Response from Professor Malcom Hooper to David Jameson


Dear Mr Jameson


As you raise some important issues in your communication of 20th February 2011 about my initial response to the PACE Trial, I will reply in detail.


I am aware that you are an engineer and I am aware of your own position and of your hypothesis about what you refer to as “CFS”, for example, I note that you believe CFS to be (quote) “a functional illness …which can be reversed by psycho-social rehabilitation treatments”. I also note that you equate “CFS” with “persistent burnout”, and that you believe (i) “the viral theories do not adequately explain why personality and mental attitude have been shown to be important in determining which patients contract CFS and which recover the most quickly”, (ii) “Psychosocial treatments do result in recovery from CFS”, (iii) “the patient’s motivation and belief in treatment are likely to be important in recovery”,  (iv) “many CFS patients have a lack of confidence and motivation”, (v) “it is likely that…CFS is simply a more severe form of burnout”, (vi) “The most effective treatments appear to be rehabilitation programmes…which encourage the patient to re-integrate back into normal life”, and that you postulate that “CFS…is essentially the same as ‘burnout’…which persists long after the triggering HPA stressor have been removed due to factors such as negative mental  attitude and loss of motivation”  (


I will now address what you describe as my “serious errors”. 


  1. You state that the PACE trial compared subsets using the CDC criteria. The criteria that are universally known as the “CDC criteria” are the 1994 Fukuda et al criteria. Indeed, the PACE Trial Identifier listed the 1994 CDC Fukuda criteria as the means of identifying the disorder and the Fukuda criteria are mentioned on page 81 of the 226 page Full Protocol (not to be confused with the shorted form of the Protocol that was published in BMC Neurology 2007:Mar 8:7:6: and originally it was these international CDC criteria that were to be used by the Principal Investigators.  However, on 22nd October 2004 the Chief Principal Investigator, Professor Peter White, wrote to the West Midlands Multicentre Research Ethics Committee (MREC) seeking substantial amendments to the Protocol and at section 2.1 of his application he substituted the Reeves et al 2003 for the 1994 Fukuda criteria, hence the criteria that are universally known as the “CDC international criteria”  (ie. the 1994 Fukuda criteria) were NOT used to compare subsets in the PACE Trial.  The criteria that were used (misleadingly described in the Lancet paper as “international criteria for chronic fatigue syndrome”) were the Reeves et al 2003 criteria.


  1. You state that the trial compared subsets using “the London criteria for ME (requiring postexertional malaise…”). The original intention of the PIs was to use the Ramsay definition of ME, and you will see from page 417 of “Magical Medicine” these were date-stamped by the MREC as received on 21st March 2003  (  Once again, however, Professor White amended the Protocol and he substituted what appears to be his own version of the “London Criteria” for the Ramsay definition.  You will see from page 417 of Magical Medicine that the Ramsay definition required the following: fluctuation of symptoms from day to day or within the day; headaches; giddiness; muscle pain; muscle cramps; muscle twitchings; muscle tenderness; muscle weakness; pins and needles; frequency of passing water; blurred vision; double vision; increased sensitivity of hearing; increased sensitivity to noise; feeling generally awful, and muscle weakness after exercise. In contrast, Professor White’s version of the “London Criteria” specifically states on page 188 of the Full Protocol that neurological disturbances “are not necessary to make the diagnosis” and they further state that “the usual precipitation by ‘physical or mental exercise’ should be recorded but is not necessary to meet criteria”. Notwithstanding this clear statement in the Full Protocol that postexertional malaise is not necessary to meet the London Criteria, the text of the Lancet article states that participants were also assessed by “the London criteria for myalgic encephalomyelitis (version 2) requiring postexertional fatigue” so there is a significant discrepancy that requires explanation by Professor White, since two such divergent criteria cannot both have been used in the PACE Trial (note that Professor White’s “version 2” is dated 26.11.2004). According to Professor White’s version of the “London Criteria”, there is no requirement for impairment of short-term memory and loss of concentration, nor is there any requirement for primary depression or anxiety disorder to be present (indeed, if depression or anxiety disorder are present, the Full Protocol states “This means if any depressive or anxiety disorder is present, the London criteria are not met”). This makes the fact that the PIs reported a 47% prevalence of mood and anxiety disorder at baseline particularly notable, because the PIs state that of the 641 participants, 329 (ie. 51.3%) met Professor White’s version of the “London Criteria”; in other words, virtually everyone who did not have anxiety or depression met the “London Criteria” used in the PACE Trial, but Professor White’s “London Criteria” in the Full Protocol (to which the PIs were obliged to adhere) do not require precipitation of symptoms by physical or mental exercise.  Put another way, of the 53% who did NOT have anxiety or depression at baseline, 96.8% met Professor White’s  “London Criteria”, but those criteria do not require the cardinal feature of ME to be present. This begs the question as to what disorder was being studied under the title of ME/CFS, because the clear distinction between Ramsay-defined ME and somatisation disorder has been significantly lessened by the PIs.  Whilst the Ramsay definition does exist (Postgrad Med J 1990:66:526-530), I would remind you that the “London Criteria” do not in fact exist and that the reference cited in the Lancet is to the 2004 Westcare Report, which simply said that they were “proposed” criteria.  The “London Criteria” have no known authors; they have never been published; there is no methods paper which specifically describes them as a “case definition”; they have never been approved nor have they even been finally defined (there are various versions); they have never been validated and they are not on PubMed thus are not available for scrutiny so they cannot be accessed for comparison. This means that Professor White was essentially able to create his own version of the “London Criteria” as evidenced on page 188 of the Full Protocol. Your assertion that the London Criteria required postexertional malaise is thus incorrect despite the PIs having said in their Lancet paper that it was required, and this is an issue for Professor White to address ie. he needs to clarify whether or not he adhered to his own Protocol.


  1. You state “there is nothing in the Oxford criteria that ‘excludes people with neurological disorders’ ”. You may not be aware that one of the authors of the Oxford criteria, Professor Anthony David, clarified the issue of whether or not the Oxford criteria exclude people with neurological disorders:British investigators have put forward an alternative, less strict, operational definition which is essentially chronic…fatigue in the absence of neurological signs, (with) psychiatric symptoms…as common associated features” (AS David; BMB 1991:47:4:966-988).  The Oxford criteria (JRSM 1991:84:118-121) suggest that people with a neuromuscular disorder should be used as a comparison group, which rules out the inclusion of people with ME, a WHO classified neurological disorder since 1969.  The fact that the Wessely School do not believe or accept the WHO classification does not mean that ME is a somatisation disorder as they continue to assert despite the irrefutable biomedical evidence to the contrary. If their psycho-social model of ME/CFS were correct ie. if the symptoms are caused by deconditioning consequent to fear of activity, it would be expected that a programme of CBT/GET would be curative, yet the results of both the FINE and PACE Trials do not support the PIs’ model. I note that you fail to reference Professor Wessely’s statement that the PACE Trial interventions are “not remotely curative” made in his JAMA editorial of September 2001. Furthermore, the Oxford criteria specifically state “There are no clinical signs characteristic of the condition”, a criterion which immediately rules out ME/CFS, since there are numerous characteristic, objective, reproducible, abnormal signs that are discernable by any reasonably competent physician.  They include the following:


·         labile blood pressure (this is a cardinal sign); low systolic BP --  <100 in 50%

·         nystagmus  and vestibular disturbance (vestibular dysfunction seen in 90%)

·         sluggish visual accommodation

·         fasciculation

·         hand tremor

·         neuromuscular incoordination

·         cogwheel movement of the leg on testing

·         muscular weakness

·         marked facial pallor

·         postural orthostatic tachycardia syndrome (POTS)

·         positive Romberg

·         abnormal tandem or augmented tandem stance

·         abnormal gait

·         evidence of Raynaud’s syndrome and vasculitis (vascular signs cross dermatomes)

·         mouth ulcers

·         hair loss

·         singular reduction in lung function (shortened breath-holding capacity seen in 60% of patients tested)

·         enlarged liver (not usually looked for by psychiatrists).



4.  You state that the PACE Trial did use an objective outcome measure (“6 min walking ability in metres”).  As the only objective measure of outcome, this is completely inadequate as a measure of physical capacity.  A single test is unlikely to reveal any abnormality and serial testing is essential because it is the second test that provides objective evidence of abnormalities in ME/CFS patients and of their inability to work. The reference provided by the PIs for
the six minute walking test is Buckland RJA et al (BMJ 1982:284:1607-1608) but the paper itself cites McGavin CR et al (BMJ 1976:i:822-823), which draws attention to the difficulty of achieving reproducible results with such a test. Moreover, the Chief Principal Investigator himself, Peter White, has published evidence supporting the need for serial post-exercise testing (Immunological changes after both exercise and activity in Chronic Fatigue Syndrome: a pilot study. White PD, KE Nye, AJ Pinching et al. JCFS 2004:12 (2):51-66 ).  None of the interventions in the PACE Trial enabled participants to achieve anything like a normal walking speed for the full six minutes when compared with a healthy individual. It is regrettable that Professor White decided to abandon the use of an actometer, which would have provided unequivocal objective evidence of improvement or non-improvement.  The only reported improvement on the six minute level walking test for those allocated to CBT was an increase of 21 steps, whilst for those allocated to APT (note that APT is not the same as pacing, as APT is a vehicle for incremental aerobic exercise and involves planning, achieving and sustaining targets) there was an increase of 20 steps, these improvements having cost the nation £5 million.


The NHS Choices website provides the following comment on the success or otherwise of the PACE Trial:  “Compared with specialised medical care alone, CBT plus specialised medical care improved fatigue scores by 3.4 points on a 33-point scale, while GET plus specialised medical care improved scores by 3.2 points. Physical function score improvements were 7.1 for CBT and 9.4 for GET on a
100-point scale"

The two favoured interventions (CBT and GET) had side-effects rates of 89% and 93% respectively and according to the PIs, “adverse events were common”


Rated on their 33-point and 100-point scales, participants improved on average only 10% and 8.25% with the two recommended interventions, which I believe hardly qualifies as even “moderately effective” as the PIs claim.

You accuse me of “doing potential damage to CFS patients by putting them off the only treatments that have been proven to be effective”. I refute your allegation that I appear to be putting out deliberate misinformation, but you are of course free to carry out your threat to complain about me in any forum you choose, including to my University. However, if you exercise this option, be aware that you will need supportive evidence and that your own credibility will come under scrutiny.


Malcolm Hooper