Wolfson Institute of Preventive Medicine - Barts and The London

GETSET Trial

Centre for Psychiatry

Project Investigator:  Peter White

Overview

What is the GETSET trial?

This was the first trial to test the effectiveness of adding Guided graded Exercise Self-help (GES) to specialist medical care (SMC) for people suffering from chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME). The participants in the trial were recruited from two CFS clinics: one in East London and one in Kent. All participants had been diagnosed as suffering from CFS/ME, as described in the NICE guidelines, and were on a waiting list for a therapy. Participants were randomly allocated to GES plus SMC or SMC alone. GES offers ways for patients to deal with and improve the symptoms of CFS/ME and its effects on disability. Those randomised to SMC alone continued on the waiting list, whilst those offered GES were, in addition, given a Booklet [PDF 1,868KB]  which describes a six-step graded exercise self-help programme. They were also offered four individual supportive guidance sessions from a physiotherapist. The sessions supported the participant in how to apply the GES programme, (with up to 90 minutes of four face-to-face/telephone and/or Skype sessions), by a physiotherapist experienced in treating people with CFS/ME. The trial recruited 211 participants, aged 18 and over. Follow up occurred 12 weeks after entering the trial, with mailed questionnaires. A longer term follow up also occurred one year after entering the trial.

What is CFS/ME?

CFS/ME is a common disorder. Estimates vary, but it is believed that between one in 40 and one in 250 of the population will suffer from the illness at any one time. CFS/ME causes disability as a result of persistent, abnormal tiredness and other symptoms, which are made worse by activity. Other symptoms can include disturbed or unrefreshing sleep, problems concentrating or remembering, pain in the muscles and/or joints, headaches, sore throats and tenderness in the neck. The diagnosis of CFS/ME requires that a large number of other possible causes of the symptoms, such as thyroid gland disease and severe depressive illness, are excluded.

What were the interventions being tested?

The two interventions were specialist medical care (SMC) alone and Guided graded Exercise Self-help (GES) in addition to SMC.
SMC: All participants received SMC, which means that they followed the advice of their GP and specialist doctor as usual. Specialist doctors could  prescribe or advise regarding medication as indicated for symptomatic treatment of associated symptoms (e.g. insomnia and pain) and comorbid conditions (e.g. depressive illness).
GES: In addition to receiving SMC, participants in the GES arm were given a copy of a Booklet [PDF 1,868KB] describing a six-step programme of graded exercise. A physiotherapist trained to support GES then either saw the participant face-to-face in the clinic or by speaking via telephone/Skype for a 30 minute appointment. The physiotherapist then provided up to three further 20-minute telephone or Skype support appointments over the next 8 weeks. The emphasis of GET guidance manual [PDF 862KB] was to help the participant to better understand the principles of GES, and to help the participant solve any problems associated with doing GES. The physiotherapist followed a support guidance checklist to aid them.

What were the outcomes to test the interventions?

We chose a fatigue scale and a self-reported physical function scale as our two primary outcomes. Other outcomes included a global self-rating regarding overall health and CFS, a measure of anxiety and depression, a measure of physical symptoms, and measures of global functioning and physical activity and healthcare and other costs. All these measures were rated by the participant. More details can be found in the published protocol.

News

Date: Wednesday 20th March 2019
As of March 2019, the data for this trial will be available to scientists through the Yale University Open Data Access (YODA) Project (here). The YODA Project performs independent scientific reviews of investigator requests for the participant-level data underlying the GETSET trial. QMUL has conferred on the YODA Project the authority to make decisions about the release of this clinical trial data. This allows all requests for the clinical data to be fairly judged and decided upon by an independent academic partner. To enquire about access to this data please e-mail: yodap@yale.edu

8th June 2016 - Protocol published:
http://www.researchprotocols.org/2016/2/e70/

23 June 2016
The Lancet have now published the main results from the GETSET trial with follow up 12 weeks after trial entry. Free access to the paper and accompanying commentary are available following free registration with The Lancet.

Trial Information

Trial Manager: Lucy Clark

Information of trial on ISRCTN Registry
http://www.isrctn.com/ISRCTN22975026

GET Booklet [PDF 1,868KB]available online
 

Therapist’s
GET guidance manual [PDF 862KB]

FAQs

What is CFS/ME?
How should CFS/ME be treated?
The GETSET trial

GETSET main results:
1.    What did you find out?
We found out that Guided Exercise Self-help (GES) moderately improves symptoms of fatigue for patients in the trial, and to a lesser extent physical functioning, when compared to Specialist Medical Care (SMC) alone. This was equally the case in those who met other definitions of chronic fatigue syndrome (CFS). Secondly, GES was as safe as SMC as a treatment. About a third of patients improved in both physical function and fatigue after GES compared to one in seven after SMC. But only about one in five (18%) rated their overall health as “much better” or “very much better” after GES, compared to one in twenty (5%) after SMC, so 12 weeks of GES helped only a minority of patients in a substantial way.

2.    What does this mean for patients?
These findings mean that guided exercise self-help may be a useful and safe treatment for some people with CFS/ME, with the help of a booklet and some support from an appropriately qualified and trained physiotherapist. However, only 18% of participants rated their overall health as much or very much better after GES, compared to 5% after SMC; so the self-help approach only helped a minority in a substantial way over the 12 week period of the trial. Most patients need more treatment than this.

3.     What are the strengths and limitations of this research?
The main strength of this research is that it is the largest trial of a self-help intervention for CFS/ME and the first investigating a guided graded exercise intervention. We were able to deliver GES through a number of different media (telephone and SkypeTM), which made it more accessible to those who might find it difficult to attend a clinic regularly. We also used a definition of CFS/ME commonly used by clinicians in the UK, so that we were able to recruit into the trial willing patients who would typically be found in such specialist clinics.

The limitation of this research is that it only applies to patients who attend a specialist clinic, and it needs to be tested in other groups of patients.

4.    Does this research prove once and for all that GET is the best therapy for CFS/ME?
This research did not look at graded exercise therapy (GET), as GET is a treatment that is delivered face-to-face in clinics. The principles of GET were incorporated into GES, delivered as guided graded exercise self-help (GES). These results add to the evidence that interventions based on GET are safe and moderately effective for some people with CFS, and that it is not always necessary to have face-to-face therapy in a clinic to make improvements.

Guided self-help approaches, based on cognitive behaviour therapy, have also been tested and found to be helpful.

5.    How do you know there is no harm caused by GES?
We know that there was no harm in patients who tried GES because none of the adverse outcome measures were significantly more frequent after GES, compared to the control treatment of SMC.

6.    How do we know that the results were not biased in any way?
Bias means that the results were incorrect because of a limitation in the methods. There are many forms of bias:
Bias in design and conduct of the trial: The trial was subject to independent scrutiny by both a Trial Steering Committee and a Data Monitoring and Ethics committee throughout. A patient charity helped to design, implement and oversee the study throughout its existence. A patient representative also sat on the trial management group.

Outcome measurement bias: This can sometimes occur when the research assessor knows which treatment each participant has received, as in this trial. However, as the participants rated the main outcomes themselves, any measurement bias would have been determined by participants themselves. It is possible that participants expected GES would work better than SMC. However, most patient organisations in the UK do not recommend treatments based on GET, and even suggest they  can be damaging, which makes a positive expectation less likely.

Bias in assessing safety outcomes: These were reported by participants themselves, and finally assessed by independent scrutineers, so this is unlikely.

Bias in the analysis: The statistician who analysed the main results did not know which outcome data referred to which treatment, so this is unlikely.

Whilst it is never possible to completely eliminate all bias in trials we are confident that the findings of the trial were not significantly affected by bias.

7.    Do the treatments give value for money?
Our health economic analysis will be reported in a separate paper. It is important to think about the costs of these treatments to the National Health Service as well as the costs of the illness to patients’ families and society in general.

8.    Did all GES participants get to the end of the 6-steps described in the guide during the 12-weeks?
Not all GES participants would have completed all 6-steps of the guide in the 12-weeks, but they were given guidance on all of the steps during their four guidance sessions, as described in the therapist manual.

9.    If patients continued GES for longer would they continue to get better?
The GETSET trial was designed to measure benefits of 12 weeks of guided support.  We will be reporting 12-month outcomes in a separate paper.

10.    Do the effects of GES last?
We have followed participants up to 12-months and will be able to make a better assessment of whether the positive effects shown in the trial last when we report these results.

11.    Most patients did not improve: was it worth it?
As with many treatments in most areas of medicine, there will be patients who do not respond to treatment. A self-help approach with minimal guidance would not be expected to be as effective as receiving a therapy. Most patients, who had been ill for a little over three and a half years in this trial, will need a therapy to help them to improve their health. But it is still worth knowing that GES has helped some people with CFS, so others could benefit if it was rolled out more widely.

12.    What would you say to participants who did not get better?
After participation in the trial, all patients went on to be offered further or alternative treatments; we hope this would happen in general clinical practice.

13.    Did you ask people what they thought about GES afterwards?
Yes, we did an interview study that asked people what they thought about GES. We interviewed both patients who said that GES had helped them, as well as those who said that they had felt a little worse afterwards. Our paper exploring the experiences and perceptions of GES for these patients can be found here: http://dx.doi.org/10.1080/09638288.2018.1499822