Monday, 16 July 2012

Update On The PACE Trial

Professor Malcolm Hooper

11th July 2012

Many people have submitted formal complaints about the flawed methodology of the £5 million publicly-funded PACE Trial; these include complaints about the with-holding of the recovery statistics, the mis-reporting of the results by Principal Investigators themselves and by the media through the auspices of the Science Media Centre, and the apparent manipulation of the raw data, widely believed to be an attempt by the Investigators to salvage a trial that could not be allowed to fail.

Those complaints have been made to the Medical Research Council (MRC), whose Head of Corporate Governance and Policy, Dr Frances Rawle, chose not to address the issues raised and then to mock the complaint (BMJ 22nd June 2011); to The Lancet, whose editors admitted in writing that its erroneous reporting of the trial results must be corrected but almost 18 months later have still not done so and who – against the Elsevier complaints protocol -- dismissed a formal complaint entirely; to the Secretary of State (who referred it back to the MRC); to the editors of numerous newspapers who mis-reported the trial results (the way in which ME/CFS patients have been vilified in the press has just been put before Lord Leveson’s Inquiry by the Neuroimmune Alliance), and to the Royal Statistical Society, who enthusiastically requested an analysis of the statistics but then refused to publish it but provided no reason.

All complaints and concerns were ignored or dismissed and met with determined refusal to address the issues raised.

The redoubtable Countess of Mar therefore tabled a number of questions on 9th May 2012 and replies to her questions were provided by Baroness Wilcox, Parliamentary Under-Secretary of State in the Department for Business, Innovation and Skills (the Department responsible for the MRC).

Those replies were widely regarded as being unsatisfactory and Lady Wilcox was clearly anxious about the situation; following discussions between Lady Mar and Lady Wilcox, the latter offered Lady Mar a meeting with BIS officials to discuss the concerns, which Lady Mar accepted. It was anticipated that four prominent people from the ME community would accompany Lady Mar to that meeting with officials from the MRC and BIS.

Consequently, the attached document “Briefing Notes for meeting with BIS officials about incorrect answers to Parliamentary Questions re: the MRC-funded PACE Trial and ME/CFS” was compiled.

Given that it was accepted that BIS officials would have little knowledge of the situation, the document was written in plain English and was in five easy-to-understand sections: (i) Objectives of meeting with officials from the Department for Business, Innovation and Skills (BIS); (ii) Essential background information about ME/CFS (iii) Problems with the replies to Parliamentary Questions (PQs) of the Parliamentary Under Secretary of State in the Department for Business, Innovation and Skills (Baroness Wilcox); (iv) Problems with the Medical Research Council’s role in the PACE Trial and its repeated denial of accountability and (v) Failure of the PACE Trial Principal Investigators (PIs) to report primary outcome measures as set out in the Trial Protocol; evidence of misrepresentation of the data and evidence of unacceptable selectivity in the results of the trial published in The Lancet.

However, on 21st June 2012, Lady Wilcox informed Lady Mar that the BIS officials were “concerned” about Lady Mar’s “associations” and suggested that she and Lady Mar should have tea together to enable her to get a handle on the problem before the full meeting with BIS officials.

Before any such discussions could take place, on 25th June 2012 Jamie Ballantyre, Assistant Private Secretary to Baroness Wilcox, wrote to the Countess of Mar asking if she would be available to meet Baroness Wilcox, Officials from the MRC and Officials from BIS at 16.30 on 12th July 2012. The letter was specific: “This meeting would be to discuss MRC funding opportunities for CFS/ME and the actions the MRC has taken to try to build capacity in this area…It will not be possible for the technical details of the trial or interpretation of the data to be discussed”. The reasons given were (i) “The research itself has been conducted independently of government and results of the trial, following peer review, have been published (ii) Although funding for the trial was provided by the MRC, this decision to fund would have been made based on peer review. In line with the Haldane Principle of scientific independence, the department would not and should not have any influence on this process (iii) None of the officials who will be present have the relevant technical expertise and knowledge”. The letter continued: “It is important to note that there are channels for challenging scientific results through journals and other publications, speaking at conferences, further research work etc”.

Not only was the DWP a co-funder of the PACE Trial (so it cannot be argued that the trial was independent of government, which has a strong vested interest in getting people with ME/CFS off state benefits and back to work, this being the non-clinical rationale for the “clinical” trial), it has been acknowledged that the PACE Trial protocol that was published in BMC Neurology on 8th March 2007 (BMC Neurology 2007, 7:6 doi:10.1186/1471-2377-7-6) was not peer-reviewed by the journal before publication (“This study protocol was not peer reviewed by the journal because it had already received ‘ethical’ and funding approval by the time it was submitted….We strongly advise readers to contact the authors or compare with any published results article(s) to ensure that no deviations from the protocol occurred during the study” -- Editor’s comment 31st January 2007: ).

In the case of the PACE Trial, The Lancet’s peer review process has patently failed, since no non-biased peer-reviewer would have approved such a significant deviation from the published Protocol including the highly selective publication of results, the abandonment of primary end-points and the shifting of goal posts such that the post-hoc “normal range” overlapped with the entry criteria.

It seems remarkable that officials from the MRC would not have the relevant knowledge to discuss very basic concerns about the methodology of one of its own clinical trials or its own role in that trial.

Moreover, the Haldane Principle (ie. that decisions about how research funds should be spent should be made by researchers and not by politicians) has nothing to do with the issues raised: the key issue is that BIS is responsible for the MRC’s failure to adhere to elementary rules of scientific procedure that occurred in the PACE Trial and as a result of the MRC’s failure, sick people continue to be put at risk of iatrogenic harm.

What is at stake here is the fact that the PACE Trial is scientifically flawed and the results have been misrepresented so NICE, insurance companies, the DWP and private companies contracted by the government (including Atos) are relying on false interpretation of the data to the serious detriment of very sick people.

Lady Mar’s response was that such a meeting would “get us nowhere” and that she would meet Baroness Wilcox privately and explain the situation to her.

A private meeting between the Countess of Mar and Baroness Wilcox took place on 11th July 2012, at which Lady Wilcox agreed that the best way to deal with the situation would be a debate in the House of Lords; this will be arranged for October when the House returns after the recess.

At the conclusion of that meeting, Lady Mar gave Lady Wilcox a copy of the attached Briefing Notes, so there can be no argument that she did not receive a copy.

These facts are being made publicly known in accordance with the government’s keenness for transparency and accountability.

To read the Briefing Notes mentioned, click on the link

For further information about the PACE Trial, please read Magical Medicine: How To Make A Disease Disappear by Prof Malcolm Hooper. A PDF file is available here (442 pages, 6Mb file size).

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