What would have been the outcome of the PACE trial had the investigators followed its original protocol instead of relaxing the criteria for “recovery” as the trial progressed?
Researchers have just published a paper seeking to answer this question in a reanalysis of the PACE trial based on its original protocol.
The authors concluded that Graded Exercise Therapy (GET) and Cognitive Behavioral Therapy (CBT) – the two forms of treatment explored in the PACE trial – did not improve the rate of recovery for people with Chronic Fatigue Syndrome (CFS). In other words, the PACE trial showed no evidence that GET or CBT helps people with CFS.
“We found that the groups receiving CBT or GET did not significantly outperform the control group after correcting for the number of comparisons specified in the trial protocol,” said lead author Carolyn Wilshire. “Rates of recovery were consistently low and not significantly different across treatment groups.”
In the reanalysis, using the protocol-specified definition of recovery, rates of recovery never exceeded 8 percent in any treatment group, and there were no statistically significant effects of treatment on recovery rates.
This conclusion is similar to a previous reanalysis of the PACE trial published in Nov. 2016 in which the authors concluded:
“When recovery was defined according to the original protocol, recovery rates in the GET and CBT groups were low and not significantly higher than in the control group (4%, 7% and 3%, respectively).”
Another major problem with the PACE trial, argued the papers’ authors, is that the primary measurement of recovery was based on participants’ self-assessments, which can be highly misleading when people know exactly which treatment they are receiving.
“Some groups were even assured their treatment was ‘highly effective’, even though this was the very question the trial set out to answer,” Wilshire said. “As a result, people are likely to have rated their improvements as greater than they actually were.
“To be sure the effects were genuine, we would need to see accompanying objective improvements, such as an increase in people’s activity or employment hours,” Wilshire continued. “These were not observed. Therefore, findings of the trial cannot safely be used to support behavioural interventions for chronic fatigue syndrome.”
The authors of the reanalysis of the PACE trial acknowledge that there are limitations to their study since the dataset they obtained through the Freedom of Information legislation was not as complete as the original dataset. They caution that their analysis is informal based on such limitations.
Read the BBC’s report on the reanalysis here.
Evidence of Harm
People with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis have continually reported deterioration from following the advice of their doctors to gradually increase their exertion levels based on the GET protocol. Yet, governments and doctors in the UK, Australia and other parts of the world continue to prescribe GET and CBT as the main course of treatment to people with CFS and ME, ignoring the response from patients that it is making them worse.
There are no studies that show GET helps people with ME or CFS where the definition of the disease requires post-exertional malaise, not just fatigue, according to the primer, “Post-Exertional Malaise (PEM) and Graded Exercise Therapy (GET) in ME/CFS.”
The primer explains:
“GET is a treatment intervention, commonly recommended to people with ME/CFS, which is based on the premise that ME/CFS is a condition driven largely by deconditioning from lack of activity. By gradually increasing activity, the assumption is that deconditioning can be reversed and the individual will return to health.
“Graded Exercise Therapy (GET) studies focus on fatigue, not post-exertional malaise (PEM), and have used broad criteria, which do not require the presence or reporting of PEM.
“When excluding studies which used the broadest diagnostic criteria (Oxford) from a review of the evidence that GET is a beneficial treatment for ME/CFS, the US Agency for Healthcare Research and Quality (AHRQ) downgraded evidence for GET to insufficient in 2016.
“There are currently no GET studies which have used ME/CFS diagnostic criteria which require PEM for diagnosis.”