Pace Trial : the facts at a glance :

Stonebird

Pace Trial : the facts at a glance :
Updated : 25th Feb 2011

“at best, PACE is telling us that the two main therapies currently recommended by the National Institute for Health and Clinical Excellence (NICE) are only moderately effective.” Action for ME

“The results of the PACE Trial may mean that patients who have genuine ME as opposed to chronic “fatigue” will continue to be denied appropriate investigation and treatment; they may be deprived of State benefits necessary for survival; their insurance claims may be rejected, and they will be condemned to an even lower quality of life.” Professor Malcolm Hooper

1.The PACE Trial reports that patients who received a six-month course of cognitive behavioral therapy (CBT) or graded exercise therapy (GET) had improvement in self-reported symptom scores at higher rates than those who were provided specialized medical care alone (SMC) or adaptive pacing
therapy (APT).

2.The PACE Trial authors acknowledge that the studied treatments were only moderately effective and that the effectiveness of behavioural treatments does not imply that the condition is psychological innature.

3.Headlines, in the Press, have touted far more conclusive results than the data support.

 4.The PACE Trial was funded by the U.K. Medical Research Council, the U.K. Department of Health and the U.K. Department for Work and Pensions.

5. There is a concern of serious conflicts of interest at the UK Department of Work and Pensions (DWP) who part-funded the PACE Trial. Like the permanent health insurance industry, the DWP has a potential financial vested interest if patients' disability can be portrayed as caused by or largely exacerbated by behavioural factors. 

6.The patient population was selected using the Oxford criteria for CFS. 3,148 patients diagnosed with CFS recruited from six CFS speciality clinics were screened to identify 641subjects who met study criteria.

7.The MRC PACE Trial excluded children and those who are severely affected. The results of any trial that excluded those who are severely affected cannot be taken seriously.

8.The PACE Trial used no objective measures of outcome to show improvement or non-improvement and relies upon participants’ subjective answers to questionnaires. This is an unscientific way to gather evidence. There can be no empirical science without objective measures – objective measures are at the heart of the scientific method.

9.Professor White and his co-Principal Investigators all have financial links with the health insurance industry. (Professor Hooper)

10. Professor Simon Wessely, who directed the PACE Clinical Trial Unit, is on record stating that CBT provides no effective treatment: in his Editorial (JAMA 19th September 2001:286:11) he stated that CBT and GET are only “modestly effective” and that neither is “remotely curative”.

11. The MRC FINE Trial (sibling of the PACE Trial) failed spectacularly. It found that “pragmatic rehabilitation” (PR, based on CBT/GET) was minimally effective in reducing fatigue and improving sleep only whilst participants were engaged in the programme and that there was no statistically significant effect at follow-up.

12. The PACE Trial selected people who met the Oxford Criteria and had a physical function score of >65. People who had psychosis, bipolar disorder, substance abuse, an organic brain disorder or eating disorder were excluded (58 people in total). No exclusions for other disorders were noted. Many people declined to assessed or to engage in a randomized treatment (n=398) (It’s possible that these people included people afraid of being assessed the GET or CBT protocols). A good number of people simply refused to be assessed (n=143). Another chunk of people (n=139) couldn’t follow the protocols for one reason or another (too sick?). 


Update : the text of the Lancet article states that participants were also assessed by “the London criteria for myalgic encephalomyelitis (version 2) requiring postexertional fatigue”  however, according to Professor Hooper,  Professor White amended the Protocol and he substituted what appears to be his own version of the “London Criteria” for the Ramsay definition.  blurred vision; double vision; increased sensitivity of hearing; increased sensitivity to noise; feeling generally awful, and muscle weakness after exercise. In contrast, Professor White’s version of the “London Criteria” specifically states on page 188 of the Full Protocol that neurological disturbances “are not necessary to make the diagnosis” and they further state that “the usual precipitation by ‘physical or mental exercise’ should be recorded but is not necessary to meet criteria”. Professor White’s  “London Criteria”do not  appear to require the cardinal feature of ME to be present. This begs the question as to what disorder was being studied under the title of ME/CFS.

Response from Professor Malcom Hooper to David Jameson

http://www.meactionuk.org.uk/Response-to-David-Jameson.htm

13.Ahead of the PACE trail report, Peter White published a report : Psychiatric misdiagnoses in patients with chronic fatigue syndrome, which found that out of 135 participants at a PACE trail center , diagnosed with "CFS" according to the Oxford Criteria , 56% had a" co-morbid psychiatric diagnosis."

Of these :

• 31% had a major or minor depressive episode
• 11% had dysthymia
• 35% had an anxiety disorder
• 2% had a an obsessive compulsive disorder
• 6% had post-traumatic stress disorder
• 8% had Social Phobia
• 15% had a "specific phobia"

14.The Oxford criteria upon which the PACE and FINE trials were based , were drawn up by psychiatrists in 1990 and broaden the 1988 Holmes CFS criteria to include all those with psychiatric “chronic fatigue" , while specifically excluding those with neurological disorders. The Oxford criteria state: "The following guidelines were agreed. There are no clinical signs characteristic of the condition. Psychiatric disorders (including depressive illness, anxiety disorders and hyperventilation syndrome) are not necessarily reasons for exclusion". (Williams 2004) . 0ne of the authors of the Oxford criteria, Professor Anthony David, clarified the issue of whether or not the Oxford criteria exclude people with neurological disorders: “British investigators have put forward an alternative, less strict, operational definition which is essentially chronic…fatigue in the absence of neurological signs, (with) psychiatric symptoms…as common associated features” (AS David; BMB 1991:47:4:966-988). 


The PACE Trial conflated two diseases that the WHO rightly categorises separately - neurological 'ME/PVFS' (ICD-10-G93.3) and psychiatric 'Fatigue Syndrome' (ICD-10-F.48.0) - and misrepresented the latter as the former. 

15. PACE Trial participants were referred from six specialist hospital CFS/M.E. clinics in Edinburgh, Oxford, Bristol and London.

16. The average age of participants was 38; 77% were female, 56% met the London criteria for ME, 47% were diagnosed with a psychiatric disorder during their clinical interview (depression, anxiety, obsessive compulsive disorder, PTSD), a high percentage of people in the study were on antidepressants (@33%), half had a history of depression, their average duration of illness was 32 months (2 ½ years) and their average body mass index (BMI) was 25.5…(normal BMI = 20-25). 

17. Participants had to be able to attend sessions at a hospital or clinic, and therefore more severely ill or homebound patients were not included. The study recruited patients age 18 and older. The average duration of illness was about three years and no subject had been ill longer than six years.

18. A high percentage of the group were confident about how successful the GET protocol would be (70%) as well as pacing (71%). They had lower confidence in CBT (57%) and low confidence in the efficacy of the specialist medical care (41%). 

19. Participants were randomly divided into 4 treatment arms :

• 'Adapted Pacing' : a form of pacing , specifically created for this study that focused on adapting to available energy levels and systematically increasing them over time.
• Cognitive behavioral therapy (CBT) : In the Medical Research Council’s PACE trial on CFS/ME, CBT  was “ based on the illness model of fear avoidance”; in the Guide to Mental Health in Primary Care it is described in the following terms: “This is used to change a patient’s thought processes and behaviour”, while the NICE Guideline itself describes CBT as “a psychological therapy”. CBT services were delivered by clinical psychologists and nurse therapists. They guided patients to establish a baseline of activity and rest and a regular sleep pattern, and then make collaboratively planned gradual increases in both physical and mental activity. Participants were helped to address social and emotional obstacles to improvement through problem-solving.
• Graduated Exercise Therapy (GET) : GET was described in the MRC PACE trial on CFS as being “based on the illness model of both deconditioning and exercise avoidance”, whilst the CG53 graded exercise plan specifies that the intensity of GET should be incrementally increased (with the patient’s agreement), leading to aerobic exercise. GET services were provided by physiotherapists and one exercise physiologist. Therapeutic strategies in the GET group consisted of establishing a baseline of achievable exercise or physical activity,followed by a negotiated, incremental increase in the duration of time spent physically active. Target heart rate ranges were set when
  necessary to avoid overexertion, which eventually aimed at 30 minutes
  of light exercise five times a week.
• Specialized Medical Treatment care At least three sessions of
  medical care were provided to all 641 participants over the six-month
  study period, and additional sessions were available as needed. These
  sessions included basic pharmacologic support, especially for sleep,
  pain and mood.

20. Participants were given 14 therapy sessions over the first 23 weeks and then one at 36 weeks. Their health was assessed at baseline, 23 weeks and 52 weeks using a wide variety of self report measures.

21. An actigraphy test that measured movement over time was included in the original protocol , but that test was dropped from the final protocol .

22. There were no biological measures reported. Studies of CBT in other conditions including HIV/AIDS and cardiovascular disease, routinely collect data on immune markers or other biological measures in attempt to understand how and why CBT works in the context of the condition studied.

23. The practitioners measured treatment effectiveness using a broad array of self-report tests including a clinical global health scale, work and social adjustment scale, 6 min walking ability, Jenkins score for disturbed sleep, anxiety and depression scales, symptoms and others.

24. Negative change was reported by six percent of the CBT group,seven percent of the GET and pacing groups, and nine percent of the group receiving specialized medical care alone.

25.Serious adverse events were lowest in the CBT and medical care alone group with four percent; highest was the pacing group with nine percent.

26. Eighty-four percent of the subjects reported post-exertional relapse at baseline and the distribution of subjects into the four groups resulted in
fairly even distribution of this symptom across the four treatment
groups.

27. At the end of the study, 63 percent of the pacing participants reported post-exertional malaise. In the group that received specialized medical care only, participants were simply counseled to avoid the extremes of rest and activity; 63 percent of them reported post-exertional malaise at follow-up. In the CBTgroup where participants were encouraged to do more than they thought they could, post-exertional relapse was reported by 49 percent of the
participants at follow-up. in the GET group, where participants were advised to gradually return to appropriate physical activities and reverse deconditioning. At the one-year mark the report of post-exertional relapse in this group had
dropped from 82 percent to 44 percent of participants.

28. The clinical global impression, CGI, saying that number of trial participants rating themselves as "much" or "very much" better after 52 weeks were 41% for cognitive behaviour therapy, 41% for graded exercise, 31% for adaptive pacing and 25% for specialised medical care. In other words, the overwhelming majority of participants reported they did not feel better.

29. The clinically useful difference CUD ie. the numbers of participants who showed statistically significant but, from the patient perspective, modest  improvements in fatigue and physical function at 52 weeks were graded exercise 61% (94/154), cognitive behaviour therapy 59% (87/148), specialised medical care 45% (68/152) and adaptive pacing 42% (64/153).

30. Action for ME comment : “ to focus on modest improvements in fatigue and physical functioning, which researchers can measure *CUD) – rather than on how much better patients themselves say they feel overall (CGI)– overstates the benefits and of these therapies."

31. The goal of the PACE trial was to “was to change the behavioural and cognitive factors assumed to be responsible for perpetuation of the participant’s symptoms and disability."

32. The authors did not conclude CBT/GET/PACING were cures for CFS or even 'effective' treatments for it; they said they were 'only moderately effective', a decidedly weak assessment of its effects and that assessment is the crux around which we should understand this study. (Phoenix Rising)

33. When asked did the treatments have significantly positive effects, about 40% of the participants said they did (for CBT) - meaning that almost 2/3rds of them received minimal or negative benefits from them. 

34.While most participants improved the tests revealed that few improved really significantly and none suggested a return to health had been achieved.

35. The therapies still left the participants with ‘more than usual’ fatigue/cognitive issues. 

36. The criteria for what constituted a ‘clinically useful result’ was quite low. All it took was a movement of less than 10% (scale-wise) on two questions for the therapies to be determined 'clinically useful.

37. Even with these lax criteria only 42% of Adaptive Pacing, 59% of CBT, 61% of GET and 45% of Specialist were able to meet them. To put it another way even with these low criteria fully 40% of the CBT participants ( the most effective therapy) did not achieve what the authors determined was a ‘clinically useful ‘result. 

38. CBT and GET were better than 'Adaptive Pacing' , however in the most effective treatments , participants went from an average of a five to a four - or from reporting they were in the first tier of being ‘very severely impaired’ to being almost very severely impaired. 

39. None of the therapies assisted the participants to come close to even maintaining an ‘easy health walk’ for all of six minutes.


Update : "None of the interventions in the PACE Trial enabled participants to achieve anything like a normal walking speed for the full six minutes when compared with a healthy individual. It is regrettable that Professor White decided to abandon the use of an actometer, which would have provided unequivocal objective evidence of improvement or non-improvement.  The only reported improvement on the six minute level walking test for those allocated to CBT was an increase of 21 steps, whilst for those allocated to APT (note that APT is not the same as pacing, as APT is a vehicle for incremental aerobic exercise and involves planning, achieving and sustaining targets) there was an increase of 20 steps, these improvements having cost the nation £5 million."

Response from Professor Malcom Hooper to David Jameson

http://www.meactionuk.org.uk/Response-to-David-Jameson.htm

40. None of these treatments returned their health to the participants or close to it. They were still highly bothered by fatigue, had high levels of symptoms and lacked endurance. If the objective was to get patients well -and the stated objective was to remove the factors that perpetuated their symptoms (ie that caused their condition) - the trial failed spectacularly. (Phoenix Rising)

41.The thesis that chronic fatigue syndrome results from deconditioning or fear avoidance or negative thoughts was not borne out by this study.

42. The word “biology” is not mentioned once in the PACE Trail Report.

43. The UK National Institute for Health and Clinical Excellence (NICE) have already said that they will review their 'CFS/ME' Guideline 53 when the PACE Trial is published: having previously refused to do so on the basis of biomedical research evidence presented to them - even though the Guideline was due for a scheduled three-yearly review last August. 

44. With the published PACE Trial results under their belt, NICE are widely expected to firm-up their behavioural guideline and make it harder for doctors to treat 'CFS/ME' patients in any way other than with CBT/GET in spite of growing international evidence contraindicating such an approach. (Anglia ME Action)

References :

Action for ME PACE: “surprising and disappointing”

18 February 2011 http://www.afme.org.uk/news.asp?newsid=1047

Margaret Williams ME/CFS: Terminology: 27 April 2009

May 1, 2009 http://www.meactionuk.org.uk/ME_CFS_TERMINOLOGY.htm

Cort Johnson A Hitch in its Step: PACE Trial Indicates CBT/GET No Cure For CFS, 60% of Patients Show No Significant Effects. Phoenix Rising http://forums.aboutmecfs.org/content.php?369-A-Hitch-in-its-Step

Professor Hooper’s Initial Response to the MRC PACE Trial Press Release hosted by The Lancet 17th February 2011

www.meactionuk.org.uk/Hooper-response-to-PACE-Trial-Press-Release.htm

CFIDS Association of America Falling Off the PACE Analysis of the Lancet study http://www.facebook.com/notes/the-cfids-association-of-america/falling-off-=the-pace/10150148445700539

Anglia ME Action Collective International Professional Response to PACE Required?

http://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind1102c&L=co-cure&T=0&F=&S=&P=6265