Westminster Hall Debate on the PACE trial and its effects on people with ME:

an analysis of the response from Caroline Dinenage MP, Minster of State for Care

On the 20 February 2018 a debate was held in the Palace of Westminster (UK) on the PACE trial and its effects on people with ME. (See #MEAction summary.)

Carol Monaghan MP, who secured the debate, raised many valid and important concerns, as did several MPs who intervened during her speech. This article, however, is concerned only with analysing the comments made by Caroline Dinenage MP, the minister who was assigned to speak on behalf of the Department for Health and Social Care (DHSC).

The full transcript of everything that the minister other MPs said during the debate is available from Hansard. There is also a video of the 30 minute debate on parliamentlive.tv.

Selected quotes from Caroline Dinenage, and analysis:

“As we have heard, chronic fatigue syndrome, also known as myalgic encephalomyelitis or encephalopathy, is a debilitating and very poorly understood condition, which is estimated to affect more than 200,000 people in England.”

It was notable that during the debate Carol Monaghan consistently referred to ME (myalgic encephalomyelitis) not chronic fatigue syndrome, observing that “labels such as chronic fatigue syndrome or post-viral fatigue syndrome simply do not come close to the living hell experienced by many ME sufferers”. It was therefore disappointing that the minister chose to refer to the illness primarily as chronic fatigue syndrome, and later as CFS/ME (see further comment below).

It was interesting to hear that the DHSC estimates that the number of people affected by ME/CFS in England is more than 200,000. In 2013, Professor Sir John Savill, Chief Executive of the Medical Research Council (MRC) sent a letter to Francis Maude MP, in which he stated that there were fewer than 20,000 (twenty thousand) people in the UK with a diagnosis of “CFS/ME or Post Viral Fatigue Syndrome (PVFS)” [1]. This low estimate of the disease burden was used to partly justify the low levels of funding for biomedical ME research by the MRC. It is unclear whether the MRC acknowledges that this was an error. No clarification or apology has been issued, and there has been no increase in investment in biomedical research or ringfencing of funds to compensate for the apparent miscalculation.

It was also notable that the minister referred only to the estimated number of people affected in England, with no mention of the other parts of the UK. This was surprising given that the MP who secured the debate represents a Scottish constituency.

“The condition, which for brevity and to avoid covering you in a thin layer of spittle, Mr Hollobone, I shall refer to in the abbreviated form CFS/ME, can stop a life in its tracks, leaving sufferers unable to carry out the most basic tasks.”

No patients or patient groups refer to the illness as CFS/ME. The preferred term among patients and charities is ME. The term CFS/ME was used by the PACE authors. It was also adopted by the CFS/ME Research Collaborative (CMRC) at the request of Professor Sir Simon Wessely and Professor Peter White (lead investigator of the PACE trial), against the wishes of all of the charities involved (Action for ME, The ME Association and ME Research UK) [2].

“In the most serious cases, people can be bedbound for weeks at a time.”

This comment betrays a concerning lack of understanding. In the most serious cases, people can be bedbound for decades, not “weeks at a time”. The most severely affected are unable to speak, feed themselves, tolerate light, sit up in bed, watch TV or listen to the radio. As Carol Monaghan said during the debate, it is a “hell that is made worse by the lack of understanding”.

“It is also true that the difficulties in diagnosis mean that patients with CFS/ME often experience delays in getting the treatment and support that they need.”

This is true but it implies that effective treatments exist, which is not true. Pacing is considered by patient charities to be the best way to manage the illness, but management is not the same as treatment. There are currently no proven effective treatments for ME.

The “support” which is currently offered by most CFS clinics is usually based on the flawed results of the PACE trial, i.e. CBT and GET. Such support is not only unhelpful but often harmful. It would be disastrous for patients if more money was wasted on more inappropriate services.

“In recognising the need for GPs to be aware of the condition, the Royal College of General Practitioners identified CFS/ME as a key area of technical knowledge that GPs should have as part of their qualifying exams, which answers a question raised by the hon. Lady.”

The RCGP has a poor track record with regard to ME. GPs must be taught that the current NICE guidelines are not fit for purpose and that CBT and GET are not effective or appropriate treatments for ME. To be taught otherwise would be negligent.

“The recommended treatments for CFS/ME, namely cognitive behavioural therapy, or CBT, and graded exercise therapy, or GET, and the evidence for them are the subject of today’s debate. Those treatments were first recommended for patients with mild or moderate CFS/ME in 2007 in the NICE guidance, in line with the best available evidence, which showed that the treatments offered benefits.”

ME patient organisations have been consistent in their opposition to CBT (as defined by PACE [3]) and GET because there has never been any reliable or objective evidence of their effectiveness, and there is good evidence to suggest that they may be harmful [4].

ME is characterised by post-exertional malaise (PEM). A 2015 report by the US Institute of Medicine concluded that “There is sufficient evidence that PEM is a primary feature that helps distinguish ME/CFS from other conditions” [5]. And the evidence continues to grow [6].

If ME is defined by a significant and prolonged worsening of symptoms following exertion (PEM), then it is logical to infer that anybody whose symptoms improve or are reversed through the prescrption of repeated exertion (as with PACE-type CBT and GET) does not have ME by definition.

Furthermore, independent re-analysis of the PACE trial [7,8] along with the results of its long-term follow-up study [9] provide compelling evidence of the ineffectiveness of CBT and GET in treating people with ME, even if PEM is not considered to be a requirement for diagnosis (as with the Oxford Criteria that was used in the PACE trial [10]).

“The guidance sets out that there is no one form of treatment to suit every patient and that the personal needs and preferences of patients should be taken into account. Doctors should explain that no single strategy will be successful for all patients; that in common with all people receiving NHS care, CFS/ME patients have the right to refuse or withdraw from any part of their treatment…”

The NICE Guideline [11] has been criticised by all ME charities, patient organisations and representatives registered with NICE as stakeholders [12].

The minister was correct to state that patients should have the right to refuse or withdraw from any treatment. However, the experience of patients and the parents of children with ME is often inconsistent with her assertion.

In a 2014 article entitled “False Allegations of Child Abuse in Cases of Childhood Myalgic Encephalomyelitis (ME)”, Jane Colby, Executive Director of the Tymes Trust charity wrote, “parents who decline, or withdraw children from, management regimes, which may have worsened their illness, can find themselves facing investigation for child abuse or neglect, or have their child forcibly confined to a psychiatric unit.” [13] Some of these issues were also touched upon in the File on 4 documentary on BBC Radio 4, Children with ME [14].

Other ME patients report problems with receiving insurance payments or benefits if they refuse treatments, while relationships with GPs, which are often strained or non-existent anyway, are commonly reported to suffer.

“…those with severe symptoms may require access to a wider range of support, managed by a CFS/ME specialist.”

It is unclear who these specialists are and what sort of support is supposed to be offered to people with Severe ME. There are no proven effective treatments and very few, if any, NHS consultants who are willing to visit ME patients in their homes.

“The results of the PACE trial, which examined pacing therapy, cognitive behavioural therapy, graded exercise and specialist medical care for chronic fatigue syndrome, were published four years after the NICE guidance. The trial ran from 2005 to 2011 and, contrary to what the hon. Lady said, was primarily funded by the Medical Research Council, not the DWP. Total funding was £5 million and the MRC contributed almost £3 million.”

This is correct, but the minister does not acknowledge that the DWP was one of the funders. The 2011 Lancet paper lists the funders as: “UK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, Department for Work and Pensions.” [15] The exact contribution from the DWP has not been disclosed. However, the Department has confirmed that PACE is the only clinical trial in history that has received funding from the DWP [16].

“The study was undertaken by the Queen Mary University of London. It was the largest ever trial for CFS/ME, including more than 600 participants in England and Scotland. It sought to assess and compare the effectiveness of the four main treatments for CFS/ME—adaptive pacing therapy, CBT, GET and standardised specialist medical care.”

It might have been more accurate to say that trial was purportedly designed to assess and the compare the effectiveness of the four main treatments. As Professor Steve Lubet has pointed out, by describing the trial as an ocean liner with a fixed destination, Professor Sir Simon Wessely (who was intimately involved with the trial and describes it as “a thing of beauty” [17]) virtually admitted “that the PACE Trial was always intended to reach a particular result, and that adjustments along the way were necessary to get it there.” [18]

“The trial had ethical approval from the NHS research ethics committee and had ongoing oversight from an independent trial steering committee, which included patient representatives. Trial reports were regularly provided to a data monitoring and ethics committee that had the power to halt the trial if harm was indicated.”

Queen Mary University of London (QMUL) refused to release the minutes of the steering committee and the trial management group. The Information Commissioner’s Office (ICO) has just ordered QMUL to release this data following another FOI request [19].

“The Government are aware that the use of CBT and GET in treating CFS/ME has long been a controversial issue for patient groups, charities and some clinicians. That began with the publication of the NICE guidance 10 years ago and continued with the PACE trial.”

The use of CBT and GET in treating ME has been a controversial issue for about 30 years.

“Since 2011, PACE trial data has been shared with many independent scientists as part of normal research collaboration, including the internationally respected research organisation Cochrane, which independently validated the findings.”

This is very misleading. The PACE authors have refused to share the trial data with any independent scientists who may be critical of the study. For example, Dr Keith Geraghty, a researcher in public health at the University of Manchester (UK) was refused access to the data, as was Alem Matthees who eventually took QMUL to court and won [20, 21].

The Cochrane reviews [22] relied heavily on data from the PACE trial, along with multiple studies which suffer from similar design flaws such as the use of the Oxford Criteria, which the US National Institute of Health (NIH) recommended should be “retired” because they are seriously “flawed” and may “cause harm” [23,24]

In April 2016, Professor Trudie Chalder (one of the PACE authors) gave evidence under other oath in support of QMUL which was trying to prevent the release of data from the PACE trial. It was put to her that it must be possible to anonymise the trial data for independent analysis as the data had already been shared with the Cochrane review group. In response, Prof Chalder stated that “disclosure to the Cochrane review does not count as disclosure to independent scientists as all three of the PACE principal investigators sat on the review panel.” [24b]

Indeed, Peter White, Michael Sharpe and Trudie Chalder are all listed as authors of the 2014 Cochrane review, “Exercise therapy for chronic fatigue syndrome” [25].

As Professor Jonathan Edwards has stated, “many studies have replicated the uninterpretability of the PACE trial, and the failure to show any objective evidence of benefit [from CBT or GET].” [26]

“However, in the last 18 months, the attention on the trial has increased substantially, following a tribunal ruling in August 2016 ordering the release of the trial data to a member of the public, which the hon. Lady referred to. The data has since been examined more widely and critics, including some clinical academics, have suggested that it shows that CBT and GET are not as effective as the trial results suggested.”

This understates the level of criticism. The PACE trial has been challenged by numerous academics [7,8] in peer-reviewed articles and open letters to the editors of The Lancet and Psychological Medicine [27,28].

“As has already been said, it is important that we listen to patients.”

Sadly, the minister’s comments during the debate provided very little evidence that the DHSC is listening to people with ME.

“As I have already set out, sometimes it can take a really long time for this to be diagnosed. People have to keep going backwards and forwards to GPs and others with their symptoms. Many other potential conditions have to be discounted before it can be fully diagnosed, which often leaves people feeling that their symptoms are not being taken seriously or they are being dismissed. Obviously, that is massively concerning, which is why, as we have already said, it is important that patients are listened to and that clinical professionals are well-equipped to be able to recognise the symptoms and identify them.”

Whilst diagnosis is important, it is also important to acknowledge that even with early diagnosis and sympathetic care, the prognosis for most people with ME is still very poor. What is needed above all is massive investment in biomedical research in order to develop diagnostic tests and effective treatments. In order to be proportional to the funding for other diseases of similar disease burden, and to compensate for decades of underinvestment, this needs to be of the order of hundreds of millions of pounds. Acknowledgement of such a need was notable by its absence from the minister’s speech.

“As I said, the data has been examined more widely. Critics, including some clinical academics, have suggested that it shows CBT and GET are not as effective as the trial results suggested. In turn, the trial authors have defended their work. They have responded to criticisms in medical journals and the wider medical printed press.”

This understates the level of criticism. The trial was so badly designed that it should never have been funded in the first place.

The PACE authors have responded to criticism but they have not answered the specific questions asked by their critics; they have not released all the anonymised data from the trial; and they have consistently refused to engage in debate with academics (such as Professor Ron Davis, Dr David Tuller and Professor Mark Davis) who have challenged them.

“I know the hon. Member for Glasgow North West raised one such criticism at the oral evidence session of the Science and Technology Committee in January, concerning possible conflicts of interest of the PACE trial authors. On that point, in line with normal practice, all such conflicts were published with the trial protocol as well as the results. If she has evidence to the contrary, I would be very happy to discuss that with her afterwards.”

As Carol Monaghan correctly stated during the debate, the PACE authors did not disclose their conflicts of interest (COIs) to the trial participants. This contravened the Declaration of Helsinki to which they had agreed to adhere in the trial protocol. The failure to disclose these COIs means that the participants were unable to give informed consent [29].

“I know it is a priority for the CFS/ME community that more research into identifying the underlying causes of the condition be undertaken. I would like to reassure those affected that both the MRC and the National Institute for Health Research welcome high-quality applications for research into CFS/ME, including studies to investigate its biological causes…”

This statement is not supported by the evidence. The MRC and NIHR have a history of rejecting biomedical ME research proposals in favour of behavioural and psychological research. The underinvestment in biomedical ME research for the past three decades is a significant part of what Carol Monaghan suggested will be considered “one of the biggest medical scandals of the 21st century”.

“…it will come as welcome news that the MRC is currently funding a project to examine the relationship between abnormal brain structures and symptoms of CFS/ME.”

The study referred to by the minister appears to be a £662k project entitled: “A Unified Mechanism for Functional Neurological Symptoms” [30]. The study description explains that “functional” is synonymous with “hysteria”, meaning symptoms which do not have an “organic cause”.

If this is the best evidence that the DHSC can provide that it is listening to patients, people with ME are unlikely to be convinced.

However, that this debate took place at all is a sign of significant progress. The support and understanding of the MPs who spoke during the debate was very encouraging. Despite the disappointing response from the Minister for Care, it is still to be hoped that she and others at the DHSC will not only start listening to patients but also examine the scientific evidence about ME for themselves, and act accordingly. Too many lives have been destroyed by this illness and the inadequate responses from governments, doctors, scientists and institutions around the world. The need for action is urgent.

HOW YOU CAN ACT:

If you live in the UK and are affected by any of the issues raised in this article in any way, please consider emailing your MP to make them aware of the need for:

Proportional Government investment in biomedical ME research as a matter of urgency

A wider debate in the House of Commons about ME research and treatment

A Parliamentary Inquiry into PACE and its effects on people with ME

Please also ask them to sign EDM 271 calling on NICE to remove all recommendations of CBT and GET for people with ME, if they have not already done so.

You can find your MP’s email address here.

If you live outside the UK, please write to your political representative and ask them to take action for people with ME.

References:

1. Letter from Prof Sir Jon Savill to Francis Maude MP (2013):

https://drive.google.com/file/d/1Jn95k88F8AQjrPdGy5_wgsoFRpnoffbk/view

2. The Tymes Trust. Behind the scenes: Setting up the UK CFS/ME Research Collaborative (UK CMRC):

https://www.dropbox.com/s/92m09l9tq55pihh/Behind%20the%20Scenes%20-%20Research%20Collaborative.pdf?dl=0

3. PACE Manual for therapists. Cognitive Behavioural Therapy for CFS/ME:

http://www.wolfson.qmul.ac.uk/images/pdfs/3.cbt-therapist-manual.pdf

4. Geraghty et al. Myalgic encephalomyelitis/chronic fatigue syndrome patients’ reports of symptom changes following cognitive behavioural therapy, graded exercise therapy and pacing treatments: Analysis of a primary survey compared with secondary surveys. Journal of Health Psychology. 2017:

https://doi.org/10.1177/1359105317726152

5. Institute of Medicine. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. Washington, DC: National Academies Press. 2015:

https://www.ncbi.nlm.nih.gov/pubmed/25695122

6. Twisk FNM. Dangerous exercise. The detrimental effects of exertion and orthostatic stress in myalgic encephalomyelitis and chronic fatigue syndrome. Phys Med Rehabil Res. 2017:

http://dx/doi.org/10.15761/PMRR.1000134

7. Wilshere C et al. Rethinking the treatment of chronic fatigue syndrome—A reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. 2018:

https://www.researchgate.net/publication/322568480_Rethinking_the_treatment_of_chronic_fatigue_syndrome-A_reanalysis_and_evaluation_of_findings_from_a_recent_major_trial_of_graded_exercise_and_CBT

8. Journal of Health Psychology Special Issue: The PACE trial. Vol 22. Issue 9. 2017:

http://journals.sagepub.com/toc/hpqa/22/9

9. Sharpe M et al. Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial. The Lancet Psychiatry. 2015:

https://doi.org/10.1016/S2215-0366(15)00317-X

10. ME-pedia artilce on the Oxford Criteria for the diagnosis of Chronic Fatigue Syndrome:

http://me-pedia.org/wiki/Oxford_criteria

11. NICE Guideline CG53:

https://www.nice.org.uk/guidance/cg53

12. NICE Guideance CG53 stakeholder consultation comments:

https://www.nice.org.uk/guidance/cg53/evidence/appendix-c-stakeholder-consultation-comments-table-pdf-4602203536

13. Colby J. False Allegations of Child Abuse in Cases of Childhood Myalgic Encephalomyelitis (ME). Argument and Critique. 2014:

http://www.tymestrust.org/pdfs/falseallegations.pdf

14. BBC Radio 4. File on 4, Children with ME. 2017:

http://www.bbc.co.uk/programmes/b08vyly5

15. White PD et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. The, Lancet. 2011:

https://doi.org/10.1016/S0140-6736(11)60096-2

16. Benyon D. FOI request to the DWP. 2011:

https://www.whatdotheyknow.com/request/part_funding_of_the_pace_trial_b

17. Wessely S. Health in Mind and Body. The Journal of the Foundation for Science and Technology. 2011:

http://www.foundation.org.uk/journal/pdf/fst_20_07.pdf

18. Lubet S. An Open Letter to Dr. Simon Wessely, Defender of the PACE Study. The Faculty Lounge. 2016:

http://www.thefacultylounge.org/2016/11/an-open-letter-to-dr-simon-wessely-defender-of-the-pace-study.html

19. Information Commissioner’s Office Freedom Of Information decision notice. 2018:

https://www.dropbox.com/s/xbos0l3k6ylr0ew/ICO%20decision%20minutes.pdf?dl=0

20. Geraghty K. Letter to Private Eye magazine. Issue 1345. 13 January 2017: https://drive.google.com/file/d/1lNqvmxTtaT3fq7_h05MIPiPRXS1o3BGz/view?usp=sharing

21. Faulkner G. Major Breakthrough on PACE trial. Centre for Welfare Reform. 2016:

http://www.centreforwelfarereform.org/news/major-breaktn-pace-trial/00296.html

22. ME-pedia artlice on Cochrane Reviews with links to the three studies:

http://me-pedia.org/wiki/Cochrane

23. Tuller D. Trial by Error: QMUL and FOI; Nature and Cochrane; the Pineapple Fund. Virology Blog. 2018:

http://www.virology.ws/2018/02/13/trial-by-error-qmul-and-foi-nature-and-cochrane-the-pineapple-fund/

24. Carmen R et al. Pathways to Prevention Workshop: Advancing the Research on Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome. National Institute of Health. 2014:

https://prevention.nih.gov/docs/programs/mecfs/ODP-MECFS-DraftReport.pdf

24b. Kennedy B et al. First-Tier Tribunal, Information Rights. Appeal Number: ΕΑ/2015/0269. 2016:

http://www.informationtribunal.gov.uk/DBFiles/Decision/i1854/Queen%20Mary%20University%20of%20London%20EA-2015-0269%20(12-8-16).PDF

25. Larun L et al. Exercise therapy for chronic fatigue syndrome (individual patient data). Cochrane Library. 2014:

http://dx.doi.org/10.1002/14651858.CD011040

26. Edwards J. Comment on Science for ME forum. 2018:

https://www.s4me.info/threads/tues-20-feb-uk-parliamentary-debate-pace-trial-and-its-effect-on-people-with-me-carol-monaghan-mp.2481/page-5#post-46691

27. Davis RW et al. An Open Letter to The Lancet, again. Virology Blog. 2016:

http://www.virology.ws/2016/02/10/open-letter-lancet-again/

28. Ablashi DV et al. An Open Letter to Psychological Medicien, again! Virology Blog. 2017:

http://www.virology.ws/2017/03/23/an-open-letter-to-psychological-medicine-again/

29. Tuller D. Trial by Error, Continued: Is PACE a Case of Research Misconduct? Virology Blog. 2017:

http://www.virology.ws/2017/06/24/trial-by-error-continued-is-pace-a-case-of-research-misconduct/

30. Edwards MJJ et al. A Unified Mechanism for Functional Neurological Symptoms. Research Councils UK. 2015:

http://gtr.rcuk.ac.uk/projects?ref=MR%2FM02363X%2F1