E1 ReplicatedModerate confidencePEM not requiredRCTPeer-reviewedMachine draft
Standard · 3 min
Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial.
Sharpe, Michael, Goldsmith, Kimberley A, Johnson, Anthony L et al. · The lancet. Psychiatry · 2015 · DOI
Quick Summary
This study followed up with people who participated in the PACE trial 2-3 years after it ended to see how they were doing long-term. People who received cognitive behavioral therapy (CBT) or graded exercise therapy (GET) maintained their improvements in fatigue and physical function. Interestingly, people who initially received standard medical care or adaptive pacing therapy also improved over time, though many had sought additional treatment on their own after the trial ended.
Why It Matters
Long-term follow-up data are critical for understanding whether ME/CFS treatments produce sustained benefit or represent temporary improvement. This study provides rare multi-year outcome data, which informs patient expectations and treatment planning, though the high rate of additional treatment-seeking complicates interpretation of which interventions are most beneficial.
Observed Findings
- Improvements in fatigue and physical functioning achieved by CBT and GET at 1 year were sustained at long-term follow-up (median 31 months post-randomization)
- APT and SMC-alone groups showed continued improvement from 1-year to long-term follow-up, narrowing differences between original treatment groups
- 44% of trial participants (210/481) sought additional treatment after the trial, with highest rates in SMC-alone (63%) and APT (50%) groups and lowest in CBT (31%) and GET (31%) groups
- At long-term follow-up, there was little evidence of differences in fatigue or physical functioning outcomes between the four originally randomized treatment groups
- Median time to long-term assessment was 31 months (range 24-53 months)
Inferred Conclusions
- The benefits of CBT and GET observed at 1 year persist at 2-3 year follow-up
- Initial treatment allocation differences narrow over time, potentially due to post-trial treatment-seeking and natural recovery trajectories
- Future research should identify which patients respond to CBT/GET versus which require alternative approaches
- Long-term outcomes appear complex and may reflect multiple factors beyond the original trial intervention
Remaining Questions
What This Study Does Not Prove
This study does not prove that CBT or GET are definitively superior long-term, because 44% of participants received additional treatments after the trial that were not controlled for in the long-term analysis. The improvement in SMC-alone and APT groups after 1 year may reflect regression to the mean, natural recovery, or the additional therapies received rather than the original intervention. The study also cannot establish causation for what drove improvement in any group.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
- What are the predictors of long-term response to CBT and GET versus non-response?
- How do the additional treatments received post-trial (mostly CBT or GET) explain the convergence of outcomes between groups?
- What are effective treatments for ME/CFS patients who do not respond to CBT or GET?
- Do improvements reported in questionnaire-based outcomes reflect changes in patient-perceived disability versus objective functional capacity or post-exertional malaise?