PACE Trial: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Countess of Mar Excerpts

Wednesday 6th February 2013 Grand Committee

Tabled By

[The Countess of Mar]

To ask Her Majesty’s Government what assessment they have made of the effects of the PACE trial (Pacing, graded Activity and Cognitive behaviour therapy: a randomised Evaluation) on provision of health and social care and welfare benefits for people with chronic fatigue syndrome/myalgic encephalomyelitis.

[The Countess of Mar]

My Lords, I declare my interests as chairman of Forward-ME, a vice-chair of the All-Party Parliamentary Group on ME and a patron of a number of ME charities. The PACE trial was funded by the MRC, the Department of Health, the Scottish Chief Scientist Office and the Department for Work and Pensions to the tune of £5 million. The researchers, led by chief principal investigator, Professor Peter White, have consistently and confidently advised medical professionals and the Government of the success of cognitive behavioural therapy, or CBT, and graded exercise therapy, or GET. The PIs’—the principal investigators’—objective was to reverse the behavioural and cognitive factors which they believe to be responsible for the perpetuation of symptoms and disability. Despite the extensive biomedical evidence base of peer-reviewed papers which undermines their belief and despite the fact that the MRC now states that there is evidence of,

“inflammatory mechanisms in the brain and spinal cord”,

their view has prevailed.

Throughout the history of medicine there has been a predominance of doctrine over science and currently there is a similar conflict between the doctrine, which asserts that CFS/ME results from a disordered psyche, and the scientific view that it is a devastating organic disease. We do not know what disorder was being studied because in March 2011, the chief PI wrote to the editor of the Lancet. He said:

“The PACE trial paper ... does not purport to be studying CFS/ME but CFS defined simply as a principal complaint of fatigue”.

To whom, then, can CBT and GET be safely applied? The Minister cannot answer because on 17 January her right honourable friend Norman Lamb confirmed that no assessment of the PACE trial has been made. Furthermore, the PACE trial results have not been presented transparently. This is not uncommon and Dr Ben Goldacre, known for his “Bad Science” column in the Guardian, has initiated a campaign calling for publication of all results of all trials, not just selective results. Already more than 7,000 signatures have been collected, including from high-profile organisations such as the MRC, the Cochrane Collaboration, the Public Library of Science and the BMJ. It calls for all universities, ethics committees and medical bodies to recognise that under-reporting of trials, as occurred in the PACE trial, is misconduct. Misreporting of clinical data leads to harm, wastes money and prevents scientific progress.

As regards the PACE trial, a recent Science Media Centre press release states that,

“the authors worked hard to define recovery based on the data available from the PACE trial”.

Investigators must define their primary outcomes before a trial begins and abide by them, not define recovery based on the trial data. Once the PACE trial was under way, the PIs changed the outcome measures so that the very same score on physical functioning—the SF-36 scale—represented both eligibility to enter the trial and “normal” function at the end of it. Indeed, according to the Lancet, a participant could have achieved a worse score at the end of the trial yet still be classed as “recovered”.

When funding was granted and ethical approval agreed, a participant had to score 85 to be considered recovered but by the time of publication in the Lancet, this “recovery” score had dropped to 60, which was five points lower than that required to enter the study. This illogical situation resulted from departure from the published protocol. To overcome this, the chief PI created his own meaning of terms; for example “recovery” does not mean recovery as the world understands it, and a return to “normal” does not mean a return to normal health. The chief PI does, however, concede that,

“improvement and not reaching research criteria are different from recovery”.

We do not know how many patients reached the initial target for recovery because the PIs have refused requests to release that data. Instead, they introduced significantly lower measures of improvement and abandoned an objective measure, the wearing of an actometer. The results of the subjective reporting in the six-minute walking test after graded exercise therapy were very poor, placing participants below the performance of patients awaiting heart or lung transplant. Had the PIs achieved their anticipated level of success, a level consistent with their claims over many years and a major factor in the award of research grants, they would have achieved international acclaim.

What hit the headlines was the Lancet “Comment” claiming a 30% recovery rate, yet the best that has been shown from CBT and GET is a maximum 15% improvement rate. A recent paper by the PACE authors, published on 1 February and purporting to show recovery rates, is a masterpiece of obfuscation. The authors have substituted “recovery” for “reversal” of CFS without any explanation, yet they admit that,

“although many patients improved, the question of how many patients recovered remains unanswered”.

As one of the members of the Forward-ME Group said:

“It really is quite bizarre that there is absolutely no data whatsoever in this paper on what most people would regard as markers for recovery … a return (or ability to return) to full time employment or education … no longer claiming any DWP sickness or disability benefits”.

The original claims made for recovery made it into the media and into the minds of GPs, DWP officials, social care providers, private insurance companies and even the National Institute for Health and Clinical Excellence. Professor Trudie Chalder, one of the PACE trial PIs, said that,

“twice as many people on graded exercise therapy and cognitive behaviour therapy got back to normal”.

This was widely but incorrectly interpreted as “recovery”.

The fact is that, as opposed to the spin that accompanied the publication of selective results, only 15% of patients improved with CBT and GET, leaving 85% with no benefit from those interventions. Furthermore, of the combined CBT/GET groups of 321 people, 91% experienced adverse events, and only those who were well enough to attend regular hospital appointments were included in the trial; the severely affected and housebound were excluded. This is not mentioned when the “recovery” rates are discussed. From where have the PIs derived the figure of 22% for recovery in their latest paper?

Where does that leave us? The only information, published in A Cost-Effectiveness Analysis of the PACE trial, shows that there was no significant improvement after CBT and GET in the average number of days lost from work or the number of participants who lost days at work. In fact, claims for income-related benefits, illness and disability-related benefits, and from private pensions and income protection schemes, increased across all intervention groups during the trial.

As it is cheaper for CFS/ME to be dismissed as a behavioural problem, patients are denied access to diagnostic facilities by NICE guidelines, and very few medical consultants specialise in anything but the supposed “behavioural” aspects of the disease. ME charities are inundated with cries for help as their members struggle with the benefits and social care systems. Bed-ridden and housebound claimants are put into the WRAG for ESA and are too ill to appeal. If they manage to get to an Atos assessment, they feel that they are not listened to and are told that they are fit for work. The DWP part-funded the PACE trial because it was assured that CBT and GET would get people off benefits and back to work, but the promised return-to-employment figures have still not been provided by the PIs.

I am relieved that the Medical Research Council’s expert group, under the chairmanship of Professor Stephen Holgate, is launching a UK chronic fatigue syndrome and myalgic encephalomyelitis research collaborative on 22 April. It recognises that in light of the,

“magnitude of the disease burden on those affected and their families involving both adults and children, there is an urgent need to increase research effort in the field”.

Some £1.6 million has already been allocated by the MRC. There is an equally urgent need to assess the effects that the outcome of the PACE trial has had upon people with ME. However, how can the Government act responsibly in assessing them when the results have not been presented transparently?

It is widely accepted within the ME/CFS community that the PACE trial PIs changed the primary outcome measures with the intention of artificially inflating the success of CBT and GET—treatments they promoted for more than 20 years—and that, consequently, they are guilty of scientific misconduct. They believe that White and his colleagues have shown that they are not responsible guardians of the valuable data collected in the trial. It is therefore a matter of great importance that they are re-analysed by an independent group, using the original criteria for recovery and the positive outcomes described in the published protocol. This would enable healthcare commissioners to make decisions based on data that they know have not been misrepresented.

I know that the Minister understands the problem and ask that she and her colleagues from the other affected departments order such an assessment so that we do not consign thousands of people to the shadows. To quote Orwell, we must not allow the PACE trial to,

“give an appearance of solidity to pure wind”.

Lobbyists: Register

Countess of Mar Excerpts

Wednesday 12th December 2012 Lords Chamber

[Lord Wallace of Saltaire]

There might be no more cakes and wine, I am afraid. Let us be clear: lobbying is an entirely legitimate part of the political process, which would be poorer if we did not have lobbying. The problem is that we have lobbying from professional companies, advocacy groups—many of which are also charities—the CBI, trade unions and others. It is a very complicated area to try to pin down to a single statutory register.

[The Countess of Mar]

My Lords, when you get a company lobbying, would it be helpful if it were to register on whose behalf it was lobbying, so that when it writes to us, we know who it is lobbying for?

[Lord Wallace of Saltaire]

My Lords, that is the narrowest definition and where the Government started. The replies to the consultation have taken us much wider than many of us originally intended to be taken. Certainly, the concern—and I am very struck by this in the documents that I am looking at—and perception that there is undue lobbying is very much about large sums of money being paid to professional companies, very often by foreign Governments.