Response to Authors’ Response: ICL/KCL McClure/Wessely XMRV study

Response from Angela Kennedy to Authors’ Response, PLoS One: ICL/KCL McClure/Wessely XMRV study

Shortlink for Post #3: http://wp.me/p7FYk-2N

Related material: Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome

Abstract and links for full paper:http://wp.me/p5foE-2Bd
Media coverage Round up 1:http://wp.me/p5foE-2Bj
Patient organisation responses Round up 2:http://wp.me/p5foE-2BA
Imperial College London News Release PDF:Imperial College London News Release XMRV

Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome

Otto Erlwein¹, Steve Kaye¹, Myra O. McClure¹*, Jonathan Weber¹, Gillian Wills¹, David Collier², Simon Wessely³, Anthony Cleare³

1 Jefferiss Research Trust Laboratories, Section of Infectious Diseases, Wright-Fleming Institute, Faculty of Medicine, Imperial College London, St Mary’s Campus, Norfolk Place, London, United Kingdom, 2 Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry (King’s College London) De Crespigny Park, Denmark Hill, London, United Kingdom, 3 Department of Psychological Medicine, Institute of Psychiatry, King’s College London, Camberwell, London, United Kingdom

The website of PLoS One, online publishers of the Imperial College London study “Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome” (5 January 2010), maintains a Comments Section here

In response to criticism around subject selection procedures and methodology, study authors from the Institute of Psychiatry, King’s College London, have published the following response:

Original Article Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome

Authors Response

Posted by Anthony_Cleare on 12 Jan 2010 at 19:55 GMT on behalf of

Professor Simon Wessely, Professor of Psychological Medicine Professor David Collier, Professor of Psychiatric Genetics Dr Anthony Cleare, Reader in Neuroendocrinology

On 13 January, a version of the commentary below was published on the PLoS One site in response to Wessely, Collier and Cleare, by sociologist, Angela Kennedy:

Angela Kennedy

The authors’ reply to the concerns about patients selection for research for this paper raises more problems in addition to those of the original paper. My comments here should be read in addition to other problems raised by authors on this forum.

Firstly, the authors express some resentment towards those who have legitimately questioned this research cohort and the criteria over the years, which is rather surprising. Contrary to insinuation by the authors, no person on the PloSOne Responses Forum has insinuated that the research cohort they use are somehow ‘ess deserving’ than say, the WPI cohort, purely that they are a different type of patient, using different criteria that select a different population, and that this may cause problems with the findings, and claims made based on those findings, with regard to the British ‘CFS’ population.

This is a reasonable concern to express, and such a deduction can be made based on the evidence the authors provide themselves in their paper, citations, and their response. For example, their paper states:

“Patients in our CFS cohort had undergone medical screening to exclude detectable organic illness.”

In the authors’ response here, they also write:

“Thus patients in our service have also co-operated in studies of PET and fMRI neuroimaging, autonomic dysfunction, neurochemistry, respiratory function, vitamin status, anti nuclear antibodies, immune function, neuroendocrine function and genetics “

While patients being processed for a research cohort may well, indeed are likely, to have co-operated and had such tests done, this does not necessarily mean that patients with positive results are part of the research cohort.

Indeed, positive results, which would indicate organic abnormality, would surely be likely to prevent a patient being selected for a cohort, by the very logic described in the author’s paper here, by their own response (the additional tests are considered ‘not clinically necessary’?) and in at least one of their citations (Quarmby et al)?

In the Quarmby et al paper, the cohort is described, in which the criteria used (in addition to ‘Fukuda/CDC’) is ‘Oxford’. The Oxford criteria (Sharpe et al 1991), in particular, actually do allow for patients who fulfil organic abnormality to be selected out of a research cohort. Indeed, Anthony David, referring to these, commented at the time:

“British Investigators have put forward an alternative, less strict, operational definition which is essentially chronic (6 months or more) severe disabling fatigue in the absence of neurological signs with myalgia, psychiatric symptoms and previous viral infections as common associated features.”

Here, special attention needs to be paid to the term ‘previous viral infections’ and ‘absence of neurological signs’, in order to contextualise the cohort selection process applied using the Oxford Criteria.

It is therefore quite reasonable to presume that patients in the cohort described in the Erlwein et al paper are less likely to be suffering from organic abnormalities associated with ‘CFS’ populations than in other research cohorts.

It is also rational to be concerned that the cohort described here may not be representative of many people diagnosed with ‘CFS’ in Britain.

NICE guidelines for example, acknowledge that very little research has been done on ‘severely affected’ patients, who comprise, possibly, at least 25% of the population of people given a ‘CFS’ diagnosis (though so little research has been done on ‘severely affected’ in Britain, the true number is not yet clear).

While patients potentially destined for a research cohort which weeds out ‘detectable organic abnormality’ may be subjected to a rigorous amount of investigations, those not undergoing this process do not undergo such testing – at least not in the NHS. Indeed, such investigations of clinical patients are severely proscribed in the majority of ‘guidelines’: NICE, and the RCPCH guidelines as just two examples.

Ironically, Fukuda guidelines also make the following comment:

“The use of tests to diagnose the chronic fatigue syndrome should be done only in the setting of protocol-based research.

“In clinical practice, no additional tests, including laboratory tests and neuro-imaging studies, can be recommended. Examples of specific tests (which should not be done) include serologic tests for enteroviruses; tests of immunologic function, and imaging studies, including magnetic resonance imaging scans and radionuclide scans (such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) of the head.

“We consider a mental status examination to be the minimal acceptable level of assessment.” (1994)

That clinical populations are not to be afforded the types of investigations given to research populations makes the whole idea of ‘medically unexplained’ or ‘unexplained by disease’, or ‘functional’ (as synonymous with ‘non-organic’ or not discernibly ‘organic’) as common characterisations of CFS (including by at least one of the authors themselves in previous publications – for just one example, Page et al, 2003), highly problematic at best.

It is also significant that ‘CFS’ is so often described as a ‘diagnosis of exclusion’ (see, for example, the Centre for Disease Control CFS information website.

(Footnote: http://www.cdc.gov/cfs/cfsdiagnosis.htm )

Certain research case definitions comply with this assumption, such as the Oxford Criteria (Sharpe et al, 1991) and CDC Criteria (Fukuda et al, 1994). Here, ‘diagnosis of exclusion’ also functions as a euphemism of ‘medically unexplained’. The key problem within this recurring theme in the literature, which most frequently remains un-addressed, is how a clinical patient’s condition can all too easily become ‘medically unexplained’ because of the practice of encouraging doctors to severely limit investigations in the first place: except, it would appear, ironically, in research populations in which ‘organic’ illness is being weeded out to provide the type of cohort that might fulfil ‘not organically ill’ definitions.

The issue of ‘disability’ also needs to be clarified. The references cited in the Erlwein paper to support the statement that the patient cohort was of ‘high levels of disability’ refer only to ‘disability’ in psycho-social terms or feelings of ‘fatigue’, and not in terms of physical impairment, a key omission.

Mundt et al’s paper, in particular, focuses on specific mental health problems and the social exclusionary effects of living with these. While in no way invalidating or trivialising the disability caused by mental health problems, it must be pointed out that both Mundt et al and Chalder Scales nevertheless fail to elucidate a high level of physical or physiological (say, for example, neurological, mitochondrial and/or cardiovascular) impairment – key problems present in people given a clinical diagnosis of ‘CFS’, usually related to specific organic abnormalities that can be found, if they are tested for in the first place.

With regard to the Canadian criteria (Carruthers et al), in fact they have undergone some ‘validation’. Jason et al found:

        “…Canadian criteria selecting cases with less psychiatric co-morbidity, more physical functional impairment, and more fatigue/weakness, neuropsychiatric, and neurologic symptoms. The overall findings suggest that the Canadian clinical criteria appear to select a more symptomatic group of individuals than the CFS criteria, and these individuals do demonstrate less current and lifetime psychiatric impairment than those selected according to the CFS criteria. In contrast, the CFS group was not significantly different from the Chronic fatigue-psychiatric group in psychiatric impairment.

“Predictably, the Chronic fatigue-psychiatric group evidenced the highest frequency of current and lifetime psychiatric disorders… Overall, there were 17 significant symptom differences between the Canadian and Chronic fatigue-psychiatric group, but only 7 significant symptom differences between the CFS and Chronic fatigue-psychiatric group. Findings suggest that the Canadian criteria select a group of patients with more symptoms, and the Canadian criteria identify a group with higher levels of physical functional impairment and less psychiatric comorbidity.

“Findings from the present study indicate that the Canadian criteria does capture many of these cardiopulmonary and neurological abnormalities, which are not currently assessed by the current CFS case definition (Fukuda et al., 1994).

“However, it is worth noting that when the Fukuda et al. (1994) CFS case definition was conceived, the research had not yet been done investigating these abnormalities. In combination with symptom patterns, it is possible to conclude that the Canadian group does select individuals with greater impairment, particularly given the physical composite score, fatigue/weakness, neurologic and neuropsychiatric symptoms, as these symptoms can interfere with daily living and occupational performance. Results from this present investigation highlight the importance of contrasting different diagnostic criteria in order to gain a greater understanding of the syndrome now known as CFS. The findings do suggest that the Canadian criteria point to the potential utility in designating post-exertional malaise and fatigue, sleep dysfunction, pain, clinical neurocognitive, and clinical autonomic/ neuroimmunoendocrine symptoms as major criteria for future attempts to define this syndrome…”

(Comparing Definitions )

In addition to using the Carruthers et al criteria (or ‘Canadian Criteria’), the WPI give this information about their patient cohort in their supporting online material:

“Their diagnosis of CFS is based upon prolonged disabling fatigue and the presence of cognitive deficits and reproducible immunological abnormalities. These included but were not limited to peturbations of the 2-5A synthetase/RNase L antiviral pathway, low natural killer cell cytotoxicity (as measured by standard diagnostic assyas) and elevated cytokines particularly interleukin-6 and interleukin-8. In addition to these immunological abnormalities, the patients characteristically demonstrated impaired exercise performance with extremely low VO2 max measured on stress testing…”

(http://www.sciencemag.org/cgi/content/full/117905/DC1 )

It is therefore highly unlikely, as the authors indeed acknowledge in their reply here, that Erlwein et al were testing the same type of patient as those tested by the WPI, which inevitably makes the Erlwein et al findings – and perhaps some of the wilder claims that they have ‘cast serious doubt’ on the WPI’s findings, unfortunately made in some of the lay media – not scientifically tenable. The failure of Erlwein et al to include such type of patient in their cohort, does not mean that such patients do not exist in Britain. Copious patient anecdotal experience, research reports, and charity surveys indicate that they do exist. Whether XMRV is present or not is another matter, but there are enough identifiable problems around patient selection alone with the Erlwein et al paper to indicate this is not a definitive disproving of the existence of the virus in Britain.

Ongoing neglect of the importance of establishing a possible ‘CFS’ patient population in Britain, clinically and in research settings, using the Canadian Guidelines, is preventing the development of knowledge that might help extremely ill and disabled people here in Britain.

The problems I have briefly outlined here do not fully express the range and depths of problems with regard to: the identity of an accurate ‘CFS’ population; the instabilities of ‘CFS’ criteria per se; the faulty concepts of ‘medically unexplained’ or ‘functional’ and relation to ‘psychogenic’ explanations for somatic illness; the vagaries of criteria that claim to facilitate a ‘diagnosis of exclusion’; and the psychogenic dismissal of serious organic dysfunction of patients given a ‘CFS’ diagnosis, problems that have happened for many years. These problems are relevant to the Erlwein et al paper. Furthermore, they are highly relevant to all research that claim a psychological and/or behavioural aetiology to the condition or conditions that get deemed as ‘CFS’.

REFERENCES

Carruthers, B. et al (2003): Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols. Journal of Chronic Fatigue Syndrome, Vol. 11(1), pp 7-115.

Chalder, T. Berelowitz, G. Pawlikowska, T. Watts, L. Wessely, S. Wright, D. Wallace, E. P.:Development of a fatigue scale. Journal of Psychosomatic Research Vol 37: Issue 2: Feb 1993: 147-153.

David, A.S.:Postviral syndrome and psychiatry. British Medical Bulletin: 1991: 47: 4: 966-988.

Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A.:The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med. 1994 Dec 15;121(12):953-9.

Jason LA, Torres-Harding SR, Jurgens A, Helgerson J.:Comparing the Fukuda et al. Criteria and the Canadian Case Definition for chronic Fatigue Syndrome. Journal of Chronic Fatigue Syndrome 12(1):37-52, 2004.

Mundt, J.C. Marks, I.MShear, K. Griest, J.H.:The work and social adjustment scale: a simple measurement of impairment in functioning. British Journal of Psychiatry (2002) 180: 461-443.

Page, L.A. Wessely, S.:Medically unexplained symptoms: exacerbating factors in the doctor–patient encounter. J R Soc Med 2003;96:223-227.

Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, Edwards RH, Hawton KE, Lambert HP, Lane RJ, et al: Chronic fatigue syndrome: guidelines for research. J R Soc Med. 1991 Feb;84(2):118-21.

Competing interests declared: Social scientist critically evaluating ‘psychogenic’ explanations for somatic illnesses. Parent of adult who given a ‘CFS’ diagnosis as a child.

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More thoughts on the Gibson Report by Angela Kennedy

Shortlink for Post #2: http://wp.me/p7FYk-L

An edited version of a commentary first published in December 2006 by social scientist, Angela Kennedy, following publication of the “Gibson Report”.

These are some of my thoughts on some problems in the Gibson Report

My own concerns below are in addition to other concerns expressed by others (including but not limited to the dismissal of Lyme, the children’s section, the approval of CBT etc) and also in addition to approval of some of the more positive aspects of the report. As I have said before, the key is that no matter how positive some aspects may be, it is the dangers that we need to guard against, and therefore it may not be in the community’s best interest to wholeheartedly endorse the report, even in principle. In fact my own opinion at present is that it would be foolhardy.

It was only by reading this report about four times and reading John Sayer’s comments [Page 77: The ONE CLICK Report Gibson Inquiry], and putting my sociological linguistic analysis head on (as tedious as that appears to be to some people!) that the following problems occurred to me. I didn’t see it on the first reading at all.

With regard to point 2 below, the Report claims patient hostility TOWARDS DOCTORS THEMSELVES (not their policies) SEVEN TIMES.

With regard to point 3, I believe that comment from the Report has been made before by a psychiatrist – possibly Peter White? [Ed: Professor Peter Denton White, Barts CF Service].

These comments have been submitted to One Click as part of their consultation exercise:

1. This report is written in a very idiosyncratic style – which one would not expect from a document produced by a group of parliamentarians and where clarity is of vital importance. There are, therefore, some confusing statements requiring further clarification, for example:

The group does not intend to criticise the motivations or actions of any one group…

What does this mean? Should an enquiry not present criticism if necessary?

…indeed, the Group wishes to avoid being distracted by debates centring on semantics in this difficult and contentious field…

This statement is charged with innuendo yet nebulous at the same time. What ‘semantics’ problems have been encountered by the Group?

2.  Emotive and inappropriately inflammatory language against patients, both individually and as organised advocates (or ‘groups’), that has no place in a report ostensibly on scientific research into ME/CFS has been used on more than one occasion by both by Dr Ian Gibson himself in communications around the report – for example, in his article published in the Journal of Clinical Pathology in August 2006, and within the Report itself, for example:

…for some sufferers, their personal physical experience of the illness has led to resentment of those who favour a psychosocial/behavioural course.

This comment is unnecessary and speculative. Patient representatives who criticise the psychiatric paradigm do NOT express negative personal feelings towards the proponents of the paradigm. They critique the paradigm itself and the actions of its proponents. To claim otherwise is emotive and inflammatory.

…we are left in no doubt that this is a contentious field, and some of the evidence we heard provoked considerable hostility from the audience.

What audience? Why an emotive term such as ‘hostile’?

Quite apart from the often strongly polarised views of some patient campaigning groups and the scepticism of some of the medical profession, there have been disagreements, even amongst those who represent different groups of patients and medical professionals. This has left many patients feeling very aggrieved, and many doctors feeling misrepresented.

The comment about patients’ feeling is unnecessary and contributes to an insinuation of patients as being “over-emotional”, while doctors, in contrast, are merely and justifably feeling ‘misrepresented’.

Professor Wessely is considered by many to be the leading expert on treating CFS/ME and the CFS/ME treatment centres set up by the NHS have been to his model. Many patient groups oppose these treatments, because, although they are founded on the positive results of controlled clinical trials, they are psychologically based.

Here patients are implied as being prejudiced against psychological treatments, despite the alleged efficacy of the treatments. This is clearly not an accurate summing up of advocate critique of the psychiatric paradigm, which is based on critical analysis of the evidence and claims put forward by proponents of the psychiatric paradigm. To insinuate otherwise appears disingenuous.

Wessely gave up the research side of his work, possibly due to extreme harassment he received from a very small fringe section of the ME community.

It is quite simply ludicrous that an inquiry carried out by parliamentarians has apparently accepted such serious yet nebulous, and apparently un-evidenced allegations at face value. This part of the report is particularly inflammatory towards patients and therefore inappropriate.

Their observations that GET [Graded Exercise Therapy] may make severe sufferers feel worse, has lent fuel to their often serious antipathy to the doctors offering it.

Again, this comment is unnecessary and speculative. Patient representatives who criticise the psychiatric paradigm do NOT express negative personal feelings towards the proponents of the paradigm. They critique the paradigm itself and the actions of the proponents. To claim otherwise is emotive and inflammatory.

…there is a great deal of frustration amongst the CFS/ME community that the progress made in the late 1980s and early 1990s toward regarding CFS/ME as a physical illness has been marginalised by the psychological school of thought. It is clear the CFS/ME community is extremely hostile to the psychiatrists involved.

Again, this comment is unnecessary and speculative. Patient representatives who criticise the psychiatric paradigm do NOT express negative personal feelings towards the proponents of the paradigm. They critique the paradigm itself and the actions of its proponents. To claim otherwise is emotive and inflammatory.

The frequent categorisation of patients as angry and hostile is a highly unfortunate feature of this document. It has already been found that this tendency to describe patients thus is rife within the literature of proponents of the psychiatric paradigm (Kennedy A, 2005, Hooper, 2004, Marshall and Williams, 1996, 1999). It is therefore highly demoralising to see similar constructions of patients within the Gibson Report.

In Dr Gibson’s Journal of Clinical Pathology article, he states: “…to curtail attempts of some to suppress what they hear and what they see written down and to keep their vitriolic actions and comments at bay.” It is clear that Gibson has allowed personal prejudice to inform the way he has constructed the very people he claims to want to consult. In the circumstances, it is ironic that the Gibson report claims “…our task is to highlight the ongoing struggle of the CFS/ME community and to ensure that the voice of the patient is heard”.

By constructing patients or their representatives as hostile, ‘vitriolic’ and unreasonable is to further alienate the community from enfranchisement. It is astounding to find such emotive and inflammatory language in such a document.

3.

…for some doctors to deny the existence of a physical part of the illness is as equally unhelpful as the claim by some patient groups that there is no psychological element to the disease.

This statement is problematic on a number of fronts. There is a construction of a “straw man”- the alleged doctors who deny physical elements of the illness. In actuality, no doctors would do this. The fundamental contention arises where doctors assign psychiatric causes to physical symptoms. By ignoring this fundamental problem, the Report engages in “fence-sitting”, which, in actuality, allows the psychiatric paradigm to take ascendancy. Furthermore, to claim that ‘some patient groups’ are claiming that there is no psychological element to the disease is speculative and misrepresentative – patients have instead been arguing that any psychological aspect of ME/CFS can be seen in any other organic disease, and that there should be no special pleading for ME/CFS as somehow more ‘psychological’ than any other organic disease.

4.

A lot has been made of the link between CFS/ME and Lyme’s [sic] disease or Lyme Borreliosis.

What does “A lot has been made” mean? In light of the further statements made on this subject – it appears a very trivialising statement to make, in the face of strong research and clinical evidence demonstrating the relevance of this issue to ‘CFS/ME’.

5. The recommendations in section 4.7 are astounding, for example, “other symptoms should be treated only when the doctor had absolutely excluded any other underlying organic illness that could be the cause…” and ” if depression is felt to be a significant result from the illness and contributing to its overall effects then anti-depressants may help if prescribed with full explanation by the doctor.” In this section, the Gibson Report is actually giving medical advice to doctors, a la NICE! This could not possibly be part of its remit.

6.

…the lack of easy confirmation of the organic nature of the illness by a readily available investigation lends itself to occasional invasion by those who are not genuine sufferers. The existence of such patients, and the inability of some in the medical profession to separate them from genuine patients with CFS/ME enhances the view that all patients with CFS/ME are neurotic and/or not genuinely ill.

These comments appear to arise from pure speculation and opinion. Such comments point to the special pleading of ME/CFS being a ‘malingerer’s charter’ – a professed view of certain proponents of the psychiatric paradigm.

7. In light of the many real problems of this report, a glowing endorsement by the ME/CFS/borreliosis etc community would be dangerous.

The report has various dangerous flaws. If it is endorsed in its entirety – it could have far-ranging adverse effects on many members of the community.

The Gibson Inquiry/Report has many similarities to the CMO’s report- the usual curate’s egg situation – good in parts. But it is the flaws that form the most potential dangers to the ME/CFS community. People’s safety is at stake, and here we are faced with possible risks to that safety caused by government intervention, a valid concern of advocates since the beginning of this Inquiry.

There are some fair questions to ask: How damaging will the flawed parts of the Gibson Report be to sufferers themselves? Will we find the positive aspects not followed up because the report actually has no teeth – but the flawed comments adopted to the letter by the psychiatric lobby and their government supporters?

No patient or patient representative has to endorse the report as a whole, even if some of the recommendations / comments are considered good.

REFERENCES

Hooper, M. et al. The Mental Health Movement: Persecution of Patients? 2004

Kennedy, A. A SHORT SUMMARY OF THE PSYCHIATRIC PARADIGM OF ME/CFS  2005

Marshall, E. Williams, M. Denigration by Design? A Review, with References, of the Role of Dr (now Professor) Simon Wessely in the Perception of Myalgic Encephalomyelitis, Volume I: 1987-1996: August 1996 (217 pages); Marshall, E. Williams, M. Denigration by Design? Volume II: 1999 Update: December 1999 (270 pages).

© 2007 Angela Kennedy

The report by The Group on Scientific Research into ME (GSRME) that resulted out of the “Gibson Inquiry” can be read here: http://www.erythos.com/gibsonenquiry/Report.html