Identity – is it all in your head?

2015 blog cont’d…. Another massive campaign to discredit the authors of the PACE study into three ME/CFS interventions is underway. Over 12,000 signed the first petition to request retraction of supposed claims that some one quarter ‘recovered’ – even though the Lancet paper clearly states potential to just ‘moderately improve outcomes’, specified per the Mayo Clinical Significance Consensus. Another lobbying is underway, so far 6,300 have signed a demand to the GMC regulators that the study doctors be disciplined – suggesting 10 years custodial penalty for the crime of Fraud. The gist of concerns is than consequent to PACE report practitioners have distressed sufferers from ME/CFS with callous disregard. Claim is even made of “… harm done to children being forced to go to school and being subject to child protection plans“. This irrational outburst references the Tymes Trust’s Jane Colby regarding the potential for healthcare authorities to intervene so as to enforce adherence to clinical guidelines after PACE recommendations.

First in GP Sarah Myhill’s complaints beginning on pg 7 of 25 are that PACE “has effectively determined CFS/ME as a psychological condition“. Recall that the interventions detailed in the Lancet article were: Cognitive Based Therapy (CBT) with a psychologist; Graded Exercise Therapy (GET) with a physio; Adaptive Pacing (APT) with an Occupational Therapist (OT); and against a control group receiving standard care from a CFS specialist. CBT and GET were significantly better for fatigue and functioning, while APT was no better than the control/placebo. The authors state clearly: “The effectiveness of behavioural treatments does not imply that the condition is psychological in nature.” Dr Myhill’s 2012 reprimand by GMC and recently concluded cautionary period must be considered in grading her opinions, when the disciplinary ruling declared: “statements in relation to contraception and breast cancer screening that were factually incorrect; clinically unsubstantiated; and contrary to national guidelines. In so doing she used her position as a registered practitioner to exploit patients’ lack of medical knowledge by arousing ill found fears for their health.” Myhill’s website promotes powerlifting as High Intensity Training – but not for ME/CFS, where diet and detox are advised. And vaccinating is discouraged.

Another line of advocacy comes from Tuller, Geraghty, Wilshire et al. The link has a number of articles, including the PACE authors’ refuting of complaints re research quality. More telling is the activist’s collated manuscript ‘Rethinking the treatment of chronic fatigue syndrome’, which begins with an allegation that the Randomised Controlled Trial did not control nuisance variables, such as contact hours. This is alarming. ‘Control’ in this situation means that the intervention was compared with a control group, not their idea that control be applied so as to enforce participant compliance. The scientific complaints differ over time, but this paper zeroes in on statistical analysis in that the published protocol considers every possible comparison between therapies, and the Bonferroni principle requires stronger levels of proof ie the more permutations (ie 6 pairwise comparisons), the greater likelihood of a random fluke (odds of 1 in 125 actually) supporting the hypothesis of a therapy being better than the control ie standard care. The pairwise tests were a change to the stats plan, by dropping consideration of combo-therapy eg is APT and GET better than GET alone etc….explained as being overly convoluted.

Access to raw data was achieved by activist’s FoI request. Looking at their re-analysis of supplied data in Table1, people improved most under two therapies. No argument. The control group also did over time, where a placebo or Hawthorne effect can result from the satisfaction of working with supportive professionals towards a solution.

To the impartial eye, CBT and GET worked ‘better’

 

 

Expert opinions and agendas at play

Independent commentators are worth noting: OT Bronnie Thompson admires the study, but is concerned that their APT protocol failed to set goals to work towards. Their envelope of maximal activity was fixed within a ‘disabled identity’ focused on what COULDN’T be achieved, a problem noticed by Prof Leonard Jason. His Energy Envelope Theory relies upon success in avoiding crashes being inducement to better achievements in future. This is similar to Feldenkrais practice, progressing away from fear of movement through progressive challenges. Medical journalist Dr Norman Swan discusses the unprecedented outrage in the patient community with a study author and journal editor, but only considers the absence of harm during the trial (1% of all treatment arms reported worsening conditions). They suggest that activists hijacking the CFS community does them harm, without stopping to think about why there is even an outcry and whether their GPs are at fault.

It is obvious that distress results from unsympathetic doctors who’ve simplified the study conclusion as “get active, get counseling, and get out of my practice“. Indeed, practitioners proudly state conviction in their ability to discern CFS patient agendas. “I often use it as a diagnostic tool for MUPS (Medically Unexplained Physical Symptoms), that I get irritated by patients.” A vulnerable population then becomes prey to peddlers of solutions that are accompanied by rather more sympathetic caring. At a patient forum Dr Daniel Lewis agreed with Tuller’s complaint that the participant inclusion criteria of ‘Oxford Research’, rather than ‘Canadian Consensus’, was the problem. They weren’t suffering real ME/CFS, whatever that is. He sells meditation courses targeting chronic fatigue or pain in general however, without quibbling about specific diagnoses in attendees. Likewise a clinician’s summit unanimously supported their client’s grievances against PACE conclusions being given as guidance to doctors.

Personal injury specialist legal firm Maurice Blackburn sponsors Australia’s Emerge ME/CFS foundation, and seeks litigants who’ve been refused disability payment. They also advertise on SBS TV, who have requested patient’s stories for a program. CFS guru Dr Jacob Teitelbaum initially took a rational stance that PACE results were being misinterpreted in the media, but five years later joined the herd by stating in his blog: “… the PACE trial that wrongly concluded that CFS patients should be treated with psychotherapy.” Other experts such as Jose Montoya just focus on their research.

The study team took the controversy onboard, replying with rational argument to editorial letters. It then seemed that the time was ripe to shoot themselves in the foot. Perhaps the declared conflicted interest of team member’s consulting to insurance companies, presumably over disability payouts, made the Lancet article just a testing of the waters. Another writeup appeared, declaring ‘Recovery is possible!’ much as Chamberlain did in saying “Peace in our time”. And war broke out.

This wasn’t the only investigation into exercise as therapy for CFS. Last year’s update to the meta-analysis of 7 trials affirmed the results, every one of them showing benefit for reported Fatigue. But once again, researchers do themselves no favours with clinicians or patients: the publishing/editorial group is Cochrane’s ‘Common Mental Disorders’ .

My thoughts

CFS is an unmet challenge to medicine. There’s no fix, only symptom relief. LowDose Naltrexone relieves the brain fog (presumed to result from glial inflammatory response), beta-blockers may be used against POTS in orthostatic intolerance (light-headedness upon arising), and supplements such as CoQ10 or D-Ribose aid mitochondrial energy production. Post-exertional malaise is a constant however, which reinforces the lost sense of identity that was once based upon our function. Patient experience is of an invariant, and lifelong struggle. For anyone else we experience affliction as mostly transitory, even chronic illness can go into remission upon treatment. They who experience anxiety attacks, also know there’s moments of achievement. Joy counters sadness, emotions rise and fall again. It is possible to mentally step back and observe thoughts and sensations that may come and go, without attaching identity or sense of self to such temporary states. This is infinitely harder when the disease is so poorly understood.

CBT and GET offer slight improvement, a readiness for future solutions rather than idling whilst deconditioning – where practitioner’s pushing of anti-depressant meds worsens weight gain. Meanwhile however, you’re powerless prey to commercialism.

Right of Reply & Disclosure

Dr Lewis’ office has never replied to my correspondence. SBS passed a message on to their producer. David Tuller wrote back that the trial authors assumption of the CFS sufferer’s [de]reconditioning biased their choice of interventions offered, which is fair comment. If only there were better answers to this perplexing problem.

I’m married to a MUPS, and like others I know well, am struck by their hitherto overachieving.

 

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8 Comments

  1. 20,000 have now signed Myhill’s and the earlier call for retraction petitions to The Lancet. https://my.meaction.net/petitions/pace-trial-needs-review-now also issues a “call upon all parties to reject the view that being as disabled as patients with congestive heart failure is a good recovery of physical function in CFS.”
    I can’t see much science to sway the medicos.
    Onus is being transferred to Allied Health professionals to disseminate the message, perhaps with more sensitivity: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370222&isReview=true

  2. Perhaps a more accurate reading of the results of the PACE trial would be that a long course of CBT or GET could persuade patients to claim on the questionnaires that they had improved by more than those who did not get CBT or GET, but that all objective testing of walking, climbing steps, employment, claiming benefits etc. showed absolutely no difference.

    CBT and GET should be sold with the advice “The evidence shows that these may make you think you have improved, but that they have no real effect upon what you can do. Anecdotal reports from significant numbers of patients suggest that they may cause temporary or even long-term harm. The risk is yours.”

    What did you think of the fact that, in their recovery paper, if a specialist decided that a patient still had CFS, but that patient had scored above a fairly low level on either one of the two main questionnaires, that doctor’s diagnosis was overruled and the patient was classified as no longer having CFS? Is that appropriate behaviour from professionals running an honest study?

    I’m sure there are many worthwhile things that could come out of the data from the PACE trial, but we will never know. What we do know is that the quality of the analysis and the errors in understanding of even basic statistical methods was shockingly poor.

    • Thankyou for that. Obviously, I disagree – up until your point re ‘Recovery’. In the absence of biomarkers and defined pathophysiology, all one can ever claim is ‘Remission’.
      I’m in a partnership delivering the Breathworks protocol for chronic pain, which is reliant upon facing towards the difficulty per Stephen Levine. Fibromites can be encouraged to do this, since the alternative is exploitative pharmacology. Palliative pain relief, which worsens health even if it successfully blots out bad sensations.
      I can readily understand catastrophising about fearful ME/CFS post-exertional crashes – Pt1 of this commentary referenced van Houdenhove’s study into patient’s pasts, to find out that above average drive and energy was the norm! Grieving over lost mojo has turned to anger, but in a collective these stages don’t transition. You’re stuck.

      • It’s good to have a proper reply! Thank you. I guess the difference is that I am, very much, a pragmatist. I have ME and know that when I go through periods when the pain and fatigue are less, I achieve more. It’s easy to tell, because when the pain and fatigue are troublesome, I manage very little. I find it hard to conceive of a situation in which people genuinely feel less fatigued and feel that they are achieving more, yet are unable physically to do so. For the mind to receive some relief, but not have that reflected in the body moves away from the concept of the mind/body continuum.

        This is particularly worrying when the approach of both the CBT and GET therapists is to convince the patients that the symptoms are not as bad as they think they are: it is easy enough to change people’s ratings in questionnaires by subjecting them to appropriate experiences. It is also informative that, with PACE, these “improvements” only register in Likert scoring systems – the FINE trial showed that bimodal (Yes/No) scoring for whether fatigue symptoms were still present failed to demonstrate any effectiveness for such therapies.

        How could you convince me that it is possible to have significant improvements in pain/fatigue etc. in the brain that had no effect at all on physical performance, on people whose physical performance is very limited? (Particularly when these very people also recorded that their physical performance had improved.) When you have an unblinded trial, with treatments aimed to change responses, how can you rule out the likelihood that patients are merely responding to instructions and rating their symptoms as less severe than they think?

      • I’m a fan of PACing, which is why the outcomes were initially alarming. For my wife’s fibro Lowdose Naltrexone appeared to be a fix, but it merely suppressed neural inflammation to let her go back to over-achieving… and crashing. ME/CFS peeps are giving LdN a go too, but attitudes need to be less around any pill as curative. More on strategies toward wellness.

  3. Graham seems to get to the heart of the matter.

    The question in any scientific experiment is what are you really measuring. I learned this as an undergraduate – the signals that I am measuring with the computer aren’t necessarily the phenomena itself.

    Questionnaires are not symptoms, nor daily functioning, they are merely proxies and thus subject to a variety of reporting biases. Clinical trials can easily bias cognition and thus questionnaire answering behaviour, which is why pharmacological trials insist on double blinding – the biases are still there, but are more or less similar in each arm, so long as blinding is maintained. Without blinding, a trial is not genuinely “controlled”.

    In nonpharmacological studies, the key is to develop a robust composite measure that relies on both subjective outcomes and objective outcomes of functioning. The key is to also account directly for baseline measures (increases in activity or performance will be relative to the baseline for that patient).

    The fact that only subjective outcomes improved in the PACE trial (along with other trials, eg the meta analysis of the Dutch CBT trials that found no difference in actigraphy or neuropsychological performance) is a red flag.

    • Finding the perfect outcome measure is unhelpful. We don’t reduce to a number at all easily. A few years ago I lampooned the OMERACT.org Fibromylagia Working Group’s inexorably slow progress https://wp.me/p46gNl-4f , when all they managed to develop is the idea of subgrouping. Why not get down to the individual then, since that is the only way to comprehend the depth and breadth of their illness experience. L.Jason’s MFTQ also classifies fatigued patients, but in order to explore their circumstances it blows out to 44 questions. That’s getting tiresome, for someone with brain fog, so I validated a combo pain/fatigue instrument of 10 questions: https://www.researchgate.net/publication/263427171_The_self-administered_FibroFatigue_Scale_is_less_more
      It sufficed. Nor does it matter whether you measure a muscle car by 0-100, standing quarter, top speed, or dyno – if all you need to know is ‘did the change make an improvement?’

      • The problem is that questionnaires are easily biased in unblinded trials. This is why blinding is mandatory in pharmacological trials for diseases that don’t kill you quickly.

        It is a problem even if it is the highest quality questionnaire ever.

        I don’t think this is a controversial position to make.

        That is the fatal flaw of all of these nonpharmacological trials for CFS so far. All of this was pointed out before any patients started the PACE trial. Actigraphy was measured at baseline but suddenly dropped as a followup measure after the aforementioned Dutch trialists told them they failed to see improvements in activity levels. (see the PACE Trial steering committee minutes)

        Deliberately not collecting direct evidence because it may contradict your hypothesis seems like a red flag to me.

        Objective measures are necessary for an unblinded trial to be considered high quality.

        I see actigraphy and neuropsychological testing as meaningful objective outcomes that aren’t excessively burdensome. Patients can’t do as much and thus have lower activity levels (can be measured with actigraphy), have issues with concentration leading to poorer neuropsychological performance. Exercise performance on the 2 day CPET is also impaired in a way that is not explained by deconditioning (reduced performance/efficiency at anaerobic threshold compared to healthy and other chronic illness controls, and even a twin pair study), but this testing is more problematic in a clinical trial context.

        Choosing not to use the highest quality standard of evidence in a well funded trial, you have to ask why?

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