventions are categorised. Inconsistent terminology, measurement approaches, and theoretical specification limit synthesis across conditions, and the current evidence base remains insufficiently articulated to support a coherent cross-condition account. Conclusion: Critical gaps remain in the use of common language, outcome measures, and theory-informed approaches to intervention
development. Addressing these foundational limitations is necessary to determine whether an integrative framework for fatigue can be constructed, and whether this may support knowledge translation across diagnostic boundaries and hypothesis-driven research that is responsive to stakeholder priorities and delivers meaningful clinical benefit.