Review Effectiveness of non-pharmacological interventions for fatigue in adults with long-term conditions: a synopsis of the EIFFEL... 2026 Leaviss et al

Andy

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Full title: Effectiveness of non-pharmacological interventions for fatigue in adults with long-term conditions: a synopsis of the EIFFEL mixed-methods evidence synthesis

Joanna Leaviss, Andrew Booth, David Coyle, George Daly, Sarah Davis, Helen Dawes, Vincent Deary, Kritica Dwivedi, Jessica E Forsyth, Kate Fryer, Samantha McCormick, Marissa Martyn-St James, Julia Newton, Shijie Ren, Gillian Rooney, Anthea Sutton, Mon Mon-Yee, Christopher Burton

Background

Fatigue is common in many long-term medical conditions. Interventions to date have largely been in single conditions.

Objective

To conduct a mixed-methods evidence synthesis of the clinical and cost-effectiveness and acceptability of non-pharmacological interventions for fatigue in adults with long-term medical conditions.

Methods

Eligibility criteria

Randomised controlled trials, cost-effectiveness studies, or qualitative studies of non-pharmacological interventions for fatigue in long-term medical conditions where fatigue was either a criterion for inclusion, the primary target of the intervention, or the primary or coprimary outcome. Studies of post-infectious, post-traumatic, cancer-related or idiopathic fatigue were excluded.

Information sources

Searches used the MEDical Literature Analysis and Retrieval System, Excerpta Medica dataBASE, Cumulative Index to Nursing and Allied Health Literature, and American Psychological Association PsycInfo® (American Psychological Association, Washington, DC, USA) databases. We used systematic CLUSTER searching for qualitative studies and Epistemonikos for systematic reviews.

Involvement of patients

We held three rounds of five focus groups involving people with fatigue in long-term conditions to ensure that assumptions in, and reporting of, the research had validity with the patient population.

Risk of bias

Risk-of-bias assessment of all studies included in the network meta-analysis was undertaken using an adapted version 2 of the Cochrane risk-of-bias tool for randomised controlled trials.

Synthesis of results

Clinical effectiveness evaluation used random effects network meta-analyses at three time points. The cost-effectiveness analysis involved a de novo analysis of interventions identified as clinically effective. The qualitative synthesis involved a thematic synthesis of primary studies of interventions and a mega-synthesis of reviews of patient experience of fatigue across different conditions. Focus groups were analysed by thematic analysis, and findings from all work packages were integrated in a final synthesis by the research team.
Results

Included studies

The clinical effectiveness review included 88 randomised controlled trials, involving 27 interventions, with 6636 participants included at end of treatment, 1849 in the short term and 2322 in the long term.

Synthesis of results

Compared to usual care at long-term follow-up, cognitive–behavioural therapy-based interventions and physical activity promotion showed statistically significant reductions in fatigue (standardised mean difference −0.4, 95% credible interval −0.63 to −0.21, 9 studies; and −0.52, −0.86 to −0.18, 2 studies), respectively. Effective interventions provided positive net monetary benefit versus usual care, particularly when delivered in a group format, when valuing a quality-adjusted life-year at £20,000. Individuals vary in their experience of fatigue in ways that are not simply due to their medical condition, indicating that interventions need to be adaptable to individuals’ experiences and capabilities.

Discussion

The evidence base is relatively small, heterogeneous and includes studies at moderate to high risk of bias. More than half of the included trials were in multiple sclerosis.

Interpretation

Interventions for fatigue that support people to increase physical activity or are based on cognitive–behavioural therapy are acceptable and effective in reducing fatigue in people with different long-term medical conditions, with the potential to be cost-effective. Based on the qualitative synthesis, we propose a three-stage component model for interventions.

Future work

Future trials should focus on the feasibility and effectiveness of transdiagnostic fatigue services, fatigue interventions in multimorbidity, and investigations of emerging non-invasive stimulation interventions.

Funding

This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR154660.

Open access
 
See also
 
"Population: adults with any long-term condition, using the NHS definition as ‘an illness that cannot be cured but that can usually be controlled with medicines or other treatments’. The commissioning brief specifically excluded fatigue in people with cancer, in relation to or following from infection [human immunodeficiency virus, hepatitis C, long COVID and myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS)] or resulting from injuries or developmental disorders. It also excluded conditions in which symptoms (rather than observable pathology) were the defining features rather than observable pathology (e.g. fibromyalgia or irritable bowel syndrome)."
 

"Findings in relation to other studies​


This study is the first to take such a wide perspective of fatigue in long-term conditions, integrating clinical effectiveness, cost-effectiveness and qualitative data across multiple conditions. As such, there are few directly comparable studies. We did note two condition-specific meta-analyses in MS41 and stroke. 42 Relative to these, we applied more stringent inclusion criteria but obtained broadly similar results.

Some comparison is, however, possible with studies in conditions out of scope of this review. This is most challenging in ME/CFS, in relation to both CBT and exercise. While the most recent systematic review found evidence for effectiveness of CBT,43 its interpretation in guideline recommendations remains contested. 44,45 Interestingly, a recent review of activity pacing in ME/CFS (which can include both energy conservation and activity promotion) suggested some effectiveness, particularly where there are elements of increasing physical activity. 46 Work in ME/CFS and also more recently in long COVID has highlighted the importance of coherence of treatment to patient beliefs.

While few trials of interventions are designed to be transdiagnostic and highly personalised, lessons can be drawn from studies such as the Multiple Symptoms Study 3,47 which included people with multiple persistent physical symptoms (commonly termed ‘medically unexplained symptoms’). Here the consultation-based intervention comprised four elements: recognition, explanation, action and learning. 48 The validation of the individual and interpretation of symptoms as complex, real and tractable showed sustained benefit47 along with plausible mechanisms. 49

Take-home message(s)​


Fatigue in long-term conditions is common, multifaceted, personal and often invisible. Interventions to address it need to reflect this complexity and heterogeneity.

We have identified a set of processes that are found within effective interventions and can be used to tailor fatigue management to groups, settings or individuals. These processes appear – at least for many people – to follow some order, with some being prerequisites for others."
 
I’m starting to think that a lack of an understanding of basic research methodology is a requirement to do meta analyses for non-pharmacological interventions.

I can’t fine the RoB analysis and the website is a nightmare to navigate, but there is no way that any of theses studies have anything less than a high risk of bias. Therefore, they are useless as evidence of efficacy.
 
The clinical effectiveness review included 88 randomised controlled trials, involving 27 interventions, with 6636 participants included at end of treatment, 1849 in the short term and 2322 in the long term.
This is a tiny fraction, single digit %, of all the trials with this specific intent done on either ME/CFS or generic chronic fatigue. You can't do evidence synthesis with this level of cherry-picking, not by excluding most of the conditions to which this applies, which raises even more questions about what the hell they are even doing here. How would any of this translate into generic concepts when half the trials are on MS?
Future trials should focus on the feasibility and effectiveness of transdiagnostic fatigue services, fatigue interventions in multimorbidity, and investigations of emerging non-invasive stimulation interventions.
Why would there be any future trials at all? When this way of doing things has shown itself to be entirely useless. This has been going on for decades, when conclusions identical to this one were being published routinely, and continue to be.
Individuals vary in their experience of fatigue in ways that are not simply due to their medical condition, indicating that interventions need to be adaptable to individuals’ experiences and capabilities.
There is actually no way to verify this credibly. Assertive speculation yet again. How does "capability" not relate to medical condition here? What is this nonsense?!

Anyway, the idea that there can be universal solutions to the most common symptom in all of medicine, which clearly has multiple possible causes, is pure nonsense. This industry is entirely lacking in people willing and able to call bullshit.
 
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