The MEA calls for immediate stop to PACE an FINE trials
Here is a copy of the statement from the M.E. Association on the Pace Trial - posted 22nd May 2004
Background
In May 2003 the Medical Research Council (MRC) announced funding for two clinical trials* to assess the effectiveness of various types of non-drug treatment for patients with ME/CFS.
The PACE trial (P = adaptive Pacing, A = graded Activity, C = Cognitive behaviour therapy: E = a randomised Evaluation) intends to evaluate the results of adding one of these three treatment approaches to what the MRC describes as 'usual specialist medical care' (USMC) in the six specialist ME/CFS clinics where participants will be recruited.
The PACE trial will be led by Dr Peter White (Saint Bartholomew's Hospital, London), Professor Michael Sharpe (University of Edinburgh), and Professor Trudie Chalder (King's College Hospital, London) - all of whom work in the area of either psychiatry or psychological medicine.
Funding for the PACE trial will come from the MRC, Scottish Chief Scientist's Office, and the English Department of Health and Department of Work and Pensions.
600 patients will be recruited from six different specialist ME/CFS clinical centres across the UK. These are situated in Edinburgh, Oxford and London (Saint Bartholomew's Hospital x2, King's College Hospital, Royal Free Hospital). Those who consent to take part in the trial will be randomly allocated to USMC alone or USMC plus 14 sessions involving one of the three different management options being evaluated.
Various categories of patients will be excluded from taking part in the PACE trial. These include children, the severely affected who cannot attend a clinic on a regular basis, those who have already attended a course of one of the treatments under investigation at a specialist clinic, and people with a very poor command of English.
The PACE trial is due to start later in the year.
ME Association position
A number of criticisms concerning the overall value of the PACE trial and the way in which it is going to be carried out have now been made by the ME/CFS patient community. The ME Association believes that many of these criticisms are valid. However, we believe that some are not.
The position of The ME Association is as follows:
We fully agree that research into the use of pacing as a form of management is worthy of further research. However, we believe that the money being allocated to the PACE trial is a scandalous way of prioritising the very limited research funding that the MRC have decided to make available for ME/CFS - especially when no money whatsoever has so far been awarded for research into the underlying physical cause of the illness or for pharmacological approaches aimed at either symptomatic relief or possible disease mechanisms. We therefore believe that work on this trial should be brought to an immediate close and that the money should be held in reserve for research that is likely to be of real benefit to people with ME/CFS.
But if the PACE trial is to continue:
1 We are concerned about the validity of results that will be obtained from comparing patients with USMC alone to those where a pacing programme has been added because usual medical care per se in a specialist clinic should contain reasonably detailed advice about activity and energy management that is often very similar to pacing. To omit advice about energy management would be unethical.
2 Overall, we believe that the PACE trial is unlikely to produce any significant further information about the potential benefits (as well as possible harmful effects) of these three forms of management in addition to that which has already been reported by patients, clinicians, and in the results from previous clinical trials.
3 We share some, but not all, of the concerns being expressed about the way in which patients will be chosen to participate in the trial. We also have concerns about the secondary analysis that is intended to demonstrate which sub-groups of patients may gain benefit from the three different additional approaches to management.
3.1 With regard to concerns currently being expressed about the use of Oxford criteria for the diagnosis of CFS (or a post viral/infectious fatigue syndrome sub-group): we believe there may actually be some advantage in using the Oxford criteria for selection of patients - despite its many obvious defects. The Oxford criteria covers a very wide spectrum of chronic fatigue patients and this would also include almost all of those with Ramsay described or London defined ME of six months or more duration.
3.2 If the entry criteria were to be changed to Fukuda et al, then this would have the effect of excluding a significant minority of people with ME from taking part.
3.3 There is no point in asking for the Canadian criteria to be used as entry criteria as they are not designed or validated for research purposes.
3.4 Consequently, if the PACE trial contains a large number of people under the CFS spectrum with the intention of then doing a secondary analysis of responses according to other diagnostic criteria, there is obviously some merit in using the Oxford criteria as the starting point.
3.5 As far as secondary analysis of the results is concerned, we believe that the London criteria is a satisfactory way of sub-grouping the ME patients. But we also believe that there should be other ways of sub-grouping the results - eg presence or absence of psychiatric co-morbidity. We are not convinced that this aspect has been properly thought through.
3.6 As far as the issue of Oxford criteria excluding people with a proven clinical diagnosis of an organic brain disease (section f.ii), it could be argued that this is not consistent with WHO ICD10 classification of ME and CFS as neurological disorders under G93.3 ('other disorders of the brain'). However, in practice, we do not believe that this is going to be a way of preventing people with Ramsay described ME or London defined ME from taking part in the trial.
4 We share the concerns being expressed relating to informed consent, particularly in relation to patients who are selected to take part in graded exercise therapy. The Chief Medical Officer's report (section 4.4.2.1) noted that 50% of ME/CFS patients reported that graded exercise had made their condition worse, and we therefore believe that anyone volunteering to undergo graded exercise therapy must be made aware of these findings as well as the observations from clinicians and research studies made in the CMO report.
4.1 Furthermore, we believe it is disingenuous to describe this as a PACE trial when intervention A equates to graded exercise and not simple activity - it should therefore be a PECE trial with E = exercise. In therapeutic and physiological terms there is an important difference between the two descriptions: graded exercise involves a progressive increase in aerobic activity (ie oxygen requiring) that is designed to increase heart rate and breathing whereas simple activity does not.
5 We do not believe that patients whose primary diagnosis is fibromyalgia should be entered into the trial. Although there is some overlap between fibromyalgia and ME/CFS, and it may co-exist with ME/CFS, fibromyalgia on its own is classified as a separate clinical entity in WHO ICD10 under 'soft tissue disorders' in section M79. Fibromyalgia should therefore be one of the 'established medical conditions known to cause chronic fatigue' as described in exclusion criteria listed in section f.i of the Oxford criteria.
KEY REFERENCES
Canadian criteria:
ME/CFS: Clinical Working Case Definition, Diagnostic and Treatment Protocols. Journal of Chronic Fatigue Syndrome, 2003, 11, 7 - 116.
Fukuda et al criteria:
Fukuda K, Straus S, Hickie I, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Annals of Internal Medicine 1994, 121, 953 - 959.
London criteria:
Dowsett EG, Goudsmit E, Macintrye A, Shepherd C. London criteria for ME - Report for the National Task Force on chronic fatigue syndrome (CFS), post-viral fatigue syndrome (PVFS), myalgic encephalomyelitis (ME). Westcare, 1994, 96 - 98.
Oxford criteria:
Sharpe M, Archard L, Banatvala J, et al. Guidelines for the conduct of research into the chronic fatigue syndrome. Journal of the Royal Society of Medicine, 1991, 84, 118 - 121.
CMO report on-line:
http://www.doh.gov.uk/cmo/cfsmereport
*The second treatment trial, known as FINE, (Fatigue Intervention by Nurse Evaluation) is wholly funded by the MRC. This is a form of what the MRC term 'rehabilitation therapy' which will be delivered by specialist community nurses in the patients' own homes. The FINE trial will involve patients in the North West of England and North Wales. The ME Association is not convinced by the evidence so far put forward in support of this approach. And as with the PACE trial, we do not believe that this is a sensible way of prioritising limited research funding. Consequently, we believe that all further work on this trial should also be halted and the money kept in reserve for other ME/CFS research.
MEA
May 2004
Background
In May 2003 the Medical Research Council (MRC) announced funding for two clinical trials* to assess the effectiveness of various types of non-drug treatment for patients with ME/CFS.
The PACE trial (P = adaptive Pacing, A = graded Activity, C = Cognitive behaviour therapy: E = a randomised Evaluation) intends to evaluate the results of adding one of these three treatment approaches to what the MRC describes as 'usual specialist medical care' (USMC) in the six specialist ME/CFS clinics where participants will be recruited.
The PACE trial will be led by Dr Peter White (Saint Bartholomew's Hospital, London), Professor Michael Sharpe (University of Edinburgh), and Professor Trudie Chalder (King's College Hospital, London) - all of whom work in the area of either psychiatry or psychological medicine.
Funding for the PACE trial will come from the MRC, Scottish Chief Scientist's Office, and the English Department of Health and Department of Work and Pensions.
600 patients will be recruited from six different specialist ME/CFS clinical centres across the UK. These are situated in Edinburgh, Oxford and London (Saint Bartholomew's Hospital x2, King's College Hospital, Royal Free Hospital). Those who consent to take part in the trial will be randomly allocated to USMC alone or USMC plus 14 sessions involving one of the three different management options being evaluated.
Various categories of patients will be excluded from taking part in the PACE trial. These include children, the severely affected who cannot attend a clinic on a regular basis, those who have already attended a course of one of the treatments under investigation at a specialist clinic, and people with a very poor command of English.
The PACE trial is due to start later in the year.
ME Association position
A number of criticisms concerning the overall value of the PACE trial and the way in which it is going to be carried out have now been made by the ME/CFS patient community. The ME Association believes that many of these criticisms are valid. However, we believe that some are not.
The position of The ME Association is as follows:
We fully agree that research into the use of pacing as a form of management is worthy of further research. However, we believe that the money being allocated to the PACE trial is a scandalous way of prioritising the very limited research funding that the MRC have decided to make available for ME/CFS - especially when no money whatsoever has so far been awarded for research into the underlying physical cause of the illness or for pharmacological approaches aimed at either symptomatic relief or possible disease mechanisms. We therefore believe that work on this trial should be brought to an immediate close and that the money should be held in reserve for research that is likely to be of real benefit to people with ME/CFS.
But if the PACE trial is to continue:
1 We are concerned about the validity of results that will be obtained from comparing patients with USMC alone to those where a pacing programme has been added because usual medical care per se in a specialist clinic should contain reasonably detailed advice about activity and energy management that is often very similar to pacing. To omit advice about energy management would be unethical.
2 Overall, we believe that the PACE trial is unlikely to produce any significant further information about the potential benefits (as well as possible harmful effects) of these three forms of management in addition to that which has already been reported by patients, clinicians, and in the results from previous clinical trials.
3 We share some, but not all, of the concerns being expressed about the way in which patients will be chosen to participate in the trial. We also have concerns about the secondary analysis that is intended to demonstrate which sub-groups of patients may gain benefit from the three different additional approaches to management.
3.1 With regard to concerns currently being expressed about the use of Oxford criteria for the diagnosis of CFS (or a post viral/infectious fatigue syndrome sub-group): we believe there may actually be some advantage in using the Oxford criteria for selection of patients - despite its many obvious defects. The Oxford criteria covers a very wide spectrum of chronic fatigue patients and this would also include almost all of those with Ramsay described or London defined ME of six months or more duration.
3.2 If the entry criteria were to be changed to Fukuda et al, then this would have the effect of excluding a significant minority of people with ME from taking part.
3.3 There is no point in asking for the Canadian criteria to be used as entry criteria as they are not designed or validated for research purposes.
3.4 Consequently, if the PACE trial contains a large number of people under the CFS spectrum with the intention of then doing a secondary analysis of responses according to other diagnostic criteria, there is obviously some merit in using the Oxford criteria as the starting point.
3.5 As far as secondary analysis of the results is concerned, we believe that the London criteria is a satisfactory way of sub-grouping the ME patients. But we also believe that there should be other ways of sub-grouping the results - eg presence or absence of psychiatric co-morbidity. We are not convinced that this aspect has been properly thought through.
3.6 As far as the issue of Oxford criteria excluding people with a proven clinical diagnosis of an organic brain disease (section f.ii), it could be argued that this is not consistent with WHO ICD10 classification of ME and CFS as neurological disorders under G93.3 ('other disorders of the brain'). However, in practice, we do not believe that this is going to be a way of preventing people with Ramsay described ME or London defined ME from taking part in the trial.
4 We share the concerns being expressed relating to informed consent, particularly in relation to patients who are selected to take part in graded exercise therapy. The Chief Medical Officer's report (section 4.4.2.1) noted that 50% of ME/CFS patients reported that graded exercise had made their condition worse, and we therefore believe that anyone volunteering to undergo graded exercise therapy must be made aware of these findings as well as the observations from clinicians and research studies made in the CMO report.
4.1 Furthermore, we believe it is disingenuous to describe this as a PACE trial when intervention A equates to graded exercise and not simple activity - it should therefore be a PECE trial with E = exercise. In therapeutic and physiological terms there is an important difference between the two descriptions: graded exercise involves a progressive increase in aerobic activity (ie oxygen requiring) that is designed to increase heart rate and breathing whereas simple activity does not.
5 We do not believe that patients whose primary diagnosis is fibromyalgia should be entered into the trial. Although there is some overlap between fibromyalgia and ME/CFS, and it may co-exist with ME/CFS, fibromyalgia on its own is classified as a separate clinical entity in WHO ICD10 under 'soft tissue disorders' in section M79. Fibromyalgia should therefore be one of the 'established medical conditions known to cause chronic fatigue' as described in exclusion criteria listed in section f.i of the Oxford criteria.
KEY REFERENCES
Canadian criteria:
ME/CFS: Clinical Working Case Definition, Diagnostic and Treatment Protocols. Journal of Chronic Fatigue Syndrome, 2003, 11, 7 - 116.
Fukuda et al criteria:
Fukuda K, Straus S, Hickie I, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Annals of Internal Medicine 1994, 121, 953 - 959.
London criteria:
Dowsett EG, Goudsmit E, Macintrye A, Shepherd C. London criteria for ME - Report for the National Task Force on chronic fatigue syndrome (CFS), post-viral fatigue syndrome (PVFS), myalgic encephalomyelitis (ME). Westcare, 1994, 96 - 98.
Oxford criteria:
Sharpe M, Archard L, Banatvala J, et al. Guidelines for the conduct of research into the chronic fatigue syndrome. Journal of the Royal Society of Medicine, 1991, 84, 118 - 121.
CMO report on-line:
http://www.doh.gov.uk/cmo/cfsmereport
*The second treatment trial, known as FINE, (Fatigue Intervention by Nurse Evaluation) is wholly funded by the MRC. This is a form of what the MRC term 'rehabilitation therapy' which will be delivered by specialist community nurses in the patients' own homes. The FINE trial will involve patients in the North West of England and North Wales. The ME Association is not convinced by the evidence so far put forward in support of this approach. And as with the PACE trial, we do not believe that this is a sensible way of prioritising limited research funding. Consequently, we believe that all further work on this trial should also be halted and the money kept in reserve for other ME/CFS research.
MEA
May 2004
posted by Ingrid J. Jones at Wednesday, January 19, 2005
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