Skip to main content
×
×
Home

The planning, implementation and publication of a complex intervention trial for chronic fatigue syndrome: the PACE trial

  • Peter D. White (a1), Trudie Chalder (a2) and Michael Sharpe (a3)
Summary

The PACE trial was a four-arm trial of specialist medical care, compared with specialist medical care with a supplementary therapy: adaptive pacing therapy, cognitive–behavioural therapy or graded exercise therapy, for patients with chronic fatigue syndrome. The trial found that both cognitive–behavioural and graded exercise therapies were more effective than either of the other two treatments in reducing fatigue and improving physical disability. This paper describes the design, conduct and main results of the trial, along with a description of the challenges that had to be overcome in order to produce clear answers to the clinically important questions the trial posed.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      The planning, implementation and publication of a complex intervention trial for chronic fatigue syndrome: the PACE trial
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      The planning, implementation and publication of a complex intervention trial for chronic fatigue syndrome: the PACE trial
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      The planning, implementation and publication of a complex intervention trial for chronic fatigue syndrome: the PACE trial
      Available formats
      ×
Copyright
This is an open-access article published by the Royal College of Psychiatrists and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Corresponding author
Correspondence to Peter D. White (p.d.white@qmul.ac.uk)
Footnotes
Hide All

Declaration of interest

P.D.W. has carried out voluntary and paid consultancy work for the UK Government and a reinsurance company. T.C. has received royalties from Sheldon Press and Constable and Robinson. M.S. has carried out voluntary and paid consultancy work for the UK Government, consultancy work for an insurance company and has received royalties from Oxford University Press.

Footnotes
References
Hide All
1 World Health Organization The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. WHO, 1992.
2 Wojcik, W, Armstrong, D, Kanaan, R. Is chronic fatigue syndrome a neurological condition? A survey of UK neurologists. J Psychosom Res 2011; 70: 573–4.
3 Sharpe, M, Wessely, S. Putting the rest cure to rest – again. BMJ 1998; 316: 796.
4 White, PD, Sharpe, MC, Chalder, T, DeCesare, JC, Walwyn, R. Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurology 2007; 7: 6.
5 Cox, DL, Burgess, M, Chalder, T, Sharpe, M, White, PD, Clark, L. Training, supervision and therapists' adherence to manual based therapy. Int J Ther Rehabil 2013; 20: 180–6.
6 Sharpe, MC, Archard, LC, Banatvala, JE, Borysiewicz, LK, Clare, AW, David, A, et al. A report – chronic fatigue syndrome: guidelines for research. JRSM 1991; 84: 118–21.
7 Reeves, WC, Lloyd, A, Vernon, SD, Klimas, N, Jason, LA, Bleijenberg, G, et al. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Serv Res 2003; 3: 25.
8 National Task Force. Report on Chronic Fatigue Syndrome (CFS), Post Viral Fatigue Syndrome (PVFS), Myalgic Encephalomyelitis (ME). Westcare, 1994.
9 Nutt, DJ, Sharpe, M. Uncritical positive regard? Issues in the efficacy and safety of psychotherapy. J Psychopharmacol 2008; 22: 36.
10 White, PD, Goldsmith, KA, Johnson, AL, Potts, L, Walwyn, R, DeCesare, JC, 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.
11 McCrone, P, Sharpe, M, Chalder, T, Knapp, M, Johnson, AL, Goldsmith, KA, et al. Adaptive pacing, cognitive behaviour therapy, graded exercise, and specialist medical care for chronic fatigue syndrome: a cost-effectiveness analysis. PLoS ONE 2012; 7: e40808.
12 White, PD, Johnson, AL, Goldsmith, K, Chalder, T, Sharpe, MC. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychol Med 2013; 43: 227–35.
13 National Institute for Health and Clinical Excellence. Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy): Diagnosis and Management of CFS/ME in Adults and Children (Clinical Guideline CG53). NICE, 2007.
14 Wiborg, JF, Knoop, H, Wensing, M, Bleijenberg, G. Therapist effects and the dissemination of cognitive behavior therapy for chronic fatigue syndrome in community-based mental health care. Behav Res Ther 2012; 50: 393–6.
15 Cella, M, Stahl, D, Reme, SE, Chalder, T. Therapist effects in routine psychotherapy practice: an account from chronic fatigue syndrome. Psychother Res 2011; 21: 168–78.
16 Burgess, M, Andiappan, M, Chalder, T. Cognitive behaviour therapy for chronic fatigue syndrome for adults: face to face versus telephone treatment – a randomized controlled trial. Behav Cogn Psychotherapy 2012; 40:175–91.
17 Nijhof, SL, Bleijenberg, G, Uiterwaal, CSPM, Kimpen, JLL, van de Putte, EM. Effectiveness of internet-based cognitive behavioural treatment for adolescents with chronic fatigue syndrome (FITNET): a randomised controlled trial. Lancet 2012; 379: 1420.
18 ME Association. MEA calls for PACE trial to be scrapped. ME Essential, July 2004: 91: 34.
19 Smith, C, Wessely, S. Unity of opposites? Chronic fatigue syndrome and the challenge of divergent perspectives in guideline development. J Neurol Neurosurg Psychiatry 2014; 85: 214–9.
20 The Lancet. Patients' power and PACE. 2011; 377: 1808.
21 General Regulation Chamber (Information Rights) First Tier Tribunal. Mitchell versus Information commissioner. EA 2013/0019 (www.informationtribunal.gov.uk/DBFiles/Decision/i1069/20130822%20Decision%20EA20130019.pdf).
22 Hansard. PACE trial: Chronic fatigue syndrome/myalgic encephalomyelitis. Question for short debate. 6th February, 2013, Columns GC65–82 (www.publications.parliament.uk/pa/ld201213/ldhansrd/text/130206-gc0001.htm130206114000195).
23 Walwyn, R, Potts, L, McCrone, P, Johnson, AL, DeCesare, JC, Baber, H, et al. A randomised trial of adaptive pacing therapy, cognitive behaviour therapy, graded exercise, and specialist medical care for chronic fatigue syndrome (PACE): statistical analysis plan. Trials 2013; 14: 386.
24 Association of Young people with ME. The PACE trial results – an analysis by Vivienne Parry, OBE. Link 2011; 42: 13.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

BJPsych Bulletin
  • ISSN: 2056-4694
  • EISSN: 2056-4708
  • URL: /core/journals/bjpsych-bulletin
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

The planning, implementation and publication of a complex intervention trial for chronic fatigue syndrome: the PACE trial

  • Peter D. White (a1), Trudie Chalder (a2) and Michael Sharpe (a3)
Submit a response

eLetters

Re: Response to Dr Goudsmit

Peter D White, Professor of Psychological Medicine
14 September 2014

We thank Dr Goudsmit for the opportunity to clarify the issues she raises.

Adaptive pacing therapy (APT) was based on the envelope theory of chronic fatigue syndrome (CFS), as espoused by Jason and colleagues (1). APT was based on the idea that patients have a fixed and finite amount of energy to "spend", and pacing is an approach to balance rest and differentactivities in order not to "overspend" and thus exacerbate symptoms. APT as used in the PACE trial was designed in collaboration with two myalgic encephalomyelitis (ME) patient charities. It did not restrict patients to 75 percent of their perceived capacity, once they have established their baseline activity levels, but rather encourages patients to gradually increase their activities as able (www.pacetrial.org to access the therapymanuals used in the trial). We found no evidence of increased depression or exercise tolerance following APT (2) and a future paper will show no evidence of worsening deconditioning. We are aware of only one other (preliminary) randomised controlled trial of pacing for CFS, which found that an active rehabilitation programme was more efficacious than pacing in 13 adolescents (3).

We were grateful to Dr Goudsmit for sending us the second version of the London criteria for ME, which we used, and which was based on the original description of the Royal Free hospital epidemic of ME by Melvin Ramsay. We operationalised these criteria in order to use them in the trial. These criteria excluded any participant with any comorbid mood or anxiety disorder, and included the cardinal symptom of post-exertional fatigue. We are therefore confident that this sub-group of patients were suffering from ME as described by Ramsay.

Graded exercise therapy produced a significant increase in distance walked in six minutes, which is an objective measure of exercise tolerance(2).

We have already published the economic outcomes from the trial, whichshowed that there were no significant differences in employment rates across treatment arms at 12 months (4). We did not use employment as an outcome to judge recovery mainly because participants may not have been inemployment before becoming ill, and for other reasons stated in the paper (5).

We did find that the large majority (85%) of participants who received APT were satisfied with it (2). However, as we found no evidence that APT was efficacious in either reducing fatigue or increasing physicalfunctioning, we cannot recommend it.

References:

1. Pesek JR, Jason LA, Taylor RR. An empirical investigation of the envelope theory. J Human Behav Soc Environ 2000; 3: 59-77.

2. White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, 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. Wright B, Ashby B, Beverley D, Calvert E, Jordan J, Miles J, et al. A feasibility study comparing two treatment approaches for chronic fatigue syndrome in adolescents. Arch Dis Child 2005; 90: 369-37.

4. McCrone P, Sharpe M, Chalder T, Knapp M, Johnson AL, Goldsmith KA,et al. Adaptive pacing, cognitive behaviour therapy, graded exercise, and specialist medical care for chronic fatigue syndrome: a cost effectivenessanalysis. PLoS ONE 2012; 7: e40808.

5. White PD, Johnson AL, Goldsmith K, Chalder T, Sharpe MC. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychol Med 2013; 43: 227-35.

... More

Conflict of interest: As stated in our Bulletin paper.

Write a reply

Rectification to ensure balance

Ellen M Goudsmit, Health Psychologist (Retired.)
20 August 2014

I appreciate the value of a clear and concise summary but in this article, perhaps brevity lead to the odd error and an incomplete recollection of events. For the sake of accuracy and balance, I should like to draw readers' attention to the following:

In the PACE trial (1), White et al did not evaluate pacing as based on the Envelope theory as described by myself and colleagues (2). Adaptive Pacing Therapy (APT) is more than activity management and the advice referred to as the 70% rule is hard to justify, based on research and experience. Excessive pre-emptive rest can result in increased social isolation, depression and deconditioning. Consequently, many of us predicted that it would not work and the PACE trial confirmed this. However, studies HAVE shown that pacingas defined by Goudsmit et al (2) does help patients and the review could have been cited in this article. Pacing is not a lay construct or based on theliterature on chronic pain. I know as I believe I was the first or secondscientist to write about it. It comes from the work on MS and Parkinson's disease. The literature on chronic pain provided the basis of the concept of graded exercise.

White et al (1) also claimed to have used the London criteria to compare patients with classic ME (myalgic encephalopathy) and people with CFS (chronic fatigue syndrome). As a co-author of the Londoncriteria who sent Prof. White both the original version formulated by fourexperts plus the questionnaire that accompanies it, I know that they were not used. Having seen the manual, I am not persuaded that the criteria listed could have distinguished patients with ME from those with fatigue due to stress or depression. The cardinal symptom was missing. It followsthat the findings from the trial can not be extrapolated to patients with classic ME.

Thirdly, White et al seem to dismiss the initial objections to the trial as unscientific. I was one of those who wrote to the MRC to alert them to methodological flaws, for instance, the failure to repeat actigraphy after treatment to confirm compliance. In all other RCTs which used objective measures to assess activity levels, none documented a significant increase. One might therefore posit that while a significant number of participants felt less tired after CBT or GET (Graded Exercise Therapy), their improvementcould not be attributed to graded exercise.

I was also concerned about the lack of measures to assess symptoms other than fatigue and sleep disturbance. Dizziness is an often reported source of disability but was not examined. Although one has to limit the number of questionnaires, important data are missing. Another example: I am still not clear from the findings how many of the allegedly 'recovered'patients were able to resume their pre-illness activities and return to their jobs. Indeed, a surprisingly high percentage at follow-up appeared to be in receipt of some kind of benefits and pensions at a time when these are only awarded to those who cannot work. One additional question could have given an indication of the participant's ability to work or return to a pre-morbid lifestyle.

Finally, may I ask fellow scientists to read articles on pacing for ME and CFS as they show that it is not only highly rated by patients, but also supported by sound evidence. It does not benefit everyone but it is anadditional therapeutic option and for many, a useful component in flexible, multi-dimensional programmes.

References: 1. White PD, Chalder T, and Sharpe M.The planning, implementation and publication of a complex intervention trial for chronic fatigue syndrome: the PACE trialPsychiatric Bulletin 2014; 0: pb.bp.113.045005v1

2. Goudsmit EM, Jason LA, Nijs J, Wallman KE. Pacing as a strategy to improve energy management in myalgic encephalomyelitis/chronic fatigue syndrome: A consensus document. Disabil Rehabil 2012; 34(13):1140-7.

... More

Conflict of interest: I co-authored the London criteria for ME.

Write a reply

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *