What was the PACE trial, and why did NICE drop graded exercise therapy in 2021?
One of the biggest trials ever run on ME/CFS was praised, attacked and reanalysed for a decade, and in 2021 England's guidance changed.
The PACE trial was a large and controversial trial that compared four approaches for people with ME/CFS: (CBT), (GET), and specialist medical care. 641 patients were divided into four groups. The findings, published in 2011, concluded that GET and CBT were "moderately effective" treatments. As of 2021, NICE no longer recommends graded exercise therapy, or cognitive behavioural therapy intended as a treatment, for people with ME/CFS. Its committee found the evidence on treatments heterogenous and inconclusive, and weighed harms reported by people with ME/CFS. Critics had long questioned the trial's results.
What were the criticisms? Critics pointed out that after the initial data was collected, the method for scoring the primary outcome measures was changed, and that the definition of recovery was also changed. Critics also objected that the original findings rested only on subjective, patient-reported measures. In a 2013 paper on recovery, 22% recovered after CBT, 22% after GET, 8% after and 7% after specialist medical care. A under the original found much lower recovery rates and no statistical difference between the groups.
The authors saw it differently. According to the authors, the score change was made to "improve the variance of the measure" and was approved by the independent steering and data monitoring committees. They said they chose patient-reported outcomes because they thought patients were the best people to judge their own health. The UK Health Research Authority reported in January 2019 that the trial exceeded transparency expectations and that there were no regulatory concerns about its conduct.
Recovery as reported in the 2013 paper (the authors' measure)
| Recovered | |
|---|---|
| CBT | 22% |
| GET | 22% |
| Adaptive pacing | 8% |
| Specialist care | 7% |
So the dispute continues. As of 2024, Cochrane concluded that GET likely reduces fatigue for people diagnosed under older criteria, partly based on evidence from PACE, while NICE says not to offer any programme that uses fixed incremental increases in physical activity.
Authors and some reviewers
- Changes approved by trial committees
- Patient-reported outcomes judged best
- HRA 2019: no regulatory concerns
- Cochrane 2024: GET likely reduces fatigue
Critics
- Scoring and recovery changed after data collected
- Original : no significant difference
- NICE 2021: do not offer fixed incremental programmes
- NICE committee: treatment evidence inconclusive, harms reported
Quiz me
0/3
Recap
PACE reported moderate benefits in 2011; critics said the measures were changed, the authors disagreed, and NICE stopped recommending GET in 2021.
💡 A trick to remember it · A race where the finish line was moved: critics said the recovery line moved, the authors said committees approved it, and the argument is about where the line should sit.
Surprising fact · Under the original protocol, recovery rates were much lower and showed no difference between the groups.
Connects to
- 📊 How many people have long Covid, and why do estimates differ so much?
- 🔋 What is ME/CFS, and why is post-exertional malaise its hallmark?
- 🧠 Did an ancient Greek philosophy really inspire cognitive behavioral therapy?
- 🎲 How does a trial keep hope from fooling everyone?
- 🗄️ Why can published science look more certain than it really is?
Sources (4)
No source, no claim. Every fact in this lesson (20 claims) cites at least one of these.
- [1]PACE trial · Wikipedia
- [2]Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management (NG206): Recommendations · NICE
- [3]Myalgic encephalomyelitis/chronic fatigue syndrome · Wikipedia
- [4]Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management (NG206): Rationale and impact · NICE