Controversy has always dogged chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), the mysterious condition that leaves a patient tired all the time and exhausted from the slightest exertion. The minority of doctors who even believed their patient had an actual physical problem—as opposed to the rest who suspected it was more to do with mind than matter—were perplexed. Then, seven years ago, medicine thought they'd finally figured out how to treat it: patients could get better by combining exercise and cognitive behavioral therapy (CBT), the 'talking cure.'
It was as if a light had been switched on in a darkened room, and it all came from one 2011 study, called the PACE trial, which concluded that the two approaches dramatically improved the sufferers' fatigue—and around 22 percent went on to achieve a full recovery, the researchers claimed in a press conference.1
But it's all unraveling. Another research team has looked at the raw data that underpinned the PACE study and found that the therapies had "no long-term benefits at all." The 60 percent improvement reported by the PACE researchers was reduced to just 20 percent in the reanalysis, and the 22 percent who had experienced a full recovery evaporated to just 8 percent.2
To make matters worse, the data had to be crow-barred from the PACE research team. Freedom of information requests had been ignored, and it took two tribunals to get the researchers—who had recruited a $285,000 legal team to defend them—to conform with the request.
In a separate move, WDDTY columnist Dr Sarah Myhill is calling on the General Medical Council (GMC), which regulates the conduct of doctors in the UK, to mount an investigation. She is accusing the PACE researchers of scientific fraud and breaching 'good medical practice.'
Looking at the raw data of the PACE study, researchers from the University of Wellington in New Zealand discovered that almost all the benefits of graded exercise—where the intensity and duration of activity slowly increase—and CBT disappear when the definition of 'patient recovery' is adhered to throughout the duration of the trial and when assessing patients' outcomes afterwards.
The PACE researchers established what they meant by patient 'improvement' and 'recovery'—which included established thresholds that were statistically measurable—before the study began. However, once the study was underway, they weakened their own protocols dramatically, and a patient would be considered to have 'recovered' even when their symptoms had worsened during the trial. The bar for good physical function was lowered so far that even an 80-year-old would have passed, other researchers noted.
Ultimately, the assessment of whether a participant had recovered was determined entirely by the patient—and this was after they had been shown glowing testimonials about the therapies they were getting halfway through the study.
When the original protocols for recovery were reapplied—along with other everyday measures such as returning to work—all the benefits announced by the PACE researchers disappeared. Rates of recovery were "consistently low," the researchers said, and were hardly better than those being achieved by standard treatment. As lead researcher Carolyn Wilshere put it, the PACE researchers had "moved the goalposts."
In Dr Myhill's call to the GMC to investigate the PACE researchers, she is claiming that they have committed 'scientific fraud.' In a letter to Sir Terence Stephenson, GMC chairman, she cites three definitions laid out by the UK Fraud Act of 2006—fraud by false representation, fraud by failing to disclose information and fraud by abuse of position—which she wants the GMC to investigate.
She also argues that CFS/ME patients have been harmed by the therapies promoted by the PACE researchers, and she is urging them to also write to the GMC. "The PACE trial has effectively determined CFS/ME as a psychological condition. As a result, patients who suffer what is, in fact, a serious and debilitating physical condition have been subject to therapies which at best are ineffective and at worse exacerbate the condition," she writes.
Within months of the PACE results being published, doctors had quickly embraced the dual approach. In the UK, the National Institute for Health and Care Excellence (NICE) established it as the standard treatment, and, more bizarrely, the government's Department for Work and Pensions (DWP) was also recommending it. But the DWP wasn't an innocent bystander: it was shelling out millions in benefits to the country's 250,000 ME sufferers, and it also happened to have funded the PACE trial to the tune of about $7 million. In the US, the Centers for Disease Control and Prevention (CDC), which had worked closely with two of the PACE researchers, Peter White from Queen Mary University in London and Michael Sharpe from Oxford University, also recommended the therapy as the way forward.
The PACE results had pleased both camps in medicine: those that believed that ME was 'all in the head' and others who suspected there had to be a viral cause. The PACE researchers were acolytes of psychiatrist Simon Wessely at King's College London, who squared the circle with his hypothesis that a virus or some organic trigger may have kick-started the problem, but it was prolonged by the morbid thoughts of the sufferer. "The symptoms and disability of CFS are perpetuated predominantly by dysfunctional illness beliefs and coping behaviors," he said.3
While doctors celebrated, the analysis just wasn't ringing true for many sufferers, who couldn't believe that either approach was of much use. In fact, whenever they exercised, they collapsed with exhaustion immediately afterward, and were often confined to bed, as ME sufferer Sally Burch related after she had been advised by her doctor to take three brisk walks a day. "Those short walks were causing me to get out of breath, and to feel light-headed and dizzy. As the days went by, I found I was able to walk shorter and shorter distances before I ended up in a heap on the ground, trying to make the world stay still. Something was very wrong."4
Pace of change
Other sufferers thought there was something very wrong with the findings of the PACE trial, too. CFS sufferer Alem Matthees in Australia put in the first freedom of information request to see the underlying data, and he was soon joined by six scientists from Stanford University, who demanded a full independent investigation.
Even though the raw data was being kept under wraps, other researchers were able to spot anomalies. David Tuller at the University of California, Berkeley, discovered that 13 percent of the 641 CFS/ME sufferers recruited into the original trial had 'recovered' even before the trial had started, at least according to the very loose definition of 'recovery' the researchers were using.
Stung by the mounting criticism, the PACE researchers claimed that their critics were "young men, borderline sociopaths or psychopathic"—hardly a fitting description of scientists from Stanford University—before claiming they had been threatened and harassed, which was later found to be untrue.
Finally, they issued a new analysis of their original data, in which they concluded that the participants who hadn't improved were simply afraid of exercise.5
All of this puts our understanding about CFS/ME—what it is, what causes it and how it can be treated—back to square one. It's clearly not 'all in the mind'—or 'yuppie flu,' as it was once disparagingly described—and this acceptance is at least allowing new theories about what it might be to flourish.
So what is CFS/ME?
Researchers who have been able to move beyond the idea that CFS/ME is 'all in the mind' have uncovered common patterns among sufferers. Even back in the early 1990s—essentially the dark ages when it comes to CFS research—scientists at the National Institute of Allergy and Infectious Diseases were seeing immune system abnormalities in ME sufferers.
In Italy, researchers were also seeing a pattern—but with an inherited condition known as Gilbert's syndrome, which involves an excessive build-up of a substance called bilirubin.
The condition increases the likelihood of jaundice, and could also raise the risk for ME, researchers at the Instituto Di Clinical Medica in Rome theorized.
Sleep problems could also be a factor. CFS patients spent more time in bed but slept less well and were awake for more of the night, researchers at Littlemore Hospital in Oxford found.
WDDTY columnist Dr Sarah Myhill agrees. She has been treating CFS/ME for much of her career, and she has also noted sleep problems in her patients. But the essential hallmark is mitochondrial dysfunction, which she found when she tested 138 sufferers.
Mitochondria are the engines inside our cells that produce 90 percent of the energy we need to live. Treatment was a combination of a Paleo, or 'Stone-Age,' diet, getting good-quality sleep, taking nutritional supplements and getting the work/play balance right.1
Other researchers have seen a connection to thyroid function. The typical CFS sufferer seems to have lower levels of thyroid hormones, but not so low that it would be diagnosed as a disease.
Researchers from the University Medical Centre in the Netherlands have noted that CFS mimics many of the symptoms associated with hypothyroidism, when the thyroid gland 'under-performs.'
In one study, blood samples from 98 CFS sufferers were found to have low serum levels of key thyroid hormones, including thyroxine, compared to the levels seen in 99 healthy people who were also tested.2