David Tuller: Trial By Error: HRA Report Does Not Vindicate PACE

[large donner]

Its fairly obvious now that the HRA review was written by people within the BPS crowd.

Secondly one saving grace is that Sharpe is bringing light to the whole issue with his ingenious twitter account with his own goal scoring.

The HRA was still hot of the press when he stared tweeting about it being a vindication when it clearly wasn't and funnily enough was just a straw manning response in the style of a BPS proponent.

I am just surprised the HRA report didn't also use the phrase, "I suggest you go read the paper".

Just saying!

 

[DokaGirl]

The Big Short?

I think you're right.

 

[Alvin]

Speaking of Levin's presentation, the PDF has been taken down from the university's website. I have used the link several times (that are now dead) and it's a pretty good asset to show. Is there any way you can contact someone to get it back up?

This was the link: http://irvinginstitute.columbia.edu/pdf/How_Not_to_Conduct_in_Randomized_Clinical_Trial_Levin.pdf.

Its also not on the internet archive

 

[rvallee]

Its also not on the internet archive

Oh the PDF has been preserved elsewhere, no problem here. It's just that this link that I and others have used is now broken and it's also better to have it hosted on Columbia university's website than on scribd or other document hosting.

 

[Alvin]

Oh the PDF has been preserved elsewhere, no problem here. It's just that this link that I and others have used is now broken and it's also better to have it hosted on Columbia university's website than on scribd or other document hosting.

I'm sure it is but it reminds me of an article of David's where he linked a ridiculous trial recruitment and the website was taken down a few days later. That one was luck and preserved on the internet archive but i do think we should come up with a way to preserve references automatically and not assume the archive will catch any of them because we are a small community and most won't get preserved.

 

[Stewart]

I disagree with many aspects of this report and will discuss my concerns at length at a later point.

When you get round to this, it would definitely be worth sending copies to Carol Monaghan and Norman Lamb - they might be willing to raise a few of your concerns with Jonathan Montgomery.

It could also be interesting to ask whether it's standard practice for the HRA to blind copy the Science Media Centre in on their correspondence with Parliamentary Committee Chairs. The SMC was publicising their 'expert reaction' less than an hour and ten minutes after the HRA first tweeted that Norman Lamb had made their letter public. Even given the poor quality of the experts and their reactions, it stretches credulity to suggest that the SMC solicited, received and published three comments in such a short timeframe.

We have not seen evidence that outcome measures were changed in order to achieve a specific outcome. The decisions were made prior to analysis being carried out, as reported in the published statistical analysis plan and corroborated by the minutes of the joint meeting of the Trial Steering Committee and Data Monitoring and Ethics Committee on 10 September 2010.

I don't think the HRA understands what the word "corroborated" really means - corroboration requires evidence, proof. Simply stating that something happened is not corroboration if the available evidence doesn't support the claim.

The minutes of the joint meeting of the Trial Steering Committee and Data Monitoring and Ethics Committee on 10 September 2010 makes a point of emphasising that that the outcome changes were approved by the TSC before any analysis of the data took place. Given that this meeting also saw the two committees briefed on the preliminary trial results, the clear implication is that this approval was granted at an earlier date (because the analysis would have to have been well underway by 10 September given that they were briefing the preliminary results on that day).

If this is the case then there should be a record of the decision to approve the changes being taken in the minutes of one (or more) of the earlier meetings of the TSC. But there isn't - at least not in any of the TSC minutes that have been made public (which is supposedly all of them). So either some of the TSC minutes are being suppressed (and if so, why?) - or the TSC *didn't* discuss the outcome measure changes before analysis began, regardless of what the minutes for the meeting of 10 September 2010 officially claim.

(The minutes for the 10 September meeting also record as an action point that someone - the name is redacted - was given the responsibility of ensuring that "..the review and sign off of the analysis strategy by the TSC is well documented." That seems a really strange action point to me if the analysis strategy genuinely had been signed off at an earlier date. Surely that action would have been raised on the date when the sign-off actually occurred, rather than a subsequent meeting weeks or months later...)

 

[rvallee]

Simply stating that something happened is not corroboration if the available evidence doesn't support the claim.

This is a common rhetorical device used by shameless politicians: describing the facts in the driest possible language even though it means the same thing. (Just tune in to any of Trump's press secretaries pressers, they use it all the time)

So they didn't cheat by moving the goalposts in order to achieve a desirable outcome, they merely changed the level of accepted recovery rates in order to be more in line with past results (which is basically the excuse the PACE team used, IIRC). It means exactly the same thing. It just describes it as neutrally and dispassionately as possible. It never changes anyone's mind and it only works if you control the process.

Whenever it is used, you can be sure that a very bad situation is being whitewashed. It works very well, but it takes a highly unethical person to put their name to it, which sadly there is no shortage of. No one ever uses this without malicious intent, which says a lot that the psychosocial ideologues basically deflect most criticism this way (the other being "harassment" by whiny dangerous people).

Basically it's a big tell that they know they're full of shit but what are you going to do about it, plebe?

 

[NelliePledge]

@Stewart i just assumed that the PACE authors would have been asked to comment on the points raised so would have been aware the letter was in the pipeline and maybe they were sent an advance copy which they then shared with SMC. In any event knowing the letter was coming they would have been in a position to work with SMC on a response in advance of publication without necessarily having the final wording of the letter ETA or SMC being sent the letter direct by HRA

 

[Stewart]

@Stewart i just assumed that the PACE authors would have been asked to comment on the points raised so would have been aware the letter was in the pipeline and maybe they were sent an advance copy which they then shared with SMC. In any event knowing the letter was coming they would have been in a position to work with SMC on a response in advance of publication without necessarily having the final wording of the letter ETA or SMC being sent the letter direct by HRA

I'm sure you're right. It seems highly likely that the HRA sought assistance and input from the PACE team in responding to the issues raised by the Select Committee, and in return gave Sharpe et al advance sight of the letter they sent - allowing the SMC to prepare their 'expert reaction' so they could publicise it as soon as the HRA letter became public.

But I'm pretty sure this is not how a regulator is supposed to operate when responding to concerns raised by Parliamentary Committees. For all that it's no longer a surprise at this point, the degree of 'chuminess' that seems to exist in the UK between gamekeepers and poachers is deeply worrying. It gives the impression that the HRA is more concerned with helping researchers defend their reputations than actually performing their regulatory functions.

 

[Suffolkres]

I'm sure you're right. It seems highly likely that the HRA sought assistance and input from the PACE team in responding to the issues raised by the Select Committee, and in return gave Sharpe et al advance sight of the letter they sent - allowing the SMC to prepare their 'expert reaction' so they could publicise it as soon as the HRA letter became public.

But I'm pretty sure this is not how a regulator is supposed to operate when responding to concerns raised by Parliamentary Committees. For all that it's no longer a surprise at this point, the degree of 'chuminess' that seems to exist in the UK between gamekeepers and poachers is deeply worrying. It gives the impression that the HRA is more concerned with helping researchers defend their reputations than actually performing their regulatory functions.

https://www.hra.nhs.uk/about-us/news-updates/conflicts-interest-blog-hra-chair-jonathan-montgomery/

 

[Cinders66]

I don’t understand how it’s not a major red flag to the world and establishment that now ALL the charities involved in ME, dealing day in day out with patients real life experience state that they have issues with the PACE trial methodology, it’s underlying model, the way it was reported, that large sum of money spent on it versus that invested in biomedical research and the behaviour approach in general.
Even this latest report is low key about PACES success claims and then Michael sharpe is chirping how it’s all clear that they have safe and effective treatments.

You can claim there’s an extreme wing and disregard them as uninformed prejudiced odd balls , I don’t think you Can disregard the entire patient and charity sector even if people like wessely think quoting contented fans at their personal clinic as the general picture will be swallowed as accurate. Rona Moss Morris works high up with the ms society where her exercise advice and supportive CBT seems well received. Surely she must question why her CBT and GET for CFS isn’t and why not one, now the awful Ayme who worked with Crawley and chalder is shut, ME charity would fund her.

 

[Alvin]

I don’t think you Can disregard the entire patient and charity sector even if people like wessely think quoting contented fans at their personal clinic as the general picture will be swallowed as accurate.

Of course they can. Their 'religious' faith says ME is psychosomatic so they will use any means necessary which includes lies and worse to make sure their beliefs remain entrenched.
Reality means nothing to them.

 

[Suffolkres]

Its fairly obvious now that the HRA review was written by people within the BPS crowd.

I have been commenting elsewhere about the HRA statements by John Montgomery. (Conflict of Interest and Insurance Industry)

His statement is worrying to me. I am an elephant who never forgets.

"
Background
The PACE trial was an evaluation of the therapies that were recommended by NICE at the time that the study was proposed, with the caveat that the evidence base at this time was weak."

He states that the PACE trial came out of the recommendation of the NICE Guidance work......

That cannot be, as I have looked up my email archive from 2002 when the "birthing" of PACE was happening........

(My emphasis)

There is this,


"03 September 2002

Dear All,

This information has just been passed to me and I can assure you that my source is both reliable and trusted.

I have just been informed that the Medical Research Council is in the process of giving £2.6 million to a 4 year research project. Funding will be given over the next 2 years.

The project has three arms to it;

Arm One:

Research into the combined use of CBT and Graded Exercise as effective forms of treatment for people with ME/CFS;

Arm Two:

Research into the use of Cognitive Behavioural Therapy on its own as an effective treatment for people with ME/CFS;

Arm Three:

Research into the use of "Pacing" as an effective form of treatment for people with ME/CFS.

The £2.6 million is to be split between several centres.

Psychiatrist Professor Simon Wessely is to receive funding at his CFS Unit at Kings. (Wasn't SW on the MRC Panel for evaluation of Research bids at this time?)

Psychiatrist Michael Sharpe and Dr Carson are to receive funding at their unit in Edinburgh.

Psychiatrist Dr White and Professor A J Pinching are to receive funding at Barts Hospital in London.

I understand that funding is also going to the Cardiff Group.

Dr Findley's assistant Diane Cox has been approached to train up.

Psychotherapists and indeed Psychotherapists are being recruited.

This £2.6 million has passed its "first review" within the Medical Research Council."



and then this,



"5/5/2004

I note that there has been some comment on the e-groups regarding the criteria for the PACE study. Some time ago the researchers agreed at our request to also record all those in the study against BOTH the Fukuda criteria and the operationalised criteria for myalgicencephalomyelitis.

It is intended that this should provide information on whether any of the treatments being compared are more helpful or more harmful than the others for different definitions of CFS / M.E.

Chris Clark

Chief Executive"

 

[rvallee]

Psychiatrist Professor Simon Wessely is to receive funding at his CFS Unit at Kings

Oh, but he was totally not involved. Simon said so. Except when he conceded that he was, but totally not involved (except a lot, yes).

 

[Esther12]

Thanks for those e-mails. The pleasure I can from reading boring old PACE correspondence makes me realise I'm a true nerd. Is there any demand for a full-time PACE historian?

 

[Suffolkres]

Thanks for those e-mails. The pleasure I can from reading boring old PACE correspondence makes me realise I'm a true nerd. Is there any demand for a full-time PACE historian?

I have rather a high number of emails .....! Then I was better at filing them. It's good to know the old brain cells and memory are still working!

This is a corker of an email!

Sent: Saturday, May 15, 2004 7:01 PM
Subject: [CO-CURE] ACT: The PACE and FINE trials: correcting some misunderstandings

"From Dr. Peter D. White:

The PACE and FINE trials: correcting some misunderstandings

The UK national newspaper, The Independent, published an article on May
11th, which included a number of misunderstandings about these two
scientific trials of treatments of CFS/ME. The Independent has today
published letters of correction from us as the Principal Investigators in
the trials, and from the MRC as the main funder of the trials. We
understand that the journalist drew strongly on misunderstandings that were
first published on this web-site. We believe it will be helpful for those
who haven't had the opportunity to read the letters in the Independent to
have access to them through Co-Cure.

<http://argument.independent.co.uk/letters/story.jsp?story=521407>


There were three main misunderstandings carried by this web-site:

1. Sufferers of the neurological disease ME/CFS ICD-10 G93.3 will not be
able to enter the trial and will be excluded because the Oxford criteria
specifically states that those with an organic brain disease such as ME/CFS
must be so excluded.

The actual position: The criteria that we will use to include patients with
CFS/ME do not exclude ME. The trial is designed to answer the question as
to whether these treatments are helpful or unhelpful or even harmful in
people with different definitions of CFS/ME, including the Fukuda criteria
and the London criteria for ME.


2. Designed and set up by psychiatrists, the psychiatric PACE clinical
trial will use psychosocial management regimes and treatments that have
comprehensively been shown to be at best ineffective and in many instances
have made sufferers of the neurological disease ME/CFS ICD-10 G93.3
dramatically worse.

The actual position: The PACE and FINE trial research teams, which have
designed and set up the trials, include 6 physicians (5 specialists in
infectious disease, and one immunologist), 5 nurses, 3 statisticians, 3
health economists, 3 psychologists, 2 general practitioners, 2 counsellors,
1 physiotherapist, 1 occupational therapist, 1 cognitive behaviour
therapist, two representatives of Action for M.E., and only 5 psychiatrists.

The trials will be testing supplements to usual specialist medical care:
pacing, pragmatic rehabilitation, and graded exercise therapy (none of
which could be described as psychiatric or psychosocial) and cognitive
behaviour therapy. These treatments will be given by nurses,
physiotherapists, occupational therapists, and psychotherapists; not
psychiatrists.

Several systematic reviews have shown that these treatments show most
promise for CFS/ME and there is no evidence that they are harmful if
carried out with the help of appropriately trained and qualified
therapists. It is highly likely that reports of harm, especially after
graded exercise therapy, result from poor understanding of CFS/ME and the
misapplication of approaches by inexperienced or untrained therapists. We
will however look for evidence of harm as well as improvement in these
trials, and both trials will be overseen by two independent committees to
ensure that no treatment is intrinsically harmful to participants.


3. It is wrong that the psychiatrists carrying out this research are
themselves employed to provide the therapies being studied at the newly
operational ME/CFS centres. It is unethical for people with proven
commercial interests in these studies to be designing and running this
£2.5m trial, given the proven evidence of their commercial interest in the
desired outcome.

The actual position: None of the psychiatrists are employed to provide any
of these therapies. No researcher will make any personal financial gain
from these trials.


Conclusion

The most important point we wish to make is that these two trials will
answer important questions about what current treatments are most helpful
to people with CFS/ME, and will include treatments that will be available
to the most severely affected.

We will not post any further Co-Cure web-site correspondence on this
matter.. The trial teams will be developing websites over the next few
months to provide accurate and up to date information about the trials. We
hope these will be a useful source of information for the CFS/ME community,
including those recruited to the trial.


Dr Peter White
Professor Michael Sharpe
Professor Trudie Chalder
Dr Alison Wearden

Principal Investigators for the PACE and FINE trials

 

[Snowdrop]

Oh, but he was totally not involved. Simon said so. Except when he conceded that he was, but totally not involved (except a lot, yes).

You're channelling somebody there. I just can't put my finger on it.

 

[large donner]

I have rather a high number of emails ....


Dr Peter White
Professor Michael Sharpe
Professor Trudie Chalder
Dr Alison Wearden

Principal Investigators for the PACE and FINE trials

So the PIs who signed this rebuttal are all either psychiatrists or psychologists but rest assured cos there was like loads of other people involved.

5 nurses who just do what they are told,
3 statisticians who helped to withold the data and failed to understand the significance of having a recovery threshold worse than entry criteria,
3 health economists who presumably dropped out when they dropped the employment and return to study results as a measure of success and presumably have promotions within the DWP after continuing to ensure the economical health of certain psychiatrists,
3 psychologists because they will side with psychiatrists
2 general practitioners,
2 counsellors to reassure people to push through their symptoms as wearing a blue cardy makes the stuff you say true?
1 physiotherapist to support the notion of GET ,
1 occupational therapist,
1 cognitive behaviour
therapist so as to avoid a conflict of interest with CBT,
2 representatives of Action for M.E to throw everyone under the bus and give validity to the claim that there was patient support for the trial.


Tony who made the tea, Bob who mopped the floors in the corridors that where too short to include the walking test data, and a bunch of people who actually had some medical backgrounds but did no objective biological testing before during or after the the trial.

 

[Esther12]

No researcher will make any personal financial gain
from these trials.

That's a strong claim about a major piece of research that would should shape understanding of the value of the treatments that they had developed.

 

[Esther12]

Its fairly obvious now that the HRA review was written by people within the BPS crowd.

I don't think that's right. I think it's more likely it was written by people who i) fell for some QMUL spin and ii) did not want to challenge the systems of oversight for UK medical research.