1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
Nitric oxide and its possible implication in ME/CFS (Part 1 of 2)
Andrew Gladman explores the current and historic hypotheses relating to nitric oxide problems in ME/CFS. Part 1 of a 2-part series puts nitric oxide under the microscope and explores what it is, what it does and why it is so frequently discussed in the world of ME/CFS. Part 1 focuses...
Discuss the article on the Forums.

'Recovery' from chronic fatigue syndrome after treatments given in the PACE trial

Discussion in 'Latest ME/CFS Research' started by Sam Carter, Jan 31, 2013.

  1. user9876

    user9876 Senior Member

    Messages:
    707
    Likes:
    1,628
    I assume if the editor gets a flood of letters pointing out the most basic mistakes it might also make them think twice about being more careful with any further publications.
    Valentijn and Dolphin like this.
  2. alex3619

    alex3619 Senior Member

    Messages:
    7,017
    Likes:
    10,794
    Logan, Queensland, Australia
    This is something that I am investigating and will have more to say on in time. However for PACE the two big ones are the obvious ones, "normal" and "recovery". In general though they misrepresent more obvious things, including "there are no abnormalities" or "there are no tests" or emphasizing "deconditioning" when it cannot ever explain sudden improvement or decline in long established patients.
  3. Firestormm

    Firestormm Guest

    Messages:
    5,824
    Likes:
    5,965
    Cornwall England
    I am aware that within the NHS, 'targets' are driven by 'clinical outcome measures' or the latter is a consumer-friendly term for the former.

    Whilst our local ME Service - now newly commissioned and with a more succinct 'business' model - does not prescribe GET and CBT a la PACE manuals - it must surely at some level be able to demonstrate some outcome measure.

    I need/want to do some more work on this side of things. The outcomes are not equated with 'cure' or 'recovery' I know that much but there must be something substantive that they work towards even if only as a means of measuring quality of care.

    But what can a clinical team do when they are only - on average - able to deliver six-eight sessions per client? Compare that to PACE intensity.

    From what I have seen from my own home-delivered Occupational Therapy - there is no attempt (though it is very early days) to complete an assessment or measure outcome.

    From what little I have thus far gleaned it is entirely focused on helping me to learn how best to manage my health. To try and tailor advice and support to personal and realistic goals - my own all stemming from a desire to live independently once more but with support.

    I cannot yet - more generally - see why Clinical Commissioners would want the PACE recovery data. If you strip even the principles of CBT and GET or Graded Activity from clinical care - what have you got left?

    These principals are so ingrained if not employed with precisely those nomens that I have to ask what difference this data will make.

    If PACE was seen to have proved these therapies even if delivered solely a la PACE manuals - were ineffective - the ramifications across all of healthcare for all conditions would be... well... dire. Or would it?

    This was a model. Using the principals. Applied in such a way that was felt relevant to CFS/ME by those who figured they knew what they were doing.

    It could be argued by others outside of PACE that it was less effective than hoped because the model was wrong, not the principal behind the therapies themselves.
  4. Stukindawski

    Stukindawski

    Messages:
    79
    Likes:
    160
    It could be argued that pursuing CBT/GET research in an illness without a known cause is like licking a muddy puddle when there's a clean glass of water on the table. I think criticism of the recovery data is definitely better aimed at putting pressure on the MRC to fund investigative types of research.

    I wonder if some outcome measures only need to claim to have 'treated' a patient to meet a quota.

    I had a day surgery cancelled recently because I pass out when I fast. The admins will not keep me in the system while I navigate my way through the GP and my specialist to pin point what's causing it. I will have to start the surgery referral process from the ground up.once I'm ready - which basically equates to repeating unnecessary appointments. It seems the highest value is placed on emptying queues.
    ukxmrv likes this.
  5. biophile

    biophile Places I'd rather be.

    Messages:
    1,371
    Likes:
    4,293
    In recent correspondence between Professors White/Wessely and the Countess of Mar, White refuted claims that he did nothing to correct the erroneously reporting of "normal range" as "recovery" back in 2011. He pointed out that the difference was clarified in their authors' reply in the Lancet (several months after the fact), while the Countess of Mar later accused him of double-standards (doing nothing to combat the claims of "recovery" in news articles, while rapidly writing in response to David Tuller's article which questioned the generalizability of the results).

    Now, this so-called "normal range" in fatigue and physical function, which overlaps with trial eligibility for "disabling fatigue", is officially presented as a "recovery" in the latest paper anyway, with additional optional criteria bolted on. I have to agree with you that the confusion about recovery is not a mistake. The unnecessary ambiguity surrounding "recovery" is serving a purpose, just as the ambiguity surrounding use of the word "functional" is serving a purpose (noted in Wessely's paper).

    So far the general defense of the paper can be simplistically paraphrased as: "Give the authors some slack, recovery is very difficult to define in CFS, they have done their best in a difficult situation, and CBT and GET (the only effective therapies known) outperformed APT and SMC anyway, so all criticisms are irrelevant."

    I do not think they deserve much slack. The redefined recovery falls far short of their original conceptualization of it, does not include what many patients would deem to be important, and is contradicted by a bunch of other more objective outcomes (eg CBT and GET are being praised as leading to recovery, while the group average in welfare and insurance payments actually increased in these groups, etc). Furthermore, the redefined recovery is based almost exclusively not on major improvements but thresholds which require almost no improvement and which either overlap with or are on the border of what was defined as "disabling fatigue". When it comes to fatigue and physical function in particular, even the weakest thresholds in the original protocol, i.e. those used for a "positive outcome", are more strict than the strictest ones used in the latest redefinition of complete "recovery". It is rather questionable to call it "comprehensive and conservative".

    <sarcasm>Stop hating on mental illness and perpetuating the stigma! Did you not know that depression is real too and that mind-body dualism is unhelpful? Stop denying your psychological problems, how can you recover from a problem without first acknowledging it?</sarcasm>

    Please elaborate the differences between the principle and the model.

    I do have an open question to all you other "spicy" recalcitrants :) ...

    What would the methodological requirements be for a trial on CBT/GET in order for it to be respected and lead to a reconsideration for the role of these therapies?

    I guess that the answers will relate to using case definitions which better reflect them, stricter definitions for improvement and recovery based on actual healthy norms, consideration for other measures (employment, welfare, 6MWD, exercise test, welfare, actometer, etc), adequately defining safety, even designed and conducted and overseen by an independent authority which has not built their careers on CBT and GET (due to the lack of trust, and concerns about spin?).
    Dolphin and Valentijn like this.
  6. Stukindawski

    Stukindawski

    Messages:
    79
    Likes:
    160
    I think there is always going to be something of a methodological black hole in CBT/GET research unless the effect of the treatment is substantial.

    But I'd really like to see something massive.

    OI symptom tracking
    POTS tracking
    VO2 max repeat exercise testing
    Inflammatory response post exercise tests
    Mental acuity testing.
    3-5 years worth of follow up.
    Employment/Welfare changes are a must (of course, a factor like the ESA/PIP debacle could actually impact research at this time)

    I'd favour patient sign & symptom profiling over a strict definition. If there are responders it'd be interesting to see what symptoms they report and what signs are detected.

    I could spend hours really thinking about this, but my head hurts, so I wont :p
    Dolphin and Kati like this.
  7. In Vitro Infidelium

    In Vitro Infidelium Guest

    Messages:
    646
    Likes:
    280
    My guess is that PACE - and all that has flowed from it, has been structured/restructured to have 'confluence' with these: http://www.iapt.nhs.uk/silo/files/iapt-data-handbook-v2.pdf and http://www.iapt.nhs.uk/silo/files/iapt-data-handbook-appendicies-v2.pdf - main page: Measuring Patient Outcomes - http://www.iapt.nhs.uk/data/measuring-outcomes/

    Clinical Commissioners (more precisely the managers employed by the Commissioning Boards, as few Board members will have a day to day handle on the processes in operation) will not operate PACE derived data, but the data, as constucted in the current article will serve to provide headlines to 'sell' PACE defined services to the Commissioning Boards. Additionally although the IAPT set up closely defines what the CCBs have to report M.E/CFS could be in noman's land in that, although a service may be delivered from a Liaison Psychiatry base, there may not be a requirement to define M.E/CFS under the IAPT reporting criteria (not a mental health illness) but also it doesn't fit under any of the other described Clinical Datasets http://www.commissioningboard.nhs.uk/files/2012/12/clinical-datasets.pdf . In that case CCB's will (as far as I can tell) have freedom to choose appropriate metrics for which the PACE work could conveniently fill the gap.

    Yes indeed. The test of plausibility is wholly missing from the 'evidence based' construct that lies behind the clinical data set system - it will be down to the CCBs to make plausibility judgements (i.e just because the numbers show 'X' doesn't mean that 'X' exists beyond a statistical artefact) when commissioning a service. How many will pursue that diligently, or will instead merely default to the safety of reported numbers remains to be seen.

    Advocacy can clearly impact the process ( "Whilst our local ME Service - now newly commissioned and with a more succinct 'business' model " !!) but it will need to advanced pragmatically - the position of 'no psychiatry involvement under any circumstances' provides no basis for negotiation or the meeting of CCB level perspectives of M.E/CFS. The alternative is to leave the field open for PACE defined services to dominate the contractual landscape.

    IVI
    Firestormm likes this.
  8. Firestormm

    Firestormm Guest

    Messages:
    5,824
    Likes:
    5,965
    Cornwall England
    Speaking solely in regard to my local service. There was no 'model' in place previously for the service. No structure. The number of patients being seen was overwhelming, and still may prove to be. However, aside from the actual 'product' delivered, the clinicians are now delivering a structured service model.

    The commissioners know in advance how much money the model will require. The deliverers know how many average consultations they can deliver etc. What is not part of this model is the actual product delivered and how the effectiveness of that product is measured. I don't believe that PACE will change anything in that respect at the delivery level.

    Regular reviews will now take place to ensure that the model is appropriate and as a patient group we will be trying to ensure that patients are receiving an adequate, appropriate and timely service.

    Even with this paper we are still left largely with the status-quo we had before. The claims made in NICE about CBT and GET being (from memory) the only proven methods of help remain.

    Until such time as something comes along that can 'beat' the now published 'recovery' data - despite the valid criticisms of this paper and of the Trial itself - nothing has changed.

    Even if a drug is trialled and shown effective and applicable for all or some with our diagnosis I do not see a time when CBT or GET will disappear from the NICE Guideline.

    GET and CBT are 'safe' in so far as the regulators/advisor's are concerned and from personal experience GET is more akin with Graded Activity than a programme of progressively increased - regardless of symptom exacerbation - physical exercise.

    GET and CBT will still be seen as more effective than 'pacing' or the APT that was applied in the Trial. If you can do something structured it is better than doing very little - which is how pacing is viewed.

    However, again speaking personally, local delivery does include pacing. What I have found is that GET/CBT and pacing are very often delivered as a package as part of your tailored approach to a sustainable 'base-line'.

    Not everyone needs or wants this level of help. Not everyone can get it of course.

    I suppose the concern is that PACE and it's manuals will (perhaps are - I forget) being used verbatim in clinical service delivery.

    On the plus side, we now know that even the authors have had to admit to the less than what I would deem 'moderate' effectiveness of their Trial.

    At 22% clinical deliverers of the manuals will need to be far more upfront about their proposed regimen. No more talk of 'cure'. Or if there is then patients can throw this paper at them :)
  9. Dolphin

    Dolphin Senior Member

    Messages:
    6,585
    Likes:
    5,188
    A list like that could make a nice letter to the editor, if anyone was so inclined.
    Valentijn and Kati like this.
  10. Dolphin

    Dolphin Senior Member

    Messages:
    6,585
    Likes:
    5,188
    Which is a very high bar to set for blinded trials which will probably use more rigorous definitions of recovery.
  11. SOC

    SOC Moderator and Senior Member

    Messages:
    5,282
    Likes:
    6,234
    USA
    Do ya think they'll help us fix the economy by thinking it right? Perhaps the government just has false poverty beliefs and could actually pay for everything society needs without raising taxes. All we have to do is gather all our politicians together for a PACE-style seminar to cure their false belief in economic problems and everything will be fine. :thumbsup:
    user9876 likes this.
  12. Dolphin

    Dolphin Senior Member

    Messages:
    6,585
    Likes:
    5,188
    Not sure why you say that. They found 21-22% recovery using their most strict criteria for recovery. This in a £5m-pound MRC/DoH/ScottishChiefScientistOffice/DWP-funded multi-centre trial.
  13. Stukindawski

    Stukindawski

    Messages:
    79
    Likes:
    160
    Hmm, I've never actually written a letter to a journal before. I've drafted a letter, if you think it's good enough, let me know how I would go about sending it for publication:-


    As a patient, I have yet to see substantial data that would make me feel confident in committing to such a treatment for the third time. There is a large amount of obtainable data in respect of the growing body of research in ME/CFS, which could make the case for this treatment much more compelling:-

    Autonomic dysfunction tracking, including Orthostatic Intolerance and POTS (Based on Professor Julia Newton's work) [1][2]
    VO2 max repeat exercise testing (Based on work at the Pacific Fatigue Laboratory) [3]
    Inflammatory response testing following exercise (Based on Dr Alan Light's work) [4]
    Mental acuity testing (Has the classic symptom of Brain fog been abated?)
    A focus on welfare and employment changes which take note of external factors, I.E the migration from IB to ESA and DLA to PIP and the current state of the employment market (some attention to the availability of less demanding work and the type of work taken up by patients following treatment would also be valuable data).

    I'd expect to see at least 3-5 years worth of extensive follow up to account for symptom fluctuation and ensure that the treatment does not suffer from a 'plateau effect'. Some reconditioning may be of real benefit, which could later be lost when the patient's limit is reached (I.E relapse, being one of the most commonly reported patient experiences).

    Sign and symptom profiling in each patient, as opposed to using stricter definitions might be key in identifying likely responders. I have yet to see solid evidence of homogeneity in this patient population which would be a reasonable competing explanation for the rather modest response reported by this paper.

    [1] http://www.sciencedirect.com/science/article/pii/S2213158212000484
    [2] http://onlinelibrary.wiley.com/doi/10.1111/joim.12022/abstract
    [3] http://www.cfids-cab.org/MESA/VanNess.pdf
    [4] http://www.ncbi.nlm.nih.gov/pubmed/19647494
    Valentijn and biophile like this.
  14. Dolphin

    Dolphin Senior Member

    Messages:
    6,585
    Likes:
    5,188
    Well done on that. I've sent you a private message on it.
    Kati likes this.
  15. Firestormm

    Firestormm Guest

    Messages:
    5,824
    Likes:
    5,965
    Cornwall England
    Delivers of this/these therapies will I think have to be more realistic. 'There is a chance of some recovery' and not 'This will cure you dude!' NICE of course never spoke of cures but anecdotal evidence from patients attending assessments have inferred that some clinicians are 'selling' CBT and GET as 'cures'. I no longer believe that they can do this. Some might try but informed patients will at least now know the chances are scant. And that whilst CBT and/or GET might help you with this episode you may well need them again for the next one.

    22% may indeed be setting the bar high but perhaps only for other treatments addressing the whole disease - and how realistic are such treatments likely to be (outside of psychology) for such a heterogeneous mishmash of patients? I think what we are seeing are more focused efforts addressing either specific symptoms, aspects of the disease, or sub-categories of patients. Indeed, I think it perfectly reasonable to consider CBT and GET as pertinent perhaps to only some people with the disease or indeed some (associated?) symptoms. Neither therapy is recommended for 'severe' patients for example. And clinical delivery varies in terms of how they are delivered assuming of course that they are. Perhaps it is more the principals of CBT and GET that are built into the delivery. Not saying it hasn't happened but I have yet to hear of anyone using the PACE manuals as delivery mechanisms outside of the Trial.
  16. Firestormm

    Firestormm Guest

    Messages:
    5,824
    Likes:
    5,965
    Cornwall England
    Anyone care to explain? Should I feel enraged or is this reasonable? I haven't read the papers cited. Thanks.
  17. Dolphin

    Dolphin Senior Member

    Messages:
    6,585
    Likes:
    5,188
    I doubt it's reasonable but haven't read the paper referenced yet (it's free http://europepmc.org/articles/PMC3020067). It would be interesting to compare the average number of symptoms recorded by the "recovered" CFS patients versus the average number of these symptoms reported by the public. My guess is the figure for the CFS patients would be higher esp. if they were age-matched (and didn't involve those with any of the exclusions, although the paper might not have those details). Also, it would be interesting to check the wordings of the questions to see if they are similar. Also, CBT and GET patients have been told the symptoms are normal so might potentially be less likely to report them.

    Similar to the first point I make above, I imagine it's the case for a lot of the other measures used i.e. if they listed the mean SF-36 PF scores for the "recovered" patients, it would be lower than the mean for the general population, which would leading to rejecting the hypothesis that the "recovered" patients are like the general population, which is what would expect from a recovered group.
    Valentijn likes this.
  18. biophile

    biophile Places I'd rather be.

    Messages:
    1,371
    Likes:
    4,293
    I had a very brief look : http://europepmc.org/articles/PMC3020067 .

    Surveys sent to people drawn from general medical practices. Low response rate of 1/3. 45% had a chronic condition.

    For the whole population, overall mean of 3.66 (SD = 3.47) symptoms over the previous 2 weeks, but mean number of symptoms was higher in those with a chronic condition than those without. Notice how White et al rounded up the symptom count from the whole population figures which included 45% of those with a chronic condition. Many conditions are excluded for a CFS diagnosis, and CFS patients would have had a recent medical assessment. The authors state that "Presence of a chronic condition, age, and employment status were the three factors most commonly associated with the 2-week prevalence of different symptoms."
    Valentijn, Firestormm and Dolphin like this.
  19. Dolphin

    Dolphin Senior Member

    Messages:
    6,585
    Likes:
    5,188
    Out of 25 symptoms from what I see at a quick glance.
  20. biophile

    biophile Places I'd rather be.

    Messages:
    1,371
    Likes:
    4,293
    This argument sounds like an avoidance of dealing with the implications of the poor employment and welfare data that was published last year. The average age of CFS onset in the PACE Trial participants was roughly about 35 years old and about 3 years before recruitment, so the vast majority of these people should have been employed before illness.

    On the other hand, the "job market" argument is worth considering.

    UK unemployment during most of the 2000's was generally low and relatively stable. The economic downturn started in June 2008. The 3rd patient newsletter gives a time graph of the cumulative recruitment into the trial, which is helpful for examining this job market claim : http://www.pacetrial.org/docs/participantsnewsletter3.pdf .

    Assuming that there is about a year plus a few months at most between recruitment and collecting followup data, it appears that about half of the participants were recruited and followed up during the "good times".

    Even if the bad times affected the data for some of the remaining participants, surely if the "completely recovered" rates were 22% for CBT/GET vs 7% for SMC, there should still be some positive effect on employment and welfare outcomes, unless the study was statistically underpowered?
    Svenja, Valentijn, Simon and 3 others like this.

See more popular forum discussions.

Share This Page