BMJ comments on new PACE trial data analysis

[Sean]

Is the goal of the therapy to have the patient confirm the beliefs of the therapist?

Reverse transference?

 

[Dolphin]

The new comments are exceptional. It would be great if the BMJ actually published one (or more) in the journal, but they never do.

The BMJ has actually posted some letters in the main journal over the years. However, there is an unofficial limit of 250-300 words (for some people they will edit down a bit but they're probably less likely to do it for ME/CFS patients/experts).

 

[Kati]

And now for comic relief from Max WHD on Twitter

https://mobile.twitter.com/maxwhd/status/556448464931139584/photo/1

 

[Tom Kindlon]

I'm just reading the response from:

Carolyn E Wilshire
Senior Lecturer
School of Psychology, Victoria University of Wellington, New Zealand
PO Box 600 Wellington, New Zealand

http://www.bmj.com/content/350/bmj.h227/rr-7

Extract:

The original PACE study reported that one year after a 24-week graded exercise therapy programme (GET), 61% patients improved on a combined self-rated measure of fatigue and physical function. 2 CBT yielded a similar improvement rate of 59%. On the face of it, that looks impressive. However, the control condition - specialist medical care - also yielded an impressive 45% improvement. This in itself casts doubt on the validity of the self-report measures used to assess improvement. But more importantly, this high level of baseline improvement means that conclusions rest on the differences in improvement rates between the various conditions, some 14-16% of participants. The design of the no-treatment control therefore becomes crucial.

Somebody could highlight that the original protocol had a more demanding definition for improvers as one of its primary outcome measures (which has never been published). Instead they have used a new (post hoc) definition for improvement.

http://www.biomedcentral.com/1471-2377/7/6

Primary outcome measures – Primary efficacy measures

Since we are interested in changes in both symptoms and disability we have chosen to designate both the symptoms of fatigue and physical function as primary outcomes. This is because it is possible that a specific treatment may relieve symptoms without reducing disability, or vice versa. Both these measures will be self-rated.

The 11 item Chalder Fatigue Questionnaire measures the severity of symptomatic fatigue27], and has been the most frequently used measure of fatigue in most previous trials of these interventions. We will use the 0,0,1,1 item scores to allow a possible score of between 0 and 11. A positive outcome will be a 50% reduction in fatigue score,ora score of 3 or less, this threshold having been previously shown to indicate normal fatigue27].

The SF-36 physical function sub-scale29] measures physical function, and has often been used as a primary outcome measure in trials of CBT and GET. We will count a score of 75 (out of a maximum of 100) or more,ora 50% increase from baseline in SF-36 sub-scale score as a positive outcome. A score of 70 is about one standard deviation below the mean score (about 85, depending on the study) for the UK adult population51,52].

Those participants who improve in both primary outcome measures will be regarded as overall improvers.

I've posted two letters so think it might be better done by somebody else.

 

[Countrygirl]

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

Dr William Weir, consultant physician of Harley Street, London, has now left a comment of which the following is an extract:

Re: Tackling fears about exercise is important for ME treatment, analysis indicates
The paradigm which states that the symptoms of ME have a psychological basis continues to be promoted (Lancet Psychiatry 2015: http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(14)00069-8/abstract). Most recently “exercise phobia” has been proposed as part of the problem, although a study of which I was a co-author in 2005 explicitly disproved this proposition (J Psychosom Res 58 (2005): 367-373). This paradigm has no plausible scientific basis and can only be described as a doctrine whose adherents continue to ignore the biomedical evidence which amply confirms the organic basis of the condition. As someone with nearly 30 years’ experience of seeing patients with this severely disabling condition I continue to be dismayed by an irrational adherence by the psychological lobby to a doctrine that is not supported, even by their own studies, and which has been undermined by the published biomedical evidence.

The term “phobia” implies an irrational fear of exercise. The reason that ME sufferers avoid exercise is because they know from (sometimes bitter) experience that it makes them feel worse (often much worse) and results in post-exertional malaise (PEM). This is one of the cardinal features of the condition and can last for days, often for weeks and not uncommonly, for months. PEM is not imagined and causes a rational apprehension of exertion which should no longer be labelled as “phobia”. ME sufferers therefore avoid exercise for reasons which are entirely rational, and Dr Mark Van Ness’ recent work (now replicated elsewhere) has put much flesh on the bones of this argument.

 

[Countrygirl]

Re: Tackling fears about exercise is important for ME treatment, analysis indicates
As you can all see, the picture is not black and white. The science is often confused but more than that, emotion has been allowed to get in the way of science. Often we don't even seem to be talking about the same thing. Studies must be well planned; they must be reproducible; there must be a lack of bias (one only has to look at the immaturity of people who have clicked on the LIKE buttons next to each reply, not because it is good science but because it agrees with their prejudices. Now how can one rely on such a measure of success when thought processes are short-circuited? It's unlikely to help your cause, and one wonders whether people do in fact, want to get better, and be taken seriously or they want to wallow in their own misery? Maybe there is a psychiatric basis for it?)

Competing interests: No competing interests

19 January 2015
timothy M jordan
medical doctor


edmonton, Canada

 

[ukxmrv]

I wonder if this is the same Dr Timothy M Jordan who responded in the BMJ

"Jordan moved to Canada four years ago. He grew up in what was then Rhodesia and spent much of his life in Britain.

During his time here, Jordan stayed in a Saskatchewan Drive condo. He's active, so he did a lot of walking, running and cycling.

What he saw didn't impress: Littered streets, rampant homelessness and aggressive panhandlers, not to mention people regularly spitting on sidewalks.

But surely, I asked, people in Britain spit?

"Maybe, but I didn't see it," said Jordan. "It just seems to be the thing to do here."

Let me assure you that Jordan is a man with a sense of humour, as well as a sense of compassion.

The homeless, as well as the litter and spitting, are only symptoms of a mixed up and apathetic society, he believes."

http://www.canada.com/story_print.html?id=8ac2ad21-2c9c-4750-900b-91f5bd54308d&sponsor=

http://www.cpsa.ab.ca/PhysicianSearch/PhysicianProfile.aspx?PhysicianId=000011135667

 

[worldbackwards]

I wonder if this is the same Dr Timothy M Jordan who responded in the BMJ

"Jordan moved to Canada four years ago. He grew up in what was then Rhodesia and spent much of his life in Britain.

During his time here, Jordan stayed in a Saskatchewan Drive condo. He's active, so he did a lot of walking, running and cycling.

What he saw didn't impress: Littered streets, rampant homelessness and aggressive panhandlers, not to mention people regularly spitting on sidewalks.

But surely, I asked, people in Britain spit?

"Maybe, but I didn't see it," said Jordan. "It just seems to be the thing to do here."

Let me assure you that Jordan is a man with a sense of humour, as well as a sense of compassion.

The homeless, as well as the litter and spitting, are only symptoms of a mixed up and apathetic society, he believes."

http://www.canada.com/story_print.html?id=8ac2ad21-2c9c-4750-900b-91f5bd54308d&sponsor=

http://www.cpsa.ab.ca/PhysicianSearch/PhysicianProfile.aspx?PhysicianId=000011135667

Sounds like a real charmer - he's definitely got the whole 'blame everyone for everything that ever happens to them' schtick right down. I wish he were on our side. Arse

 

[Countrygirl]

I have bolded an interesting observation by this patient/ex-scientist.

Re: Tackling fears about exercise is important for ME treatment, analysis indicates
The recent study in the Lancet Psychiatry [1] reported that fear of exercise was a mediating factor for fatigue and physical function in the case of both CBT and GET.

However the very presence of this fear on patients' willingness to engage in physical activity is inadvertently called into question by one of the authors (Trudie Chalder) during a press interview [2], in which she states that: 'On a day when they [patients] feel less symptomatic and very energetic they may do more than they are probably able to do and then of course suffer as a consequence'. It seems strange to me that a fear powerful enough to hinder the success of CBT and GET but which then abates on days when the patient is feeling less ill can actually exist, or indeed be a factor in the successful treatment of this condition.

What is perhaps particularly important to bear in mind is that the proposed 'success' of fear reduction is predicated on an increase in walking distance that is woefully small- after a year of therapy the patients receiving GET were able to increase the distance they walked on the six minute walking test (6mwt) by only 67m, (to 379m, 35m more than the SMC-only group) [3] but still far short of the 644m [4] average for a healthy adult. Even if such a fear were to exist, given these results, it seems unlikely that a change in beliefs will be enough to increase the walking distance by a further 265m.

Unfortunately we do not know what the mean 6mwt scores were for those who have low fear of exercise nor, despite a freedom of information request [5], for the 22% of patients receiving GET who have been labelled (controversially [6]) as 'recovered' [7]. I suggest that in order to avoid wasting any more tax payers' money, these data should be made available as soon as possible, so that the true effect of overcoming fear of exercise may be properly evaluated.

What is clear is that treatments of this kind are only tinkering around the edges of an illness that is in urgent need of more rigorous indepth biomedical investigation.

 

[Aurator]

Dr Timothy M Jordan writes: "One only has to look at the immaturity of people who have clicked on the LIKE buttons next to each reply, not because it is good science but because it agrees with their prejudices."

I feel your frustration, Dr. Jordan, at finding you're trailing in the likes competition by a mile. Naturally, there was no prejudice or immaturity whatsoever behind the likes you yourself received. As for good science, is there any science at all in your posts, whether good or bad? If there is, I must have missed it.

If it's any consolation, Dr Jordan, I do like your posts in a way: they place your side of the argument in such a poor light they can't be anything but beneficial to your antagonists.

 

[A.B.]

As for good science, is there any science at all in your posts, whether good or bad? If there is, I must have missed it.

It is ironic when those who side with psychosomatic explanations for illness speak about the importance of good science. I was tempted to reply pointing this out, but it's probably better to just leave it be.

 

[eafw]

Dr Timothy M Jordan writes

I think that Timothy "medical doctor" Jordan needs to keep on digging. He's showing himself up to be quite the fool.

 

[chipmunk1]

surprised that this response got even published.

As you can all see, the picture is not black and white. The science is often confused but more than that, emotion has been allowed to get in the way of science. Often we don't even seem to be talking about the same thing. Studies must be well planned; they must be reproducible; there must be a lack of bias (one only has to look at the immaturity of people who have clicked on the LIKE buttons next to each reply, not because it is good science but because it agrees with their prejudices. Now how can one rely on such a measure of success when thought processes are short-circuited? It's unlikely to help your cause, and one wonders whether people do in fact, want to get better, and be taken seriously or they want to wallow in their own misery? Maybe there is a psychiatric basis for it?)

again no facts, real reasoning or any useful information. I wonder how IMMATURE the people are who whine and accuse others of "psychiatric illness" are because they got less likes than others.

emotion has been allowed to get in the way of science.

That's true. The concept of the emotional basis of physical illness got in the way of science.

people who have clicked on the LIKE buttons next to each reply, not because it is good science but because it agrees with their prejudices

Maybe they liked because they prefer good science instead of pseudoscientifc speculations(e.g Our culture disconnected from nature creates psychosomatic fatigue conditions masquerading as physical illness).

one wonders whether people do in fact, want to get better

No. No reasonable person would ever want to get better.

Maybe there is a psychiatric basis for it?

A new theory based on the BMJ Like ratio?

 

[Countrygirl]

http://theargusreport.com/validity-cfs-research-findings-fire/

The Validity of CFS Research Findings Under Fire
The question is, are CFS researchers manipulating results with selective reporting of their findings?
By PENNY SWIFT

The latest research report based on the widely criticized 2011 PACE Trial Study that recommends exercise for chronic fatigue syndrome (CFS) patients, is thwart with issues that compromise its credibility, according to a psychologist in New Zealand.

In addition the discovery by the ME/CFS community that at least one of its authors, Prof. Peter D. White has arrived at totally opposite conclusions in another CFS research study adds fuel to the fire.

Behavioral Intervention Studies Can be Harmful
Reacting to the controversial report, Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial, published online in The Lancet Psychiatry on January 13, an experimental psychologist from New Zealand has leveled sharp criticism stating that this type of behavioral intervention study “can do great harm in less direct ways” than “drug intervention studies.”

Dr. Carolyn Wilshire

Dr. Carolyn E. Wilshire, a senior lecturer at Victoria University of Wellington’s School of Psychology in New Zealand compared the two types of studies and concluded that behavioral research should not have “a ‘get out of jail free’ card when it comes to scientific rigor.”

Five researchers, including Prof. White stated in The Lancet Psychiatry article that when it comes to CFS patients and exercise, “fear avoidance beliefs” help perpetuate both disability and ongoing “fatigue” in the illness. This has led to a widespread public outcry internationally by both patients and professionals with hands-on experience working with CFS sufferers.

Writing in BMJ online yesterday, Wilshire said drug interventions have an agreed set of quality standards, and research authors could not “selectively report only the most favorable outcome measures.” Behavioral interventions on the other hand are not consistently evaluated by these same standards, and this can lead to “exaggerated claims as to their effectiveness.”

Any assumption that rigorous standards are not required for behavioral interventions because the risk of harm is lower than that for drug interventions must be challenged in the case of ME/CFS research she says. This is because of the factual evidence that graded exercise therapy (GET) may result in adverse effects for patients.

 

[Hip]

Good article here, which is quite critical:

Addressing Fear of Exercise Cuts Chronic Fatigue…Perhaps

Patient Selection Faulted

However, the findings of the original PACE trial have been criticized by patients and experts in the field, who cite methodological issues and point to the lack of precision in patient selection among its flaws.

In recruiting patients, the researchers relied on the 1991 "Oxford Criteria" for CFS, which define "a syndrome characterized by fatigue as the principal symptom," and specify that "the fatigue is severe, disabling, and affects physical and mental functioning." In addition, the fatigue must have been present for more than 6 months and for more than 50% of the time and not be explained by other diagnoses.

In contrast, more recent criteria for the condition known as myalgic encephalomyelitis (ME), such as those given in the 2003 Canadian Clinical Case Definition, require the hallmark symptom of postexertional malaise, along with sleep dysfunction, pain, neurocognitive manifestations, and at least one symptom from a list of autonomic, neuroendocrine, and/or immune manifestations to make the diagnosis. (A 2011 revision to the Canadian criteria drops the 6-month requirement for fatigue and makes other changes in attempts to identify an even more homogenous group of patients, but the revision has not yet been validated.)

The ME criteria are viewed as capturing a sicker population, but at this time, patients meeting any of the various criteria are typically lumped together under the heading of ME/CFS.

Andreas M. Kogelnik, MD, PhD, founder and director of the Open Medicine Institute, told Medscape Medical News, "While physical deconditioning is a factor in ME/CFS patients, time and again we've seen clear evidence in practical community settings that CBT and GET can be extremely detrimental to a patient's well-being and treatment course. The PACE trial did little to address the heterogeneity of the ME/CFS population, nor did it account well for severity of illness and fragility of many of these patients. CBT and GET need to be used very cautiously."

 

[Sidereal]

Good article here, which is quite critical:

Addressing Fear of Exercise Cuts Chronic Fatigue…Perhaps

Dr Chalder declined to comment for this story.

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.

Nice.

 

[Tom Kindlon]

Another substantial BMJ e-letter on the UK£5 million PACE Trial, this time from Alem Matthees.

He highlights various changes to the protocol.

He also highlights how the recovery criteria are much easier than planned (and there was an error in the justification given for changing them).

http://www.bmj.com/content/350/bmj.h227/rr-16

 

[Roy S]

That URL didn't work for me for the Medscape article but this one does:
http://www.medscape.com/viewarticle/838452

 

[worldbackwards]

He also highlights how the recovery criteria are much easier than planned (and there was an error in the justification given for changing them).

What was the justification for the changes? I seem to remember it being very wooly and difficult to understand, but I can't remember now what it was.

 

[Tom Kindlon]

What was the justification for the changes? I seem to remember it being very wooly and difficult to understand, but I can't remember now what it was.

Here's the paragraph from Alem's letter:

2) The previously required SF-36/PF score of ≥85/100 points was lowered to ≥60; worse than trial eligibility criteria for 'significant disability' (≤65).[6] About 13% of participants simultaneously met both definitions of 'normal physical function' (a criterion for complete recovery) and 'significant disability' at baseline.[8] The post-hoc revised threshold was derived from an inappropriate statistical calculation using a non-representative population sample which included the elderly and disabled.[13] CFS occurs at all ages but in this trial of adults, 97% were aged under 60 years at baseline, and a diagnosis of CFS requires that other chronic disabling conditions which explain the fatigue etc are excluded. 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%. Note that 92.3% of the 'healthy' working age English population score 85 to 100, and 61.4% score 100.[13]