Comment
Guided graded exercise self-help as a treatment of fatigue in
chronic fatigue syndrome
In The Lancet, Lucy Clark and colleagues1 show that, in
the GETSET trial (n=211), patients with chronic fatigue
syndrome who were treated with a 12 week guided
graded exercise self-help programme in addition
to ongoing specialist medical care had significantly
lower mean fatigue score (reduction by 4·2 points
[95% CI 2·3–6·1], p<0·0001; effect size 0·53) and higher
self-reported physical function score (increase by
6·3 points [1·8–10·8], p=0·006; effect size 0·20) than
did patients managed with specialist medical care alone.
This pragmatic randomised controlled trial was done at
two secondary-care centres in the UK, and its findings
support the results of the previously reported PACE
trial2—ie, that graded exercise therapy is an effective
treatment for chronic fatigue syndrome—although
the GETSET trial involved much less intensive use of
physiotherapists. In the GETSET trial,1 physiotherapists
guided the patients through graded exercise using a
self-help booklet, and face-to-face contact was minimal
(maximum of one episode of face-to-face contact, and
then up to three other appointments via telephone
or Skype not lasting more than 90 min in total). The
finding that graded exercise therapy is effective even
when exercise is not being witnessed and directly
guided by a physiotherapist is a substantial advance,
since many patients with chronic fatigue syndrome and
other functional impairment have difficulty getting to
physiotherapy or do not have access to appropriately
trained physiotherapists.
Following results of the PACE trial,2 advocacy groups
questioned whether the same results would have
been noted in patients defined by chronic fatigue
syndrome criteria other than those used for the
trial.3–5 In both the PACE trial and the GETSET trial,
the investigators assessed each participant with
three different diagnostic criteria and did sensitivity
analyses showing that no differences were seen in the
effect of graded exercise regardless of the definition
of chronic fatigue syndrome used. Other sensitivity
analyses in the GETSET trial1 showed that individuals
with worse physical function scores at baseline were
more likely to benefit from graded exercise and
improve in physical function than were individuals
www.thelancet.com Vol 390 July 22, 2017
with better physical function scores at baseline, further
supporting the finding that graded exercise is effective
even in individuals with severe symptoms. However,
some individuals with the most severe forms of chronic
fatigue syndrome might have been unable to attend
secondary-care clinics, which made them ineligible for
participation in this trial, and the same could be said
Patricia/Fotolia
about participation in the PACE trial.
Partly because of these concerns raised after the initial
publication of the PACE trial,6 the investigators of the Published Online
June 22, 2017
GETSET trial also looked carefully for adverse effects of http://dx.doi.org/10.1016/
graded exercise treatment, since many patients were S0140-6736(17)30577-9
concerned that any type of exercise would lead to an See Articles page 363
exacerbation of their symptoms. In both the PACE trial2,7
and the GETSET trial, relatively few serious adverse
events or reactions were reported. In the GETSET trial,
non-serious adverse events were reported by 27 (28%)
of 97 participants who received guided graded exercise
self-help and by 23 (23%) of 102 patients who received
specialist medical care only, with no significant
differences between the two groups (χ²=0·67; p=0·41).
No serious adverse reactions were reported. Only
two participants actively withdrew from graded exercise
treatment, suggesting that this treatment was well
tolerated in most individuals.
Fatigue (measured by the updated Chalder fatigue
questionnaire) is the symptom that improved the
most in the GETSET trial, and similar findings have
been noted in many previous studies that assessed
this outcome in chronic fatigue syndrome or related
conditions such as fibromyalgia, making graded
exercise a cornerstone of treatment recommendations
in these conditions.8–11 In fact, although one might
argue that some alternative pharmacological and
non-pharmacological therapies might yield similarly
small improvements in physical function or mood to
those noted in the GETSET trial, far fewer available
alternative therapies have this magnitude of effect on
fatigue. The results of the GETSET trial are consistent
with other work on exercise as a treatment of fatigue
in chronic fatigue syndrome and other related
conditions such as fibromyalgia, in which exercise has
also been used as a non-specific treatment since the
335
 Comment
cause of these conditions is not entirely clear. Results
from these studies also typically show that the effect
size for fatigue is often similar or greater than the
effect size seen for other domains such as function,
pain, and mood. Thus, results of the GETSET trial add
to the accumulating evidence that graded exercise
(with or without cognitive behavioural therapy)
should probably be considered the gold standard for
treatment of fatigue in chronic fatigue syndrome and
related conditions.12
Another concern of patient advocates regarding the
PACE trial is that the overall results of the intervention
were fairly modest, and thus it would be inappropriate
to consider graded exercise as an effective treatment
for chronic fatigue syndrome. This concern is valid,
and the same can be said about the overall effects of
the intervention in the GETSET trial. Only 17 (18%) of
97 participants who received graded exercise noted
improvements (“much” or “very much better”) in
overall health, compared with five (5%) in the control
group, and only 14 (15%) patients who received
graded exercise reported improvements in symptoms
of chronic fatigue syndrome, compared with six (6%)
in the control group.1 In the PACE trial,2 37 (25%) of
160 patients reported improvement in overall health
after therapist-delivered graded exercise therapy at
12 week follow-up.2
In summary, findings from this pragmatic
randomised controlled trial add to the evidence that
straightforward, non-pharmacological therapies can
be helpful in the management of symptoms such as
fatigue in individuals with chronic fatigue syndrome.
Many of these cognitive and behavioural therapies (of
Informing health choices in low-resource settings
Published Online Because of the abundance of health information,
May 21, 2017
http://dx.doi.org/10.1016/
available via multiple sources, it is important that
S0140-6736(17)31290-4 individuals be able to critically appraise health claims
See Articles pages 374 and 389 to make well informed decisions. This is of even greater
importance in low-income countries where individuals
cannot afford to invest in ineffective treatments.
Indeed, public health practitioners have long touted
the importance of health education; for example, a
variety of well tested and updated curricula to prevent
adolescent pregnancy and HIV have shown positive
336
which guided graded exercise self-help is an example)
can be very helpful to patients and will be used more
frequently in routine clinical practice only when we
abandon the notion that these therapies need to be
administered through face-to-face contact with highly
trained therapists.
Daniel J Clauw
Chronic Pain and Fatigue Research Center, The University of
Michigan, Ann Arbor, MI 48106, USA
dclauw@umich.edu
I declare no competing interests.
Copyright © The Author(s). Published by Elsevier Ltd. This is an Open Access
article under the CC BY-NC-ND 4.0 license.
1 Clark LV, Pesola F, Thomas JM, Vergara-Williamson M, Beynon M, White PD.
Guided graded exercise self-help plus specialist medical care versus
specialist medical care alone for chronic fatigue syndrome (GETSET):
a pragmatic randomised controlled trial. Lancet 2017; published online
June 22. http://dx.doi.org/10.1016/S0140-6736(16)32589-2.
2 White PD, Goldsmith KA, Johnson AL, et al. Comparison of adaptive pacing
therapy, cognitive behaviour therapy, graded exercise therapy, and
specialist medical care for chronic fatigue syndrome (PACE): a randomised
trial. Lancet 2011; 377: 823–36.
3 Kindlon T. Criteria used to define chronic fatigue syndrome questioned.
Psychosom Med 2010; 72: 506–07.
4 White PD, Chalder T, Sharpe M, Johnson T, Goldsmith K. PACE trial authors’
reply to letter by Kindlon. BMJ 2013; 347: f5963.
5 Kindlon T. People want to learn as much as possible from the PACE trial for
chronic fatigue syndrome. BMJ 2013; 347: f5731.
6 Kindlon T, Goudsmit EM. Graded exercise for chronic fatigue syndrome: too
soon to dismiss reports of adverse reactions. J Rehabil Med 2010; 42: 184.
7 Dougall D, Johnson A, Goldsmith K, et al. Adverse events and deterioration
reported by participants in the PACE trial of therapies for chronic fatigue
syndrome. J Psychosom Res 2014; 77: 20–26.
8 Clauw DJ. Fibromyalgia: a clinical review. JAMA 2014; 311: 1547–55.
9 Hauser W, Thieme K, Turk DC. Guidelines on the management of
fibromyalgia syndrome—a systematic review. Eur J Pain 2010; 14: 5–10.
10 Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations
for the management of fibromyalgia. Ann Rheum Dis 2016; published
online July 4. DOI:10.1136/annrheumdis-2016-209724.
11 Jones KD, Liptan GL. Exercise interventions in fibromyalgia: clinical
applications from the evidence. Rheum Dis Clin North Am 2009; 35: 373–91.
12 Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for
chronic fatigue syndrome. Cochrane Database Syst Rev 2016; 2: CD003200.
health outcomes across low-income and high-income
communities.1 Yet, these efforts have typically focused
on behavioural practices, rather than the skills necessary
to make sense of a seemingly limitless amount of
health information.
As the digital age is enhancing the speed and
frequency with which we are able to access reliable
health information, so too does it perpetuate the
spread of misinformation. Communication platforms
such as television, radio, and increasingly non-
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