Watt from MRC defends PACE in letter to Times

[Wonko]

It's the old meeting the new - all the monks that transcribe academic books now have to be paid minimum wage.

 

[Guest 102]

Limiting their audience thereby!

I don't blame @Brian Hughes (welcome to the forum!) in the slightest - this is his publishers' decision.

Exactly, available formats and pricing of books has nothing to do with the writer, I wish people would appreciate this.

Welcome to forum, @Brian Hughes - am behind the news, did not know you had joined! And I am sure your contributions will be hugely valuable.

 

[Esther12]

Still just hiding behind their processes. The only substance to the MRC statement is their reference to Cochrane's work, and we know how problematic that has been. It's already clearly laid out for them in Courtney's comments within the Larun exercise CFS review - I wonder if anyone at the MRC took the time to read it.

Yet according to the trial itself, 11 months after the trial began, they changed the entry and recovery criteria which created an overlap in being ill enough to take part and being recovered at the same time to the point that 13.3% of participants were already recovered according to one or two of the recovery criteria before receiving any treatment and without a change to their medical situation.

I thought that we still didn't know when the recovery criteria was changed? There seemed to be no reference to this in the TSC minutes. Did you find a date?

I know that you did go on to say that you were only talking about two of the trial's recovery criteria, but some people can be confused into thinking this is the same as saying a participant could have had baseline data which allowed them to be classed as recovered, so I'd be a bit more cautious with your phrasing on that point.

From the full statement:

"We are currently supporting the PACE trial investigators to anonymise the study data from over 600 participants so that it can be made available to other researchers in a way that protects the privacy of those patients who took part.

The MRC has recently started (with other research funders) a pilot of a new facility for academic researchers to share data via the Clinical Study Data Request (CSDR) web portal. We hope to include the PACE trial on the CSDR portal within the next 6-12 months. This will allow researchers to apply to the CSDR Independent Review Panel to gain access to the dataset for their own analyses."

This is more positive, is it not?

Possibly. At the PACE Information Tribunal MRC's Frances Rawles was trying to find excuses for not following the MRC's own policies on data sharing. If the MRC was arguing that the limited data released to Matthees (with no info on age, sex, location, etc) was already personal data that should not be shared, then how can they now make more data easily available?

But they can no longer claim that the data is inaccessible.

That's true. Amazing to me that they've been able to get away with this anyway.

 

[Andy]

But they can no longer claim that the data is inaccessible.

Until we see all reasonable requests for the data are honoured once it's in that system, my assumption will be that they will seek to avoid releasing it to undesirables, for one reason or another.

 

[Jonathan Edwards]

But interesting that Watt's final paragraph in The Times does not appear in the "extended" version:

"Chronic fatigue syndrome/ME remains a priority for the Medical Research Council (MRC), and it is important that researchers are not discouraged from working on the disease because of concerns that they could be subject to the level of hostility that Pace researchers have experienced. Medical research can only flourish when there is mutual respect between all parties."

Maybe someone had a quiet word about not putting your foot in your mouth when you open it.

 

[Kalliope]

 

[Tom Kindlon]

From the MRC website: https://mrc.ukri.org/news/browse/cr...rial/?utm_medium=email&utm_source=govdelivery

Text of full response from Fiona Watt
‘Call for review of ‘flawed’ ME research’opens in new window (The Times, 21 August 2018) discusses claims that the scientific evidence provided by the PACE trial for using cognitive behavioural therapy (CBT) and managed exercise in the treatment of chronic fatigue syndrome (CFS, also known as ME) is fundamentally unsound.

As funders of the trial, we reject that view: the PACE trial was funded following expert peer review, was overseen by an independent steering committee, and its published findings were also independently peer reviewed. The process through which PACE was funded, supervised and published therefore meets international standards for clinical trials.

CFS/ME is considered to be a spectrum of disorders and understanding the causes and informing the development of new treatments, or the targeting of existing treatments, will require research across a range of approaches and from a holistic view point. The PACE trial investigated the important issue of which available treatments were most likely to benefit patients, and patient consultation resulted in the addition of a treatment to the trial.

While most of the criticism focuses on the PACE trial, there is a large amount of evidence from other studies that also shows CBT and graded exercise therapy (GET) can be helpful to some CFS/ME patients. Other research groups, using different study designs, have drawn similar conclusions about the benefit of these treatments. This evidence is summarised in three Cochrane reviews. Cochrane reviews are systematic reviews of primary research in human healthcare and health policy, and are internationally recognised as the gold standard in evidence-based healthcare.

Making the data available
One criticism of the PACE trial has been that the data is not widely available to other researchers for use in further research and to confirm the reproducibility of results. The MRC strongly supports the sharing of data from clinical trials but it is critical that sensitive personal information from study participants is not released when study data is shared. We are currently supporting the PACE trial investigators to anonymise the study data from over 600 participants so that it can be made available to other researchers in a way that protects the privacy of those patients who took part.

The MRC has recently started (with other research funders) a pilot of a new facility for academic researchers to share data via the Clinical Study Data Requestopens in new window (CSDR) web portal. We hope to include the PACE trial on the CSDR portal within the next 6-12 months. This will allow researchers to apply to the CSDR Independent Review Panel to gain access to the dataset for their own analyses.

Apply for CFS/ME research funding
CFS/ME is a serious illness that is estimated to affect around 0.2-0.4% of the UK population and it remains a research priority for the MRC. The MRC has undertaken and is actively engaged in a number of strategic activities to promote and encourage research into the causes of this condition and effective treatments, and to support the research community. Activities have included a dedicated funding call – Understanding the mechanisms of CFS/ME – in 2011. We want to encourage a broad range of scientists, some of whom are wary of this controversial area, to apply to us for funding. At present, response-mode applications are encouraged through a cross-board highlight notice to undertake innovative research into the mechanisms underlying the chronic changes associated with CFS/ME, particularly in relation to immune regulation, pain, different symptom profiles, childhood CFS/ME and neurological inflammation.

The MRC also supports the UK CFS/ME Research Collaborative (CMRC): a platform for patients, researchers, clinicians and funders to coordinate strategies to increase awareness of the condition within the research community and increase research funding.

Categories

Ed Sykes
@edmsykes
Leads on mental health & neuroscience at the Science Media Centre and former Chair of Stempra - tweets mostly work-related

 

[Cinders66]

Good old ed Sykes. I’m so glad he sat on the CMRC board and changed his views zero and helped us so much.
Michael sharpe retweeted and liked it.

 

[Anthony Carney]

WHAT IS A PRIORITY FOR THE MRC?

I was intrigued to read Fiona Watt's assertion that research into CFS "remains a priority" for the MRC.

Having a look at the data....

1. In the past 13 years to 2016/7 £6.4m was allocated to CFS projects.

2. 45% of the £6.4m was spent on PACE. ie £2.9m.

3. less than one pound in £2000 spent on MRC research projects in 2016/7 was spent on CFS. £286k of £586m per accounts.

So

A. Not a priority is it?

B. The amounts spent have declined in the years 2015 to 2017.

In summary only loose change is spent on CFS research. PACE expenditures only appear significant in a pitifully small bucket.


The real damage from PACE is that it perpetuates the myth that "if only the patient tried harder..persevered they would recover." It's victim blaming.
The physiological problems of immune system recovery and directly related research receive pitiful allocations of cash.

EXPENDITURES MAY BE GLEANED FROM THIS DOCUMENT
Medical Research Council Expenditure on CFS/ME Research, by Project, from 2004/05 -2016/17, £k1

 

[Stewart]

Until we see all reasonable requests for the data are honoured once it's in that system, my assumption will be that they will seek to avoid releasing it to undesirables, for one reason or another.

If you look at the "How It Works" section of the Clinical Study Data Request website, it gives a list of grounds on which the MRC will be able to refuse a request. And if you've been following previous attempts to access the PACE data, some of these reasons may sound familiar...

"I'm afraid this research proposal is not compatible with the participants' consent forms. Refused."
"I'm afraid we don't have the data available in the form you've requested. Refused."
"The study team is already planning to publish an analysis along those lines. Refused."
"You have a clear agenda to discredit our research... sorry, I meant to say we feel you have a conflict of interest. Refused."

I hate to be a cynic - and I hope I'm wrong - but the list of sponsors/funders checks that any research proposal will have to pass looks like it was specifically compiled to allow the PACE team to justify keeping their data locked away. And after Fiona Watt's Times letter I don't feel the MRC can be trusted to perform the role of honest broker.

 

[Adrian]

The MRC strongly supports the sharing of data from clinical trials but it is critical that sensitive personal information from study participants is not released when study data is shared.

Lets not forget that the MRC went to court for QMUL to help suppress the data that showed how much the results were spun

While most of the criticism focuses on the PACE trial, there is a large amount of evidence from other studies that also shows CBT and graded exercise therapy (GET) can be helpful to some CFS/ME patients. Other research groups, using different study designs, have drawn similar conclusions about the benefit of these treatments. This evidence is summarised in three Cochrane reviews. Cochrane reviews are systematic reviews of primary research in human healthcare and health policy, and are internationally recognised as the gold standard in evidence-based healthcare.

A major element of the criticism is around the methodology that was followed in PACE and most of the other CBT and GET trials. Hence this just shows that Fiona Watt has not bothered to read or understand the criticism of PACE but probably listened to QMUL or Sharpe and Wessely complaining, This is basically their message and they hide behind Cochrane even though it is following a flawed methodology and did its own outcome switching.

 

[Adrian]

From the full statement:

"We are currently supporting the PACE trial investigators to anonymise the study data from over 600 participants so that it can be made available to other researchers in a way that protects the privacy of those patients who took part.

The MRC has recently started (with other research funders) a pilot of a new facility for academic researchers to share data via the Clinical Study Data Request (CSDR) web portal. We hope to include the PACE trial on the CSDR portal within the next 6-12 months. This will allow researchers to apply to the CSDR Independent Review Panel to gain access to the dataset for their own analyses."

This is more positive, is it not?

Its probably a way of hiding data. I would expect it will keep it out of the hands of patients and pressure seems to be applied to those in the UK who may speak out. But then wasn't the PACE data lost?

 

[Jonathan Edwards]

I get the distinct impression that the MRC and SMC feel on the defensive!

There is a guy with orange hair who tweets like this.

 

[AR68]

But interesting that Watt's final paragraph in The Times does not appear in the "extended" version:

"Chronic fatigue syndrome/ME remains a priority for the Medical Research Council (MRC), and it is important that researchers are not discouraged from working on the disease because of concerns that they could be subject to the level of hostility that Pace researchers have experienced. Medical research can only flourish when there is mutual respect between all parties."

Forgive me - I'm not entirely following the story as my attention is elsewhere somewhat - but is the suggestion that the 'extended version' is, in reality, a revised version?

Rhetorical questions and points but, firstly, they're not being entirely accurate if they're saying 'extended version' as there is some excision (which they appear to have not alerted readers to), also, what was the reason for the removal of that inflammatory paragraph? Was there some concern that - as was pointed out to them - the 'harassment' issue had more or less been rubbished in a legal setting?

The original inclusion of the 'harassment' stuff was, I'm suggesting, knowingly done as I simply cannot believe that Ms. Watt was unaware of the judgment two years ago. It was untrue propaganda the inclusion of which was highly unprofessional.

Again, sorry if I'm being a bit dim/repeating the obvious again etc!

 

[Adrian]

I thought that we still didn't know when the recovery criteria was changed? There seemed to be no reference to this in the TSC minutes. Did you find a date?

Its not clear. The statistical analysis plan dropped the step test and the recovery criteria as secondary outcomes but it is not the protocol. I think in the plan it says something about setting out the way that the primary analysis would be done.

If I remember correctly.
From the TSG minutes I don't think protocol changes were approved at the end but instead the statistical analysis plan was accepted (in an undocumented meeting). The stats plan doesn't mention the changes explicitly so we have no way of knowing whether this was clear to those approving it but the changes are mentioned in the last meeting when the the committee are reminded that they approved the plan in a meeting between the TSG and the data monitoring committee (but no minutes are given).

So it could be argued recovery was dropped as a secondary outcome measure when the stats plan was written but then explored in an adhoc analysis later. Or it could be argued that the recovery secondary outcome was never dropped just not mentioned in the stats plan which was intended for the primary analysis paper.

 

[Esther12]

Its not clear. The statistical analysis plan dropped the step test and the recovery criteria as secondary outcomes but it is not the protocol. I think in the plan it says something about setting out the way that the primary analysis would be done.

If I remember correctly.
From the TSG minutes I don't think protocol changes were approved at the end but instead the statistical analysis plan was accepted (in an undocumented meeting). The stats plan doesn't mention the changes explicitly so we have no way of knowing whether this was clear to those approving it but the changes are mentioned in the last meeting when the the committee are reminded that they approved the plan in a meeting between the TSG and the data monitoring committee (but no minutes are given).

So it could be argued recovery was dropped as a secondary outcome measure when the stats plan was written but then explored in an adhoc analysis later. Or it could be argued that the recovery secondary outcome was never dropped just not mentioned in the stats plan which was intended for the primary analysis paper.

Yes, that's my understanding too. And there's no sign of any TSC approval for the recovery criteria they eventually used, or any evidence that this criteria was devised before they analysed data for the 2011 Lancet paper.

 

[Brian Hughes]

Exactly, available formats and pricing of books has nothing to do with the writer, I wish people would appreciate this.

Welcome to forum, @Brian Hughes - am behind the news, did not know you had joined! And I am sure your contributions will be hugely valuable.

Thank you! I have just landed. Am delighted to be here! I hope I can contribute constructively now and again...

 

[Barry]

You can read here part of the pages dedicated to the PACE trial (from p132 to 140, p 138 is missing)
https://books.google.fr/books?id=CkNmDwAAQBAJ&pg=PA139&lpg=PA139&dq=psychology+in+crisis+brian+hughes+pace+trial&source=bl&ots=6b2ZGi3Jl5&sig=TbuDSeUWlJdPHkYsWrdO79EJ7og&hl=fr&sa=X&ved=2ahUKEwjKttzZ5o_dAhUBxoUKHTTFBD0Q6AEwAnoECAgQAQ#v=onepage&q=psychology in crisis brian hughes pace trial&f=false

Oh boy! MS and Co will not be amused! And given the how the book's blurb on the back cover says it's "essential reading for students wanting to understand how to better scrutinize psychological research methods ...", I think that very neatly confirms that PACE is being used as an educational example of appalling research methodology. A slam dunk as @dave30th might say .

Also:



"Ruinous" is a good word for it.

Could someone clarify Brian Hughes' point 'b' for me please in the context of PACE. I presume he means how treatments the authors favoured were selectively hyped, but not sure if I'm missing something beyond that.

Feels like it could be worth a whip round to send Michael Sharpe a complimentary copy!

 

[Adrian]

But they can no longer claim that the data is inaccessible.

Data won't be available to patients. We should remember that it was patients requesting and analyzing the data that exposed the spin they had put on it not academics or researchers. Also its patients that are most affected.

So the MRC are essentially keeping data within a small club and probably avoiding criticism. Will the MRC fund someone who does a reanalysis?

 

[Barry]

It appears they may have a menu, to make constructing non responses from previously constructed drivel less taxing.

It was hogwash then, it's still hogwash, even when put next to hogwash from previous other non responses.

A random hogwash generator maybe.