By Amy Maxmen, Nature News Feature, 03 January, 2018.
ME Association comment:
This is an excellent in-depth feature article that focuses on the developing research situation in America, but also includes items relevant to the UK. You can read the complete article at the link above (and below), but for the purposes of this blog, we have taken some UK relevant highlights.
The invisible disability
Research into this debilitating disease has a rocky past. Now scientists may finally be finding their footing.
Name a remedy, and chances are that Elizabeth Allen (pictured) has tried it: acupuncture, antibiotics, antivirals, Chinese herbs, cognitive behavioural therapy and at least two dozen more. She hates dabbling in so many treatments, but does so because she longs for the healthy days of her past. The 34-year-old lawyer was a competitive swimmer at an Ivy-league university when she first fell ill with chronic fatigue syndrome, 14 years ago. Her meticulous records demonstrate that this elusive malady is much worse than ordinary exhaustion. “Last year, I went to 117 doctor appointments and I paid $18,000 in out-of-pocket expenses,” she says.
The US National Institutes of Health (NIH) in Bethesda, Maryland, bolstered the field last year by more than doubling spending for research into the condition, from around US$6 million in 2016 to $15 million in 2017. Included in that amount are funds for four ME/CFS research hubs in the United States that will between them receive $36 million over the next five years.
The stakes are high because the field’s scientific reputation has been marred by controversial research. A 2009 report1 that a retrovirus called XMRV could underlie the disease was greeted with fanfare only to be retracted two years later. And in 2011 and 2013, a British team reported that exercise and cognitive behavioural therapy relieved the symptoms of ME/CFS for many people in a large clinical study called the PACE trial2,3. US and UK health authorities had made recommendations based on the findings, but, starting around 2015, scientists and patient advocates began publicly criticizing the trial for what they saw as flaws in its design. The organizers of the trial deny that there were serious problems with it, but health officials in both countries have nevertheless been revising their guidelines.
In many ways, people with ME/CFS remain invisible. Most have been dismissed by at least one physician. And society often ignores them, too. In the United States, financial pressures are common because health insurers might consider experimental treatments unnecessary, and employers might not feel that disability payments are justified. Even in countries where health care is a right, the situation has been dire. Many patient advocates say that UK government agencies have essentially treated ME/CFS as if it were a strictly psychological condition, a conclusion that they argue was bolstered by the PACE trial’s findings that exercise and cognitive behavioural therapy relieve symptoms. The National Health Service (NHS) recommended these interventions, even after many patients complained that exercise dramatically worsens their condition.
Epidemiologists have suggested8 that the anguish of contending with the disorder and society’s general dismissal of it contribute to an up to sevenfold increase in the rate of suicide for people with ME/CFS.
Through the 2000s, advocates accused the NIH of favouring grant proposals focused on psychiatric and behavioural studies, as opposed to those exploring physiological pathways. A sea change occurred in 2015, however, with the IOM’s review5 of more than 9,000 scientific articles. “The primary message of this report,” concluded the IOM, “is that ME/CFS is a serious, chronic, complex and systemic disease.” Soon afterwards, NIH director Francis Collins said that the agency would support basic science to work out the mechanisms of the syndrome.
Some CFS researchers argue that the NIH’s contribution remains too lean. “A real problem is that funders want to see papers coming out in a short time period, but this is a complex disease that requires long-term studies that are expensive to conduct,” says Eleanor Riley, an immunologist at the University of Edinburgh, UK. Beginning in 2013, Riley helped to launch and maintain an NIH-supported biobank of ME/CFS samples at the London School of Hygiene and Tropical Medicine. But the bank has been limited by funding constraints.
In 2015, David Tuller, a journalist turned ME/CFS advocate, published a critique of the PACE studies11. Weeks later, six researchers signed an open letter to the editor of The Lancet, which published the initial PACE results, requesting a reanalysis of the data. Last March, scientists and advocates did the same in a letter to Psychological Medicine — the journal that published the 2013 PACE results — requesting a retraction. A leading criticism was that the investigators had changed how they measured recovery during the course of the trial, making that outcome simpler to achieve. The PACE investigators have denied this charge and others on their website, writing that changes were made before they analysed the data, and wouldn’t have affected the results.
Patients and advocates disagree, and although the paper has not been retracted, the CDC subsequently abandoned the trial’s recommendations. In September last year, the NHS announced that it would also revise its recommendations. In a corresponding report12, a panel concluded that recent biological models based on measurable physiological abnormalities require greater consideration.
Despite the setbacks and the long delays, many argue that science is operating as it should — being self-critical and open to revision. In five years’ time, researchers should be able to pinpoint specific aberrations in the immune, metabolic, endocrine or nervous systems of people with ME/CFS, and perhaps find genetic predispositions to the condition. These indicators might yield diagnostic tests — and, further down the road, treatments.