“I’m shocked that the Lancet published it… The PACE study has so many flaws and there are so many questions you’d want to ask about it that I don’t understand how it got through any kind of peer review.”
— Professor Ronald W. Davis, Stanford University
“It’s a mass of uninterpretability… All the issues with the trial are extremely worrying, making interpretation of the clinical significance of the findings more or less impossible.”
— Emeritus Professor Jonathan Edwards
University College London
- The PACE trial is the largest ever clinical trial conducted on ME/CFS. It had 641 patients, took place in six UK centres, and cost £5 million in public funds.
- PACE compared graded exercise and other behavioural therapies with receiving no therapy.
- PACE’s main results were published in The Lancet in 2011. Its authors claimed that graded exercise therapy — when added to specialist medical care — was moderately effective, based on patients’ self-reports: but the main analyses listed in the study’s original plan had been abandoned and replaced with others.
- New analysis (September 2016) shows that only 1 in 10 people showed any additional benefit from graded exercise therapy, according to the original protocol. The proportion who got worse has not yet been reported.
- The trial used a well-known 100-point scale to measure physical function, in which “0” is severe disability and “100” is good health. In the new analyses, patients were considered to be in the “normal range” for physical function if they scored 60 or more — but they were considered disabled enough to enter the trial if they scored 65 or lower. That is, patients could worsen during the trial and be classed as being in the “normal range” for physical function. Patients with congestive heart failure score only a little worse (57/100). Mathematician and journalist Julie Rehmeyer presented this analysis at a statisticians’ conference and said, “I saw jaws drop.”
- Both scientists and laypersons pointed out the flaws immediately and their letters were published in The Lancet but no correction notice was issued — meaning that reading the paper would not alert individuals to the paper’s fundamental flaws.
“One of the most damaging cases of bad statistical practice that I have personally encountered in my career as a journalist.”
— Julie Rehmeyer
Mathematician and journalist
- In 2015, years after PACE’s publication in 2011, journalist and public health scientist Dr David Tuller published a detailed critique exposing the many problems in PACE, quoting harsh criticism of the study from world-leading scientists.
- Shortly after Dr Tuller’s article, a group of over 40 scientists wrote an open letter to The Lancet, strongly criticising the trial and calling for independent analysis of the data, but were ignored. Other scientists asked for the data from the study so that they could analyse it themselves, but were refused.
- Now a court has ordered the release of the data. Summary data already published in The Lancet suggest that when the data are analysed according to the original plan, the results for graded exercise therapy will be poor.