Researchers at Queen Mary University of London (QMUL), have been ordered to release a full data from a controversial ME/CFS (myalgic encaphalomyelitis/ chronic fatigue syndrome) study known as the PACE trial. A preliminary analysis of the data reveals a shocking difference to the original published results, if the trials original data analysis method had been followed. The new analysis suggests that the therapies tested in the DWP funded trial are not nearly as effective as the published results claimed them to be. The new data calls into question the decision by the National Institute for Clinical Evidence (NICE) to recommend the therapies as standard treatment for ME/CFS in the NHS. After repeatedly refusing to release the data, QMUL were ordered to do so by a freedom of information (FOI) tribunal appeal. QMUL spent £200,000 on legal costs trying to suppress this information. The data released vindicates the many esteemed scientists and ME/CFS patients, who have heavily criticised the trial and its negative effects on the public perception of ME/CFS. One of the scientists critical of the study is Dr Jonathan Edwards of University College London, who said: "It’s a mass of un-interpretability to me…All the issues with the trial
are extremely worrying, making interpretation of the clinical
significance of the findings more or less impossible." CFS is a disease characterised by a collection of symptoms including physical and mental fatigue, muscular/neurological pain and cognitive dysfunction; these symptoms can be exacerbated by exertion. It varies in severity and a minority of CFS patients are severely affected and bed-bound. It is estimated that 250,000 people in Britain are currently affected by this debilitating chronic illness. PACE trialThe PACE medical trial compared four therapies to determine their effectiveness in treating CFS, which is also known as myalgic encephalomyelitis (ME) and is commonly referred to in the UK as ME/CFS. The randomised trial included 641 people with mild to moderate CFS, those with severe CFS were excluded. The therapies under investigation were adaptive pacing therapy (APT) similar to an informal pacing strategy commonly used in CFS, cognitive behavioural therapy (CBT), graded exercise therapy (GET) and specialist medical care (SMC), which consisted of the standard NHS treatment for CFS. There are two competing, and fiercely debated, theories for the causes of CFS. One theory favoured by patients and a number of prominent scientists, with much evidence to support it, is that the illness is caused by a pathological disease process, sometimes described as a physical or biomedical cause. The other theory prominent with British mental health experts, and the authors of the PACE trial is that the illness is primarily due to psychological issues. This theory contends many of the symptoms of CFS are due to physical deconditioning caused by lack of exercise and could be cured if aberrant thought processes were changed. The authors of the PACE trial are proponents of the psychological theory, and the medical trial was designed in light of this. The initial successful results of PACE added weight to that theory and the many years of previous work some of the authors had put into supporting it. Conflicts of interestBut the results of the trial also suited the aims of the Department for Work and Pensions (DWP), who part funded the trial, and the medical insurance industry which have connections to the PACE trial via the researchers. Four of them declared working for the insurance industry in a conflicts of interest statement: Professors Peter White, Trudie Chalder and Michael Sharpe and physiotherapist Jessica Bavington. The DWP is particularly keen on psychological explanations, a.k.a the bio-psychosocial (BPS) model for chronic ill health. Professor Tom Shakespeare says, in the Disability News Service, BPS “played a key role” in the narrowing of eligibility criteria for disability benefits such as Employment and Support Allowance (ESA). Shakespeare goes on to say BPS is used to “underpin increasingly harsh and at times punitive measures targeted at disabled people”, in an attempt by the government to cut the number of people receiving ESA. One of the medical insurance companies White had previously done work for is called Unum Provident Insurance (UPI). They are also proponents of the BPS model of ill health as it helps them to deny disability claims. In 2003 UPI were fined $31.7 million in California for running ‘disability denial factories. In 2005 they were fined $15 million and the California Department of Insurance Commissioner said that “Unum Provident is an outlaw company. It is a company that has operated in an illegal fashion for years…”. UPI is one of the UK’s biggest providers of income protection insurance (IPI) . As a consequence of more holes appearing in the social security safety net, more people are likely to take out IPI, increasing UPI’s profits. Sir Mansel Aylward, Chief Medical officer for the DWP, sat on the PACE Trial Steering Committee which approved the mid trial changes to the methods. Aylward has also worked for UPI and is a keen proponent of the BPS model, being very influential in promoting it to the DWP. PACE results publishedThe results of the £5 million PACE trial were published in The Lancet in 2011. The paper stated that around 60% of the patients treated with CBT or GET gained improvements in fatigue and physical activity levels, while improvements for APT and SMC were minimal. There was extensive criticism of the published paper at this time, including : conflicts of interest, how trial participants were recruited and how the data was analysed and presented. In 2013 a second PACE paper was published, in Psychological Medicine looking at the recovery of the PACE trial participants 52 weeks after the study. This paper claimed the following recovery rates after treatment: CBT 22%, GET 22%, APT 7% and SMC 7%. These claims again proved contentious as full recovery from CFS is uncommon. A previous systematic review had shown that only 5% fully recovered over time; another inconsistency of the 2013 PACE paper as it wrongly quotes this figure as 7%. Dr Charles Shephard of the ME Association was one of many voices that criticised the findings and inconsistencies of the paper, concluding:
NICE did indeed adopt GET and CBT as therapies to treat CFS, even before the PACE trial had finished. As a result it has become the standard NHS treatment for CFS and is still recommended as such. The press lapped up the stories emerging from the PACE trial. The Daily Mail declared in 2011 ‘Fatigued patients who go out and exercise have best hope of recovery, finds study”. The BMJs report on the trial said some PACE participants had been “cured”, before any claims for their recovery had been made by the PACE trial. Another Daily Mail headline in 2013 read “Chronic fatigue victims ‘suffer fear of exercise’: Patients are anxious activities such as walking could aggravate the condition”. There were many more headlines like these, providing false hope and further stigmatising those with ME/CFS by implying that it is within their power to recover if only they would try a little harder. The data PACE researchers didn’t want to see the light of dayThe anonymised PACE trial data released to Aleem Mathees, of Perth, Australia, has undergone a preliminary analysis using the trial methods published in the original protocol. They are compared to the results published by the PACE trial researchers using a substantially altered version of the protocol, changed mid trial, that has been the subject of widespread criticism due to being poorly justified and overly lax. The changes to the methods were equivalent to widening the goal posts during a game of football. The four criteria used to define their version of recovery were relaxed, resulting in participants being classed as recovered at much lower scores after the methods had been changed (a more detailed account of the changes can be found here) This initial publication of the preliminary analysis is not peer-reviewed. However, the data analysis has been carried out by the authors which include two expert statisticians, Professor Philip Stark from the University of California and Professor Bruce Levin from Columbia University. As can be seen in the graph below the mid-trial changes to the PACE protocol inflated the results.And, there were no significant differences between the groups, which contradicts the claims of the PACE trial results which showed that GET and CBT were significantly more likely to be associated with recovery when compared to SMC. The recovery scores calculated in Mathees publicatione were: CBT 7%, GET 4%, APT 2% and SMC 3%.
![]() Graph: Conrad Bower. Source: Aleem Mathees et al (2016) The authors of the preliminary report call for a thorough, transparent and independent analysis be carried out on the PACE trial results. They suggest:
CFS activists accused
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