‘Recovery’ in PACE, the 6 Minute Walking Test and Other Issues:

How Well Can ‘Recovered’ Patients Walk?


Susanna Agardy  (Australia)


In the recent issue of Psychological Medicine several letters commenting on the PACE recovery paper (White et al 2013a) noted the absence of published data showing the relationship between the self-reported recovery scores and the results of the 6 Minute Walking Test (6MWT).  (Agardy, Maryhew, Shepherd, 2013) http://www.meassociation.org.uk/?p=16209


White et al’s response (2013b) and other matters in the PACE reports raise a number of concerns:



Once a patient is considered ‘recovered’, by whatever measure, ultimately they need to demonstrate that they can fulfill the physical demands of daily life. Even if several measures are required to demonstrate recovery, patients should be able to walk for at least 6 minutes in a one-off test at a rate better than patients awaiting lung transplants and those with severe heart failure. If they cannot do this, there is little hope that they will be able to function continuously in real life. Any definition of recovery which excludes this ability is meaningless, especially when the physical ability score defining recovery is allowed to be lower at recovery than it was at the outset (White et al 2013a).


If the statement that ‘Objective measures of physical activity have been found previously to correlate poorly with self-reported outcomes…’ (White et al 2013a) is intended to convey that the recovery measures used in PACE are not correlated with  physical capacity, then these measures should not be used as a basis for recommending the CBT and GET treatments.  If the 22%  (31 out of 143) of the CBT and GET ‘recovered’ participants far exceeded the poor average walking distance of these groups as a whole, this has not been reported.



‘Perhaps the prime indicator of the condition is the way in which symptoms behave after activity is increased beyond what the patient can tolerate. Such activity, whether physical or mental, has a characteristically delayed impact, which may be felt later the same day, the next day, or even later. This is followed by a recovery period, which again may last for days or even weeks. In some instances, the patient can sustain a level of activity for some time, but a cumulative impact is seen, with a setback after several weeks or more.’ (2002)  A repeat test would have helped to fulfill the PACE Protocol intention that the trial will ‘indicate which patient characteristics predict a successful outcome’ (White et al, 2002) for example, the characteristic of suffering from PEM.



While testing for PEM a repeat test would have contributed to testing the hypothesis that CFS consists mainly of deconditioning (White et al 2011) and provided a comparison with response to exercise in other conditions. The American Thoracic Society guidelines cite a multicentre study in which ‘…470 highly motivated patients with severe COPD (Chronic Obstructive Pulmonary Disease) performed two 6MWTs 1 day apart, and on average, the 6MWD was only 66 ft (5.8%) higher on the second day’ (2002). The improvement of ‘only 66 ft’ or 20 metres in 24 hours is about the same as the improvement in 52 weeks for the APT and SMC groups as well as the CBT group in which 22% were reportedly recovered.

As it turns out, the poor average gain of 67 metres included in the 379 metres walked after 52 weeks of GET in PACE (White et al 2011) appears to provide grounds for rejecting the deconditioning hypothesis. On the basis of this hypothesis a reversal of the condition was expected (White et al 2011).  Further, if deconditioning can no longer be considered the influencing factor in the poor physical capacity experienced by patients, arguably, the patients cannot be claimed to be dysfunctional in their attributing their illness to a physical condition.

At least two studies related to exercise suggest that deconditioning is not the influencing factor in this condition and demonstrated that a second walking test in ME may have been worse than the first for at least a sub-group of PACE participants. After measuring maximal oxygen consumption Van Ness et al (2007) concluded ‘That the CFS patients could not reproduce their performance on the first test is indicative of the post-exertional malaise that may be unique to this illness. The control group actually improved slightly from test 1 to test 2.’  


A later study confirms this finding: ‘… results from the second test (of two maximal exercise tests separated by 24 hours) indicate the presence of a CFS related post-exertional fatigue. It might be concluded that a single exercise test is insufficient to reliably demonstrate functional impairment in individuals with CFS. A second test may be necessary to document the atypical recovery response and protracted fatigue possibly unique to CFS, which can severely limit productivity in the home and workplace.’  (Snell et al, 2013).  (In these studies ‘CFS’ incorporates the ME definition.)



Fifty-one percent of participants reportedly met the London criteria for ME which includes PEM (White et al 2011).  Yet, the study design failed to cater for specific measures for even this truncated definition of PEM. As well as a repeat of the 6MWT, perhaps the 36-SF subscale could have been modified to provide a more specific measure of PEM by asking how many of the activities listed in this scale could be

carried out by a participant in one day without suffering from PEM on subsequent day/s. Instead, PEM was reportedly measured by ‘a mixture of self-ratings and research assistant assessments, making some observer bias possible’ (White et al 2013a).   





Would physically recovered patients with a healthy walking pace have performed worse than those with heart failure and those awaiting lung transplantation because of these factors?  It can be argued that the weaknesses in the testing protocol could only detract significantly from the performance of participants who were still physically debilitated at the end of treatment. For persons who had regained their pre-illness physical condition, a 6 minute walk, with or without turns, would have counted as a trivial activity. 



This study and the later Snell and Van Ness studies (as well as many others) provide evidence that CFS (or ME) is not a condition which is merely ‘defined by a patient’s reported symptoms’ as suggested by White et al (2013b).  Unfortunately, the investigators have excluded a consideration of physiological explanations for the continuation of disability in ME or CFS and therefore the need to confront the proposition that CBT and GET are unlikely to be effective. 





The 6MWT results are an important finding in PACE and should not be explained away. The investigators have not produced any acceptable explanation for the poor results of the test and have not demonstrated a connection between the test and reported recovery. The claims of recovery made in the PACE reports are not supported by the evidence.  It is time to turn to the physiological explanations documented in thousands of published studies which indicate ME to be specifically unsuited to the promoted CBT and GET treatments.




Agardy S (2013). Comments on `Recovery from chronic fatigue syndrome after treatments given in the PACE trial’ |letter]Psychological Medicine / Volume 43 / Issue 08 / August 2013, pp 1787-1787 DOI: http://dx.doi.org/10.1017/S003329171300113X (About DOI), Published online: 19 July 2013



American Thoracic Society (2002). ATS Statement: Guidelines for the six-minute walk test.

American Journal of Respiratory and Critical Care Medicine 166, 111–117.


CFS/ME Working Group (2002). A Report of the CFS/ME Working Group: Report to the Chief Medical Officer of an Independent working group. Department of Health London.



Kadikar A, Maurer J, Kesten S  (1997). The six-minute walk test: a guide to assessment for lung transplantation. The Journal of heart and lung transplantation 16, 313-9.


Lipkin DP, Scriven AJ, Crake T, Poole-Wilson PA (1986). Six minute walking
test for assessing exercise capacity in chronic heart failure. British Medical Journal 292,


Maryhew C [Z013]. Comments on ‘Recovery from chronic fatigue syndrome after treatments given in the PACE trial’ [Letter] Psychological Medicine doi:10.1017/ S0033291713001293 PACE Trial: letters and reply | Journal of Psychological Medicine | 1789-90 August 2013  http://www.meassociation.org.uk/?p=16209


Shepherd C (2013) Comments on `Recovery from chronic fatigue syndrome after treatments given in the PACE trial’ [Letter]. Psychological Medicine doi:10.1017/S003329171300130X 

Journal of Psychological Medicine letters and reply |Volume 43 / Issue 08 / August 2013, pp

 1789-90 August 2013   Published online: 19 July 2013



Snell CR, Stevens SR, Davenport TE, Van Ness JM (213) Discriminative Validity of Metabolic and Workload Measurements to Identify Individuals With Chronic Fatigue Syndrome. Physical Therapy 27 June 2013             

27 June 201310.2522/​ptj.20110368 Physical Therapy



Van Ness JM, Snell CR, Stevens SR,  Diminished Cardiopulmonary Capacity

During Post-Exertional Malaise. Journal of Chronic Fatigue Syndrome, Vol. 14(2) 2007

Available online at http://jcfs.haworthpress.com

2007 by The Haworth Press. All rights reserved.

doi:10.1300/J092v14n02_07 77   http://www.cfids-cab.org/MESA/VanNess.pdf 


Van Ness JM, Snell CR, Strayer DR,  Dempsey L, Stevens SR, Subclassifying chronic fatigue syndrome through exercise testing. Medicine & Science in Sports & Exercise (impact factor: 4.43). 06/2003; 35(6):908-13. DOI:10.1249/01.MSS.0000069510.58763.E8 http://www.researchgate.net/publication/10728803_Subclassifying_chronic_fatigue_syndrome_through_exercise_testing


White PD, Goldsmith K, Johnson AL, Chalder T, Sharpe M; Psychological Medicine, 43 (2013b). doi:10.1017/S0033291713001311 Letter to the Editor Response to correspondence concerning `Recovery from chronic fatigue syndrome after treatments in the PACE trial' . Journal of Psychological Medicine | August  2013 Volume 43 / Issue 08 / August 2013, pp

 1789-90  Published online: 19 July 2013



White PD, Goldsmith K, Johnson AL, Chalder T, Sharpe M; PACE Trial Management Group (2013a). Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychological  Medicine Jan 31: 1-9 available on CJO2013. doi:10.1017/S0033291713000020.

White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, Baber HL, Burgess M, Clark LV, Cox DL, Bavinton J, Angus BJ, Murphy G, Murphy M, O'Dowd H, Wilks D, McCrone P, Chalder T, Sharpe M; PACE trial management group (2011). Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 377, 823-36.

White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R and the PACE trial group  (2006) 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

PACE trial protocol: Final version 5.0, 01.02.2006 ISRCTN54285094



Independent Working Group