PACE Trial and PACE Trial Protocol

[user9876]

Hmm... But that seems to be a fundamental question in relation to ME...
i.e. Do the symptoms of ME indicate 'harm'? And do increased symptoms indicate a higher level of harm?
Maybe any studies that show higher levels of biomarkers (unique to ME) in relation to increased symptoms after exertion, could be considered evidence of this?

At a very basic level, it could be said that a decrease in physical function (or an increase in disability), is evidence of harm.
And if any decrease in physical function corresponds to changes in biomarkers, then surely that's evidence of physical harm.

I think it could also be argued that an increase in distressing symptoms of fatigue is also 'harm', whatever the nature of the fatigue.

Even if they believe that there is no evidence that an increase in symptoms indicates harm there statement is very misleading because it is not safe to conclude the oposite. If they believed that the thing they should accurately conclude is that 'we don't understand the relationship between a worsening of symptoms and harm'. If they have reason to believe that there was no relationship as they imply they would simply state that and point to the evidence.

In logic there is a concept of a closed world which was introduced due to the inability to express 'don't know' as a concept. The concept basically says if you don't know something is true then assume it is false. Logicians of course know this is dangerous and are very careful to limit the scope. It seems to me that Wessely and White fall into the trap of assuming things they don't know must be false. Its a theme that comes out in quite a lot of the things they write.

An evidential approach would look at various bits of evidence for the harm/no harm hypothesis. They would persumably find a lot of anicdotal evidence from patients who relapse after pushing themselves too hard and ignoring symptoms. I assume it is very hard to give a definative answer without having an explanation of how ME works. They of course have their all in the mind theory and hence they confidently make a statement about not causing harm. There problem is that they have no evidence for their theory.

Just of of curiosity do they have a definition of harm, is it equated with a tempory relapse, a perminant relapse how do they measure it?

 

[Enid]

Well I suggest they all "get it" for all their "papers" mean nothing until they understand the basic pathologies underlying this disease ME. Papers are a bore until they can. Who's for their papers - are we to blinded by the psyche creepy volume - come on. Real science and medical findings are already out there.

 

[Esther12]

I seem to remember OB saying that this wasn't that compelling a study, but this prospective Wessely study found:

Participants who later reported CFS continued to exercise more frequently even after they began to experience early symptoms of fatigue.

http://www.psychosomaticmedicine.org/content/70/4/488.short

Even if far from conclusive, I'd expect this study provides as much 'evidence' that exercising in spite of symptoms is harmful as any of their opposing 'evidence' that it is not.

 

[Dolphin]

To develop the theme (of inconsistency) a little further it's worth (re) mentioning this GP training video, which shows a fictional consultation where a "pretend patient" (Vincent Deary, I think) discusses his ongoing problems with ME/CFS. Vincent, in this scenario, is a teacher working four days a week, with a heavy burden of homework to mark in the evenings, so we can infer that his problem isn't deconditioning, but rather doing too much.

The CBT model is a "Goldie Locks" theory - not too much, not too little, just the right amount of activity (a secret formula of rest and exercise known only to the therapist.) Yet this terrible inability to find the correct balance only strikes people after viral infections, people who, without any help from a therapist, have managed their whole lives (through luck one assumes) to not succumb to the curse of doing too much or doing too little, and becoming ill as a consequence.

(It would also be possible to describe the the CBT model as "complete cobblers" and the product of incurious and fixed minds :~)

Good points.

There's a thread on those videos for anyone who wants to know more: http://forums.phoenixrising.me/index.php?threads/training-videos-for-english-gps-on-how-to-deal-with-cfs-patients.3079/

Here's an extract:
=============

​

Vignette 5​

Reconstruction of a typical GP consultation​

​

Dr Clare Gerada (Simon Wessely's wife) and Alicia Deale (playing the patient):​

​

"...can I have a little look at​

your diary?.....I think what your diary shows is again how important it is that we develop a consistent approach because what we talked about was that it's important that we break this association between activity and your symptoms .... we've talked before about the fact that you walk at the moment to the bus stop to go to work, how long extra would it be if you walk to the next bus stop?...."​

​

"...what we're trying to do here as I've said to you is to break this association between activity and your symptoms because equally if you feel rotten I still want you to do that activity...even if you're absolutely exhausted I still want you to do your ten minute walk in the morning and the ten minute walk in the evening after work...​

​

Alicia Deale (Patient): 'Is that going to be safe?'​

​

Clare Gerada: it will be safe - all the evidence that we've put together and all the the research literature shows that is absolutely safe you will not do yourself any harm..."​

 

[user9876]

I seem to remember OB saying that this wasn't that compelling a study, but this prospective Wessely study found:



http://www.psychosomaticmedicine.org/content/70/4/488.short

Even if far from conclusive, I'd expect this study provides as much 'evidence' that exercising in spite of symptoms is harmful as any of their opposing 'evidence' that it is not.

I thought this was an interesting comment in the paper you mention

At the age of 36 years, there was no significant difference
in the levels of fatigue reported by participants who were later
to suffer from CFS compared to the rest of the sample.
However, by the age of 43 years, participants who were to
report a diagnosis of CFS at the age of 53 years were beginning
to report significantly more fatigue than the rest of the
sample (OR adjusted for gender  2.62; 95% CI  1.1.5–
5.96; p  .02). However, despite this, those who were later to
report a diagnosis of CFS were still persisting in exercising
more frequently than those who did not go on to report CFS.
Figure 1 shows that, by the age of 53 years, once the patient
is diagnosed with CFS, the frequency of exercise undertaken
by individuals with CFS reverts to the level maintained by the
rest of the population.

Those diagnosed with CFS by 53 had reported unusual fatigue at 43 but carried on exersicing (ignoring symptoms?) then later were diagnosed with CFS (persumably having got worse). What happened to those who reported additional fatigue at 43 who reduced their activity?

 

[Bob]

We do have some evidence that symptoms correlate with oxidative stress so they may cause problems, sometimes to a level from which it can't recover in the short- to medium- term (I know I went from mildly affected to severely affected in just over a year and have been stuck severe for 18 years so I think something was damaged).

Yes, just for clarity, I personally have absolutely no doubt that physical 'damage' is caused by the processes of CFS/ME. (Whether the damage reverses or not, when/if symptoms improve, I don't know.)

I was purely discussing whether there is evidence of 'harm' or not. I can't see how it can possibly be argued that we don't have evidence of 'harm' in CFS/ME.

Even psychiatric illnesses have biological causes, or biological underpinnings. So those who consider ME to be a psychiatric illness (which it isn't), cannot rule out biological abnormalities, any more than they can with schizophrenia or bipolar.

Pain and fatigue are physical processes, even if they only happen in the brain. Even if fatigue and pain are not related to physical injury of the body, they are still physical processes. So if we do something (or if we do 'nothing', if we buy into their ridiculous model of illness) that increases fatigue/malaise/pain to the point that the symptom is distressing, then surely that must be considered to be 'harm'. At the very least, it is 'harm' to the pain/fatigue brain pathways.

As we've all been discussing, their model of illness is convoluted, and blind to the evidence. They want it to be purely a maladaptive psychological response to stress. Just a thinking problem, that can be cured by thinking differently. And the more they attempt to explain their model, the more ridiculous that model looks, in the face of the evidence and patient experiences. Not to mention the results of the PACE Trial, which conclusively disproved their model.


Edit: Sorry, rant over. You all know all this already, but it's nice to have a bit of a rant now and then.

 

[Dolphin]

I am of the opinion that they always planned to do a bait-and-switch. Deviation from the protocol is the norm, not the exception in science after all. The only difference here is the cover-up.

I think it's important to distinguish between RCTs and experimental science. Investigating outcoming reporting bias is a relatively big area with regard to RCTs. Similarly, registries to post protocols for RCTs are becoming the norm. (The rest of) experimental science is much more lax in this area.

 

[Dolphin]

Bob, you are raising some good points about the reporting of harms. Symptoms produced as "side effects" of drugs don't have to be long-term to be considered relevant when reporting harms/"side effects".

 

[Bob]

So, most CFS/ME patients recognise that exertion exacerbates their symptoms, and that rest and pacing help to alleviate symptoms.
But the psychiatrists say that exertion alleviates symptoms, and that rest and pacing exacerbates symptoms.
How did we get into this bizarre situation?!? (rhetorical question)

 

[Dolphin]

So, most CFS/ME patients recognise that exertion exacerbates their symptoms, and that rest and pacing help to alleviate symptoms.
But the psychiatrists say that exertion alleviates symptoms, and that rest and pacing exacerbates symptoms.
How did we get into this bizarre situation?!? (rhetorical question)

Probably due to "when all you have is a hammer, everything can start to look like a nail"* Rehab is what they have to offer/want to offer. The need to offer a theory to match this.

* or whatever the quote is.

 

[Bob]

However, I'd be surprised if most participants' daily activities were so uniform and their symptom severities were so stabilised that occasional and unexpected events and exacerbations did not interfere.

Yes. And the best way to ensure a person was being consistent would be for them to use actometers/pedometers every day. (Of course, this doesn't control for other types of drains on the body). Except patients handed them back at the start of the trial as I recall.

Also, I think if one wanted to stabilise activity, one would allow patients getting parking badges. This would avoid patients suddenly have to walk further than they might normally do, or plan to do. Without a parking badge, how far one has to walk is going to be random, simply due to where there happens to be a parking space. It's interesting then that the Barts CF team (Peter White presumably) objected to even a "mild" mention of it in the draft NICE guidelines...

Yes, I agree. It's almost impossible to carry out a life in the way that GET prescribes...

If the max activity someone does, on most days of the week, is to walk around their home, prepare food, and to shower (i.e. some basic essential household tasks), but then occasionally they have to go to get groceries, or have to attend to other occasional activities that max out their energy or cause symptoms to flare up, then how can GET possibly fit in with that life style?

The scheduled GET activities would have to abandoned on those days of extra activity.

And many of us rest for a few days in advance of a major activity, so we can handle the activity more comfortably. And then we rest again afterwards to avoid a prolonged relapse. So GET would be an inconvenience.

Life would be very oppressed, and almost impossible, if following a GET activity schedule, because it wouldn't allow for spontaneous, sporadic, or out of the ordinary activities.

In my experience, my energy can often be directed towards essential activities that need to be carried out.
And when I'm feeling a little better, I can catch up with some (not-quite-so-pressing) other essential activities.
I couldn't waste that extra energy worrying about a scheduled GET activity.

Few people can realistically plan their lives so carefully as GET requires.
So I'm sure that many GET-group participants were forced to reduce/ignore many of their scheduled GET activities, and were forced to moderate/reduce their regular non-GET activities in order to save energy and rest so that they could achieve the GET activities.
It's not surprising that they dropped the actometers.

 

[Bob]

I seem to remember OB saying that this wasn't that compelling a study, but this prospective Wessely study found:

Participants who later reported CFS continued to exercise more frequently even after they began to experience early symptoms of fatigue.

http://www.psychosomaticmedicine.org/content/70/4/488.short

Even if far from conclusive, I'd expect this study provides as much 'evidence' that exercising in spite of symptoms is harmful as any of their opposing 'evidence' that it is not.

And, if we look back to the beginning of our illness, we weren't incapacitated because of inactivity or deconditioning. We became ill, suffered from severe symptoms, and when we exerted ourselves, our symptoms got worse. So we learned to moderate our activity in order to protect ourselves. The "boom and bust" cycle seems like further proof against their model. How could we possibly have a "boom" if we were so afraid of activity that we couldn't do anything?

 

[Sean]

The CBT model is a "Goldie Locks" theory - not too much, not too little, just the right amount of activity (a secret formula of rest and exercise known only to the therapist.) Yet this terrible inability to find the correct balance only strikes people after viral infections, people who, without any help from a therapist, have managed their whole lives (through luck one assumes) to not succumb to the curse of doing too much or doing too little, and becoming ill as a consequence.

Nicely put. And it sounds truly ludicrous when put that way. Which it is.

 

[Graham]

Dammit! I've just realised why I'm not improving. You just have to look at my avatar to know that I don't stand an earthly chance of achieving the Goldilocks approach.

So I am proposing the SKIN approach – So Knackered I'm Notgoingtodoanymore.

 

[alex3619]

Its a premise of psychosomatic medicine that the mental factors cause the physical symptoms. Most of the diseases they are focussing on have a raft of provable physical symptoms and findings (proteins, enzymes, cytokines, whatever). So there must be mechanisms mediating the mental cause that result in physical symptoms, if you believe their explanation. If they really practiced and researched a biopsychosocial approach they would be looking for those mediating mechanisms. They don't seem to want to find any, and when they do find something (as I think both White and Wesseley have found abnormalities in studies) they then ignore those abnormalities in following studies.

I don't see how anyone could be happy with that approach, even psychiatrists using a biopsychosocial model. Its deeply flawed. If they were serious, if they wanted to legitimize a biopsychosocial approach, they would be grappling with the physical mediators in order to develop their mental causation models. The fact that they don't do this is another example of why their approach is a failure. They don't just ignore contrary evidence from others, they ignore it when it is produced in their own studies.(See the papers outlined in ME Analysis for examples, in the biomarkers section.)

Bye, Alex

PS I should add that the original psychosomatic medicine was about how thoughts and feelings affect disease - causation was not presumed.

 

[Snow Leopard]

I read one patient talk about how she personally was counting house work for her exercise allotment.

I would probably do that too. It makes you wonder how much activity substitution there really was.

The "boom and bust" cycle

The boom-bust cycle is mostly a myth in that the evidence to support it (actometers and rigorous activity logs) is little to non-existant.

 

[alex3619]

Hi Snow Leopard, I wonder if the boom-bust is not another misnomer? Anecdotally the boom phase consists either of normal activity or decreased activity that is over our capacity to cope. So it would more accurately be called a relapse-recover cycle. However, from anecdotal reports pacing can decrease prevalence and severity of relapses. Its amazing nobody has actually done the research to investigate this using objective methods. You would think this would be an obvious thing to do. Bye, Alex

 

[Dolphin]

Somebody sent me this and said I could post it. They said I didn't need to credit them, etc.

Just poking through some old stuff and came across the following
(again)- In P. White's peer review for the 2007 CDC paper in which he
critiques the use of the Empirical Definition, he makes the following
statement- "5. Furthermore the authors need to refer to the studies
from which they took these population norms. I am aware of several
population studies of working age adults using the SF36, but they give
slightly different results, and the readers need to know which one
they chose and why. I am not aware of any population studies of
working age adults using the MFI. This reference should be given."
(http://www.pophealthmetrics.com/content/5/1/5/prepub)

So P. White notes the necessity of stating both which study on
population norms was used and more importantly, why the authors chose
to use it. AFAIK, the PACE authors never addressed this in any of
their Q&A's, FAQ's, BS's, etc.

 

[Bob]

Could someone help me with a brief question please?
I know the diagnostic criteria have been discussed in detail, but I've not focused on them before.
The PACE paper does not state which 'International Criteria' were used for the study, but only gives a reference to a Reeves 2003 paper which critiques the 1994 Fukuda criteria.
Are we to take it from this that the "International Criteria" that they used are the Fukuda criteria, or the Reeves 2005 criteria?

 

[Dolphin]

Could someone help me with a brief question please?
I know the diagnostic criteria have been discussed in detail, but I've not focused on them before.
The PACE paper does not state which 'International Criteria' were used for the study, but only gives a reference to a Reeves 2003 paper which critiques the 1994 Fukuda criteria.
Are we to take it from this that the "International Criteria" that they used are the Fukuda criteria, or the Reeves 2005 criteria?

They are referring to the Reeves et al 2003 criteria which update a little the Fukuda criteria.