BMJ comments on new PACE trial data analysis

[Sean]

terrorism

I think it can be argued that how depict and treat us, and the way their work is used by others (particularly governments and corporations), often takes the form of pretty nasty physical, psychological, and economic terrorism.

Threatening to withhold basic economic, medical, and social support from the very sick and disabled, if they don't submit to your insane violent fantasies, is about as despicable and immoral, and cowardly, as it gets.

I humiliated and kicked a cripple today, in public, while repeatedly lecturing him that it was for his own good. Really showed him who is boss.

Yeah, yeah, you are real fecking hero.

 

[worldbackwards]

You may be convinced that there is enough evidence to refute GET as a treatment for ME/CFS but out in the real (medical) world this is NOT what my medical colleagues, or the people who prepare the NICE guideline, or the insurance companies who try to deny payments to people with ME/CFS because they will not undertake GET etc etc believe.

I'm not saying that a robust assessment of pacing that the UK medical profession would take seriously is a number one research priority - but it would be quite high on my list!

As to who would pay - as I've already indicated this is the sort of expensive research that the charities such as MEA could only HELP to fund. Someone would have to submit an application to the MRC, or a big funder such as The Wellcome Trust.

Isn' t the point here that what PACE really proves is that the peer review system has entirely broken down in relation to this illness. Chandler, White, et al can throw together any half baked mix of dodgy statistics and subjective measures and it will sail through because they have so effectively branded the opposition as delusional that nothing we say can be taken seriously. Consequently, 'serious' people must feel that they can only embarrass themselves by standing on our side. Given this, a pacing trial, whatever it were to prove, would simply be ignored - they have their treatments and they've 'proved' that they work. This is not an argument that can be won on their terms.

XMRV may have ended badly, but what it did prove is that the psychiatrists can be genuinely frightened by a 'lightning strike' piece of research that gets a lot of media coverage. I believe that the only way to win this battle is by winning the battle of proof in biomedical research. Management is their territory and, as such, we will always lose, because they make the rules.

 

[Jonathan Edwards]

After giving it a bit of thought, I think a new trial for pacing would probably lead to disappointment, and we'd possibly be setting ourselves up to fail... I'll explain why...

Just my views.

I think you make a good case, Bob.

 

[Sean]

Bob said:

I don't think that there is likely to be a lot of difference in outcomes between pacing and GET, in any trial that allows for GET to adapt to the patients' health fluctuations.

[snip]

It would also be incredibly complex and expensive to set up such a trial, if it was to be done well, and it might lead to resentment that yet more money is being wasted. Any patient organisation setting up such a trial would have a lot of explaining to do, when the money could have been spent on ground-breaking biomedical research instead. The MRC would get no thanks for funding it. They'd be accused of all sorts. AfME still haven't been forgiven for their involvement in the PACE trial. It's possible that we'd unwittingly set up another trial that was doomed to failure, for reasons that i've given above. The PACE trial cost $5m, and is still being analysed, 5ish years later. So you'd have to have some extremely motivated researchers to throw themselves into a rigorous trial of pacing, with possibly little to show at the end of it. It wouldn't be much of a career move.

This is probably the reality of it.

And well said generally. I'd rather that precious research money was spent on basic biomedical research than anything else right now.

 

[worldbackwards]

Despite what the authors would have us believe, GET, as administered in the PACE trial, was actually a form of pacing, because therapists were instructed to 'adapt' the therapy if patients had a relapse, to "avoid difficulties". (You have to search the therapists manuals hard to find this, but it's there - see bottom of this post for the quote.) So GET was a form of pacing but with an emphasis on pushing activity levels upwards where possible. It's not like the old-style GET where patients were instructed to completely ignore their symptoms and push through regardless - the psychiatrists have learned their lessons about that. If it had been that sort of graded exercise in the PACE trial, then the results would not have been poor, they'd have been utterly disastrous.

I don't think that there is likely to be a lot of difference in outcomes between pacing and GET, in any trial that allows for GET to adapt to the patients' health fluctuations. But CBT/GET train/instruct the patients to interpret their symptoms differently, which makes trials vulnerable to response bias, esp for self-report outcomes. So CBT and GET are perhaps likely to always have better self-report outcomes than pacing which doesn't instruct patients to interpret their illness differently.

Doesn't this basically lay the ideological project bare - all they're really looking to do is make sure that the patient blames themselves if management doesn't work. The theoretical underpinnings are all gone - surely "avoiding difficulties" ought to equate to 'fear avoidance' in their book. I think their view can best be encapsulated in a quote that sprung to mind from 'One Hundred Years Of Solitude'

“That means",Colonel Aureliano Buendía said, smiling when the reading was over, “that all we’re fighting for is power."

 

[Sean]

Isn' t the point here that what PACE really proves is that the peer review system has entirely broken down in relation to this illness.

In some ways that is the most important (repeat) lesson for medical science out of all this.

 

[daisybell]

Three new responses now loaded on the BMJ page - from Tom Kindlon, Jonathan Edwards and Carolyn Wilshire (who is a lecturer in psychology in NZ). All three very good!

 

[Sasha]

Three new responses now loaded on the BMJ page - from Tom Kindlon, Jonathan Edwards and Carolyn Wilshire (who is a lecturer in psychology in NZ). All three very good!

Got a link?

 

[Artstu]

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

 

[charles shepherd]

Two more very good BMJ rapid responses this morning from Professor Jonathan Edwards (UK) and a Senior Lecturer in Psychology (New Zealand) - who is once again pointing out the various methodological flaws in the PACE trial:
http://www.bmj.com/content/350/bmj.h227/rapid-responses

I have written to Dr William Weir to ask if he will submit his observations on this paper to BMJ rapid responses as well - because this is the only way in which the medical profession is going to see constructive criticism from other health professionals

I'm going to have to opt out of this discussion on The Lancet paper from now on for a bit - as I must do some prep for two important parliamentary meetings tomorrow and then head off for London

On Tuesday morning the All Party Parliamentary Group on ME will be discussing medical education on ME/CFS at the House of Commons

On Tuesday afternoon at the House of Lords the Forward ME Group, chaired by the Countess of Mar, will be discussing BACME and NICE guideline issues with Dr Alastair Miller from BACME - as well as DWP benefit issues, including the change of contract for carrying out medical assessments from Atos to Maximus:
http://www.theguardian.com/society/...ll-maximus-make-work-assessments-less-arduous

We will also be discussing the latest analysis of PACE trial data in The Lancet at both meetings

I will be back on Wednesday
CS

Dr Willie Weir's submission to Lancet Psychiatry on the latest PACE paper:

Rational understanding of the symptoms of ME/CFS.

The paradigm which states that the symptoms of ME have a psychological basis continues to be promoted (Lancet Psychiatry 2015:http://dx.doi.org/10.1016/S2215-0366(14)00069-8). 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.

As a simple analogy, a newly broken leg causes pain and most people so affected have an entirely rational fear of walking or even bearing weight on the affected limb. The pathophysiological basis of pain caused by a fracture is well understood, and now Dr Van Ness’ work has provided considerable insight into the pathophysiology of PEM. Not only do his findings give a clearer understanding of this devastating symptom of ME but they also effectively dispose of the argument that ME patients have “exercise phobia” or indeed that the disease is caused by patients wrongly believing they are physically ill.

Unfortunately, promotion of the doctrine that ME/CFS has a psychological basis continues to be disseminated by the inappropriately named “Science” Media Centre. They are not, in respect of ME, disseminating science at all, and continue to promote scientifically unsustainable and disproven theory, simultaneously ignoring proper scientific evidence. Sadly this is not an abstruse controversy, and patients whose genuine incapacity continues to be attributed to the psychological paradigm suffer enormously. I regard this as morally indefensible.

W.R.C.Weir FRCP, FRCP (Edin), Consultant Physician, 10 Harley Street, London W1G 9PF

 

[charles shepherd]

And there is, of course, a very good analysis from Tom Kindlon now up on the BMJ site!

 

[Sasha]

Great stuff from Dr Weir @charles shepherd!

Well done, @Tom Kindlon!

Thank you, @Jonathan Edwards! I particularly liked your final para:

I do not treat people with this illness and have no other personal interest other than feeling that I may be of use in encouraging useful research. Apart from anything else I am saddened to see poor data of this sort being used in a way that will perpetuate the lack of trust between patients and their carers. The patients are very aware of the weaknesses of the study and I am surprised that those designing the study are not equally aware.

It's sad but true that a clinical researcher of your standing can achieve more with a single paragraph than ten thousand patients saying that same thing until they're blue in the face.

It's hugely important that academic clinicians write in and torpedo this PACE crap. Your succinct contempt for it is going to sway opinion among people who won't wade through lots of well-argued points, because your judgment is trusted.

I'm very grateful to you, and all the others writing in, particularly the medical scientists.

I hope more will do so!

 

[A.B.]

The responses are great. I like the one Carolyn E Wilshire in particular.

What is missing though is a comment on how the study discredits its own illness model. In the illness model, a change in belief should be followed by a concrete improvement in physical health. The apparent change in belief in the study may reflect a placebo or conditioning effect, but let us assume for a moment that it is just a change in belief. The expected improvement in physical health is absent, which casts doubt on the illness model. And it can't be deconditioning either because that would change with just exercise therapy.

There may be a minority of patients where the illness model seems to apply, but given the methodological problems I would be wary about making any conclusions about effects that are not very significant.

At least these are my thoughts as amateur.

 

[brenda]

It's all a waste of time. This illness is not the only one that is not recognised and therefore not treated. Sub clinical hypothyroidism is another, and 'post Lyme disease is another' to name a few.

We need to get back to what is causing all of this sickness because if it is intentional, and there is enough evidence around to convince anyone, then we are wasting time trying to prove biological causes as more and more of the world's population are heading this way and guess what - there is not going to be the money available to keep them alive.

While we waste time, the world becomes increasingly polluted, and genetically modified, and bioweaponed as well as having harmful additives to our food and supplements which increase daily ( just try to find riboflavin without mg stearate added)

We need to join forces with these other communities and say enough - get your hands off!

 

[Sean]

Carolyn E Wilshire's excellent letter to the BMJ has a killer comment:

The new paper’s most valuable contribution is that it reports one new objective measure: the fitness test (heart rate after a step exercise test). However, GET patients – the group predicted to show the greatest improvement – did not differ from the non-treatment control on this measure. This result, and its lack of prominence in the original paper, leads to further concerns about the selective reporting in the study and the heavy reliance on self-report.

If the GET group did not show any improvement on this fitness test, – i.e. it did not corroborate the result from the 6MWT – then the value of the already borderline 6MWT result is greatly reduced.

There is now clearly no significant body of objective evidence in support of their approach and theory. Time for a burial.

 

[Bob]

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

 

[Bob]

If the GET group did not show any improvement on this fitness test, – i.e. it did not corroborate the result from the 6MWT – then the value of the already borderline 6MWT result is greatly reduced.

And the improvement for GET in the 6MWT really was marginal. We worked out that it is a small effect size, which is not usually considered clinically useful, and they've not published anything to contradict this. They've not said it was a medium effect size or a clinically useful outcome. They're strangely silent about it. So I think it's safe to assume that they couldn't jiggle the stats sufficiently to make it look like a good outcome.

 

[Tom Kindlon]

And there is, of course, a very good analysis from Tom Kindlon now up on the BMJ site!

Thanks Charles.
Here's a link:

Objective measures found a lack of improvement for CBT & GET in the PACE Trial: subjective improvements may simply represent response biases or placebo effects in this non-blinded trial
http://www.bmj.com/content/350/bmj.h227/rr-10

 

[Bob]

The trial appears to be based on the supposition that these may be unrealistic beliefs, so it is hard to see why a shift in these beliefs should be considered even relevant unless there is some way of establishing that they become more realistic - which there is not.

A canny observation that is usually overlooked - how can you trust self-report outcomes when you don't trust your patient in the first place! The illness beliefs are supposedly false at baseline but are suddenly presumed reliable at the end of the trial! If patients are reliable at the end of the trial, even if they continue to report that they are substantially ill, there's no point in continuing with CBT which aims to correct false illness beliefs. Reliable self-reporting negates the whole hypothesis that the trial is based on. And unreliable self-reporting negates the validity of the self-report outcomes. They can't have it both ways. (But they do.)

 

[A.B.]

They can't have it both ways. (But they do.)

Is the goal of the therapy to have the patient confirm the beliefs of the therapist? To keep it all spinning for a little longer.