The Lancet publish the results of the PACE study, 18 February 2011

February 18, 2011


TRIAL SHOWS THAT COGNITIVE BEHAVIOURAL THERAPY AND GRADED EXERCISE THERAPY ARE SAFE AND EFFECTIVE TREATMENTS FOR CHRONIC FATIGUE SYNDROME

Despite previous evidence that both cognitive behavioural therapy (CBT) and graded exercise therapy (GET) can be effective treatments for chronic fatigue syndrome (CFS), some patients’ organisations have reported that these treatments can be harmful and instead prefer pacing and specialist medical care (SMC). The PACE trial, published *Online First* and in an upcoming /Lancet/, shows that while CBT and GET have positive effects on CFS when combined with SMC as compared to SFC alone, adaptive pacing therapy (APT) with SMC is no more effective than SMC alone. The *Article*is by Profs Peter White (Barts and The London School of Medicine, UK), Trudie Chalder (King’s College London, UK), Michael Sharpe (University of Edinburgh, UK) and colleagues. The trial is funded by the UK Medical Research Council and various departments of UK governments.

CFS, sometimes called Myalgic Encephalomyelitis (ME), is a long-term, complex and debilitating condition that causes fatigue and other symptoms such as poor concentration and memory, disturbed sleep, and muscle and joint pain. The cause of the condition— affecting some 250,000 people in the UK alone—is unknown.

SMC consists of advice about CFS, including avoidance of activity extremes, and rest and self-help strategies. APT is based on the theory that CFS is an irreversible condition that leaves patients with a limited amount of energy, and that individuals adapt their lives to this available energy through use of a daily diary. CBT is based on the premise that cognitive responses (fear of engaging in activity) and behavioural responses (avoidance of activity) are linked and interact with physiological processes to perpetuate fatigue. GET helps a CFS patient gradually step up their level of physical activity to counter the deconditioning that has set in as their activity has fallen. Walking is a popular choice for this.

In PACE, 640 patients were assigned to one of SMC alone (160 patients), SMC/CBT (161), SMC/GET (160) and SMC/APT (159). After a follow-up of one year, mean fatigue and physical function scores had improved more after CBT and GET than after both APT and SMC alone. Serious adverse reactions to treatment were recorded in two APT patients (1%), three CBT patients (2%), two (1%) GET patients, and two (1%) in the SMC-only group.

The group plans to report in the near future on cost-effectiveness of these various treatments, and say that since even CBT and GET only offer a moderate improvement in symptoms, research into new effective treatments must go on.

The authors conclude: “We affirm that cognitive behaviour therapy and graded exercise therapy are moderately effective outpatient treatments for chronic fatigue syndrome when added to specialist medical care, as compared with adaptive pacing therapy or specialist medical care alone. Findings from PACE also allow the following interpretations: adaptive pacing therapy added to specialist medical care is no more effective than specialist medical care alone; our findings apply to patients with differently defined chronic fatigue syndrome and myalgic encephalomyelitis (ME) whose main symptom is fatigue; and all four treatments tested are safe.”

In a linked *Comment*, Dr Gijs Bleijenberg, and Dr Hans Knoop, Expert Centre for Chronic Fatigue, Radboud University NijmegenMedical Centre, Netherlands, say: “The central role of cognition in relation to fatigue might explain why graded exercise therapy is effectiveand adaptive pacing therapy is not.” They note that /in adaptive//pacing patients learn to focus on the fatigue in order to stop “in time”, which does not seem to help, while in graded exercise patients learn that they are able to do more than they thought possible.

They conclude: “Remarkably in this context, confidence in the treatment at the start is substantially lower with cognitive behaviour therapy than it is with adaptive pacing therapy. Despite lowered confidence in cognitive behaviour therapy, this therapy is more effective than is adaptive pacing therapy. Patient’s confidence in treatment can only change if a change in abilities is perceived, which generally seems to happen in cognitive behaviour therapy.”

ABSTRACT HERE:

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60172-4/abstract

FULL TEXT HERE:

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60096-2/fulltext

33 thoughts on “The Lancet publish the results of the PACE study, 18 February 2011”

  1. PACE Trial is not about the neurological disease ME/CFS. The study excluded those with neurological signs.

    Adaptive Pacing Therapy (APT) is not pacing. Real pacing is a common sense approach where a person listens to their body to survive. APT is based on the myth that patients experience a “boom and bust” pattern of activity. Targets of activity are set and inreased. It is GET by another name!

    1. The study excluded those with neurological signs.

      This is false. The ‘Oxford Criteria’, whatever its failings does not exclude neurological symptoms of undiagnosed cause.

      No doubt we are about to see an endless repetition of the ‘GET kills’ meme along with a raft of other representations of how evil psychiatrists are.

      PACE for all its hype (and excessive cost) does no more than confirm that current NHS Clinic practice is in broad terms, ‘safe’. Despite this I fully expect a vocal portion of M.E sufferers to perpetuate the crass psych/phys war.

      The smart thing to do would be to simply accept PACE for what it is: a study of limited relevance which results from the use of the Oxford Criteria which not effectively exclude purely psychiatric diagnosis – and move on from there.

      Causation and epidemiolgy are what we should be looking to and PACE offers nothing that need distract from that.

      IVI

      1. I would tend to agree here IVI.

        And would add that Ayme are wrong to go to the lengths of acceptance of the trial that they have, but that Action for ME are likewise going too far (in my opinion), in their condemnation.

        The Lancet article (as I have said) is not inherently to be condemned. Challenged certainly, but not condemned.

        The mis-selling of CBT and GET does need urgent attention as this is one of the main problems.

        In my experience, responsible doctors and consultants on the NHS now, will recognise the limitations of both ‘treatments’.

        They are a help to some and nothing more to others. Some people benefit to a greater extent from them, some do not.

        Same goes with the current raft of prescribed medications and medical opinion.

        1. They [CBT & GET] are a help to some and nothing more to others. Some people benefit to a greater extent from them, some do not.

          Absolutely.

          Certainly there are problems where the ‘negotiated’ element (stressed in PACE) has been neglected by some practitioners in some NHS clinics, but that’s a delivery issue, not an inherent failing of CBT or GET.

          There is a huge irony in the PACE results for those people who have criticised the selection criteria – the participant reported outcomes (Fig 2. in the full text) show that those selected under the London criteria actually achieved reduced fatigue under CBT treatment compared to the Oxford selected participants. And when it comes to improved physical function both CBT and GET produced better results for the London selected participants than for the Oxford ones.

          IVI

          1. The Oxford criteria was applied first. There would be no people displaying neurological signs in the study after this. Therefore, it is irrelevant if the London criteria or Fukuda criteria were applied later.

            The PACE Trial would not have contained people with ME/CFS.

        2. The PACE Trial is to be condemned. It did not use the patient population it claims to have. It did not adhere to the Declaration of Helsinki.

          The PACE Trail results will now be incorrectly and unscientifically pushed onto everyone with fatigue.

          CBT and GET are potentially very dangerous for people with ME.

        3. PACE is being rightfully condemned.

          The ME Association, Action for ME, Invest in ME have all issued statements about it already, as has Professor Hooper, author of the detailed critique of PACE, “Magical Medicine: how to make an illness disappear”.

          The only charity that I know of that has welcomed the results is AYME – its opinion is highly suspect, given its involvement with the study of The Lightning Process in children with ME, itself based on a behavioral techniques, and led by its medical adviser Esther Crawley, who defends the use of CBT and GET, and given that its president, Esther Rantzen, has also sung the praises of CBT and GET in the media over the years with the claim that her daughter, Emily, was cured by it – that was before she was later cured by the Lightning Process and then cured again a few weeks ago by eliminating gluten from her diet.

          At the very least, anyone with a true interest in either good science or treatment for ME/CFS should apply a critical appraisal of the design., execution and conclusions of PACE, bearing in mind the ramifications it has for thousands of people in Britain and potentially millions around the world, as USA and other countries meekly follow UK’s lead on ME/CFS.

          We cannot afford to allow the blind to lead the blind in this.

          This is not just about the vested interests of the researchers. It is not unusual for experiments to be constructed in such a way to achieve the desired outcome of the researcher. One cannot fail to see the inherent flaws in research being conducted and results analysed by the very people who stand to gain from its widespread use. If CBT and GET were drugs and PACE was undertaken by the company that stands to profit from the drug sales, would we be so trusting and accepting of it? Would conclusions be allowed to be drawn without extensive and independent corroboration of those results?

          I don’t think so. Moreover, there are studies of CBT and GET in US and Europe for ME/CFS that show them not be useful, not forgetting the UK FINE trial too.

          The serious issue here is that anyone with real knowledge of authentic, organic Myalgic Encephalomyelitis knows the harm that can be caused by stating categorically that both CBT and GET are actually safe for patients with ME/CFS, as do the doctors around the world who have true understanding and a great deal of experince in treating patients with this disease, such as Dr. Klimas, Dr. Cheney, Dr. Lerner ..

          This is why I feel that PACE has overstepped the mark.

          Outcomes from its overstated and misleading conclusions could have great potential for harm to patients who are genuinely sick and disabled by this neuro-immune disease, including children if AYME have their way.

          Those of us who have had ME for many years may know the score but my concern for the children, young people, newly-diagnosed and those yet to contract this disease.

          I suspect that divide and rule tactics have been used against our charities in the past and I accept there will be different views on certain issues, but I sincerely hope that this is one on which they can unite for the sake and safety of those they exist to represent – people with M.E.

      2. CBT is based on a patient having incorrect thoughts, feeling and emotions. Would you say that you have these?

        GET is based on a patient being de-conditioned, with a boom and bust pattern of activity. Would you say you do this?

        No, ME/CFS is not caused or perpetuated by incorrect thoughts, feeling and emotions, nor is it that a person has become de-conditioned with a boom a bust pattern of activity.

    2. Of even greater concern to my mind than the dubiousness of just which group of people they were assessing (and whether or not they even had ME) is the disturbing Serious Adverse Effects found only on the webappendix of the report. It states that for the group receiving CBT 3 people attempted to self harm. I find it astounding in some quarters a PACE trial is now being advocated for children when there is a risk that 3 out of 160 of them who are put in the CBT group will attempt to self harm! If CBT becomes the treatment of choice by the NHS and we extrapolate the self-harm figures to the group of children in the country that have severe ME then we could see a huge number of children self harm.

  2. Good morning JT and all.

    I guess this is going to be a day that tests all our mental dysfunction.

    So, PACE = Oxford Criteria.

    Is that why you have said it, ‘excluded those with neurological symtoms’ or because it only included those who were not ‘bed-bound’?

  3. I would like to add a further comment.

    Over the course of my 14 years I have received numerous GET and CBT ‘treatments’ along with prescribed medications, other therapies, and ‘alternative’-type remedies.

    CBT and GET are, I believe, a necessary part of the process. At times they have proved more successful than others.

    They are not ‘cures’ but they can help enhance recovery to a ‘plateau’. As such they should not be dismissed outright or condemned.

    However, my experience during the course of my illness has proven that my underlying illness is ‘relapsing and remitting’, and that severe relapses that leave me bed-bound and house-bound, as at present, do not respond well to said ‘treatments’.

    For some, at certain times in their illness cycle, they will find that CBT and GET are of help, along with suitably prescribed medications.

    We are all in the same ‘pot’ when it comes to the NHS, and will remain so until such time as biomedical research better establishes the reasons behind our suffering.

    It is right to challenge the PACE trial. When a patient is asked ‘does it help?’ he or she is often replying subjectively, and in relation to (arguably) mood and increased physical ability, which would anyway be the result of an improving illness cycle.

    That is in my experience of continued ‘treatments’ over 14 years, within and outside of the NHS, and in this country and in various countries abroad.

  4. I have been able to work in my former career, study at college and at University, and work subsequently…

    At no time could I honestly say that GET or CBT were responsible for my ‘recovery’ to the plateau that allowed me to function at a higher level and achieve what I have done.

    On all occasions a persistent ‘viral infection’ has caused a severe relapse in my underlying health condition, now labelled CFS.

    That is my experience to date.

    Currently, as I said, I am ‘recovering’ from a severe relapse in 2009 and am mainly out of bed, if house-bound. This is my ‘normal’ pattern of disease experience.

  5. Two simple points, having read the Lancet paper:
    1. Participant-reported positive change in overall health after 52 weeks:
    Specialist medical treatment 25%,
    APT (pacing) 31%,
    CBT 41%,
    GET 41%
    So it looks as though the major factor in improvement is a combination of passage of time and specialist medical treatment, with the percentages boosted by the other treatments. On that basis the first and most important recommendation must surely be that all patients have access to specialist medical treatment as a minimum. Many of us don’t. If we could get really focused and knowledgeable help with things like sleep and pain we would at least get that 25% chance of improving. Odd how that doesn’t rate a mention in all their conclusions.

    2. The measures used to test changes, both physical and fatigue seem to be completely subjective – even the distance walked in 6 minutes will depend on patient attitude to what they can safely do without side effects. Surely the pacing and medical-only groups are likely to be a bit more cautious in assessing their outcomes and abilities, so it’s not surprising they didn’t do so well. All they seem to be measuring is patient belief. Where are the objective tests of physical function?

    On the other hand, those with mild to moderate CFS surely should be offered a choice of all these treatments, with data to help them decide which to use. Those of us with severe ME are none the wiser.

  6. Sorry, the descriptors should read:
    SMT (Specialist medical treatment) 25%,
    SMT and APT (pacing) 31%,
    SMT and CBT 41%,
    SMT and GET 41%

    1. I haven’t checked your stats fish, but I agree with where you are coming from.

      There is much in this Lancet report, that ‘we’ sufferers could make use of to better our treatment overall.

      Much of the reaction is, I hope, a knee-jerk one, and further analysis will reveal details that can be worked on better.

      This report is not as much of a success as those who initiated it were hoping for – if you believe the conspiracy theorists.

      Far from being something I was fearing, I am actually finding it something I can work with and use…

    2. @Fish
      I think your reading of the figures may be a bit awry. The only 31%, 41%, 41%, 25% set that I could find is on Table 5, and the those figures refer to the percentage of participants in each treatment cohort who are reporting Positive, Minimum, Negative, changes. You’ll see these add up to close to 100 in each case (rounding means the figures aren’t exactly 100%)

      You are quite right though in your judgement that the study doesn’t allow exclusion of SMC from the equation. Your point about the lack of objective test of improved health is also very significant in terms of how this study may be used to justify the use future of CBT and GET. Objective measures could have been used as demonstrated by the Frenchay study: http://www.hta.ac.uk/execsumm/summ1037.shtml

      @Eleanor

      the Supplementary webappendix gives a listing of the SMC treatment providers as 4 general practitioners, 7 physicians, 27 liaison psychiatrists.

      And on Panel 1:

      Specialist medical care (SMC)
      SMC was provided by doctors with specialist experience in chronic fatigue syndrome (webappendix p 1). All participants were given a leaflet explaining the illness and the nature of this treatment. The manual was consistent with good medical practice, as presently recommended.2 Treatment consisted of an explanation of chronic fatigue syndrome, generic advice, such as to avoid extremes of activity and rest, specific advice on self-help, according to the particular approach chosen by the participant (if receiving SMC alone), and symptomatic pharmacotherapy (especially for insomnia, pain, and mood).

      IVI

  7. I notice the Lancet article did not explain what ‘specialist medical treatment’ consists of. I have had no medical treatment at all, save for an incease in the anti-depressants I was already taking prior to my illness.

  8. According to the full version of the Lancet article, SMC consisted of an average of 5 sessions with a doctor with specialist experience in CFS. Patients were given a leaflet explaining the illness and SMC treatment, explanation, generic advice such as to avoid extremes of activity and rest, specific advice on self-help, and symptomatic drugs especially for insomnia, pain and mood. I seem to remember they also point out somewhere that it was different from GP treatment.
    They express some surprise that this approach alone caused significant benefit, but completely fail to conclude that everyone should be offered it.
    All their conclusions relate to the benefits of CBT and GET. I have a sinking feeling this will mean that more people will be offered these without SMC – it’s cheaper not to give us 5 sessions with a consultant and to fob us off with a few sessions with a CBT or GET practitioner!

  9. When a new study is published it can be very easy to be carried away by impressive P values. One must be aware that P values give no indication of the magnitude of benefit. When the amount of improvement is looked at in objective terms then a completely different picture unfolds. The patients were able to walk an extra 21 metres in 6 minutes compared to baseline. Physical function improved by a mere 7% compared to standard medical treatment (which is a lecture and a leaflet). There was an improvement of one point on the sleep scale. The benefits were not a chance observation, but neither were the benefits clinically significant. The patients all had a value of 8.1 on the depression scale used at baseline, so the patients were not actually depressed at all. GET did not improve physical functioning compared to CBT, and neither improved the symptoms of depression at all compared to standard treatment. Finally the patients at the end of the study still had a chandler fatigue score of 22, bearing in mind that 33 is totally disabled. The initial value at baseline was on average 27. This can hardly be called a breakthrough of any kind. The results are in fact worse than those examining the role of CBT in patients with MS conducted by some of the same authors.

    1. Yep as I said JT and my own reading is not as thorough as yours, there is much in here that ‘we’ can work with.

      Headlines have caused much worry and concern. Rightly so in my opinion.

      As Dr Shepherd said in the Guardian comments yesterday, it is more of a worry how the NHS will take to all this and use it to implement policy.

      But I am ready for that I believe.

      However, I would say that the medical treatment also included prescribed medications and not, as you and others have said, a leaflet and a lecture.

      The details and the actual comments inside the Lancet publicaton, are not as damaging to our inherent belief that something physical lies behind our suffering.

      1. Not mine. Only passing along good information.

        The NHS should do nothing with it. Neither should NICE. NICE should be reacting to the life time blood ban caused by MRV retroviruses.

  10. to in vitro…
    I don’t see what’s wrong with my figures. Of course the figures in each cohort add up to 100%, but the percentages in each group who report significant overall improvement in symptoms in each group is, as I stated, 25, 31, 41, 41. That means that 75%, 69%, 59% and 59% respectively of each group showed minimal change (including negative minimal change) or got worse.
    Taking a single comparison:
    Medical only: 25% improved, 75% not improved.
    Medical + GET: 41% improved, 59% not improved.

    It would be reasonable to assume that about 25% of the latter group would have, like the first group, improved with just Medical help and the passage of time. This means the addition of exercise only helped an additional 16% to improve. The same argument and figures apply to CBT. Not to be dismissed, certainly, but hardly the ringing endorsement that the PACE trial claims.

  11. @Fish

    don’t see what’s wrong with my figures. Of course the figures in each cohort add up to 100%, but the percentages in each group who report significant overall improvement in symptoms in each group is, as I stated, 25, 31, 41, 41.

    I thought you were suggesting those figures represented % changes in improvement – but fine we are talking about the same thing.

    It would be reasonable to assume that about 25% of the latter group would have, like the first group, improved with just Medical help and the passage of time. This means the addition of exercise only helped an additional 16% to improve.The same argument and figures apply to CBT. Not to be dismissed, certainly, but hardly the ringing endorsement that the PACE trial claims.

    I don’t think that is a reasonable extrapolation. To test the role of SMC in either CBT or GET effectiveness would require a comparative test with cohorts receiving SMC only, CBT only, GET only, SMC+CBT and SMC+GET. Not that I think such test is necessary, the Frenchay study is good enough to support the current clinic delivery, so long as everyone involved recognises the profound limitations on achievable outcomes for the majority ofpeople referred to the clinics.

    And certainly PACE provides no ringing endorsement of anything – if I were the MRC medical panel I’d be asking for a £4.5 million refund from the study managers for producing such a paltry effort.

    IVI

    1. ‘And certainly PACE provides no ringing endorsement of anything – if I were the MRC medical panel I’d be asking for a £4.5 million refund from the study managers for producing such a paltry effort.’

      Bang-on.

      PACE has afforded more ammunition to those seeking better biomedical research and for patients wanting better physiological help in terms or more specific neurological medications, then it was ever hoped it would.

      In my humble opinion.

  12. As someone who was turned down for the PACE trial because I had re-lapsed, I see little of value in this report regarding my condition.

    Having suffered from ME for 14 years I now find myself in the position of being unable to get any treatment whatsoever, I can’t even get referred as I am classed as “unlikely to respond to treatment” and therefore have been repeatedly refused funding.

    I suspect that this is likely to be the case for any long term sufferer.

  13. I don’t know what illness the PACE trial actually studied but 5 million pounds seems to have been squandered when it could have been used on biomedical research for ME.

  14. When a new study is publishedi t can be very easy to be carried away by impressive P values.One must be aware that P values give no indication of the magnitude of benefit. When the amount of improvement is looked at in objective terms then a completely different picture unfolds. The patients were able to walk an extra 31 metres in 6 minutes compared to baseline. physical function improved by a mere 7% compared to standard medical treatment (which is a lecture and a leaflet).There was an improvement of one point on the sleep scale.The benefits were not a chance observation but neither were the benefits clinically significant. The patients all had a value of 8.1 on the depression scale used at baseline so the patients were not actually depressed at all. GET did not improve physical functioning compared to CBT and neither improved the symptoms of depression at all compared to standard treatment. Finally the patients at the end of the study still had a chandler fatigue score of 22 bearing in mind that 33 is totally disabled. The initial value at baseline was on average 27. This can hardly be called a breakthrough of any kind. The results are in fact worse than those examining the role of CBT in patients with MS conducted by some of the same authors

  15. according to the PACE protocol standard medical care involved giving no explanation about the symptoms encouraging positive thinking an increase in activity .literature was also supplied at each visit.This was the control group. CBT produced a 7% decrease in activity compared to controland there was no evidence of synergistic activity

  16. I think there is a serious risk of dignifying all this PACE psychobabble by spending so much time discussing and analysing it.

    1. It is unwise to ignore the PACE trial. NICE won’t. They believed it to be significant before it had even been published. Neither will the MRC, who funded it, and are now ignoring serious concerns about its design. As for the Department of Health, what do they care. They need to keep everything cheap.

Comments are closed.

Shopping Cart