Adverse events and deterioration reported by participants in the PACE trial of therapies for chronic fatigue syndrome.

Observed Findings

• Physical function deteriorated in 25% of participants receiving APT, compared to 9% receiving CBT, 11% receiving GET, and 18% receiving standard medical care alone
• Non-serious adverse events were common across all groups, with a median of 4 events per participant over one year
• No significant differences were found in the total number of adverse events between the four treatment groups
• Baseline factors including higher physical symptom count, higher BMI, and presence of depressive disorder were associated with more reported adverse events
• Substantial variation in adverse event rates existed between different recruitment centres, suggesting methodological differences in how events were recorded

Inferred Conclusions

• Physical deterioration is not equally distributed across ME/CFS treatments and should be monitored carefully, particularly with pacing-based interventions
• The high frequency of non-serious adverse events across all treatment groups may reflect disease characteristics rather than treatment effects
• Standardization of adverse event assessment methods is essential for accurate safety monitoring in CFS trials
• Centre-level differences in ascertainment suggest that training and standardized protocols significantly impact the reliability of adverse event data collection

Remaining Questions