GETSET - Graded Exercise Therapy guided Self-hElp Treatment (GETSET)

BurnA

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If you compare the details of SMC (which are practically non-existent) in the protocol, with the plentiful details of GES, for which there is considerable input from a therapist, it's very clear that SMC is not an adequate control and that the trial is biased in favour of a positive response rate for the patients receiving GES. Not to mention the post-hockery of the entire protocol.
What about the fact that every patient on "SMC" will recieve completely different treatment to the next patient.
 

Bob

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@charles shepherd, i thought you might like to know that the ME Association survey is briefly mentioned in the GETSET protocol...
Trial Protocol said:
The PACE trial (pacing, graded activity, and cognitive behavior therapy: a randomized evaluation) is the largest ever trial testing GET and CBT for CFS with 641 secondary care patients recruited [10]. Specialist medical care (SMC) alone was compared with SMC plus one of three therapies (adaptive pacing therapy, CBT, or GET). GET was found to be an effective and safe treatment, with 82% being satisfied with GET [11]. In contrast to this research, surveys of ME charity members have suggested that GET is perceived as a harmful and unacceptable treatment. In a recent survey, 56% of those who had received GET reported feeling “worse” afterwards, with 53% reporting GET to be unacceptable [12].
 

Bob

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Blinding/open label...
Trial Protocol said:
Blinding to Outcome Measures
The members of the Trial Steering Committee (TSC), the DMEC, and the trial statistician will be blinded to treatment allocation. The trial manager (TM) and physiotherapists will not be blind to allocation, as they will inform participants of their allocation and deliver the intervention. To further minimize observer bias, outcomes will be self-rated by the participant, and outcome assessments will be coordinated by the TM. The trial statistician will be masked to treatment group until after the main analysis is completed.
 

Bob

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Unplanned changes to primary outcome...
Trial Protocol said:
Primary Outcomes
We initially planned to use the SF-36 PF as the primary outcome analyzed as an interval variable collected at 12-weeks postrandomization. The SF-36 PF is scored as the sum of responses to 10 items related to functioning on everyday activities from getting dressed to performing physical activities, each of which is coded 0 for “Yes, limited a lot,” 5 for “Yes, limited a little” and 10 for “No, not limited at all”. This yields a score ranging from 100 for the highest level of perceived physical functioning to 0 for being unable to bathe or dress oneself. The SF-36 PF was to be the sole primary outcome as we were primarily interested in change in physical function.

However, during recruitment we noticed that a significant minority of participants scored close to the mean of the general population (ie, normal physical function) so could be considered recovered even before any intervention [43]. This is because they had substantial reductions in functioning in other domains, such as mental or social activity levels [7].

We therefore added a second primary outcome, the CFQ, which is scored as the sum of responses to 11 items related to physical and mental fatigue, each of which is coded 0 for less than usual,” 1 for “no more than usual,” 2 for “more than usual” and 3 for “much more than usual,” where usual is how they felt the last time they were feeling well. This gives us a symptomatic measure of fatigue. The two primary outcome variables are valid and reliable and have been used in previous CFS trials [9,11]. The ethics committee, Research and Development (R & D), and the trial steering and data monitoring committees approved this change (in June 2013) before any outcome data were formally examined. Because of the change from one to two primary outcomes, we reanalyzed our power calculation and plan to recruit more participants (see section on sample size).

The main secondary outcome measure will be the validated self-rated CGI score, which we will use to measure both change in “CFS” and change in “general health” at the end of treatment, compared with baseline. Each will have 7 possible scores from "very much worse" (score of 7) to "very much better" (score of 1)[39]. Both safety and efficacy can be recorded with this item; we will count scores of 1 and 2 (“very much” and “much” better) as positive outcomes, and scores of 6 and 7 (“very much” and “much” worse) as negative outcomes. Scores of 3-5 (“a little” better, no change, and “a little” worse) will be regarded as no change.
 

Bob

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Trial Protocol said:
Compliance
The trial will be conducted in compliance with the Declaration of Helsinki, the trial protocol, Medical Research Council Good Clinical Practice (GCP) guidance, the Data Protection Act (1998), the Multi-centre Research Ethics Committee (MREC), and Local Research Ethics Committees (LREC) approvals and other regulatory requirements, as appropriate. The final trial publication will include all items recommended under CONSORT [49].
 

user9876

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Unplanned changes to primary outcome...
It is interesting that the protocol changes are justified by bad statistics (using the mean of the sf36 general population data) that people have already pointed out to them as being an issue with respect to the PACE recovery paper. What is perhaps shocking is that the research ethics committee appear to have just approved the changes, they should be questioning these poor excuses. With such a process there is no point in pre-publishing (or post in this case) protocols as rewriting will be approved on a whim.
 
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And of course we are back to the fact the the (so called) controls will be aware that they are effectively on a waiting list until they can try this amazing new therapy/leaflet.

Might they not also be concerned that if they seem to be doing ok or at least not getting worse then they might be left waiting longer for the new miracle therapy?
 
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The CFQ is neither reliable for this purpose, nor valid. The questions are inappropriate for an a treatment trial for those with chronic illness and the scoring system can easily lead to bias. There was a review of questionnaires used in ME & CFS trials and the CFQ was not one of the better ones.

"0 for less than usual,” 1 for “no more than usual,” 2 for “more than usual” and 3 for “much more than usual,” where usual is how they felt the last time they were feeling well." is not appropriate!

However, during recruitment we noticed that a significant minority of participants scored close to the mean of the general population (ie, normal physical function) so could be considered recovered even before any intervention [43]. This is because they had substantial reductions in functioning in other domains, such as mental or social activity levels [7].
The above is a red flag - if the above is true, then it suggests there could be a major issue with the trial. They need to show histograms of the SF-36 PF scores before and after the trial - not just the mean, SD. If they don't show the histograms then they have something to hide.

The PF mean of the (healthy) general population of the age range in the trial is in the 90s (scale 0-100). If their score is that high, they don't have ME or CFS and shouldn't be in the trial.[/quote]
 
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Dolphin

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Peter White was the Chief Principal Investigator of GETSET ; originally, it ran from 1 st December 2011 to 30th November 2014 (ie. before he had been forced to release the PACE trial data) and funding was £244,056.00 but Peter White changed the primary outcome measures and asked for the trial to be extended until December 2015.

http://www.margaretwilliams.me/2016/proof-positive-revisited.pdf
Not sure we knew the funding amount before?
 

Esther12

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Looks like this is being published in the Lancet.

Exercise can help chronic fatigue syndrome, study shows
22 June 2017 • 11:30pm
Increasing exercise each day can help patients with Chronic Fatigue System to feel less tired and feel better, a new study suggests.

Scientists at Queen Mary University of London placed 200 people on a 12 week programme in which they were either encouraged by a physiotherapist to walk a little more each or given a programme of medical care including medication for depression, pain and insomnia.

After four months the mean fatigue score of the exercise group was four points lower than in the control group, on a scale of 100, which researchers said was a moderate but significant impact. Physical function was also six points higher.

One in five of the group who had exercised also reported feeling ‘much better’ or ‘very much better.’

<img src="/content/dam/property/Spark/churchill-retirement-living/mature-couple-walking-along-the-beach-small_trans_NvBQzQNjv4Bqeo_i_u9APj8RuoebjoAHt0k9u7HhRJvuo-ZLenGRumA.jpg" alt="Gradually increasing walking each day could help reduce fatigue" width="320" height="200" class="responsive-image--fallback"/>

Gradually increasing walking each day could help reduce fatigue
Lead author Dr Lucy Clark said: “We found that a self-help approach to a graded exercise programme, guided by a therapist, was safe and also helped to reduce fatigue for some people with chronic fatigue syndrome, suggesting that it might be useful as an initial treatment for patients to help manage symptoms of chronic fatigue syndrome.

“We are now looking at whether the effects were maintained beyond 12 weeks.

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“The aim is to progress carefully to improve rather than pushing people too hard and towards a setback.”

CFS affects about seven in 1000 people and is characterised by chronic, disabling fatigue in the absence of an alternative diagnosis.

The self-help exercise programmed involved slowly building up physical activity levels after establishing a daily routine, with the support of a physiotherapist over the phone or Skype.

The research was published in The Lancet.

http://www.telegraph.co.uk/science/...e-syndrome-study-shows/?WT.mc_id=tmg_share_tw
 

Esther12

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Science Media Centre coverage:

June 22, 2017
expert reaction to study on guided self-help graded exercise therapy as a treatment for chronic fatigue syndrome (CFS)


Researchers publishing in The Lancet present their findings from a randomised controlled trial they conducted to test the efficacy and safety of graded exercise delivered as guided self-help, for the treatment of chronic fatigue syndrome.



Dr Jon Stone, Consultant Neurologist and Honorary Reader in Neurology, Western General Hospital, Edinburgh, said:

“The GETSET trial is a helpful addition to the evidence base for treatment of CFS which is a common and disabling condition.

“What this shows, for the first time, is that it is possible for relatively time-limited guided self-help based on a graded exercise model to make a modest positive difference overall to a group of patients with CFS over a short time window (12 weeks).

“Importantly, the trial addresses concerns that graded exercise may be harmful in CFS by showing that deterioration was no more common in the group allocated the intervention.

“In absolute terms, around 1 in 6 patients noticed a positive change overall compared to 1 in 20 patients not receiving the intervention and nearly all the secondary outcome measures were also positive.

“The trial has been well conducted but it is important to note that the long term outcome of this intervention is not yet known and that data at 12 months is yet to be published.

“This is likely to be a treatment option that is helpful for some but not all patients with CFS. Clinicians should not assume that just directing patients to a booklet is sufficient. These patient had up to 90 minutes of input from experienced physiotherapists over four sessions which is likely to have been an important part of the treatment effect.

“It’s encouraging that this effect was also achieved through technologies such as skype which help patients who find it difficult to travel to appointments.

“The study also offers encouragement for managing fatigue in a range of other conditions such as multiple sclerosis and Parkinson’s disease where this approach may also be useful for some patients

“Studies like this should encourage the NHS to invest in relatively low tech interventions which may have a significant impact on disability and distress.”


Dr David Henderson Slater, Consultant in Neurological Disability & Rehabilitation Medicine and Honorary Senior Clinical Lecturer, Nuffield Orthopaedic Centre NHS Trust, said:

“The results of this positive study will probably not be surprising to clinicians who have worked with patients suffering from CFS/ME. It is encouraging that there is further evidence that graded exercise is an effective treatment leading to clinical improvements. The evidence is that the participants who received the graded exercise self-help programme benefitted from the input of the physiotherapist advising on the graded exercise either face to face, by Skype, or by telephone. Given the difficulty some patients with CFS/ME may have in getting to hospital appointments, and the limited nature of NHS resources, this suggests that future treatments involving consultation and discussion by Skype or telephone should extend the reach of limited therapy resources and enable more patients to benefit from this treatment approach.”



Prof. Allan House, Professor of Liaison Psychiatry, University of Leeds, said:

“It is well established that physical inactivity and sedentary behaviour are bad for you, and that physical activity can have health benefits in conditions as diverse as coronary heart disease, rheumatoid arthritis and prostate cancer. It is therefore reasonable to start with an assumption that in most health problems, a sensible gradual increase in physical activity is likely to beneficial unless there is evidence to the contrary.

“In chronic fatigue syndrome there is already evidence to support this supposition of the benefit of physical activity, from for example the PACE trial. In the present study, the researchers ask whether a version of graded activity could be effective if it is largely self-managed – based upon a self-help guide with light touch help in using it.

“The study was generally well-designed, with (importantly) its protocol published in advance of conduct of the trial itself. In a group of patients with chronic fatigue syndrome who were perhaps not as severely affected as some can be, about a third made important improvements compared with 1 in 7 of those in the comparison group. On its own this trial wouldn’t be definitive, but against the background of what we know more generally about the benefits of activity for physical and mental health, including the health of people with chronic fatigue syndrome, this is further evidence of the usefulness of carefully managed increase in activity.

“Perhaps more important were the trial’s findings about harm – because so many sufferers from chronic fatigue worry about harmful effects from doing too much. About a quarter of patients in the trial reported worsening of their physical health over the three months of the trial but there was no evidence of severe untoward events at all, and no evidence that those practising graded activity did worse than those in the comparison group.

“We can be confident that responsibly managed graded activity is safe in chronic fatigue syndrome, and that for some sufferers at least, it can lead to significant improvements in their health.”



Dr Simon Day, Statistician, Clinical Trials Consulting & Training Limited, said:

“This is an important question and a randomised controlled trial is probably the best way to try to answer it. But any trial like this has limitations.

“The trial is described as ‘pragmatic’ – but it is not clear what the authors mean by that. In particular, this is not a trial of all patients diagnosed with chronic fatigue syndrome; it is a trial of all such patients who are interested to take part in such a trial. Note, in contrast, the results of trials of pharmaceutical interventions are generally assumed to apply to all patients who would meet the inclusion criteria, not just those with the enthusiasm to take part in a trial. The results of this trial, therefore, might not be as positive if GES (Graded Exercise Self-help) +SMC (Specialist Medical Care) were introduced more routinely.

“The trial is not, and cannot be, blinded – but the obvious inability to blind the trial does not negate the possible biases that may be introduced in an unblinded study. This is particularly so as the endpoints are self-reported by the patients (who knew which ‘treatment’ they were getting). The authors state, ‘Primary outcomes were self-reported by participants, thus preventing observer bias’ and also ‘all outcomes were self-rated, which might lead to bias by expectation…’.

“The authors rightly identify some other limitations of their trial. The lack of standardisation of SMC is an inevitable problem, but lack of recording and reporting of its content is unfortunate. For me, the biggest unanswered question (which the authors do recognise) is the very limited number of health-care professionals involved and, hence, the extent to which the findings might apply more broadly if GES+SMC were administered by other healthcare professionals. In trials of pharmaceutical interventions, it is usually assumed that the pharmacological effect will be independent of the treating physician, but in trials of this nature (and, for example, trials in surgery) the outcome is likely to be highly dependent on the skills of the health-care professionals delivering the intervention.”



Prof. Chris Ponting, Chair of Medical Bioinformatics and Principal Investigator at the MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, said:

“The beneficial effect was for fewer than 1 in 5 individuals, for an unblinded trial, and there was no consideration of long-term benefit or otherwise. The study could also have exploited actometers that would have more accurately measured participant activity.”


Prof. Trudie Chalder, Professor of Cognitive Behavioural Psychotherapy, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, said:

“This study contributes to a body of evidence that graded exercise can help to improve functioning and reduce fatigue in people with chronic fatigue syndrome. It replicates the finding that graded exercise if tackled in a measured way is safe. This non pharmacological intervention for CFS can be delivered to patients in their own home which gives patients flexibility. Although it doesn’t help all patients it can undoubtedly help some.”


* ‘Guided graded exercise self-help plus specialist medical care versus specialist medical care alone for chronic fatigue syndrome (GETSET): a pragmatic randomised controlled trial’ by Clark et al. published in The Lancet on Thursday 22 June.


All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/?s=%22CFS%22&cat


Declared interests

Dr Jon Stone: I am a neurologist with an interest in self-help, guided self-help and physiotherapy for a range of conditions seen in neurology, especially functional disorders.

I have published studies of physio interventions and have applied for funding for a multicentre trial of a physiotherapy intervention

I run a free website www.neurosymptoms.org for patients with functional disorders in neurology.

Dr Simon Day: Dr Day works as a paid consultant to the pharmaceutical industry. He has also received research and/or travel grants from the Medical Research Council, the European Commission and the National Institutes of Health.

Prof. Chris Ponting: “I am funded by the MRC and by the Wellcome Trust.”

Prof. Trudie Chalder: TC has authored self-help books on fatigue and collaborates with Peter White on a number of research projects.

None others received.
http://www.sciencemediacentre.org/e...a-treatment-for-chronic-fatigue-syndrome-cfs/
 

JaimeS

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Fascinating that they stepped forward with their experts first. A good media strategy, a la climate change denialism. "You have your experts? Well, we have OUR experts, too! And our three experts are of equal or greater value than your 98!"



Just in case no one remembers this episode or wants to know what's going on: http://www.hbo.com/last-week-tonigh...ideo/climate-change-debate.html?autoplay=true
 

JaimeS

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Daniel Clauw should state that he uses GET and CBT to treat fibromyalgia at his practice. It's his bread and butter.

I often wonder how honest you have to be in these papers when declaring conflicts of interest. Of course people who use the therapy support its use -- by definition. But it's still odd that he didn't declare that the use of these therapies are an important part of how he makes his living.