BMJ comments on new PACE trial data analysis

[worldbackwards]

The stated justification for this drastic change, erroneously asserted that about half the general working age population score under 85, but it is actually 17.6%.

Crikey! Even if that were the case, a score of 60 still has the ring of a number pulled out of the air. Under the circumstances, it's just bizarre.

About 13% of participants simultaneously met both definitions of 'normal physical function' (a criterion for complete recovery) and 'significant disability' at baseline.

I just thought I'd quote that as well. Bloody hell.

 

[Dolphin]

More responses to the PACE Trial piece in the BMJ posted today:

(i) "The cognitive-behavioural model of illness for chronic fatigue syndrome and myalgic encephalomyelitis is not supported by the outcomes of the PACE trial" - by Robert Courtney

(ii) "Rightly outraged" by Greg Crowhurst (Stonebird) (a carer) & Simon Lawrence (25% ME Group)

(iii) "Re: Tackling fears about exercise is important for ME treatment, analysis indicates" by Ian McIllroy (who lists various studies which found abnormal responses to exercise in ME and CFS)


http://www.bmj.com/content/350/bmj.h227/rapid-responses

 

[Dolphin]

A response from:

Nasim Marie Jafry
Writer of novel The State of Me (2008), had ME for 31 years
Edinburgh

has gone up:
http://www.bmj.com/content/350/bmj.h227/rr-3

She said

ME is a complex neuroimmune illness, yet important and current biomedical research (at home and abroad) is consistently by Professor Chalder and her colleagues.

should read

ME is a complex neuroimmune illness, yet important and current biomedical research (at home and abroad) is consistently *ignored* by Professor Chalder and her colleagues.

She believes it was edited (it was slow to go up).

 

[Countrygirl]

The latest letter to the BMJ is from Margaret WIlliams who writes articles with Prof Malcolm Hooper.
Research News
Tackling fears about exercise is important for ME treatment, analysis indicates
BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h227 (Published 14 January 2015)Cite this as: BMJ 2015;350:h227

Re: Tackling fears about exercise is important for ME treatment, analysis indicates
The BMJ is to be congratulated for advancing medical science in respect of ME/CFS by encouraging free discourse as contained in the many pertinent rapid responses relating to the publication of the latest laboured attempt by the Principal Investigators to rescue the UK PACE trial (1).

As is clear from those responses, nothing can salvage the PACE trial. Furthermore, the current iteration of the NIH Pathways to Prevention Statement deals the coup de grace by calling for the Oxford criteria (used in the £5 million trial) to be retired (2) and the CFSAC has gone further by calling for studies using the Oxford criteria no longer to be used to inform treatment recommendations for this disease (3).

How many of the clinicians who remain dismissive of ME/CFS because they have been misled by the media hype over the trial’s exaggerated recovery rates are aware that Professor Jose Montoya from Stanford (whose major study of the immune system in ME/CFS is underway) has declared ME/CFS to be an inflammatory autoimmune disorder?

His words should form part of every medical school curriculum: “There is a genetic predisposition for an overwhelming inflammatory response to an infectious agent that was supposed to help the patient but is overwhelming, triggering a tremendous inflammatory cascade” (4). No amount of directive “cognitive restructuring” and graded exercise can result in “recovery” from such a multi-system inflammatory disease process.

It is now eight years since the Presiding Officer (Speaker) of the Scottish Parliament summed up the principal concerns of the Scottish Cross Party Group, which was that “the cold grip of psychiatry is still far too deeply rooted in the world of ME” (5). Not before time, this cold grip is starting to loosen.

Ioannidis defines bias as: “the combination of various design, data, analysis and presentation of factors that tend to produce research findings when they should not be produced….Scientists in a given field may be prejudiced purely because of their belief in a… theory or commitment to their own findings…Such conflicts may lead to distorted reported results and interpretations”.

He continued: “ History of science teaches us that scientific endeavour has often in the past wasted effort in fields with absolutely no yield of true scientific information…Of course, investigators working in any field are likely to resist accepting that the whole field in which they have spent their careers is a ‘null field’ ” (6).

The day is surely approaching when it will be conclusively shown that the psychosocial lobby have spent their ME/CFS careers in a “null field”.

References:
1. http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(14)00
2. The US National Institutes of Health (NIH) Pathways to Prevention Workshop Draft Statement:
“Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome” December 2014
3. CFSAC Meets P2P http://www.occupycfs.com/2015/01/15/cfsac-meets-p2p/
4. Chronic Fatigue Syndrome: Wrong Name, Real Illness
http://www.medscape.com/viewarticle/837577_4
5. Defiance of Science? Professor Malcolm Hooper et al. July 2007
http://www.meactionuk.org.uk/Defiance_of_Science.pdf
6. Professor John P.A. Ioannidis. Why Most Published Research Findings Are False. PLoS Medicine
2005:2:8:e124

 

[Countrygirl]

http://www.medscape.com/viewarticle/838452#vp_2
Addressing Fear of Exercise Cuts Chronic Fatigue…Perhaps

Leonard Jason, PhD, professor of psychology and director of the Center for Community Research at DePaul University in Chicago, Illinois, told Medscape Medical News, "despite the application of a few case definitions, it's still possible that the sample included individuals who have chronic fatigue due to psychiatric reasons. Overall, I think that the sample would need to be more well-characterized in order to draw any conclusions about CFS or ME from this mediation model."

Dr Jason, whose article on adaptive pacing in ME/CFS was among those cited in the current study ( J Human Behav Soc Environ. 2000;3:59-77), added, "The differences found might be due to response biases, the therapies causing people to answer questions about their health differently. However, a more generous interpretation might be that small improvements were obtained for some individuals. But CFS is a very heterogeneous condition, and just because some therapies can help some people a little doesn't mean they're suitable for all or should be seen as sufficient or curative therapies."

Kenneth J. Friedman, PhD, a coauthor of an ME/CFS "primer" for clinicians and a former associate professor of pharmacology and physiology, New Jersey Medical School, Newark, pointed out another problem that the PACE trial shares with nearly every study done on ME/CFS: All have been conducted on ambulatory patients, leaving out the most severely affected, who are too sick to participate in studies.

"The extent to which the ambulatory population represents the spectrum of CFS patients is really not known," he told Medscape Medical News. "If you're lying in bed and you can't move your head and you have to speak in whispers, GET therapy is not going to help you, and were you to attempt it, it would most likely kill you."

With regard to the PACE trial, Dr Friedman said, "It does not represent all CFS patients.... Because CFS is so variable, the management must be individualized. Any mandate that this is what you do for all patients, I would be leery of and would oppose. I think that really is the take-home message."

Dr Chalder declined to comment for this story.

C.G.

 

[Countrygirl]

Now, we aren't suggesting there could be any conflict of interest for the authors of the PACE trial are we? Surely not?

Funding for the PACE trial was provided by the Medical Research Council, Department for Health for England, the Scottish Chief Scientist Office, and the Department for Work and Pensions. Dr Chalder and two coauthors were in part supported by the National Institute for Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley National Health Service Foundation Trust and Institute of Psychiatry, Psychology & Neuroscience, King's College London. One of those coauthors was also funded by a National Institute for Health Research Doctoral Fellowship. Dr Chalder has received royalties from Sheldon Press and Constable and Robinson. One coauthor has performed voluntary and paid consultancy work for the UK government and a reinsurance company. Another coauthor has performed voluntary and paid consultancy work for the UK government and for an insurance company and has received royalties from Oxford University Press. Dr Kogelnik, Dr Jason, and Dr Friedman have disclosed no relevant financial relationships.

 

[Min]

Editing Nasim's reply has totally changed the meaning, making it look as if she is praising Prof Chalder and colleagues!

 

[Wildcat]

.
Trudie Chalder has just made a response in the BMJ Rapid Responses on 'Tackling fears about exercise':
http://www.bmj.com/content/350/bmj.h227/rapid-responses
.
29 January 2015
Trudie Chalder
Professor
Kimberley Goldsmith, Peter White, Michael Sharpe, Andrew Pickles
King's College London
.

 

[Sidereal]

.
Trudie Chalder has just made a response in the BMJ Rapid Responses on 'Tackling fears about exercise':
http://www.bmj.com/content/350/bmj.h227/rapid-responses
.
29 January 2015
Trudie Chalder
Professor
Kimberley Goldsmith, Peter White, Michael Sharpe, Andrew Pickles
King's College London
.

We would like to clarify that we did not say that fear avoidance was the cause of CFS [3,4]. We did not state that the illness was psychological or an exercise phobia. Nor did we say that fear of exercise in CFS was “irrational”. Rather, in an illness where exercise increases symptoms, we believe that being cautious about engaging in activity is understandable [4].

Er, so why prescribe exercise as a treatment for an illness in which exercise increases symptoms? Their position is totally illogical and they're digging themselves into a deeper and deeper hole with each new utterance. Now they're actually conceding that fear of activity is rational.

 

[MeSci]

one only has to look at the immaturity of people who have clicked on the LIKE buttons next to each reply

19 January 2015
timothy M jordan
medical doctor


edmonton, Canada

Thanks, 'Dr' Jordan - you have given me the prompt I needed to go through the Rapid Responses 'liking' all the good ones.

If he thinks that makes me immature, I don't give a toss. Why should I care what such an idiot thinks?

 

[Bob]

Now they're actually conceding that fear of activity is rational.

A rational maladaptive illness belief?

 

[Kati]

.
Trudie Chalder has just made a response in the BMJ Rapid Responses on 'Tackling fears about exercise':
http://www.bmj.com/content/350/bmj.h227/rapid-responses
.
29 January 2015
Trudie Chalder
Professor
Kimberley Goldsmith, Peter White, Michael Sharpe, Andrew Pickles
King's College London
.

Poor poor poor Chalder and co.... They are misunderstood. They didn't mean to say that fear of exercise causes the illness.

They are in damage control mode because the rapid responses were so compelling and strong that they have felt discredited and loosing power.

They are rapidly loosing the empire and indeed the emperor is naked.

 

[A.B.]

Er, so why prescribe exercise as a treatment for an illness in which exercise increases symptoms? Their position is totally illogical and they're digging themselves into a deeper and deeper hole with each new utterance. Now they're actually conceding that fear of activity is rational.

They say whatever is good for PR. From their actions it is clear they view CFS as psychosomatic disorder. If they believed the symptoms to be real and serious they would not treat them with talk therapy and exercise.

 

[Bob]

They didn't mean to say that fear of exercise causes the illness.

Beware their slippery language. For a long time, they haven't said that illness-beliefs cause ME/CFS. They say that illness-beliefs perpetuate the illness. (They say the cause doesn't matter; It's the perpetuating illness-beliefs that matter.)

 

[Countrygirl]

Thanks, 'Dr' Jordan - you have given me the prompt I needed to go through the Rapid Responses 'liking' all the good ones.

If he thinks that makes me immature, I don't give a toss. Why should I care what such an idiot thinks?

And three such immature idiots 'like' Trudie's irrational outpourings so far. Bless her!

 

[Bob]

The three 'likes' for the post will be Sir Simon, P White, M Sharpe.

 

[Jonathan Edwards]

Dr Chalder has written:

'Whilst some correspondents have complained that the primary outcomes of the trial were self-rated, we argue that these are the most appropriate measures to judge improvement in an illness that is currently defined by symptoms.'

I am not sure which correspondents she is referring to but if this is a response to my post it is non-sequitur. I suspect that most of us would agree that a subjective self-rated measure of symptoms should be the primary endpoint in a therapeutic trial in ME. It is what Fluge and Mella used. The problem comes if the treatment is unblindable, because a subjective end point is then valueless. It is likely that there is currently no recognised methodology for getting around the problem of assessing unblindable therapies like CBT and GET in ME. However this does not validate doing an unblinded trial and saying 'this is the best we can do'. If it is no good it is no good.

 

[Sidereal]

If they believed the symptoms to be real and serious they would not treat them with talk therapy and exercise.

Actually, talk therapy has made a recent comeback in the treatment of schizophrenia, a condition universally acknowledged as real and serious. Apparently the psychologists peddling this nonsense have forgotten that even the father of psychobabble Sigmund Freud was against psychotherapy for psychosis since he saw how completely useless it was for such patients. In the present day it's worse than useless since effective biological therapies exist whereas they did not when Freud was around.

 

[Scarecrow]

The problem comes if the treatment is unblindable

Oh, it gets worse even than that. I just noticed this post from Dolphin from last year:

I came across one participant from the GET arm of the trial on another forum.
She said the physiotherapist (=physical therapist) said to her that she could use housework to replace exercise on some days if she wasn’t feeling so good, or something along those lines.
This is not part of the philosophy of GET which is about adding exercise on top of daily activities.
Also, housework can be of varying intensities including very low intensity. This is not how GET is supposed to be: the exercise session is supposed to be of the same intensity and either the same length or a bit longer.
If such measures to “play it safe” were more common across the trial, one could see how fewer adverse events would be reported than with a more rigorous program including one that stuck rigidly to the manuals.

That's like either (1) randomly giving the placebo to someone in the treatment group of a drug trial and telling them that you sometimes give them the placebo instead of the treatment, or alternatively (2) saying that it 's ok not to take the pills if they don't want to but they don't have to withdraw from the trial. With the added twist that in the context of PACE, the placebo / control was arguably the better 'treatment' anyway (depending on how much credence you're prepared to give to the results of an unblinded trial with subjective measures).

Does the fact that I'm shocked mean that I am hopelessly naïve? Whatever the shortcomings of PACE, I actually do like to believe that the investigators and therapists involved acted in good faith.

 

[Nielk]

One can argue that being that we are excessively arguing these findings, that we are suffering from fear of fear of exercise!