Statements on conflict of interest of PACE trial TSC

The minutes for the first two meetings of the TSC (attached) have been available for some years. I was always struck by the entries on COI. All agreed they had none. We know that the PIs had one.

Last year I asked QMUL for the statements. They replied with the minute from each of the first two TSC meetings:

These are the relevant extracts from the minutes of the PACE TSC.

22/04/2004 – Conflicts of Interest All members of the committee present at the meeting were asked to declare any conflict of interest. No financial conflicts of interest were declared and it was agreed that no one present had any other substantial or material conflict relevant to their work on the committee.

Action: PW to write to all members outlining potential conflicts of interest, and invite replies.

27/09/2004 – Conflicts of interest Professor White confirmed that letters had been received from all TSC members confirming no one had any conflict of interest.


I asked for actual copies and they then provided them.

It is I think because I pointed out that some members had, despite the minutes, not provided a COI statement that they then would not turn over the TMG COI statements.

I have been waiting on the ICO decisions on the TMG statements (here https://www.s4me.info/threads/ico-r...ade-to-the-trial-management-group.3117/page-2 ) and the TSC minutes (thread here https://www.s4me.info/threads/pace-trial-tsc-and-tmg-minutes-released.3150/ ) to see if they turned up anything more.

I think the following is particularly noteworthy:
Chalder and White made no statement.
Llewellyn says he has none, but p8 here says he was running a private clinic at the time.
http://wames.org.uk/cms-english/wp-content/uploads/2010/12/WAGreport.pdf

The big one for me, though, is the false and misleading statement by Sharpe, who clearly states he had no conflict of interest.
His statement about 'equipoise' is revealing, as he clearly thinks it's important. But, of course, he can't himself judge whether he is in a position of equipoise, and his previous work means that he cannot be.

I have today complained to the MRC, copied to Monaghan.

Aylward's is also interesting. It's dated 22/07, but he already knew he was going to take on a position funded by Unum as it was reported on 26/06/2004 here https://www.walesonline.co.uk/news/wales-news/curing-the-long-term-sick-2434692

TSC COI 1: https://www.dropbox.com/s/xo1iyxhiro1sgl9/TSC COI letters.pdf?dl=0

TSC COI 2: https://www.dropbox.com/s/fed34yniqqrvr8s/TSC COI letters 2.pdf?dl=0

 

Aylward headed UnumProvident Centre For Psychosocial And Disability Research, starting June 2004

https://dpac.uk.net/2016/09/two-apparent-irregularities-involving-unum-atos-and-dwp/

Letter dated 22nd July seems at odds with this report

 

See this doc http://www.investinme.org/Documents/Library/magical-medicine.pdf pg 257-262 which includes :

Since it was believed that Professors White, Sharpe and Chalder all did have obvious and serious conflicts of interest and since any such conflicts had been denied by them, representations were made questioning why their known conflicts of interest had been denied.

Following these representations, on 23rd December 2008 a remarkable revelation was made – in writing – by Dr Ira Madan, Director of Clinical Standards, NHS Plus (who, with Wessely and Chalder, is based at King’s
College):
“The Department of Health have asked me to investigate your concern that one of the guideline development group members, Professor Trudie Chalder, and the two external assessors, Professor Michael Sharpe and Professor Peter White, had conflicts of interest whilst involved in the production of the guideline. I can confirm that I was aware of the potential for competing interests that you have stated. The roles that Professor White, Professor Sharpe and Professor Chalder have undertaken for the agencies and companies that you stipulate (i.e. the DWP and the medical and permanent health insurance industry) were in the public domain prior to the
publication of the NHS Plus guideline. I am content, as the Director of that guideline, these potential competing interests did not in any way influence the synthesis of the evidence or the guideline recommendations”.

There is thus written confirmatory evidence from Dr Ira Madan that Professors White, Sharpe and Chalder all did have what she referred to as “competing interests”, but that she was “content” about the situation.
However, the MRC PACE Trial Minutes twice record that these same people had declared no conflicts of interest (recorded first in the Minutes dated 22nd April 2004 and again in the Minutes dated 27th September 2004).

Thus there is written evidence ‐‐ from Dr Madan at the Department of Health ‐‐ illustrating how the normal rules of independent peer review and conflicts of interest seems to be suspended when it comes to the “evidence‐base” for CBT/GET in people with ME/CFS because in relation to the NHSPlus Guidelines, two researchers were allowed to sit in judgment on their own publications, with the prior knowledge and permission of Dr Ira Madan.

Furthermore, they were not required to make conflict‐of‐interest declarations, even though their conflicts were known about by Dr Madan. This is not peer‐review as the rest of the scientific world understands it?

However, Professors White, Sharpe and Chalder seem to have had a change of mind and they then did declare and list serious conflicts of interest in relation to exactly the same material issues in the MRC

PACE Protocol:
ʺPDW has done voluntary and paid consultancy work for the Departments of Health and Work and Pensions and legal companies and a re‐insurance company. MCS has done voluntary and paid consultancy work for government and for legal and insurance companies. TC has done consultancy work for insurance companies, is the author of Coping with Chronic Fatigue published by Sheldon Press and co‐authors Overcoming Chronic Fatigue with Mary Burgess published by Constable and Robinson.ʺ (http://www.biomedcentral.com/1471‐2377/7/6 ).
Thus there is conflicting information provided by the Principal Investigators; is this the high standard of integrity required in an MRC clinical trial?

 

Thanks. Very interesting. Hooper did an amazing amount of work. It's disgraceful how it was all ignored.

I read it a couple of years ago, but I need to read that again.

 

It is amazing that Lord Turnbull, Cabinet Secretary at the time could have allowed the apparent breach of civil service standards.

But he did apparently allow Alastair Campbell to chair a meeting of the Joint Intelligence Committee, so nothing should surprise.

 

yes there is loads of info out there and a lot of things were raised before but I think the boys network was too strong. Hopefully now with more support things will stick.

I was going to copy the text from all of the resources that I could and put into one file if possible. That way they would be easier to search, would that be helpful in general?

 

a bit more:

A search of PubMed for Professor White’s own declarations of interest just for the years 2004 to 2009 reveals that in many of the papers, he did not declare any competing interests at all, despite clear warnings from the
journals that “Authors are responsible for recognising and disclosing financial and other conflicts of interest that might bias their work…authors must disclose any commercial associations that might impose a conflict of interest in connection with the study” (Journal of Rehabilitation Medicine, in which Peter White published
an article on Chronic Fatigue Syndrome in 2008:40(10):882‐885).

Given the long‐time involvement of so many people involved in the PACE Trial (especially the Principal Investigators and Professor Wessely) with the medical and permanent health insurance industry and with Government agencies whose intention is understood to be to target people with ME/CFS in order to remove them from benefits, there is legitimate concern that such conflicts of interest will direct the outcome of the
trial.

The Gibson Report of 2006 expressed concern about these competing financial interests at page 31, section 6.3:

“At present, ME/CFS is defined as a psychosocial illness by the medical insurance companies. We recognise that if ME/CFS remains defined as psychosocial then it would be in the financial interests of the medical insurance companies.

“There have been numerous cases where advisors to the DWP have also had consultancy roles in medical insurance companies, particularly the company UNUMProvident.

“Given the vested interest private medical insurance companies have in ensuring CFS/ME remains classified as psychosocial illness, there is blatant conflict of interest here.

“This Group finds this to be an area for serious concern and recommends a full investigation by the appropriate standard body” (http://erythos.com/gibsonenquiry/Docs/ME_Inquiry_Report.pdf ).

Those parliamentarians who expressed this concern included the former Chairman of a House of Commons Science and Technology Select Committee and former Dean of Biology; a member of the Home Affairs Select Committee; a Minister of State for the Environment; a former President of the Royal College of Physicians; the Deputy Speaker of the House of Lords, and a former Health Minister and Honorary Fellow of the Royal College of Physicians.

To date, nothing whatever has been instituted to remedy this unacceptable situation.

 

The statement @JohnTheJack is referring to was in Sharpe's formal letter to White declaring any conflicts of interest:

Given that he is a doctor, this statement signals that he has no prior beliefs regarding which treatments are more effective. But in the very same statement, he's describing the nature of his past research using particular treatment approaches, which indicates he is very likely to have particular beliefs, and therefore in fact is not in a position of equipoise.

Hardly any individual clinical researchers are in a true position of equipoise. This can only happen if you've had no experience with any of the treatments (research or clinical), so have formed no opinion, or if you've used some or all the treatments, but still have not formed an opinion as to which might be better.

Perhaps he is confusing equipoise with not having any direct financial COI? He seems not very bright for a person in his position.

 

@Woolie - you quotes from Sharpe's COI statement there, but said it was White's.

I think that he was asserting that he has a magic brain.

 

to White.

But I've clarified anyway.

 

Oops - I'm sure I went read it twice to check before posting as well! Thanks.

 

Yes, sounds a good idea.

 

It is an extraordinary statement.

We know he did have a financial COI as well. At the very least he was getting royalties from his book, first published in 2000 and still paying him royalties in 2010 when he declared them to The Lancet in the TMG COI statements.

 

Is there a similar statement from Trudie Chalder? She has several books on chronic fatigue/chronic fatigue syndrome (which are recommended on NHS sites), one published in 1995 the others in 2002 and 2005.

 

Exactly. But for her and White the point is that they didn't declare any.

I think the following is particularly noteworthy:
Chalder and White made no statement.

 

Supposing for a moment that we take Sharpe's statement at face value, then together with his recent tweets, it damns him absolutely as a scientist: if he in fact had no vested interests, then the only reason he published was because he didn't understand the trial flaws, and as he still defends the trial, he still cannot understand, even after explanation.

So either way it's unimpressive, to put it mildly.

 

It is utterly stunning that a professor of psychology is so unaware of human cognitive biases that they would even entertain making such a statement!

 

Or even more stunning that a professor of psychology is so unaware that readers of the statement might not to share his particular cognitive biases?

 

Yes, agreed. It is just an extraordinary statement. The false and misleading one about his interests may yet cause problems for him, but in many ways that bit about 'equipoise' is more damning.

 

And there was Richard Horton saying how clever it was for these guys to wager five million quid that they could prove the patients' philosophy was wrong! That is some equipoise.