Trials on certain treatments of chronic fatigue syndrome, or ME, have pitted patients against researchers, and scientists against scientists – amid furious clashes on the validity of landmark studies into the condition.
Words: Lorna Stephenson
Can chronic fatigue syndrome (CFS), also known as ME, be treated with exercise and talking therapies? It’s a question that splits the scientific and patient advocacy communities, and has become the basis of an intense international dispute.
Scientists researching the treatments claim they’ve been subjected to harassment and abuse, including death threats. But critics say evidence for these behavioural treatments doesn’t stand up to scientific scrutiny, and that pursuing such lines of inquiry runs counter to mounting evidence that CFS is biological, not psychological.
Bristol University is at the centre of these controversies thanks to ongoing trials into exercise and talking therapies for teenagers with CFS, which is characterised by debilitating long-term fatigue that’s worse after exertion, plus symptoms such as chronic pain. The illness can last months or years and in severe cases leaves people bed-bound and even tube fed. CFS has also baffled scientists as to its causes and the biological markers that characterise it – and there’s no drug treatment for it, only medications that can help manage symptoms.
Bristol University’s current research, a trial known as FITNET-NHS, focuses on the efficacy of delivering cognitive behavioural therapy (CBT – a talking therapy) via the internet. Another trial, MAGENTA, recently looked at the outcomes of graded exercise therapy (GET), an approach via which patients follow a regime of gradually increased activity.
Despite the fact that the Bristol trials have got ethics approval, they’ve thrust the university into the spotlight of a worldwide controversy. Opponents, who include scientists and CFS advocacy groups as well as people with CFS, say GET and CBT treatments are harmful, have been tried before to no meaningful effect, and are only being pursued to protect the reputations of researchers and others in the medical science establishment who continue to study them despite them being debunked by a previous, flawed, trial.
A £5m waste of money?
That trial – the largest on CBT and GET, and which dominates the evidence base for CFS – is known as PACE. It occurred between 2005 and 2010, based at Queen Mary University London and with results published in the Lancet medical journal in 2011. It looked at whether CBT and GET were more effective as treatments for CFS sufferers than ‘pacing’ – exertion management – or standard medical care. More than 600 people took part.
The Lancet reported that CBT and GET yielded significantly more improvement than for patients in other groups. A further paper published in 2013 reported that 22% of the CBT and GET groups had recovered following therapy compared with 7-8% of the other groups. The study was hugely influential, with the NHS, the US’s Center for Disease Control and other institutions subsequently recommending CBT and GET for treatment for CFS.
But not everyone was happy – the trial results caused controversy and disbelief among online networks of people with CFS, who analyse and share news of research developments. Many patients and charities experienced or heard numerous accounts that GET often worsened symptoms, with a 2015 ME Association study finding that many participants in GET courses saw their CFS worsen and that “substantial harm was done to many”. Severe CFS’s defining symptom is that people experience ‘crashes’ following exertion. Of course, researchers such as those at Bristol University say many patients benefit, and the trials are designed to prevent anyone suffering adverse effects.
The methodology of the trial was also ripped apart. Patient activists began Freedom of Information battles to get Queen Mary University to release trial data. One reanalysis of the data, following disclosure in 2015, found recovery rates were “inflated an average of four-fold”.
The new claims were helped out of the online echo chamber by David Tuller, an investigative reporter and public health expert at the University of California Berkeley. His 14,000-word piece, ‘Trial by Error’, detailed various methodological failures and inconsistencies within PACE. These included that investigators had relied solely on subjective outcomes of treatment success and dismissed their objective measures, and switched between methods of assessing fatigue and physical function. But the investigators have always defended their trial and refused to accept the criticisms leveled at them.
Financial and consulting relationships between the main researchers and disability insurance companies have complicated the picture. Conflicts of interest were not disclosed to trial participants, something critics claim violates the Declaration of Helsinki, the ethics governing trials involving humans.
“They have no right to publish any data, it all has to be retracted, so they wasted money from the get-go by not having proper informed consent. It’s a total waste of taxpayer money,” says Tuller. “The NHS has endorsed it, because the MRC [Medical Research Council] approved it – everybody’s at risk in this thing.”
Tuller spearheaded a campaign to send open letters to the editors of the Lancet, and the journal Psychological Medicine, which had published further PACE analyses, asking for independent reanalysis of the data.
One signatory was Professor Jonathan Edwards, an emeritus professor of medicine at UCL. “When it comes to CBT and GET, I think we need an open discussion on the fact that the evidence is not there, and people who are going round saying there’s evidence and accusing the patients of being unreasonable – I think that has to stop,” he says. “It’s time the Lancet editor admitted he got it as wrong as he did with [linking] MMR vaccination [to autism].”
The National Institute For Health and Clinical Excellence (NICE) guidelines for treating CFS, which (like worldwide guidelines) are based on the PACE findings, are under review in light of recent developments. Many eminent scientists now argue the £5m trial had ‘major flaws’. But aside from the money and reputations on the line, people with CFS are still waiting for progress into the causes and treatment of the disease.
FITNET and MAGENTA
All this is problematic for Professor Esther Crawley, Bristol University’s clinical lead for paediatrics, who as recently as last November described PACE as a “great, great trial” while discussing her work on BBC Radio Bristol. The FITNET and MAGENTA trials are advertised as extending to teenagers treatments based on ‘good evidence’ in adults – including the PACE trial’s original findings.
The potential impact of GET treatment on participants worries critics such as Jenny Horner, a campaigner in Bristol with pressure group StopGET with her own longstanding CFS diagnosis. “I was shocked they got ethical approval to do this graded exercise therapy research on children, after so many adult patients reported getting worse on graded exercise therapy [and with the controversy over the adult PACE trial methodology being unresolved],” she says.
Horner argues that there is evidence for the harm GET can cause. “Patient surveys consistently show graded exercise therapy to cause more harm than benefit,” she says. “Many of us know people who got severely worse for years after GET. People who were relatively independent become housebound or bedbound or have to start using a wheelchair.”
Psychiatric interventions such as CBT are also touchy subjects for people with CFS, harking back to times when, lacking a biological explanation, psychiatrists claimed the illness was purely in their heads. They were prisoners of their own faulty beliefs, the theory went, and inactivity in turn caused extreme physical ‘deconditioning’ which made activity increasingly difficult.
There’s now a raft of evidence on the physical manifestations of CFS, affecting various systems in the body. If it’s not psychological, why is CBT still recommended and touted as a potential cure? Crawley has argued that the CBT offered during FITNET encourages changes to sleep and activity routines, which benefit patients physiologically.
Nonetheless, some patients remain infuriated at the suggestion that CFS can be tackled with psychological intervention, arguing that it diminishes, in the eyes of others, the severity of the disease. It also strikes many, including Horner, as incompatible with the understanding of CFS as a biological disease.
The debate, then, is heated. But if there is truth in the criticisms from patients and CFS advocacy groups and charities, the dominance of the ‘extremist’ opponent narrative – the alleged harassment and abuse of researchers into these treatments – is also troubling. While accepting there may be some intemperate opponents, some critics of PACE and the following trials pursuing similar hypotheses, such as FITNET and MAGENTA at Bristol, say researchers are using the ‘militant’ narrative to deflect legitimate criticisms of bad science.
In 2011 the Observer published an article, ‘Chronic fatigue syndrome researchers face death threats from militants’, in which researchers into GET and CBT outlined the intimidation they said they’d been subjected to from ‘extremist’ patients – from emailed threats, to someone attending a lecture carrying a knife. Crawley featured in the article, saying she received hate mail and checked all packages sent to her office.
Horner is angered by what she sees as a purposeful attempt to discredit the patient community and deflect valid criticism of the research: “I find the nature of these accusations quite distasteful. Over the years ‘psychosocial agenda’ researchers appear to use this as a tactic to silence all patient criticism. It works particularly well in terms of newspaper coverage.”
For now, the Bristol University trials are set to continue amid the online noise of opposition, though other studies into CFS’s biological roots – more promising in the eyes of critics of the CBT and GET paradigm – are also taking place around the world. For people with CFS, for whom all too often life is put on hold, any advances can’t come soon enough.
Bristol University and Professor Crawley declined to comment for this article.