The PACE Trial recovery rates were finally published - a publication initially refused but then  forced on the Principal Investigator by patient pressure, and despite the media being used to gloss over the inadequacies and failings of the whole project.

Flawed from the start, with the goalposts changed mid-course, and ending in ignominy with requests to have the data published being met by silence or rejection, and with a media being orchestrated to stop the whole boat from sinking by making ridiculous and feeble supportive statements.

The PACE Trial was a failure!

It failed to produce any valuable data, it failed to support the biased views of those who only wish to promote ME as a somatoform illness, it failed the patients for whom £5 million of scarce funding was wasted.

Recovery was redefined to mean almost anything the authors wanted it to be as so much deviation had occurred from the original PACE protocol.[1]

Out of the four original definitions for the trial three have been changed.[2]

Recovery was supposed to be defined by meeting all four of the following criteria:

(i) a Chalder Fatigue Questionnaire score of 3 or less (out of maximum 11)

This was changed to 18 out of maximum 33

"We therefore considered a score of 18 (highest integral score below the mean plus 1s.D.) or less as within the normal range for fatigue."

(ii) SF 36 physical Function score of 85 or above

This was changed to 60 or more. The entry criteria accepted people with SF-36 scores of equal or less than 65. So patients could have entered the trial with higher scores and deemed recovered at lower scores. This does not make any sense and the investigators should have explained this as well as discussed what happened to the 78% of participants who did not recover. How many deteriorated?

(iii) a Clinical Global Impression (CGI) change score of 1

This was changed to 1 or 2

"We considered scores of 1 (‘very much better’) or 2 (‘much better’) as evidence of the process of recovery, rather than our original protocol threshold of a score of 1 only, because we considered that participants rating their overall health as ‘much better’ represented the process of recovery."
 

If recovery becomes a process of recovery then it would have been better to follow patients more frequently instead at one time point at 52 weeks and for a longer period.
 

(iv) the participant no longer meets Oxford criteria for CFS, CDC criteria for CFS or the London criteria for ME.

The judgement of this was made by the research assessor for Oxford and London criteria whereas the CDC criteria was based on patients' ratings.
 

High rate of [47%]of psychiatric co morbidity even though the CDC criteria exclude anyone with past or current psychiatric illness. [3]

The Oxford criteria exclude “Patients with a current diagnosis of schizophrenia, manic depressive illness, substance abuse, eating disorder or proven organic brain disease. Other psychiatric disorders (including depressive illness, anxiety disorders, and hyperventilation syndrome) are not necessarily reasons for exclusion. ”[4]

Did the Oxford defined patients "recover" from their possible psychiatric symptoms rather than CFS?

The authors state that the limitation of this study is the lack of generally agreed measure of recovery.

From any sick person’s point of view, be it ME or any other disease, recovery happens when patients can return to their pre illness daily activities whether it is education, employment or being an active member of the society and not having to rely on disability benefits.

Could not the study have stated, for example, how many of those people deemed to be recovered were actively seeking employment and off disability benefits at the follow up to get at least somewhat objective measures rather than using abstract terms such as ‘process of recovery’?

What can be learnt from this debacle?

Nothing, it appears, by the PACE Trial Principal Investigator.

Professor Peter White writes in a recent article -

"The considerable disagreement, particularly between ME patient organizations and medical authorities, may help to explain the gulf in understanding between doctors and patients and

the consequent reluctance of some patients to engage in behavioural treatments." [5]

This is pure nonsense, of course. One wonders how the failings of the PACE Trial have completely failed to register with Professor White.

Patients do not quarrel with doctors if the treatments or results help them. The reason why patients resist the continued recommendation by the government and establishment of "behavioural treatments" is because it is the wrong approach, for the wrong disease - and IT DOESN'T WORK!

Professor White continues in this vein:

“The confusion regarding whether the nature of the illness is physical or psychological is exemplified by the way it is classified. WHO have classified ME under the International Classification of Diseases (ICD)-10 (G93.3) as a neurological disease. The same classification suggests that a ‘fatigue syndrome’ should be classified as ‘neurasthenia’ (F48.0) in the mental and behavioural disorders chapter.”

It is quite extraordinary to believe or state that doctors and researchers could be so confused about these two distinctly different classifications.

It needs only careful diagnosis based on thorough history taking to be able to make that distinction and good guidelines along the lines of the Canadian Consensus Criteria and the International Consensus Criteria are needed instead of NICE  or Oxford which lump anyone with fatigue into one big category. This is something which should have been taken on by the MRC "expert panel" when it existed.

The PACE Trial has raised serious questions regarding the professionalism and conduct of the investigators in that project.

When the PACE Trial has so monumentally failed then perhaps the MRC should seriously examine why proper and correct controls on this project were not performed.

Serious consideration should be given to the contract which must have been present to determine whether any unscientific activity has taken place in spending the estimated £5 million of scarce funding on this project.

Serious consideration should also be given to any application requests for new funding on ME research which may be received from the PACE Trial PI, bearing in mind how procedurally flawed this project was. The MRC, and any other government agency, may wish to determine whether disqualification from future applications for research funding ought to be considered.

Soon Professor Stephen Holgate will convene a launch afternoon for a "research collaborative" for CFS.

This meeting will already include those organisations who have already spent over three years discussing in the MRC "expert panel". Charities such as AfME, AYME, MEA and MER UK will have been included in an inner circle that will have produced a charter which "will lay out the terms for membership that will strongly emphasise the need for ALL types of high quality research (into CFS) and a joined-up approach to deliver this", including fatigue. 

It will be interesting to know how this can be achieved.

The MRC "expert panel" never agreed on a standard diagnostic criteria set to define ME and differentiate from Chronic Fatigue. Yet this new collaborative will have to agree to support and fund "ALL research into CFS/ME including fatigue".

Included in this collaborative will also be the PI of the PACE Trial plus many others who may be described as leaning toward the behavioural view of ME.

This publicity event on 22nd April will be organised by the Science Media Centre in London.

Invest in ME have been invited - due to the research which we have proposed and funded.

We have written in the past that it is impossible to marry the views of those who believe in the deconditioning/behavioural and wrong illness belief model of CFS (ME) and those of the biomedical side. The shambolic PACE Trial has demonstrably proven that the behavioural view of ME cannot deliver and should not continue to command more funding.

Perhaps the best way forward for ME would be to agree on a strategy of biomedical research into ME. A biomedical research collaborative into ME could be formed.

Yet we doubt whether this suggestion will be taken forward  - too much prestige and status is riding on the Science Media Centre event in April.

But if we are seriously to have a way forward for proper research then we need not just funding, but correctly defined cohorts, standardisation on diagnostic criteria and a collaborative of researchers who will not blur science with politics.

Research into ME needs a strategic approach - but it will be destined to fail completely by attempting to establish the way forward on foundations which include so much of what has been wrong in the past.

The PACE trial was debated in the UK House of Lords Grand Committee Room on 6th February 2013, with Countess Mar raising questions about the course and lack of relevant results from the PACE Trial.

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