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PACE Trial and PACE Trial Protocol

Bob

Senior Member
Messages
16,455
Location
England (south coast)
I'm sure we've discussed this over and over again, but my brain is not helping me this evening...

Are there any studies that demonstrate that an SF-36 PF score of about 60 (the threshold for "normal range", and approx the average SF-36 scores for CBT and GET at 52 weeks), indicates a severe disability, or serious health problem?

Also, for the 6MWD test, is there a quote from the New York Heart Association, that says that scores seen in the PACE Trial equate to a "severe disability"? Or if not an exact quote, then some text along the same lines?

Grateful for any help with this.
 

currer

Senior Member
Messages
1,409
I might go. I lean towards conspiracy theories these days. I dont know what Richard Horton said about ME. Can anyone remind me? It would be interesting to attend.
It is free.

"Are conspiracy theories the greatest threat to global health?
in the series Global Health Lab Discussions
Date: Tuesday 28 February 2012
Chair(s): Martin McKee, LSHTM, ECOHOST and Richard Horton, T
http://www.lshtm.ac.uk/newsevents/ev...-global-health"
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
I might go. I lean towards conspiracy theories these days. I dont know what Richard Horton said about ME. Can anyone remind me? It would be interesting to attend.
It is free.

"Are conspiracy theories the greatest threat to global health?
in the series Global Health Lab Discussions
Date: Tuesday 28 February 2012
Chair(s): Martin McKee, LSHTM, ECOHOST and Richard Horton, T
http://www.lshtm.ac.uk/newsevents/ev...-global-health"

Richard Horton - extracts from the abc radio interview:

"There is this feeling that ME, being an organic disease in the views of some patients, that means that any view that contradicts that and offers a treatment against that particular perspective must therefore by definition be unethical."

"Indeed, and I think this is where one sees a real fracture in the patient community. One is seeing a very substantial number of patients very willing to engage in this study, desperate to get good evidence on which to base their future treatment. But one sees a fairly small, but highly organised, very vocal and very damaging group of individuals who have, I would say, actually hijacked this agenda and distorted the debate so that it actually harms the overwhelming majority of patients."

"Well, what we're doing right now is waiting for the formal response from the authors to this 43-page attack on their integrity and the study, and the request for a retraction. We plan to publish their response to that attack. We will invite the critics to submit versions of their criticisms for publication and we will try as best as we can to conduct a reasonable scientific debate about this paper. This will be a test, I think, of this particular section of the patient community to engage in a proper scientific discussion"


http://www.abc.net.au/rn/healthreport/stories/2011/3192571.htm#transcript


I can't remember if he has said anything else, somewhere else.
 

currer

Senior Member
Messages
1,409
What you need to ask yourself is WHY a society ignores illness in the young, a group that ought to be the fittest and most productive.

It is a medical rule that diseases appearing in the young should be responded to as a public health alert - this social group does not normally become ill, so when it does, it shows that something unusual is occurring.

New diseases or a spread of old disease into the young shows that something is going wrong, and must be investigated and taken seriously as a threat to society.

So why has ME been ignored for so long? Could it be the association with vaccination in a proportion of cases? (10-20%)
Could it be the welfare costs? Could it be the suspicion that a retrovirus may be a cause?

Because there will be a reason to explain why the proper medical response to the public health threat that ME poses has not occurred.
ME is constantly discussed in parliament - the government is well aware of the size of the problem. And that is where the conspiracy theory starts.

Young people live in poverty, are disabled and die from ME. The costs in lost productivity to the nation are huge.
I do not relish going to a meeting where these issues are treated with the complacency that I expect will be there. But I think I may try to go along. It is not only patients who are angry. Good doctors who have experience of managing their patients with this illness, with no help from the NHS are also angry.
 

currer

Senior Member
Messages
1,409
Does anyone have any questions they want me to ask? Or any information they want to pass on?
This is not a debate that I have followed. After thirty years of illness, and twenty advocating for people with ME I do not feel any more reasoned arguments can help. The only thing that will change attitiudes is proper medical investigation into our disease. Nothing else can refute the self-serving arguments and overpaid complacency of so - called "medical experts."
 
Messages
13,774

Ta D. I'm getting worse and worse at providing links to things.

Does anyone have any questions they want me to ask? Or any information they want to pass on?

How about:

To what extent does the panel believe that the spread of conspiracy theories is encouraged by the breakdown in trust that occurs when researchers, and others in positions of authority, make claims which are misleading, or not supported by the evidence?

Possibly with a:

For example, the Lancet was recently promoting the claim that treatments for CFS resulted in a recovery rate of 30% (or was it 28? sorry for not checking), without making it clear that the criteria for 'recovery' overlapped with the criteria used at the start of the trial to confirm a diagnosis CFS and that a patient was truly suffering from 'severe and disabling fatigue', so patients could have got worse, and still been counted as having recovered thanks to these treatments. Patient concerns about these matters were largely judged in political terms, and brushed aside without the substance of their complaints having been dealt with, or even truly recognised.

Probably needs toning down... I'm feeling permanently irate about CFS stuff!

If you want to amp it up, and be dismissed as a militant nutter, you could add:

At one point should these sorts of self-serving misrepresentations be viewed as 'conspiracies', rather than occurrences best explained by incompetence and prejudice?
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Has anyone done any work looking at why the "clinically useful difference", might be inappropriately defined in the PACE Trial?
I'm wondering if any similar studies have come up with very different definitions.
(I haven't searched through this thread yet for any info about this, so I'll do that now.)
 

oceanblue

Guest
Messages
1,383
Location
UK
Has anyone done any work looking at why the "clinically useful difference", might be inappropriately defined in the PACE Trial?
I'm wondering if any similar studies have come up with very different definitions.
(I haven't searched through this thread yet for any info about this, so I'll do that now.)
They used 0.5SD, which isn't particularly controversial. However as patients had to have a minimum score to be well enough to make it to the clinic, and a max score defined by the entry cirteria (ie enough fatigue/disability), it can be argued that the SD was artifically constrained, making SD smaller and so leading to a smaller CUD.
 

Dolphin

Senior Member
Messages
17,567
Has anyone done any work looking at why the "clinically useful difference", might be inappropriately defined in the PACE Trial?
I'm wondering if any similar studies have come up with very different definitions.
(I haven't searched through this thread yet for any info about this, so I'll do that now.)
This letter was published:
The Lancet, Early Online Publication, 17 May 2011
doi:10.1016/S0140-6736(11)60689-2

The PACE trial in chronic fatigue syndrome
Jane Giakoumakis a

In their randomised trial of treatments for patients with chonic fatigue syndrome, Peter White and colleagues (March 5, p 823)1 define a clinically useful difference between the means of the primary outcomes as 05 of the SD of these measures at baseline, equating to 2 points for Chalder fatigue questionnaire and 8 points for short form-36. They cite achieving a mean clinically useful difference in the graded exercise therapy or cognitive behaviour therapy groups, compared with specialist medical care alone, as evidence that these interventions are moderately effective treatments.

The source for this definition of clinically useful difference states that such a method has a fundamental limitation: estimates of variability will differ from study to studyif one chooses the between-patient standard deviation, one has to confront its dependence on the heterogeneity of the population under study.2 In White and colleagues' study, we do not have heterogeneous samples on the Chalder fatigue questionnaire and short-form 36 physical function subscale, since both are used as entry criteria.1

Patients had to have scores of 65 or less on short-form 36 to be eligible for the study.1 However, most, in practice, would probably need to have scores of 30 or more to be able to participate in this clinic-based study. Indeed, only four of 43 participants in a previous trial of graded exercise therapy scored less than 30.3, 4 Guyatt and colleagues2 suggest that an alternative is to choose the standard deviation for a sample of the general population, which White and colleagues have given as 24.1 An SD of 24 gives a clinically useful difference of 12; both graded exercise therapy and cognitive behaviour therapy fail to reach this threshold. Whether they moderately improve outcomes, as claimed,1 is therefore questionable.


I am chair of a myalgic encephalomyelitis support and advice groupan unpaid voluntary position.

References

1 White PD, Goldsmith KA, Johnson AL, et alon behalf of the PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; 377: 823-836. Summary | Full Text | PDF(309KB) | CrossRef | PubMed

2 Guyatt GH, Osaba D, Wu AW, et al. Methods to explain the clinical significance of health status measures. Mayo Clinic Proc 2002; 77: 371-383. PubMed

3 Fulcher KY. Physiological and psychological responses of patients with chronic fatigue syndrome to regular physical activity. Loughborough: Loughborough University of Technology, 1997. http://hdl.handle.net/2134/6777. (accessed March 4, 2011).

4 Fulcher KY, White PD. Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. BMJ 1997; 314: 1647-1652. PubMed

a xxxxxxxxxxxxxx, Glasgow xxxxxxxxx, UK

Dutch CBT studies sometimes thresholds e.g.

We defined patients as showing clinical significant improvement3 at
follow-up if they had a reliable change index of >1.96
and a score of <35.7 (1 SD above the mean for 420
healthy adolescents) on the fatigue severity subscale,
had an increase of >50 or an end score of >=75 for on the
physical functioning subscale of the SF-36,7 and were
fully attending work and/or school at follow-up.

3. Stulemeijer M, de Jong LW, Fiselier TJW, Hoogveld SWB,
Bleijenberg G. Cognitive behaviour therapy for adolescents
with chronic fatigue syndrome: randomized controlled trial
[published correction appears in BMJ. 2005;330(7495):820].
BMJ. 2005;330(7481):14

7. Powell P, Bentall RP, Nye FJ, Edwards RH. Randomised controlled
trial of patient education to encourage graded exercise
in chronic fatigue syndrome. BMJ. 2001;322(7283):387390
from
Efficacy of cognitive behavioral therapy for adolescents with chronic fatigue syndrome: long-term follow-up of a randomized, controlled trial.
Pediatrics. 2008 Mar;121(3):e619-25.
Knoop H, Stulemeijer M, de Jong LW, Fiselier TJ, Bleijenberg G.

This threshold is often used in Dutch CBT studies:
We defined patients as showing clinical significant improvement3 at
follow-up if they had a reliable change index of >1.96
and a score of <35.7 (1 SD above the mean for 420
healthy adolescents) on the fatigue severity subscale,
 

biophile

Places I'd rather be.
Messages
8,977
The 'clinically useful difference' replaced 'clinically important difference'

As with all the other outcome measurements in the 2011 Lancet paper of the PACE Trial, a tighter/stricter version of this goalpost existed in the original 2007 protocol but was replaced with a weaker version halfway through the trial. A (post-hoc) "clinically useful difference" of a mere -2 points on the Chalder fatigue scale (Likert scoring, range 0-33) lead to the unexpected situation where 65% of the SMC quasi control group reported a "clinically useful difference" in fatigue at 52 weeks vs 76% for CBT and 80% for GET. A similar situation exists for physical function with +8 points (range 0-100, 5 point increments) for the "clinically useful difference": 58% for SMC, 71% for CBT, 70% for GET.

The 2007 protocol had a "clinically important difference" instead, defined as somewhere between 2 to 3 times the improvement rate of SMC. This calculates on average to about minus 9-14 points for fatigue and 20-30 plus points for physical function. I don't recall any reason given for this change, but it is certainly a major change in goalposts and would have made the researchers' pet therapies appear much worse if the original goalpost was used.

In the 2007 protocol, based on previous research, the authors expected a "positive outcome" for about 60% of patients undergoing CBT, 50% for GET, 25% for APT, and only 10% for SMC. For the purposes of the PACE Trial a "positive outcome" was going to be defined as one of the three following goalposts: (a) for fatigue either a 50% reduction in fatigue score or a score of 3 or less on the CFQ (bimodal scoring); (b) for physical function either a 50% increase in physical function score or a score of 75/100 points or more on the PF/SF-36 subscale; (c) a self-rating of 1 or 2 ("very much better" or "much better") on the Clinical Global Impression (CGI, range:1-7).

In the 2011 Lancet paper, the same % expectations are not given in terms of a "positive outcome" but a "response". When looking at the various baseline and outcomes measurements, it is a safe bet that the trial did not even come close to reaching their original expectations for CBT and GET. The only way any measurement came close to reaching a 50-60% response rate for CBT/GET was with the very low threshold for a "clinically useful difference", which as mentioned in the beginning of this post, had the effect of greatly inflating the proportion of SMC participants also reporting improvements.

As well as the weak/wide goalpost for a clinical difference, other possibilities for the unexpected improvement rate in the SMC group include: (a) the way the participants were selected for the trial using the Oxford criteria on new onset patients who have not been ill long so may be more likely to improve; (b) giving any sort of "standardised medical care" to a group of people who by default are usually subjected to neglect and incompetence and misdiagnosis.
 

currer

Senior Member
Messages
1,409
"Are conspiracy theories the greatest threat to global health?
in the series Global Health Lab Discussions
Date: Tuesday 28 February 2012
Chair(s): Martin McKee, LSHTM, ECOHOST and Richard Horton, T
http://www.lshtm.ac.uk/newsevents/ev...-global-health"

Well, I attended this meeting last night. Im too tired to post much about it now, but I do think that it might be worthwhile approaching Mr Horton on our issues with the Pace Trial. He appeared to be a sincere man who trusts scientific medicine as an enlightened benefit to the human race and I suppose this is why he defends aspects of it's application and value system when these come in to question.
I think he would be open to a reasoned and not too involved (as a busy man) criticism of Pace.

At this meeting, the issue of vacines, polio spread and global health was discussed by Heidi Larson, but the question of them ever damaging recipients, never mentioned (in fact, unmentionable.) She said that the main conspiracy theory surrounding modern medicine in the third world was the fear that vaccines are introduced to sterilise recipients (because "sterile" is written on the cases of medicine) But she never mentioned the other conspiracy theory - vacines introduced HIV into the african population, which is also believed in Africa.

These people believe in science and medicine, and would be unwilling to accept that the things they teach and value so highly could ever harm. One man in the audience did raise the question of the young girl who recently became so severely damaged following HPV vaccination, and made a plea for truth in the vaccine debate, but his point was ignored by the panel, which went on to other subjects as if they had not heard his question.

These are all individually highly successful, healthy and energetic people. They cannot identify personally with sickness, much as it is their area of study. I wonder if they realise how huge the health and social differential in Britain now is, and how disempowering their paradigm is to those who fall outside it.

However they did not appear to be part of a conscious conspiracy against PWME!
Just, probably, as such successful people themselves, unable to identify with sick and disadvantaged people in their own country.
And this is where PACE comes in. As personally such energetic and successful individuals, they would be unconsciously drawn to a theory of ME that "blames the victim" I think, as their lives would have been made successful by effort and hard work. They would not identify with an illness that disempowers the sufferer from effort, in the way our illness does. And of course, should a graduate of LSHTM ever develop severe ME, they would cease to belong to this social group. So their own social group never includes our disease. It is a paradox that has intrigued me for some while, that medical professionals because of the pressures of their work MUST be healthy and energetic - and in many cases feel threatened if required to empathise with "weakness."

Unconscious bias, and found in well meaning and intelligent, sucessful people. The question about the poor girl disabled by the HPV vaccine was ignored as if her problem did not exist and the question had never been heard. Why? because they cannot themselves imagine such a thing occurring in their lives and because it threatens their value system, which they sincerely believe in and trust.

It would be worth trying to discuss our concerns with Mr Horton.

To their credit, many of those speaking, who all knew each other, and appeared to be friendly colleagues, had put pressure on this government to block privatisation of the NHS, and modify the Health and Social Welfare Bill, and they were hoping their efforts would be succesful. They found it amusing, that by cooperating with each other in this aim, they could be described as "conspirators."
So good people in most ways - just our disease that falls into a black hole of awareness because of the way intellectual and scientific paradigms have been constructed and perpetuated.

This was a very interesting meeting, it was nice to be with such intellegent people, I would like to go to further meetings at LSHTM.

I did consider asking a question and introducing myself to the audience as the conspiracy theorist in their midst!
But the right moment did not occur, and I felt, surrounded by such health, energy and achievement, like a refugee from a disaster these people could not imagine. So I did not embarrass myself.

Any issue that questions the success of vaccination policy will take a very long time to be politically addressed, as it was clear from this meeting just how much vaccination is the basis of health policy in the developing and developed world. It is the very last thing these professionals would be open to.

I realise this thread is about Pace, so I am sorry to go on about vaccination in my post, but this was a large part of what was discused at the meeting and of the fears of the panel on conspiracies that spread via the web.
In a way, their concerns are patronising. They are unwilling to acknowledge that disempowered victims can have good reason for their apparently crazy beliefs, and that enlightened humanitarian intervention from the rich does not always achieve the ends it sets out to achieve.
 

Graham

Senior Moment
Messages
5,188
Location
Sussex, UK
It might be more effective if we got hold of another part of his anatomy - that way we might get his undivided attention.
 
Messages
13,774
It might be more effective if we got hold of another part of his anatomy - that way we might get his undivided attention.

Militant CFS patient threatens sexualised violence against respected science journal editor for defending psychological approach to CFS!!!!

Why have given them another reason to hate us Graham!?

edit: Actually - I should probably make it clear that was a joke. Sadly, it's not as absurd a concern as it should be.

re Horton: I've heard previous things where he's sounded good, and spoken of a sense that the Lancet should be challenging unsupported orthodoxies, etc... which is exactly why his lazy response to the concerns of patients about the way in which the results from PACE were presented was so disappointing.

There seem to be this desire to pretend that the only reason patients could be upset about the criteria for recovery over-lapping with the criteria for diagnosis, or any other aspect of the psychosocial approach to CFS, is if they are stigmatising mental health issues, or fail to understand how mind and body can interact. It's such a pathetic straw-man, that it's continued use does make me rather despair.
 

biophile

Places I'd rather be.
Messages
8,977
In April 2011 I sent Horton a 1200 word email explaining the physical function related error made in the paper and editorial (which somehow evaded what Horton called "endless rounds of peer review" on ABC radio), before the authors admitted to this error. I never got any reply except some automated message: "I am on holiday...trying to avoid EuroDisney, but knowing that, in the end, you can't deny a ten-year-old her destiny. I will be back in the office on April 26." Forgot EuroDisney, many of us aren't even well enough to go outside and have to endure reams of psychobabble directed at us from the ivory tower ...

eurodisney-400x294.jpg

I never received a real reply of any kind, which by itself doesn't bother me, but later on elsewhere as mentioned on this thread he has made comments which were dismissive and questionable, so I have to wonder how fruitful any further attempts would be at engagement. I don't care how "good" he is supposed to be on other scientific issues, when it comes to ME/CFS he appears to be incompetent and perhaps somewhat unethical, I'm not holding my breath for a significant change regardless of reasonable arguments.

The way all criticism of the PACE Trial has been dismissed using strawmen and redherrings based on the supposed beliefs and agendas of the critics is irritating and disheartening. Don't forget that Horton has played a central role in that dismissal and the attacks on the critics, even blaming us for an alleged 750,000 cost blowout for the PACE Trial.

At least when I sent Zoe Mullan of the Lancet an email about their editorial falsely implying that Hooper's complaint was "now available via Wikipedia" when no such document exists on Wikipedia, there was a response, albeit one which suggests to me the Lancet has wavering interest in accuracy, the email admitted that "Wikipedia" meant a wiki style document on the mecfsforums.com website but a correction was not deemed warranted.