In response to this fraudulent study, Dr Myhill reported the authors of PACE, and its directors, to the General Medical Council in January 2018. The GMC has a duty, and is empowered by Parliament, to regulate doctors and this includes research misconduct. Despite taking six months to consider Dr Myhill’s request, the GMC refused to investigate. Dr Myhill supplied extensive scientific proofs but in its refusal the GMC failed to supply its scientific defence.
So, Dr Myhill, through FoI legislation, asked that the GMC supply her with the scientific references on which it relied in coming to its decision not to investigate the PACE authors. The GMC refused. It gave no reasons whatsoever.
Consequently, Dr Myhill reported the GMC to the Information Commissioner who in a ruling of 30 September 2019 agreed with her. The ICO informed the GMC that it must supply her with the scientific references on which it relied in deciding not to investigate the PACE authors. This was because Dr Myhill was asking simply for scientific references already in the public area. This was only fair to the thousands of patients who have been damaged by graded exercise and who have a right to a proper explanation as to why.
At this point you would think the GMC had to comply. However, it is suspected that the GMC refusal arose for reasons of cronyism – it did not want ex-Presidents of Royal Societies up in front of the GMC and the Police. It did not want to admit that actually it held NO scientific evidence, and it had no good reason to proceed as it did.
So, the GMC had to think up some sort of legal argument for refusal. Hitherto it had no argument – simply blunt refusal. The GMC consulted with its legal beavers within and outside the GMC and came up with the argument that to comply with the ICO demands would infringe the personal privacy of the PACE authors. What a nonsense! Dr Myhill has no interest in the personal data of the PACE authors. She simply requested scientific references which should all be in the public arena!
This was the subject of the ICO Hearing on 22 March 2021: Myhill vs GMC and ICO.
The outcome was a split decision. It boiled down to the Public Interest test. Tribunal member Mr Malcolm Clarke agreed with Dr Myhill. He stated:
“I conclude that Dr Myhill’s legitimate interest in seeking this information, if it exists, as a practising doctor with patients, who has a deep professional interest in ensuring that national recommended treatments in this area of medicine are evidence-based, is a very strong one …Dr Myhill’s legitimate interest in knowing whether the information she requests is held by the GMC is a very strong one. I therefore conclude that ……Dr Myhill’s legitimate interests are not overridden by the rights and freedoms of the data subjects.”
Ref paragraphs 42-47,EA-2020-0018 Myhill v IC & GMC
Luckily for the GMC, the Judge Hazel Oliver and Panel member Gareth Jones disagreed. They decided the other way round.
This Ruling sends a very clear message to doctors who commit scientific fraud – it is easy to get away with it, you can easily hide behind Data Protection issues and the General Medical Council will assist. Cronyism works.
………and so now to round 4. Dr Myhill will not give up.
Review of the evidence indicates that none of the Wessely School’s hypotheses about the causes of ME/CFS are supported by the science (see here, here and here). Under these circumstances it would be scientifically impossible for ME/CFS treatments based on these incorrect principles to actually work. Only if there is a ‘fix’ and evidence is craftily manipulated by scientific sleight-of-hand could the therapies be made to look effective.
Which is exactly what has happened.
ME/CFS patients have known the truth for donkey’s years. Only the perpetrators of the ‘CBT/GET Illusion’ have claimed otherwise.
I review here the PACE trial and present a few details of an exposure by Carolyn Wilshire, Tom Kindlon, Alem Matthees and Simon McGrath (2017), which reveals the true null effect.
What was the PACE Trial?
Rarely in the history of clinical medicine have doctors and patients been placed so bitterly at loggerheads. The dispute had been a long time coming. Thirty years ago, a few psychiatrists and psychologists offered a hypothesis based on a Psychological Theory in which ME/CFS is constructed as a psychosocial illness. According to the Wessely School, ME/CFS patients have “dysfunctional beliefs” that their symptoms are caused by an organic disease. The ‘Dysfunctional Belief Theory’ (DBT) assumes that no underlying pathology is causing the symptoms; patients are simply being ‘hypervigilant to normal bodily sensations‘ (Wessely et al., 1989; Wessely et al., 1991).
The Wessely School Theory assumes that the physical symptoms of ME/CFS are the result of ‘deconditioning’ or ‘dysregulation’ caused by sedentary behaviour, accompanied by disrupted sleep cycles and stress. Counteracting deconditioning involves normalising sleep cycles, reducing anxiety levels and increasing physical exertion. Attentional biases also divert the patients towards their symptoms.
To put it bluntly, the DBT asserts that ME/CFS is ‘all in the mind’. Small wonder that patient groups have been expressing anger and resentment in their droves.
‘Top-down research’ uses a hierarchy of personnel, duties and skill-sets. The person at the top sets the agenda and the underlings do the work. The structure is a bit like the social hierarchy of ancient Egypt. Unless carefully managed, this top-down approach risks creating a self-fulfilling prophecy from confirmation biases at multiple levels. At the top of the research pyramid sits the ‘Pharaoh’, Regius Professor Sir Simon Wessely KB, MA, BM BCh, MSc, MD, FRCP, FRCPsych, F Med Sci, FKC, Knight of the Realm, king-pin and originator of the Wessely School. The principal investigators (PIs) for the PACE Trial were Professors White, Chalder and Sharpe, the ‘Inner Circle’ of the Wessely School. Another Inner Circle member, Sir Mansel Aylward, then at the Department for Work and Pensions, was a funder of the trial. The PIs all have or had connections both to the Department for Work and Pensions and to insurance companies.
The investigators obtained close to £5,000,000 of tax payers’ money to run the PACE trial.
The objective of the trial was to demonstrate that two treatments based on the DBT, cognitive behavioural therapy (CBT) and graded exercise therapy (GET), help ME/CFS patients to recover.
There was a zero chance the PACE researchers would fail to obtain the results they wanted. As the PACE ship left port, it went directly towards its destination. Only when it struck that unfortunate iceberg called “Null Result” did things begin to go seriously wrong.
Groupthink, Conflicts and Manipulation
The PACE trial team were operating within a closed system or groupthink in which they ‘know’ their theory is correct. With every twist and turn, no matter what the actual data show, the investigators are able to confirm their theory. The process is well-known in Psychology. It is a self-indulgent processes of subjective validationandconfirmation bias.Groupthink occurs when a group makes faulty decisions because group pressures lead to a deterioration of “mental efficiency, reality testing, and moral judgment” (Janis, 1972). Given this context, we can see reasons to question the investigators’ impartiality with many potential conflicts of interest (Lubet, 2017). Furthermore, critical analysis suggests that the PACE investigators involved themselves in manipulating protocols midway through the trial, selecting confirming data and omitting disconfirming data, and publishing biased reports of findings which created a catalogue of errors.
‘Travesty of Science’
The PACE Trial has been termed a ‘travesty of science’ while sufferers of ME/CFS continue to be offered unhelpful or harmful treatments and are basically being told to ‘pull themselves together’. One commentator has asserted that the situation for ME patients in the UK is: “The 3 Ts – Travesty of Science; Tragedy for Patients and Tantamount to Fraud” (Professor Malcolm Hooper, quoted by Williams, 2017). Serious errors in the design, the protocol and procedures of the PACE Trial are evident. The catalogue of errors is summarised below. The PACE Trial was loaded towards finding significant treatment effects.
When Disaster Strikes
The claimed benefits of GET and CBT for patient recovery are entirely spurious. The explanation lies in a sequence of serious errors in the design, the changed protocol and procedures of the PACE Trial. The investigators neglected or bypassed accepted scientific procedures for a RCT, as follows:
Category of error
Description of error
Ethical issue: Applying for ethical approval and funding for a long-term trial when the PIs knew already knew CBT effects on ME/CFS were short-lived.
On 3rd November 2000, Sharpe confirmed: “There is a tendency for the difference between those receiving CBT and those receiving the comparison treatment to diminish with time due to a tendency to relapse in the former” (www.cfs.inform/dk). Wessely stated in 2001 that CBT is “not remotely curative” and that: “These interventions are not the answer to CFS” (Editorial: JAMA 19th September 2001:286:11) (Williams, 2016).
Ethical issue: Failure to declare conflicts of interest to Joint Trial Steering Committee.
Undeclared conflicts of interest by the three PIs in the Minutes of the Joint Trial Steering Committee and Data Monitoring Committee held on 27th September 2004.
Ethical issue: Failure to obtain fully informed consent after non-disclosure of conflicts of interest.
Failing to declare their vested financial interests to PACE participants, in particular, that they worked for the PHI industry, advising claims handlers that no payments should be made until applicants had undergone CBT and GET.
Use of their own discredited “Oxford” criteria for entry to the trial.
Patients with ME would have been screened out of the PACE Trial even though ME/CFS has been classified by the WHO as a neurological disease since 1969 (ICD-10 G93.3).
Inadequate outcome measures.Using only subjective outcome measures.
The original protocol included the collection of actigraphy data as an objective outcome measure. However, after the Trial started, the decision was taken that no post-intervention actigraphy data should be obtained.
Changing the primary outcomes of the trial after receiving the raw data.
Altering outcome measures mid-trial in a manner which gave improved outcomes.
Changing entry criteria midway through the trial.
Altering the inclusion criteria for trial entry after the main outcome measures were lowered so that some participants (13%) met recovery criteria at the trial entry point.
The statistical analysis plan was published two years after selective results had been published.
The Re-definition of “recovery” was not specified in the statistical analysis plan.
Sending participants newsletters promoting one treatment arm over another, thus contaminating the trial.
Lack of comparable placebo/control groups with inexperienced occupational therapists providing a control treatment and experienced therapists provided CBT.
Repeatedly informing participants in the GET and CBT groups that the therapies could help them get better.
Giving patients in the CBT and GET arms having more sessions than in the control group.
Allowing therapists from different arms to communicate with each other about how patients were doing.
Lack of transparency
Blocking release of the raw data for five years preventing independent analysis by external experts.
Credit where credit is due
A significant amount of investigation about the PACE trial was carried out in 2015 by David Tuller.
The PACE Trial Invalidates the Use of Cognitive Behavioral and Graded Exercise Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review. J Neurol Neurobiol 2(3).
PACE-Gate: the Cover-Up
Blocking release of the raw data for five years and preventing independent analysis by external experts was tantamount to a cover-up of the true findings. An editorial by Keith Geraghty (2016) was entitled ‘PACE-Gate’. ME/CFS patient associations were rightly suspicious of the recovery claims concerning the GET arm of the trial because of their own experiences of intense fatigue after ordinary levels of activity which were inconsistent with the recovery claims of the PACE Trial reports. For many sufferers, even moderate exercise results in long ‘wipe-outs’ in which they are almost immobilized by muscle weakness and joint pain. In the US, post-exertional relapse has been recognized as the defining criterion of the illness by the Centers for Disease Control, the National Institutes of Health and the Institute of Medicine. For the PACE investigators, however, the announced recovery results validated their conviction that psychotherapy and exercise provided the key to reversing ME/CFS.
Alem Matthees Obtains Data Release
When Alem Matthees, a ME/CFS patient, sought the original data under the Freedom of Information Act and a British Freedom of Information tribunal ordered the PACE team to disclose their raw data, some of the data were re-analysed according to the original protocols. The legal costs of the tribunal at which QMUL were forced to release the data, against their strenuous objections, was over £245,000. The re-analysis of the PACE Trial data revealed that the so-called “recovery” under CBT and GET all but disappeared (Carolyn Wilshire, Tom Kindlon, Alem Matthees and Simon McGrath, 2016). The recovery rate for CBT fell to seven percent and the rate for GET fell to four percent, which were statistically indistinguishable from the three percent rate for the untreated controls.
Graded exercise and CBT are still being routinely prescribed for ME/CFS in the UK despite patient reports that the treatments can cause intolerable pain and relapse. The analysis of the PACE Trial by independent critics has revealed a catalogue of errors and provides an object lesson in how not to conduct a scientific trial. The trial can be useful to instructors in research design and methodology for that purpose.
Following the re-analyses of the PACE Trial, the DBT is dead in the water. There is an urgent need for new theoretical approaches and scientifically-based treatments for ME/CFS patients. Meanwhile, there is repair work to be done to rebuild patient trust in the medical profession.
Can patients with chronic fatigue syndrome really recover after graded exercise or cognitive behavioural therapy?
These authors gave a critical commentary and preliminary re-analysis of the PACE trial. I quote their Abstract:
BACKGROUND: Publications from the PACE trial reported that 22% of chronic fatigue syndrome patients recovered following graded exercise therapy (GET), and 22% following a specialised form of CBT. Only 7% recovered in a control, no-therapy group. These figures were based on a definition of recovery that differed markedly from that specified in the trial protocol. PURPOSE: To evaluate whether these recovery claims are justified by the evidence. METHODS: Drawing on relevant normative data and other research, we critically examine the researchers’ definition of recovery, and whether the late changes they made to this definition were justified. Finally, we calculate recovery rates based on the original protocol-specified definition. RESULTS: None of the changes made to PACE recovery criteria were adequately justified. Further, the final definition was so lax that on some criteria, it was possible to score below the level required for trial entry, yet still be counted as ‘recovered’. When recovery was defined according to the original protocol, recovery rates in the GET and CBT groups were low and not significantly higher than in the control group (4%, 7% and 3%, respectively). CONCLUSIONS: The claim that patients can recover as a result of CBT and GET is not justified by the data, and is highly misleading
The PACE trial is/was/and always will be an unmitigated disaster. I use it in my textbook as an example of how not to do a trial.
The authors and sponsors have done a disservice to science and to patients that will be hard to forget.
An apology is the least that the principal investigators can do to make amends for this dreadful piece of pseudo-science.
The universities involved should return the public funds that were wasted on the PACE trial project.
A government enquiry is necessary to investigate the full facts in relation to the connections between the investigators, the insurance industry and the UK Department of Work and Pensions.
Note: This post is dedicated to Alem Matthees who has dedicated his life to the search for the truth about ME/CFS and was responsible for obtaining the release of the PACE trial data.
A previous post examined the Wessely School hypothesis that ME/CFS is caused by unhelpful beliefs. This idea was exploded as a myth. Here I examine a second Wessely School hypothesis (H2) that states:
Deconditioning causes, or exacerbates the symptoms of, ME/CFS and MUS.
Deconditioning refers to multiple, potentially reversible changes in body systems brought about by physical inactivity and disuse. The theory proposes that patient’s claims of an inability to exercise or exert themselves is due to a reluctance to or fear of exercise. Psychological interventions in the form of CBT are indicated to help the patient overcome their dysfunctional beliefs and physical exercise such as GET is offered to help the patient to recondition their body. Without properly controlled trials and investigations it is impossible to determine which is cause and effect, the illness or the deconditioning. If deconditioning causes or contributes to ME/CFS, then signs of deconditioning should be more pronounced in the sicker patients and less pronounced in the less sick ones. In this section, I review the evidence for and against the deconditioning hypothesis of ME/CFS and MUS. Relevant studies have been conducted over a period of 20+ years. An early uncontrolled study suggested an association between CFS and deconditioning (De Lorenzo et al. (1998). To take a study seriously it must meet the minimum criteria for a controlled study: groups matched at baseline, blinded testing, with objective measures.
Fulcher and White (2000)
measured strength, aerobic exercise capacity and efficiency, and functional incapacity in pwCFS who did not have a current psychiatric disorder. Compared with sedentary controls, pwCFS were found to be physically weaker, had a significantly reduced exercise capacity, and perceived greater effort during exercise, but were equally unfit. Fulcher and White concluded that pwCFS were weaker than sedentary and depressed controls and as unfit as sedentary controls. The data were consistent with the hypothesis that physical deconditioning helps to maintain physical disability in CFS and that a treatment designed to reverse deconditioning would help to improve physical function. However there was a problem with the procedures used to test the participants. However, as the authors acknowledge, the lack of ‘blind’ testing and other issues could have biased the results: “ We would in any case advise caution in interpreting and generalising from these data because of the bias inherent in a case-control study, the need for replication of these data, the lack of blindness in some of the measures, and the few comparison patients with a major depressive illness.” (Fulcher & White, 2000, p. 307).
Timmers et al. (2002)
found that head-up tilt evokes postural tachycardia or (pre)syncope in a minority of CFS patients. The authors concluded that observations in head-up tilt-negative CFS patients of a higher heart rate at baseline together with a marked decrease in stroke volume in response to head-up tilt could point to deconditioning.
Not so fast! Please read on to the end…
A narrative review
by Clark and White (2005) concluded that: “Patients with CFS are at least as deconditioned as sedentary but healthy controls. Supervised graded exercise therapy reduces fatigue and disability in ambulant patients with CFS; efficacy may be independent of reversing deconditioning…Further work is necessary to elucidate the risks, benefits, and mechanisms of such treatment, especially in children and the severely disabled” (p. 237).
A subjective measure and high drop-out rate
Moss-Morris, Sharon, Tobin and Baldi (2005) investigated GET in a sample of 49 CFS patients who were randomized to a 12-week graded exercise programme or to standard medical care. After treatment the group who had received GET rated themselves as significantly more improved and less fatigued than the control group. A decrease in symptom focusing rather than an increase in fitness mediated the treatment effect. The authors concluded that GET “appears to be an effective treatment for CFS and it operates in part by reducing the degree to which patients focus on their symptoms” (p. 245). The main problem with this study was the use of subjective measures of illness improvement and the high drop-out rate of 47% (23/49) from the physiological tests and the non-significant physiological improvement with ten patients refusing to have a second test as they believed the initial test was harmful to them.
A skeptical Catalonian study
concluded that “the decrease in the peak workload achieved in arm or leg exercise by CFS patients would not be justified exclusively by their personal characteristics or deconditioning” (Javierre et al., 2007).
A curiously Contrarian study
Harvey, Wadsworth, Wessely and Hotopf (2008) reviewed the aetiology of CFS and tested hypotheses relating to immune system dysfunction, physical deconditioning, exercise avoidance, and childhood illness experiences, using a large prospective birth cohort consisting of 4779 participants from the National Survey of Health and Development. Participants were prospectively followed for the first 53 years of their lives with 20 separate data collections. The authors identified CFS through self-report during a semi-structured interview at age 53 years with an additional case notes review. Of 2983 participants assessed at age 53 years, 34 percent reported a diagnosis of CFS and were no more likely to have suffered from childhood illness or atopy. Interestingly, the authors found that “increased levels of exercise throughout childhood and early adult life and a lower body mass index were associated with an increased risk of later CFS. Participants who later reported CFS continued to exercise more frequently even after they began to experience early symptoms of fatigue…Continuing to be active despite increasing fatigue may be a crucial step in the development of CFS” (p. 488). Based on Harvey et al.’s prospective evidence, which can give a valid interpretation of causality, exercising rather than its lack appears as a possible cause of later ME/CFS.
This temporal, dose–response relationship suggests that psychiatric disorders, or shared risk factors for psychiatric disorders, are likely to have an aetiological role in some cases of CFS/ME.
An inconclusive update
of an earlier review (Larun et al., 2014) observed that: “Exercise therapy did not worsen symptoms for people with CFS. Serious side effects were rare in all groups, but limited information makes it difficult to draw firm conclusions about the safety of exercise therapy” (Larun, Brurberg, Odgaard-Jensen & Price, 2019). The authors arrived at a set of appropriately modest conclusions. In comparing exercise therapy with a ‘passive’ control, they state:
“Exercise therapy probably reduces fatigue at end of treatment… We are uncertain if fatigue is reduced in the long term because the certainty of the evidence is very low…We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low…Exercise therapy may moderately improve physical functioning at end of treatment, but the long‐term effect is uncertain because the certainty of the evidence is very low. Exercise therapy may also slightly improve sleep at end of treatment and at long term. The effect of exercise therapy on pain, quality of life and depression is uncertain because evidence is missing or of very low certainty.” In sum, no definite conclusions about exercise and CFS patients could be reached.
The literature’s a mess
Nijs et al. (2011) conducted a systematic review to examine whether pwCFS differ from healthy sedentary controls in physiological exercise capacity, physical activity level and muscle strength. They refer to the conflicting data concerning physiological exercise capacity of pwCFS but suggest that the “weighted available evidence points towards a reduced physiological exercise capacity in CFS. Future studies should use a wash-out period for medication use, blinded assessments, a priori power calculation and a sedentary control group comparable for age, gender, body weight, body length and current physical activity level” (p. 1493).
A deleterious immunological effect of GET predicted
Another review by Pierce, Pierce and Campus (2008) discussed the deleterious immunological effect that is likely to follow the use of GET in pwME: “initial over-exertion (a period of metabolic stress) in conjunction with viral infection depletes concentrations of the metabolic regulator glutathione, initiating a cascade of physiological dysfunction…the exacerbation of symptoms for the majority is not subjective but has a physiological basis. Blanket recommendation of GET is not prudent for such a heterogeneous group of patients, most of which are likely to respond negatively to physical activity” (p. 55).
Finally, a properly controlled cardiological study
As noted, previous studies have established that effort intolerance along with a prolonged recovery from exercise and post-exertional exacerbation of symptoms are characteristic features of ME/CFS. Finally, Van Campen and Visser (2018), two cardiologists in the Netherlands, carried out a well-controlled investigation entitled: “The abnormal Cardiac Index and Stroke Volume Index changes during a normal Tilt Table Test in ME/CFS patients compared to healthy volunteers, are not related to deconditioning.”
At last, a well-controlled cardiological study of the deconditioning hypothesis that leaves no doubt about its findings.
Figure 2: shows the percent change of the stroke volume and cardiac index in ME/CFS patients with mild, moderate and severe disease according to the ME criteria.Reproduced from van Campen and Visser (2018).
There were no significant differences between the three groups suggesting that deconditioning does not explain the larger decrease in stroke volumes and cardiac output in ME/CFS patients compared to healthy volunteers.
Over the 20-+ year period since research on ME/CFS and deconditioning first began, this is the first controlled investigation that looks at disease severity in a test of the conditioning hypothesis. The study clearly indicates that deconditioning is NOT causally associated with ME/CFS severity, contrary to H2.
After 20+ long years, a study by two cardiologists in the Netherlands, van Campen and Visser, have laid to rest the idea that ME/CFS symptoms are caused by deconditioning.
It seems far more likely that ME/CFS causes deconditioning, not vice versa.
This is the second of the Wessely School myths that has been exploded.
The use of GET for ME/CFS patients should be banned immediately.
ME/CFS patients must be listened to. At this stage, they are the only genuine experts, so it would appear.
In a series of posts I review the Wessely School’s influence on science, treatment and – most importantly – ME/CFS patient experience. In previous posts I outlined here the likely biological basis of ME/CFS and here treatment harms to patients. This post introduces the Wessely School’s approach to ME/CFS and medically unexplained symptoms.
What is ME/CFS?
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystemic disease of unknown aetiology, affecting thousands of individuals worldwide. The severity of symptoms can range from mild to severe with incidence peaks between age 10-19 years and 30-39 years. Women are more often affected than men in a 3:1 ratio. ME/CFS has been described as an “incurable, invisible contested and unsupported illness” (Farrell Delaney, 2020). The report by the Institute of Medicine (IOM) of the Academy of Sciences in the USA in 2015 concluded that ME/CFS is a physiological/medical, not a psychiatric illness (Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, 2015; Clayton, 2015). The International Consensus Criteria (Carruthers et al., 2011), the Centers for Disease Control and Prevention (2018), the ICD-10, and the ICD-11 (World Health Organisation, 2018), all classify ME/CFS as a neurological disease.
In spite of evidence that the disease is associated with marked biological changes (Loebel et al., 2016, Schreiner et al., 2020; Sotzny et al., 2018; van Campen et al., 2020) and what appears to be a breakdown in homeostasis (Marks, 2021), the disease is often perceived by doctors and nurses as having a psychological or psychosomatic origin that is ‘all in the head’ (Åsbring & Närvänen, 2002; Dickson et al., 2007; Ware, 1992). This ‘all in the head’ perception causes stigmatization as an extra burden for patients with ME/CFS.
Paediatrician Ola Didrik Saugstad has stated: “A reorientation of the understanding and attitude to ME patients occurs worldwide. ME patients, especially the worse cases, suffer enormously. Among them, the paediatric patients are most vulnerable, representing a special challenge due to the occurrence in the midst of somatic growth and emotional development. We are waiting for a biomarker of this disease, and some are in the pipeline. And even more, we are hoping for an effective treatment. Still, it is already now time for the medical profession as well as the whole society to repent, as these patients have previously often not been treated with the respect and care they need and deserve” (Saugstad, 2020).
In addition to the stigma and stress burdens, the most used therapies for pwME/CFS based on the psychosocial model have caused significant harms to patients that are well documented in the literature.
Owing to the absence of an established biomarker, current diagnostic methods proceed by a process of eliminating other diseases with similar symptoms and there is no universally agreed or empirically derived definition of ME/CFS. The illness was first described in the mid-1980s when almost nothing was known about its underlying biology. Some clinicians explained to patients that “there is nothing wrong.”
Post-exertional malaise (PEM) is a cardinal symptom of ME/CFS reported by many, but not all, patients (Jason, Evans, So, Scott & Brown, 2015; VanNess, Snell & Stevens, 2007; McGregor, Armstrong, Lewis & Gooley, 2019).). In the International Classificatory System, PEM is a mandatory feature of the condition (Carruthers et al., 2003, 2011). Another commonly reported feature of the illness is its tendency to wax and wane (Friedman, Bateman, Bested, & Nahle, 2019; Morris, Anderson, Galecki, Berk & Maes, 2013; Morris & Maes, 2014). The onset and duration of ME/CFS have been debated with some researchers suggesting a sudden onset and others a gradual onset. An interview study revealed descriptions of ME/CFS onset experiences that were both varied and complex indicating that onset can be sudden or gradual in different cases (Evans & Jason, 2018).
For more than thirty years
a group of psychiatrists and psychologists at King’s College London and the Institute of Psychiatry together with a large group of collaborators has advanced a psychosomatic approach to ME/CFS. This group is given the sobriquet ‘Wessely School’ in honour of its leading representative, Professor Sir Simon Wessely. Simon Wessely has been the UK’s leading authority in establishing healthcare for patients with ME/CFS and MUS. According to the Wessely School, ME/CFS is neither a neurological nor an immunological condition but a psychosomatic condition, a functional illness with a primarily psychological origin. For the Wessely School, ME/CFS belongs in a spectrum of medically unexplained symptoms (MUS) including irritable bowel syndrome, non-ulcer dyspepsia, premenstrual syndrome, chronic pelvic pain, fibromyalgia, atypical or non-cardiac chest pain, hyperventilation syndrome, tension headache, atypical facial pain, globus syndrome and multiple chemical sensitivity (Wessely, Nimnuan & Sharpe, 1999). Early in the piece these authors opined that “the existing definitions of these syndromes in terms of specific symptoms is of limited value”.
The psychologists and psychiatrists within the Wessely School favour the
Cognitive Behaviour Therapy (CBT) Model
of emotional distress as proposed by Aaron T Beck (1976). The model distinguishes between developmental predispositions and precipitants of distress, and perpetuating cognitive, behavioural, affective and physiological factors, the so-called “three Ps”: predisposing, precipitating and perpetuating factors (Beck, 1976). This approach is not dissimilar to Hans Eysenck’s view that personality and feelings of hopelessness and helplessness are causal determinants of diseases such as cancer and coronary heart disease (Eysenck, 1991, Figure 1).
In line with Beck’s and Eysenck’s approach, the Wessely School has promoted what it has called a “broadly conceptualized cognitive behavioural model of MUS suggest(ing) a novel and plausible mechanism of symptom generation.” In a nutshell, fears and beliefs about the harmful effects of activity are related to poorer outcomes in ME/CFS (Deary, Chalder & Sharpe, 2007).
The school holds the hypothesis that the ‘three Ps’ inform behaviour such as activity avoidance and the belief that the illness has an organic basis, which, in turn, are said to affect the patient’s physiology and symptoms, providing a vicious circle of symptom maintenance irrespective of symptom type.
Some of the main influencers on the school have been Aaron T Beck, George Engel, Hans J Eysenck and Isaac M Marks. Eysenck’s theory assigns to cortisol and immune deficiency a mediating role between feelings of hopelessness and helplessness and development of the disease (see Figure 1).
Eysenck: Psychosocial -> Biological -> Disease
Figure 1. Hans Eysenck’s theory of personality and stress, dysfunctional feelings, as the causes of cancer. From Eysenck (1991).
Wessely’s theory attributes causal status to fear, behaviour and de-conditioning (Figure 2). Eysenck’s theory and Wessely’s theory share a strongly biopsychosocial orientation but with a difference in the sequence of the three key elements:
Wessely: Biological -> Psychosocial -> Disease
Figure 2. The Wessely School’s theory of the aetiology of CFS. From Harvey and Wessely, 2009.
Treatment of ME/CFS in the Wessely School’s approach focuses on the alleged ‘self-perpetuating cycle’ of inactivity that is assumed to disrupt the “self-maintaining interlock of cognitive, behavioural and physiological responses hypothesised to perpetuate the symptoms” (Deary et al. 2007, pp. 2-3; Harvey & Wessely, 2009; Figure 2).
The role of doctors in MUS is said to be similar to that of “parents of sick children. Both can reinforce unhelpful illness behaviour and symptom interpretations” (Deary et al., 2007, p. 7).
A group of investigators in Nijmegen, The Netherlands, holds a similar hypothesis that emphasizes the role of physical activity in attempting to correct the so-called ‘vicious circle’ of ME/CFS (Vercoulen et al., 1998; Wiborg, Knoop, Stulemeijer, Prins & Bleijenberg, 2010).
Influencers of the Wessely School
There have been several major influencers on the School including:
Hans J Eysenck: a leading theorist in personality theory and behaviour therapy. However, Eysenck’s publications on smoking, cancer and CHD were recently considered ‘unsafe’ in an enquiry within King’s College London.
Key members of an ‘inner circle’ are also shown in the illustration:
Trudie Chalder: Professor of Cognitive Behavioural Psychotherapy, King’s College London. Chalder has co-authored multiple publications on ME/CFS and MUS with Professor Wessely and she was one of the co-principal investigators of the PACE trial.
Peter D White: retired Professor of Psychological Medicine at Queen Mary University of London, United Kingdom, one of the co-principal investigators of the PACE trial.
Michael Sharpe: Professor of Psychological Medicine at the University of Oxford (previously at the University of Edinburgh) and one of the co-principal investigators of the PACE trial.
A larger ‘outer ring’ of collaborators work at King’s College London and at many other institutions all over the world.
The Wessely School’s Contribution
The Wessely School’s influence on the treatment of patients with ME/CFS has been huge. Some main influencers and contributors are listed in the table together with statements and publications reflecting the approach.
INFLUENCERS AND CONTRIBUTORS
PUBLICATIONS AND PERSONNEL
“People are not disturbed by things, but by the views they take of them”.
Thought control in everyday life. (1928). Funk & Wagnalls, New York.
Aaron T Beck
Depression: Causes and treatment. (1967). University of Pennsylvania Press, Philadelphia.
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Core Team Members at King’s College London
T Chalder, J Chilcot, P McCrone, K Goldsmith, M. Hotopf, R Moss-Morris, J Weinman, S Wessely
M. Alyward (UnumProvident Centre, Cardiff), C. Bass (Oxford), G. Bleijenberg (Nijmegen), S. Borgo (Rome), K. Brurburg (Norwegian Institute of Public Health), C. Burton (Sheffield), D. L. Cox (Cumbria), E. Crawley (Bristol), V. Deary (Newcastle), L. Dennison (Southampton), R. Horne (UCL), A.L. Johnson (MRC Clinical Trials Unit, London), H. Knoop (Nijmegen), M. Loades (Bath), D.Oakley (UCL), K. Petrie (Auckland), M. Sharpe (Oxford), L. Sibelia (Rome), P. D. White (Queen Mary University of London)
In later posts I present the scientific evidence on the Wessely School’s approach to ME/CFS and MUS.
Despite evidence of physiological and cellular abnormalities in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS), the dominant therapeutic approach has been cognitive behaviour therapy (CBT) and graded exercise therapy (GET). Patients report distress and dissatisfaction following healthcare encounters based on GET and CBT. A significant body of research suggests that CBT and GET are harmful for many patients with ME/CFS. These findings raise ethical concerns and suggest that more collaborative working between scientists, therapists and patients would be helpful in making scientific progress in this difficult field.
CBT and GET follow the discredited biopsychosocial approach of influential psychiatrists and psychologists of the Wessely school (Wessely, David, Butler & Chalder, 1989; White et al., 2011). Multiple patient reports and studies indicate stigmatization, distress and dissatisfaction following GET and CBT. A significant body of research suggests what patients have known for a very long while that CBT and GET are not only ineffective, but harmful for many patients with ME/CFS.
A review of CBT and GET by Twisk and Maes (2009) found that CBT and GET are “not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS” (p. 284). Twisk and Maes (2009) suggested that CBT/GET is hardly more effective than non-interventions or standard medical care, but also that “many patients report that the therapy had affected them adversely, the majority of them even reporting substantial deterioration”. Exertion which is almost bound to occur with GET is most likely to have a negative impact on many ME/CFS patients. Exertion produces post-exertional malaise (PEM) which decreases aerobic capacity, increases muscoskeletal pain, neurocognitive impairment, “fatigue”, and weakness, and produces a slow recovery time. Twisk and Maes concluded that it is “unethical to treat patients with ME/CFS with ineffective, non-evidence-based and potentially harmful “rehabilitation therapies”, such as CBT/GET”.
High rates of adverse effects have been reported with CBT and GET by ME/CFS patients. Kindlon (2011) reviewed 10 patient surveys from four countries found that 51per cent of respondents (range = 28%–82%, n = 4338, eight surveys) reported GET worsened their health, whereas 20 per cent of respondents (range = 7%– 38%, n = 1808, five surveys) reported similar results for CBT.
Kindlon (2017) also reviewed evidence that low-intensity exercise has the potential to exacerbate symptoms in CFS. The effects of exercise can persist for more than a week after exertion e.g. gentle exercise of less than 7-minute duration can lead to worsening of fatigue, pain, sore throat and/or general health (Nijs et al., 2008; Van Oosterwijck et al., 2010). Longer-term, the effects of exercise can persist beyond 24 hours (VanNess et al., 2010). Lapp (1997) followed 31 patients for 12 days after a maximal exercise test and found that the average relapse lasted 8.82 days with 22 per cent still in relapse at 12 days. Kindlon (2017) observed that: “interventions involving exercise could provoke a general and persistent worsening or exacerbation of symptoms in CFS. They also offer an explanation as to why it might be difficult for patients with CFS to adhere to graded activity/exercise interventions” (p. 1147). As noted, post-exertional malaise is a key symptom of ME/CFS. Numerous biological abnormalities have also been found following exertion (Lane et al., 2003; Light et al., 2009; Sorensen et al., 2009; Twisk and Maes, 2009).
1. difficulties in reaching an acceptable diagnosis;
2. misdiagnosis, including of other medical and psychological conditions;
3. difficulties in accessing the sick role, medical care and social support;
4. high levels of patient dissatisfaction with the quality of medical care;
5. negative responses to controversial therapies (cognitive behavioral therapy, CBT, and graded exercise therapy, GET);
6. challenges to the patient narrative and experience;
7. psychological harm (individual and collective distress).
Geraghty and Blease (2019) concluded that the “biopsychosocial framework currently applied to ME/CFS is too narrow in focus and fails to adequately incorporate the patient narrative. Misdiagnosis, conflict, and harm are observable outcomes where doctors’ and patients’ perspectives remain incongruent. Biopsychosocial practices should be scrutinized for potential harms. Clinicians should consider adopting alternative patient-centred approaches.”
Friedberg, Sunnquist and Nacul (2020) also reviewed evidence suggesting that claims of safety of CBT and GET are “not adequately supported by the evidence and are contradicted by the experiences of clinicians and patients.” They quote the 2014 Agency for Healthcare Research and Quality (AHRQ) reviewthat reported, “Harms [worsening of symptoms and/or disability] were generally inadequately reported across trials” (p. vi). The AHRQ report concluded that GET studies reported more adverse events and withdrawals. As early as 2012, experienced clinicians were not recommending PACE-type GET or CBT as treatments (Friedberg et al., 2012). They also cite Kindlon’s (2015) analysis of large international patient surveys in which more than 50% of pwME/CFS reported that CBT and GET fell short of delivering significant improvements and often led to worsened health due to ill-advised activity and exercise prescriptions.
McPhee et al. (2019) surveyed the National Health Service–affiliated ME/CFS specialist clinics in England to assess how harms following treatment are detected and to examine how patients are warned about the potential for harms. The researchers sent 57 clinics standardised information requests under the UK’s Freedom of Information Act. Data were received back from 38 clinics. Clinics were highly inconsistent in their approaches to the issue of treatment-related harm. Clinics placed little or no focus on the potential for treatment-related harm in their written information for patients and for staff. Furthermore, no clinic reported any cases of treatment-related harm, despite acknowledging that many patients dropped out of treatment. McPhee et al. recommended that clinics need to “develop standardised protocols for anticipating, recording, and remedying harms, and that these protocols allow for therapies to be discontinued immediately whenever harm is identified”.
The draft NICE guideline released on 10 November 2020 stated:
1) NICE “recognises that ME/CFS, which is estimated to affect over 250,000 people in England and Wales, is a complex, multi-system, chronic medical condition where there is no ‘one size fits all’ approach to managing symptoms. It stresses the need for a tailored, individualised approach to care that allows joint decision making and informed choice.”
2)“Because of the harms reported by people with ME/CFS, as well as the committee’s own experience of the effects when people exceed their energy limits, the draft guideline says that any programme based on fixed incremental increases in physical activity or exercise, for example graded exercise therapy (GET) should not be offered for the treatment of ME/CFS.”
3) “Instead, it highlights the importance of ensuring that people remain in their ‘energy envelope’ when undertaking activity of any kind and recommends that a physical activity programme, in particular, should only be considered for people with ME/CFS in specific circumstances.”
4) “The draft guideline also emphasises that CBT it is not a treatment or cure for ME/CFS. However, as a supportive therapy which aims to improve wellbeing and quality of life, the draft guideline says CBT may be useful in supporting people who live with ME/CFS to manage their symptoms.”
It is self-evident that healthcare professionals seek to avoid and minimize harms when assisting ME/CFS patients. As suggested by Geraghty and Blease, a “concordant ‘patient-centred’ approach that give greater prominence to the patient narrative and experience of illness” is required.
In light of the findings on patient harms, extreme caution is required in offering pwME /CFS treatments such as CBT and GET which involve increased exercise or activity levels.
The findings on patient harms suggest that treatments using CBT and GET involve ethical dilemmas which practitioners can be helped to resolve by working with patients using a more collaborative approach.
Clinics should develop standardised protocols for anticipating, recording, and remedying harms, and these protocols should allow for therapies to be discontinued immediately whenever harm is identified.
Somewhat belatedly, the revised NICE draft guidance (2020) recognises the evidence on harms to ME/CFS patients from the use of GET and, to a lesser extent, CBT. The change in guidance is, in no small measure, a tribute to the researchers and patients who are cited here.
Dedication: This post is dedicated to Tom Kindlon and his indefatigable search for the truth about ME/CFS.