Media Reports of the PACE Trial Research published in The Lancet, Feb 18 th 2011 REUTERS

http://www.reuters.com/article/2011/02/18/us-fatigue-me-idUSTRE71H02320110218 Pushing limits can help chronic fatigue patients

By Kate Kelland LONDON | Thu Feb 17, 2011 7:11pm EST Pushing limits can help chronic fatigue patients (Reuters) - Helping chronic fatigue syndrome patients to push their limits and try to overcome the condition produces a better rate of recovery than getting them to accept the illness and adapt to a limited life, new research has found. British researchers conducted the largest trial to date of people with the mysterious and debilitating condition, also known as ME, and found that up to 60 percent of patients improved if therapists encouraged them gradually to do more. By contrast, patients whose therapists encouraged them to accept the limits of their illness and adapt their lifestyles to live with it showed significantly less improvement when they were followed up after 24 and 52 weeks. Chronic fatigue syndrome (CFS) is a long-term debilitating condition of disabling physical and mental fatigue, poor concentration and memory, disturbed sleep and muscle and joint pain. It also known as myalgic encephalomyelitis (ME) and affects around 17 million people worldwide. There is no cure for CSF/ME and scientists don't know what causes it. Many sufferers say they think their illness started after a viral infection, but suggested links to a virus known as XMRV were shown in a recent scientific paper to have been based on contaminated samples in a lab. There is also controversy about what kinds of treatments should be given, with some patients reluctant to accept that psychotherapies might help. Some patient groups in Britain, where more than a quarter of a million people are estimated to have CFS/ME, have expressed concern that treatments like cognitive behavior therapy (CBT) that encourage patients to try to overcome or push the limits of their condition may even be harmful. But in this study, which involved 640 patients in Britain, researchers found that CBT and another therapy called gradual exercise therapy (GET) were far more successful

than adaptive pacing therapy (APT), in which the patient tries only to match activity levels to the amount of energy they have. "It is very encouraging that we have found not one but two treatments that are similarly helpful to patients," said Trudie Chalder from King's College London, who worked on the study and published its findings in the Lancet medical journal on Friday. All patients in the trial received specialist medical care which included advice about managing the illness and prescribed medicines for symptoms such as insomnia and pain. The success of the added therapies was measured by patient ratings of fatigue, physical function, overall health and the ability to lead a normal life, plus tests of how far the patient could walk in six minutes, and of sleep, mood and fatigue levels after exertion. The results showed that CBT and GET benefited up to 60 percent of patients, and around 30 percent of patients in each of these treatment groups said their energy levels and ability to function and returned to near normal levels. External experts commenting on the study said its design was robust and its findings important. "This study..matters a lot. CFS/ME is common, and causes a lot of suffering," said Professor Willie Hamilton of Britain's Peninsula College of Medicine and Dentistry. "I now know what to suggest to my patients." (Reporting by Kate Kelland, editing by Paul Casciato)

DAILY EXPRESS
http://www.express.co.uk/posts/view/229817

TRIAL OFFERS HOPE FOR ME SUFFERERS

ME sufferers have been offered new hope following a landmark study which suggests the condition can be reversed with counselling and exercise. Researchers have now identified two forms of treatment for chronic fatigue syndrome (CFS), both of which could help thousands of patients. The ground-breaking study is the most comprehensive to date and challenges the widely accepted belief that the illness cannot be cured. Scientists, who spent eight years on the research, believe it could herald a new dawn for the treatment of ME. They hope their findings will dispel the notion that nothing 2

can be done for those living with the condition in the UK - a figure which currently stands at around a quarter of a million. Researchers found six in 10 patients reported significant improvements after undergoing either cognitive behavioural therapy (CBT) - a type of counselling which helps people take charge of issues, while encouraging them to increase their activity or graded exercise therapy (GET), which is based on gradually increasing exercise. Half of these people reported a return to "normal" energy levels. However, the study showed one of the most common CFS treatments has no definitive medical benefit. Adaptive pacing therapy (APT), which teaches patients to match their activity level to the amount of energy they have, does little more than help sufferers manage their illness, the study showed. Though it has been widely advocated, the therapy has never before been scientifically tested. Michael Sharpe, Professor of Psychological Medicine at the University of Edinburgh and co-author of the report, said scientists had achieved a significant "milestone" by proving GET and CBT were both effective and safe. Read more: http://www.express.co.uk/posts/view/229817Trial-offers-hope-for-MEsufferers#ixzz1HXxQiBDX

BBC
http://www.bbc.co.uk/news/health-12493009

Brain and body training treats ME, UK study says

Cognitive Behavioural and Graded Exercise therapies most successful for ME Chronic Fatigue Syndrome, also known as ME, should be treated with a form of behavioural therapy or exercise, say British scientists. Writing in The Lancet, they argue that the approach preferred by some charities, managing energy levels, is less successful. Action for ME disputed the claims, which it said were exaggerated. A quarter of a million people in the UK have the condition, yet its cause remains unknown. Symptoms include severe tiredness, poor concentration and memory, muscle and joint pain and disturbed sleep.

This study looked at which treatments were the most successful. It compared CBT (cognitive behavioural therapy - changing how people think and act), graded exercise therapy - gradually increasing the amount of exercise, and adaptive pacing therapy planning activity to avoid fatigue. All of the 641 people who took part in the study had chronic fatigue syndrome, but were not bed-bound. The authors say cognitive behavioural and graded exercise therapies were the most successful, both at reducing fatigue and increasing physical function. This study matters, it matters a lot. Professor Willie Hamilton, Peninsula College of Medicine and Dentistry With cognitive behavioural therapy, 30% of patients returned to normal levels of fatigue and physical function. They say that adaptive pacing therapy is little better than basic medical advice. Professor Michael Sharpe, co-author of the study from the University of Edinburgh, said: "One of the difficulties in the field is ambiguity, what is the cause and most importantly, what is the treatment? "The evidence up to now has remained controversial. The helpful thing about this trial is that it actually gives pretty clear cut evidence about effectiveness and safety." Exaggerated But the charity Action for ME said the conclusions were exaggerated and questioned the safety of graded exercise therapy. Its CEO, Sir Peter Spencer, said: "The findings contradict the considerable evidence of our own surveys. "Of the 2,763 people with ME who took part in our 2008 survey, 82% found pacing helpful, compared with 50% for cognitive behavioural therapy and 45% for graded exercise therapy. "Worryingly, 34% reported that graded exercise therapy made them worse." The authors suggest that poor advice, such as suggestions to just go to the gym, could be responsible for bad experiences with the exercise therapy. They said that the amount of exercise needed to be tailored to each person. The Association of Young People with ME welcomed the findings. It said it hoped that fears about graded exercise and CBT were laid to rest, and that the study needed to be repeated in children. Professor Willie Hamilton, GP and professor of primary care diagnostics at Peninsula College of Medicine and Dentistry, said: "This study matters, it matters a lot.

"Up until now we have known only that CBT and graded exercise therapy work for some people. We didn't know if pacing worked. This caused a real dilemma, especially for those in primary care. We didn't know whether to recommend pacing, or to refer for CBT or GET. "Worse still, not all GPs have access to CBT or GET, so ended up suggesting pacing almost by default. This study should solve that dilemma." NICE (the National Institute for Health and Clinical Excellence) said the findings were in line with current recommendations. Dr Fergus Macbeth, director of the centre for clinical practice at NICE, said: "We will now analyse the results of this important trial in more detail before making a final decision on whether there is a clinical need to update our guideline."

DAILY MAIL
http://www.dailymail.co.uk/health/article1358269/Chronic-fatigue-syndrome-MEpatients-exercise-best-hope-recovery-findsstudy.html#ixzz1HXo9GehT

Got ME? Fatigued patients who go out and exercise have best hope of recovery, finds study
By DAILY MAIL REPORTERS Last updated at 11:32 AM on 18th February 2011

It may seem counter-intuitive to patients suffering with fatigue, but scientists have found encouraging people with ME to push themselves to their limits gives the best hope of recovery. British researchers conducted the largest trial to date of people with the mysterious and debilitating condition and found that up to 60 per cent of patients improved if therapists encouraged them gradually to do more. ME is a condition that causes long-term disabling physical and mental fatigue By contrast, patients whose therapists encouraged them to accept the limits of their illness and adapt their lifestyles to live with it showed significantly less improvement when they were followed up after 24 and 52 weeks. Chronic fatigue syndrome (CFS) is a long-term debilitating condition of disabling physical and mental fatigue, poor concentration and memory, disturbed sleep and muscle and joint pain.

It also known as myalgic encephalomyelitis (ME) and affects around 17million people worldwide. There is currently no cure for it and scientists don't know the cause. Many sufferers say they think their illness started after a viral infection, but suggested links to a virus known as XMRV were shown in a recent scientific paper to have been based on contaminated samples in a lab. There is also controversy about what kinds of treatments should be given, with some patients reluctant to accept that psychotherapies might help. Some patient groups in Britain, where more than a quarter of a million people are estimated to have the condition are concerned that such treatments may even be harmful. But in this study, which involved 640 patients in Britain, researchers found that CBT and another therapy called gradual exercise therapy (GET) were far more successful than adaptive pacing therapy (APT), in which the patient tries only to match activity levels to the amount of energy they have. 'It is very encouraging that we have found not one but two treatments that are similarly helpful to patients,' said Trudie Chalder from King's College London, who worked on the study and published its findings in the Lancet medical journal today. All patients in the trial received specialist medical care which included advice about managing the illness and prescribed medicines for symptoms such as insomnia and pain. The success of the added therapies was measured by patient ratings of fatigue, physical function, overall health and the ability to lead a normal life, plus tests of how far the patient could walk in six minutes, and of sleep, mood and fatigue levels after exertion. The results showed that CBT and GET benefited up to 60 per cent of patients, and around 30 per cent of patients in each of these treatment groups said their energy levels and ability to function and returned to near normal levels. External experts commenting on the study said its design was robust and its findings important. 'This study... matters a lot. CFS/ME is common, and causes a lot of suffering,' said Professor Willie Hamilton of Britain's Peninsula College of Medicine and Dentistry. 'I now know what to suggest to my patients.'

SCOTSMAN
http://news.scotsman.com/health/ME-sufferers-given-hope-as.6720159.jp

ME sufferers given hope as Scottish team leads way to new therapy

Published Date: 18 February 2011 By Katie Hodge ME SUFFERERS have been offered hope following a study which suggests the condition can be reversed with counselling and exercise. Researchers in Scotland have identified two forms of treatment for chronic fatigue syndrome (CFS), both of which could help thousands of patients. The study is the most comprehensive to date and challenges the belief that the illness cannot be cured. Scientists, who spent eight years on the research, believe it could herald a new dawn for the treatment of ME. They hope their findings will dispel the notion that nothing can be done for the quarter of a million people living with the condition in the UK. Researchers found six in 10 patients reported significant improvements after undergoing either cognitive behavioural therapy (CBT) - counselling which helps people take charge of issues, while encouraging them to increase their activity - or graded exercise therapy (GET), which is based on gradually increasing exercise. Half of these people reported a return to "normal" energy levels. However, the study showed one of the most common CFS treatments has no definitive medical benefit. Adaptive pacing therapy (APT), which teaches patients to match their activity level to the amount of energy they have, does little more than help sufferers manage their illness, the study showed. Though it has been widely advocated, the therapy has never before been scientifically tested. Michael Sharpe, Professor of Psychological Medicine at the University of Edinburgh and co-author of the report, said scientists had achieved a significant "milestone" by proving GET and CBT were both effective and safe. "This trial has clarified that picture, finding both GET and CBT have substantial beneficial effects and they are safe if delivered properly." Meanwhile, the trial found that while APT patients claimed to be satisfied with their treatment, it ultimately failed to reduce fatigue. Some 640 adults with CFS from England and Scotland took part in the year-long trial. The findings are published in The Lancet today.

Trudie Chalder, professor of Cognitive Behavioural Psychotherapy at King's College London and a co-author of the study, said: "It is very encouraging that we have found not one but two treatments that are similarly helpful to patients, which provides them with a choice. "We now need to find out what the common essential ingredient is that makes these treatments work, and which particular types of patients will respond best to which therapy." The trial was led by researchers from Queen Mary, University of London, King's College London and the University of Edinburgh. ME (myalgic encephalomyelitis), or CFS, causes debilitating tiredness and symptoms can include poor concentration, disturbed sleep and muscle and joint pain. Its cause is unknown.

THE INDEPENDENT
http://www.independent.co.uk/life-style/health-and-families/health-news/got-me-just-get-out-andexercise-say-scientists-2218377.html

Got ME? Just get out and exercise, say scientists

By Jeremy Laurance, Health Editor Friday, 18 February 2011SHARE PRINTEMAILTEXT SIZE NORMALLARGEEXTRA LARGE

The UK's largest study of treatments for chronic fatigue syndrome has provided the first definitive evidence of what helps those who suffer from the disabling condition that affects 250,000 people in the UK. The best therapies are those which help patients test the limits of their capacity, such as by gradually increasing the amount of exercise they take, the research shows. Therapy aimed at helping patients live within the limits of their capacity, by balancing rest and activity, is much less effective. But patients' support groups angrily rejected the findings yesterday, saying they were "surprised and disappointed" by the "simplistic" results. The attempt to settle the argument over the most effective treatment for chronic fatigue syndrome (CFS) also called Myalgic Encephalomyelitis (ME) was never going to be easy. It is marked by poor memory and concentration, disturbed sleep, aches and pains and disabling fatigue. It can last for years and controversy has raged for decades over the best treatments.

Now researchers from London and Edinburgh who monitored 640 severely affected adults for a year have concluded that cognitive behaviour therapy (CBT), in which patients are helped to think about and test how they can do more, and graded exercise therapy (GET), in which they are helped gradually to overcome the limits imposed by the illness, are the most effective treatments. In contrast, helping sufferers live within their limits, called Adaptive Pacing Therapy (APT), was much less helpful. Overall, 60 per cent of patients who received CBT or GET made progress and 30 per cent recovered sufficiently to resume normal lives. Among those who received APT, half as many (15 per cent) resumed normal lives. Fewer than one in ten patients left untreated recover, the researchers said. Michael Sharpe, professor of psychological medicine at the University of Edinburgh, and co-author of the report, said: "This is a useful effect for a substantial proportion of those affected, but it is not a solution to the illness." The findings, published in The Lancet, were hailed by experts in chronic fatigue as "very significant." Derrick Wade, professor of neurological enablement at the Oxford Centre for Enablement said: "This means we can allocate resources to treatments that will benefit patients and stop allocating resources to treatments that will not." However, Sir Peter Spencer, chief executive of Action for ME, said its own survey showed 82 per cent of respondents found pacing therapy helpful and a third said graded exercise made them worse. The ME Association said the findings were based on an outmoded model of the illness. "Deconditioning due to fear of activity is not the cause of the debilitating fatigue," it said.

THE GUARDIAN
http://www.guardian.co.uk/society/2011/feb/18/study-exercise-therapy-me-treatment

Study finds therapy and exercise best for ME

Chronic fatigue syndrome study finds more people recover if they are helped to try to do more than they think they can The biggest-ever study of treatments for ME, also known as chronic fatigue syndrome, has found that more people recover if they are helped to try to do more than they think they can rather than adapting to a life of limited activity. The findings of the study, published in the Lancet, are clear, but attracted immediate controversy. One of the biggest

patient groups, Action for ME, said it was surprised and disappointed, while others denounced the trial in its entirety. The strongest opposition comes from patient groups who believe there is a conspiracy by the psychiatric establishment to brand ME/CFS "all in the mind" a mental illness that will respond to psychological therapies. They insist it is a physical disease, which probably has a viral cause. The claim last year from US researchers that a viral trigger had been found caused enormous excitement, and many refuse to believe the subsequent studies that concluded lab contamination was to blame. Doctors involved in the new trial say they are looking only at treating the symptoms, not the cause. Their aim, they say, is to help the many people they see who are unable to go shopping, see friends or do ordinary active things. In about 25% of cases, sufferers including young people and children are unable to leave the house. The symptoms include exhaustion, poor concentration, memory problems, disturbed sleep, and joint and muscle pains. The trial, known as PACE and funded by the Medical Research Council together with the Department of Health, involved 641 patients across the country. It compared six months of four different treatments. The participants were followed up for a year. It found that patients showed more improvement and a small minority recovered completely after cognitive behaviour therapy (CBT), one of the so-called psychological "talking therapies", or graded exercise therapy (GET), where the patient is encouraged gradually to become more active, walking further and increasing the amount they do in a day. Surveys have shown a preference for care and advice from a specialist in ME/CFS or "adaptive pacing therapy". Pacing involves rest and restricting activity to those things the patient feels they can cope with. In the trial, patients had access to a specialist, but fewer improved with specialist care alone or pacing therapy. Although the numbers who recovered were small, Trudie Chalder, professor of cognitive behavioural psychotherapy at King's College, London, said that "twice as many people on graded exercise therapy and cognitive behaviour therapy got back to normal" compared with those in the other two treatment groups. Those on CBT and GET generally had less fatigue and were more physically active than the other patients at the end of the year. Another author, Professor Peter White from Barts and the London school of medicine and dentistry, said: "While there is still room for improvement, this is a real step forward in informing patients with CFS/ME which treatments can help to improve their health and ability to lead a more normal life. "The Association of Young People with ME welcomed the findings and said it hoped it would begin to lay to rest fears about graded exercise therapy and CBT being harmful. It called for the study to be replicated in children. Mary-Jane Willows, AYME's chief executive, said: "These treatments should be made available to all patients by those who are trained and experienced in dealing with CFS/ME." She added that there was "an urgent need" to find a way to include house-bound patients in a trial. Participants in the study had to be able to get to hospital.

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But the largest patient group, Action for ME, which had been involved in developing the trial, rejected its findings. Sir Peter Spencer, its chief executive, said: "The findings of the PACE trial contradict the considerable evidence of our own surveys and those of other patient groups. "Of the 2,763 people with ME who took part in our 2008 survey, 82% found pacing helpful, compared with 50% for CBT and 45% for GET. Worryingly, 34% reported that GET made them worse." But one of the trial participants, a 27-year-old man from Northamptonshire, said the trial had changed his life. "It's like night and day," he said. "I owe so much to the trial, it's unbelievable." He had ME for 13 years. "It affected my schooling quite badly. I left without any GCSEs. I was quite isolated." He could go out only with careful planning and got no support from his GP. He now has a full-time job and his employer has no idea he ever had ME.

DAILY RECORD
http://www.dailyrecord.co.uk/news/health-news/2011/02/18/exercise-and-therapy-can-reverse-effects-ofme-86908-22931725/

Exercise and therapy can reverse effects of ME

Feb 18 2011

CHRONIC fatigue syndrome can be reversed with counselling and exercise, a new study claims. Researchers have identified two forms of treatment for the debilitating condition, also known as ME. The study, led by a team in Edinburgh University, gives hope to the 250,000 sufferers who have to live with the illness in the UK. Symptoms include severe tiredness, poor concentration and memory, disturbed sleep and muscle and joint pain. Researchers used cognitive behavioural therapy - counselling to helps sufferers take charge of issues while encouraging activity - or graded exercise therapy, which is based on gradually increasing exercise. Six in 10 patients reported significant improvements, with half reporting a return to normal energy levels. Scientists, who spent eight years on the research, believe it could herald a new dawn for treatment. In journal The Lancet, report co-author Professor Michael Sharpe said: "Previously, it has been thought that these treatments could harm patients and there was a very confused picture. "This trial has found both have substantial beneficial effects and they are safe if delivered properly."

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DAILY STAR
http://www.dailystar.co.uk/posts/view/177405/Trial-offers-hope-for-ME-sufferers/

TRIAL OFFERS HOPE FOR ME SUFFERERS

ME sufferers have been offered new hope following a landmark study which suggests the condition can be reversed with counselling and exercise. Researchers have now identified two forms of treatment for chronic fatigue syndrome (CFS), both of which could help thousands of patients. The ground-breaking study is the most comprehensive to date and challenges the widely accepted belief that the illness cannot be cured. Scientists, who spent eight years on the research, believe it could herald a new dawn for the treatment of ME. They hope their findings will dispel the notion that nothing can be done for those living with the condition in the UK - a figure which currently stands at around a quarter of a million. Researchers found six in 10 patients reported significant improvements after undergoing either cognitive behavioural therapy (CBT) - a type of counselling which helps people take charge of issues, while encouraging them to increase their activity or graded exercise therapy (GET), which is based on gradually increasing exercise. Half of these people reported a return to "normal" energy levels. However, the study showed one of the most common CFS treatments has no definitive medical benefit. Adaptive pacing therapy (APT), which teaches patients to match their activity level to the amount of energy they have, does little more than help sufferers manage their illness, the study showed. Though it has been widely advocated, the therapy has never before been scientifically tested. Michael Sharpe, Professor of Psychological Medicine at the University of Edinburgh and co-author of the report, said scientists had achieved a significant "milestone" by proving GET and CBT were both effective and safe. "Previously it has been thought that these treatments could harm patients and there was a very confused picture," he said. "This trial has clarified that picture, finding both GET and CBT have substantial beneficial effects and they are safe if delivered properly." Some 640 adults with CFS from England and Scotland took part in the year-long trial.

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EurekAlert
http://www.eurekalert.org/pub_releases/2011-02/l-tst021811.php

Public release date: 18-Feb-2011 Contact: UK Medical Research Council Press Office Press.office@headoffice.mrc.ac.uk 44-207-395-2345 Lancet Trial shows that cognitive behavioral therapy and graded exercise therapy are safe and effective treatments for chronic fatigue syndrome Despite previous evidence that both cognitive behavioural therapy (CBT) and graded exercise therapy (GET) can be effective treatments for chronic fatigue syndrome (CFS), some patients' organisations have reported that these treatments can be harmful and instead prefer pacing and specialist medical care (SMC). The PACE trial, published Online First and in an upcoming Lancet, shows that while CBT and GET have positive effects on CFS when combined with SMC as compared to SFC alone, adaptive pacing therapy (APT) with SMC is no more effective than SMC alone. The Article is by Profs Peter White (Barts and The London School of Medicine, UK), Trudie Chalder (King's College London, UK), Michael Sharpe (University of Edinburgh, UK) and colleagues. The trial is funded by the UK Medical Research Council and various departments of UK governments. CFS, sometimes called Myalgic Encephalomyelitis (ME), is a long-term, complex and debilitating condition that causes fatigue and other symptoms such as poor concentration and memory, disturbed sleep, and muscle and joint pain. The cause of the condition affecting some 250,000 people in the UK aloneis unknown. SMC consists of advice about CFS, including avoidance of activity extremes, and rest and self-help strategies. APT is based on the theory that CFS is an irreversible condition that leaves patients with a limited amount of energy, and that individuals adapt their lives to this available energy through use of a daily diary. CBT is based on the premise that cognitive responses (fear of engaging in activity) and behavioural responses (avoidance of activity) are linked and interact with physiological processes to perpetuate fatigue. GET helps a CFS patient gradually step up their level of physical activity to counter the deconditioning that has set in as their activity has fallen. Walking is a popular choice for this. In PACE, 640 patients were assigned to one of SMC alone (160 patients), SMC/CBT (161), SMC/GET (160) and SMC/APT (159). After a follow-up of one year, mean fatigue and physical function scores had improved more after CBT and GET than after both APT and SMC alone. Serious adverse reactions to treatment were recorded in two APT patients (1%), three CBT patients (2%), two (1%) GET patients, and two (1%) in the SMC-only group. The group plans to report in the near future on cost-effectiveness of these various treatments, and say that since even CBT and GET only offer a moderate improvement in symptoms, research into new effective treatments must go on. The authors conclude: "We affirm that cognitive behaviour therapy and graded exercise therapy are moderately effective outpatient treatments for chronic fatigue syndrome when added to specialist medical care, as compared with adaptive pacing therapy or specialist medical care alone. Findings from PACE also allow the following interpretations: adaptive pacing therapy added to specialist medical care is no more effective than specialist medical care alone; our findings apply to patients with

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differently defined chronic fatigue syndrome and myalgic encephalomyelitis (ME) whose main symptom is fatigue; and all four treatments tested are safe." In a linked Comment, Dr Gijs Bleijenberg, and Dr Hans Knoop, Expert Centre for Chronic Fatigue, Radboud University Nijmegen Medical Centre, Netherlands, say: "The central role of cognition in relation to fatigue might explain why graded exercise therapy is effective and adaptive pacing therapy is not." They note that in adaptive pacing patients learn to focus on the fatigue in order to stop "in time", which does not seem to help, while in graded exercise patients learn that they are able to do more than they thought possible. They conclude: "Remarkably in this context, confidence in the treatment at the start is substantially lower with cognitive behaviour therapy than it is with adaptive pacing therapy. Despite lowered confidence in cognitive behaviour therapy, this therapy is more effective than is adaptive pacing therapy. Patient's confidence in treatment can only change if a change in abilities is perceived, which generally seems to happen in cognitive behaviour therapy." ###
For the authors of this study please contact UK Medical Research Council Press Office. T) +44 (0) 20 7395 2345 E) Press.office@headoffice.mrc.ac.uk Dr Hans Knoop, Expert Centre for Chronic Fatigue, Radboud University Nijmegen Medical Centre, Netherlands. T) +31 243610042 / +31 6 28925677 E)J.Knoop@nkcv.umcn.nl Dr Gijs Bleijenberg, Expert Centre for Chronic Fatigue, Radboud University Nijmegen Medical Centre, Netherlands. T) +31 243610042 / +31 6 81786918 E)G.Bleijenberg@nkcv.umcn.nl NOTE: THE ABOVE LINK IS FOR JOURNALISTS ONLY; IF YOU WISH TO PROVIDE A LINK TO THE FREE ABSTRACT OF THIS PAPER FOR YOUR READERS, PLEASE USE THE FOLLOWING, WHICH WILL GO LIVE AT THE TIME THE EMBARGO LIFTS: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60172-4/abstract

The Lancet
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60172-4/fulltext? _eventId=login The Lancet, Volume 377, Issue 9768, Pages 786 - 788, 5 March 2011 doi:10.1016/S0140-6736(11)60172-4 Published Online: 18 February 2011 Chronic fatigue syndrome: where to PACE from here? Gijs Bleijenberg Hans Knoop In The Lancet, Peter White and colleagues1 report the four-group PACE randomised trial in adults with chronic fatigue syndrome. PACE stands for Pacing, graded Activity, and Cognitive behaviour therapy: a randomised Evaluation. The investigators report the efficacy of three behaviour interventions and specialist medical care. The Article provides a useful panel to summarise the interventions. PACE tested the safety of the interventions. Concerns about the safety of cognitive behaviour therapy and graded exercise therapy have been raised more than once by patients' advocacy groups. Few patients receiving cognitive behaviour therapy or graded exercise therapy in the PACE trial had serious adverse reactions and no more than those receiving adaptive pacing therapy or standard medical care, which for cognitive behavioural therapy has already been shown.2 This finding is important and should be communicated to patients to dispel unnecessary concerns about the possible detrimental effects of cognitive behaviour therapy and graded exercise therapy, which will hopefully be a useful reminder of the potential positive effects of both interventions.

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Another important aspect of PACE (the largest randomised trial of cognitive behaviour therapy and graded exercise therapy to date) is that the efficacy of both interventions was compared with another therapy and specialist medical care alone. Also, for the first time, adaptive pacing therapy was empirically tested. Both graded exercise therapy and cognitive behaviour therapy assume that recovery from chronic fatigue syndrome is possible and convey this hope more or less explicitly to patients. Adaptive pacing therapy emphasises that chronic fatigue syndrome is a chronic condition, to which the patient has to adapt. Although PACE was not intended to compare cognitive behaviour therapy and graded exercise therapy with each other, there was actually no difference between the two. Both were more effective than adaptive pacing. Graded exercise therapy and cognitive behaviour therapy might assume that recovery from chronic fatigue syndrome is possible, but have patients recovered after treatment? The answer depends on one's definition of recovery.3 PACE used a strict criterion for recovery: a score on both fatigue and physical function within the range of the mean plus (or minus) one standard deviation of a healthy person's score. In accordance with this criterion, the recovery rate of cognitive behaviour therapy and graded exercise therapy was about 30%although not very high, the rate is significantly higher than that with both other interventions. Although the PACE trial shows that recovery from chronic fatigue syndrome is possible, there is clearly room for improvement with both interventions (cognitive behaviour therapy and graded exercise therapy). Both interventions could be improved if more was known about the mechanisms of change. These mechanisms could differ between the interventions, but we think this is unlikely. The rationale behind graded exercise therapy is that increasing the level of physical activity and fitness will cause symptoms to be reduced. The basis of cognitive behaviour therapy is described in PACE as the fear-avoidance theory. There is little empirical support for these proposed mechanisms of change. Mediation analysis of a randomised trial4 which tested the efficacy of graded exercise therapy for chronic fatigue syndrome showed that a decrease in symptom focusing, rather than an increase in fitness, mediated the reduction in fatigue. Wiborg and colleagues5 have shown that the effect of cognitive behaviour therapy on fatigue in chronic fatigue syndrome is not mediated by a persistent increase in physical activity. We noted that a decrease in focus on fatigue mediated the effect of cognitive behaviour therapy on fatigue and impairments in patients with the syndrome.6 Similarly, we have shown that higher levels of perceived activity and an increased sense of control over symptoms contribute to the treatment effect. The central role of cognition in relation to fatigue might explain why graded exercise therapy is effective and adaptive pacing therapy is not. Both treatments aim to increase activity, but the activity-related cognition is probably different in adaptive pacing therapyI have to focus on how fatigued I am in order to stop in time, I can't do more, I have to stopfrom that in graded exercise therapyI am able to do more than I thought I could (ie, less focused). Remarkably in this context, confidence in the treatment at the start is substantially lower with cognitive behaviour therapy than it is with adaptive pacing therapy. Despite lowered confidence in cognitive behaviour therapy, this therapy is more effective than is adaptive pacing therapy. Patient's confidence in treatment can only change if a change in abilities is perceived, which generally seems to happen in cognitive behaviour therapy.

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Future studies into mechanisms of change are urgently needed and could help to improve the efficacy of the interventions, by focusing on the elements that are crucial for change. We have received funding from The Netherlands Organisation for Health Research and Development, the Dutch Cancer Society, the Dutch MS Research fund, and the Princess Beatrix Foundation.

Science Media Centre PRESS RELEASE

http://www.sciencemediacentre.org/pages/press_releases/11-02-17_cfsme_trial.htm

Expert reaction to Lancet study looking at treatments for Chronic Fatigue Syndrome/ME The study made the first definitive comparison of various treatments for CFS/ME to deduce the most effective treatments.
17 February 2011 Dr Alastair Miller, Consultant Physician at Royal Liverpool University Hospital, Clinical lead for CFS services in Liverpool, Independent assessor of trial safety data for PACE trial and Principal Medical Advisor, Action for ME, said: "Although NICE have previously recommended graded exercise and CBT as treatments for ME/CFS, this was on the basis of somewhat limited evidence in the form of fairly small clinical trials. This trial represents the highest grade of clinical evidence a large randomized clinical trial, carefully designed, rigorously conducted and scrupulously analysed and reported. It provides convincing evidence that GET and CBT are safe and effective and should be widely available for our patients with CFS/ME. "It is clearly vital to continue our research into biological mechanisms for ME/CFS but recent 'false dawns' for example, over the role of retroviruses (XMRV) have shown how difficult this can be. In the current absence of a biomedical model for the causation and the absence of any pharmacological intervention, we have a pragmatic approach to therapy that works and we should use it." Dr Derick Wade, Consultant and Professor in Neurological Rehabilitation and Clinical Director, Enablement Directorate, Oxford Centre for Enablement, said: "CFS is common, and it is vital to know whether treatments proposed and/or used are safe and are effective. Randomised controlled trials provide the best and only reliable evidence on safety and effectiveness of any intervention in any condition. The trial design in this study was very good, and means that the conclusions drawn can be drawn with confidence. "This is a very significant finding. It identifies that one commonly used intervention is not effective (and therefore should not be used), and it confirms the effectiveness of 16

two treatments, and their safety. The study suggests that everyone with the condition should be offered the treatment, and every patient who wishes to be helped should be willing to try one or both of the treatments. It also means that we can allocate resources to treatments that will benefit patients and, more importantly, stop allocating treatments that do not have proven efficiency. Further research should identify ways that treatments derived from these may deliver greater benefits. "Research needs to investigate both treatments and factors that increase the risk of developing CFS. However, it is probably more effective to research treatments, and proving a treatment is effective starts to give clues about causative factors." Dr Fergus Macbeth, Director of the Centre for Clinical Practice at NICE, said: "We welcome the findings of the PACE trial, which further support cognitive behavioural therapy and graded exercise therapy as safe and effective treatment options for people who have mild or moderate CFS/ME. These findings are in line with our current recommendations on the management of this condition. "We will now analyse the results of this important trial in more detail before making a final decision on whether there is a clinical need to update our guideline. Until then, healthcare professionals should continue to follow our existing recommendations, especially as this latest research appears to endorse them as best practice for the NHS." Dr Esther Crawley, Consultant Paediatrician and Clinical Lead for the Bath Specialist Paediatrics Chronic Fatigue Syndrome/ME Service, said: "All children with chronic fatigue syndrome and their parents are desperate for new research to understand how to treat this condition. The next step is to do a study like this for children to find out if these treatments work." Prof Willie Hamilton, GP in Exeter and Professor of Primary Care Diagnostics, Peninsula College of Medicine and Dentistry, said: "At least half of patients improved with CBT or GET. The study also allays fears that CBT or GET may be harmful. There are a minority of patients who didn't see improvement so the next step must try and find treatments to help them. "This study matters: it matters a lot. CFS/ME is common, and causes a lot of suffering. Up until now we have known only that CBT and GET work for some people. We didn't know if pacing worked. This caused a real dilemma - especially for those in primary care. We didn't know whether to recommend pacing, or to refer for CBT or GET. Worse still, not all GPs have access to CBT or GET, so ended up suggesting pacing almost by default. This study should solve that dilemma. "At a patient level, I now know what to suggest to my patients. Almost as important, it sends a powerful message to PCTs - and the soon-to-be-formed GP consortia - that they must fund CBT or GET. NICE proposed that before this study came out - the evidence is even stronger now."

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Dr Brian John Angus, Clinical Tutor in Medicine and Honorary Consultant Physician, University of Oxford and Centre Leader for the PACE Trial in Oxford, said: "This study is the largest ever done in CFS/ME and as such is critically important. The study should reassure patients that there is an evidence based treatment that can help them to get better and there is no need to worry about harm from the treatment. The other significant result is that looking at different ways of classifying the condition through different diagnostic criteria do not make any difference to the effect of treatments. "We do not know what the underlying cause of CFS/ME is. There is ongoing research to find the cause, and I have been involved with this, but none of these studies has shown any consistent evidence of cause never mind any rationale for treatment. However in the meantime I see many patients in my clinic who need help with their fatigue. This was a pragmatic trial to help patients while there is no other treatment available. "It was extremely rigorous. It was large and it was randomised. The study was carefully conducted in the manner of a drug intervention study to not only establish the superiority of one treatment over the other but also to carefully report any side effects or harm from those treatments. Since the treatments were therapies and not drugs stringent efforts were made to ensure the 'purity' of each treatment and to rapidly report any adverse effects. As a trial this involved a huge amount of checking and cross checking. "This should mean that GET and CBT should be widely available throughout the country. Despite NICE recommendations I still see patients who are unable to access any treatment for their CFS/ME in their local GP area. Travelling is obviously difficult for patients with CFS/ME. The increase in the availability of CBT therapists for other conditions should be mirrored for CFS/ME. "The trial was conducted to a high ethical standard. Patients were fully informed and randomised to the different treatments. It was rigorously performed. The study has definitively shown that there is no harm associated with GET."

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