'Recovery' from chronic fatigue syndrome after treatments given in the PACE trial

[Dolphin]

Dolphin][/SIZE]

What was in the protocol was:

“4. “Recovery” will be defined by meeting all four of the following criteria:​

(i) a Chalder Fatigue Questionnaire score of 3 or less [27],
(ii) SF-36 physical Function score of 85 or above [47,48],
(iii) a CGI score of 1 [45],
and
(iv) the participant no longer meets Oxford criteria for CFS [2], CDC criteria for CFS [1] or the London criteria for ME [40].”​

They only left (iv) unchanged. They loosened the requirements for the other three.​

I'm not even certain about that... Didn't participants only have to be excluded from the Oxford Criteria for a single week (or something similar) to be consider 'recovered'? So even that criteria was drastically watered down. (I'm not sure I've got this entirely accurate, without checking.)

They might not have operationalised it well. But I don't see that they mentioned in the protocol they would do this part differently.

 

[Bob]

They might not have operationalised it well. But I don't see that they mentioned in the protocol they would do this part differently.

I think you're right, but the Oxford Criteria states that patients should be assessed over a 6 month period. If the authors were going to ignore that important aspect of the Oxford Criteria, then they should have stated it in the protocol. By not stating differently, then a 6 month period was implicitly implied.

It's just not possible to consider a patients' symptoms over a single one-week period and then decide whether or not they have Chronic Fatigue, or that they have 'recovered' from Chronic Fatigue. Particularly when the diagnostic criteria states that it should be assessed over 6 months, with fatigue present at least 50% of the time. A one-week time period just isn't credible.

 

[Sam Carter]

I'm not even certain about that... Didn't participants only have to be excluded from the Oxford Criteria for a single week (or something similar) to be consider 'recovered'? So even that criteria was drastically watered down. (I'm not sure I've got this entirely accurate, without checking.)

According to the trial's protocol, to not meet the Oxford Criteria you would have to answer 'no' to this question:

"Have you had your fatigue for the last 6 months, during which it was present for more than half of the time?"

For lots of reasons, many of which have already been discussed, I'm not convinced that "no longer satisfying the Oxford Criteria" is a useful or meaningful metric. It does, however, serve as a handy rhetorical tool for PDW so that he can make the claim that, following 'active' treatment, a person no longer has CFS.

 

[Firestormm]

I have been pondering this 'recovery' malarkey like I guess many of us have. And I wonder if 'rehabilitation' wouldn't be a better word for them to use. I was thinking, you know, if a person lost his legs or had cancer or ME for example; but had learned to essentially make adjustments, gain acceptance, and basically live with it: whether this didn't correspond to what they believe they are trying to achieve with their black magic mumbo jumbo. What do you think? Would rehabilitation be a better word? Or am I speaking complete bollocks once again

 

[Sam Carter]

Thanks Sam.
For 'recovery' I think this was reduced to something like: "Have you had fatigue for the last week?"
But I'm not absolutely certain about this, without double-checking.

Hi Bob,

Looking at Psy Med 2013, White et al write that, for each of the three diagnostic criteria used in the trial - Oxford, London and CDC - all required the presence of fatigue (or 'symptoms' in the case of London) for six months. However, the protocol's version of the CDC criteria asks only "whether you have had any of the following symptoms in the last week", which is perhaps what you were thinking of?

 

[Bob]

I have been pondering this 'recovery' malarkey like I guess many of us have. And I wonder if 'rehabilitation' wouldn't be a better word for them to use. I was thinking, you know, if a person lost his legs or had cancer or ME for example; but had learned to essentially make adjustments, gain acceptance, and basically live with it: whether this didn't correspond to what they believe they are trying to achieve with their black magic mumbo jumbo. What do you think? Would rehabilitation be a better word? Or am I speaking complete bollocks once again

I think that 'rehabilitation' isn't perhaps quite the right word, as it suggests that ME patients can be 'rehabilitated' with these therapies, which means to 'restore to a state of good condition or operation'. And, as we know, many patients continue to be very ill, even when they learn to cope with the illness, or when they learn to manage the illness.

Considering how lacking CBT and GET are in efficacy, I also think it would be misleading to suggest that they are rehabilitative therapies for CFS/ME patients. Remember that CBT made no difference to physical disability in the PACE trial, and GET was little better.

I don't personally think that CBT or GET are worth considering important, considering the very meagre benefits, but if they are going to be promoted, then I would rather that they were simply promoted as 'symptom management techniques' or 'coping techniques' that perhaps a very small minority of patients will find helpful, and nothing more than that. With a strong warning that they can be very harmful for CFS/ME patients.

And I'd only find GET acceptable if it is in the form of 'pacing with goals', and I'd only find CBT and GET acceptable if they move away from the 'fear', 'avoidance' and 'deconditioning' model of illness, otherwise they are ignorant, stupid, and unhelpful, and potentially dangerous, as shown in the many patient surveys.

 

[Bob]

Hi Bob,

Looking at Psy Med 2013, White et al write that, for each of the three diagnostic criteria used in the trial - Oxford, London and CDC - all required the presence of fatigue (or 'symptoms' in the case of London) for six months. However, the protocol's version of the CDC criteria asks only "whether you have had any of the following symptoms in the last week", which is perhaps what you were thinking of?

Thanks Sam. I was being lazy, and couldn't be bothered to look up the details.
I've found the details now, and it seems that I got it totally wrong in the past few posts, so I'll delete or amend them...

In the 'recovery' paper it says that Oxford was assessed over 6 months (not one week).
So, apologies to everyone for the nonsense I've written in my previous few posts.

Where I got muddled is that, in the 'recovery' paper, for the CDC criteria, it says the following:

"The research assessor used participant ratings to judge whether participants met the International (CDC)
criteria for CFS at 52 weeks (Reeves et al. 2003), which included: (1) severe chronic fatigue for at least
6 months with other known medical conditions (whose manifestation includes fatigue) excluded by
clinical diagnosis; and (2) concurrently have four or more of the following symptoms: post-exertional
malaise, impaired memory or concentration, unrefreshing sleep, muscle pain, multi-joint pain without
redness or swelling, tender cervical or axillary lymph nodes, sore throat, headache.
For the purposes of this study, the four or more symptoms needed to be present within the previous week of the assessment date, rather than the previous 6 months (Reeves et al. 2003)..."

 

[Bob]

Apologies to everyone, it appears that I've been posting some nonsense in my previous few posts.
The 'recovery' paper says that participants were assessed for a 6 month period, for the Oxford Criteria, and not one week.
My stupid brain isn't working properly, as usual.
See the above post for why I got muddled.
I'll amend/delete my recent posts.

Dolphin

 

[Sam Carter]

I have been pondering this 'recovery' malarkey like I guess many of us have. And I wonder if 'rehabilitation' wouldn't be a better word for them to use. I was thinking, you know, if a person lost his legs or had cancer or ME for example; but had learned to essentially make adjustments, gain acceptance, and basically live with it: whether this didn't correspond to what they believe they are trying to achieve with their black magic mumbo jumbo. What do you think? Would rehabilitation be a better word? Or am I speaking complete bollocks once again

Hi Fire,

Rehabilitation is in fact the word Peter White uses, only it isn't rehabilitaion as I understand it, or as you describe it.

Making adjustments, gaining acceptance and learning to live with the illness have no place in his kind of rehabilitation, and in fact, he considers such behaviours and attitudes to be barriers to recovery.

You can see this from the Swiss Re article you linked to:

""""
It is thought that behavioural activation helps to treat the illness itself, whereas “pacing” (staying within limits imposed by the illness) only results in adaptation to the illness.

The key message is that pushing the limits in a therapeutic setting using well described treatment modalities is more effective in alleviating fatigue and dysfunction than staying within the limits imposed by the illness traditionally advocated by “pacing”. If a CFS patient does not gradually increase their activity, supported by an appropriate therapist, then their recovery will be slower. This seems a simple message but it is an important one as many believe that “pacing” is the most beneficial treatment.

...

Key takeaways for claims management

...

It is likely that input will be required to change a claimant’s beliefs about his or her condition and the effectiveness of active rehabilitation.
""""

And this last section is particularly vile because it is advocating that sick people be coerced into believing things that are not true.

ETA: @Fire : sorry if this reads like a mini rant directed at you! It isn't meant that way - it's just my poor writing skills tripping me up (again).

 

[Dolphin]

Thanks Sam. I was being lazy, and couldn't be bothered to look up the details.
I've found the details now, and it seems that I got it totally wrong in the past few posts, so I'll delete or amend them...

In the 'recovery' paper it says that Oxford was assessed over 6 months (not one week).
So, apologies to everyone for the nonsense I've written in my previous few posts.

Where I got muddled is that, in the 'recovery' paper, for the CDC criteria, it says the following:

"The research assessor used participant ratings to judge whether participants met the International (CDC)
criteria for CFS at 52 weeks (Reeves et al. 2003), which included: (1) severe chronic fatigue for at least
6 months with other known medical conditions (whose manifestation includes fatigue) excluded by
clinical diagnosis; and (2) concurrently have four or more of the following symptoms: post-exertional
malaise, impaired memory or concentration, unrefreshing sleep, muscle pain, multi-joint pain without
redness or swelling, tender cervical or axillary lymph nodes, sore throat, headache.
For the purposes of this study, the four or more symptoms needed to be present within the previous week of the assessment date, rather than the previous 6 months (Reeves et al. 2003)..."

Thanks Bob.
Although you also make a useful general point: the Oxford criteria only needs not to be satisfied at one moment in time. So if a person got a CFQ score of less than 6 (bimodal) or a SF-36 PF of greater than 65 on one questionnaire at one time, they would no longer satisfy the Oxford criteria.

I think recovery should require more than one timepoint.

 

[Firestormm]

Sam Carter I hear what you are saying. To me (and you probably) rehabilitation is a process - ongoing; whereas recovery implies an end. For a chronic illness and/or amputation etc. rehabilitation would seem more appropriate: unless I am speaking to a stubborn shrink of course.

 

[urbantravels]

Rehabilitation means a return to a former state of good health or good standing. The only difference between "recovery" and "rehabilitation" is that one can happen naturally and the other is a conscious intervention. But they both imply an end point. It wouldn't make much sense to speak of continuous "rehabilitation."

 

[Firestormm]

Rehabilitation means a return to a former state of good health or good standing. The only difference between "recovery" and "rehabilitation" is that one can happen naturally and the other is a conscious intervention. But they both imply an end point. It wouldn't make much sense to speak of continuous "rehabilitation."

Oh. Well how can you rehabilitate someone who has lost their legs? I suppose you help them to walk again. Oh right. I see. Buggar. Thanks Urban.

 

[Bob]

Rehabilitation has a number of meanings. It can also mean to 'help to readapt' or 'the restoration of someone to a useful place in society' or to 'restore to useful life'.

There's also political rehabilitation, but that's probably not relevant, unless we consider CBT to be a small 'p' political tool, which I suppose it is.

 

[Firestormm]

Rehabilitation has a number of meanings. It can also mean to 'help to readapt' or 'the restoration of someone to a useful place in society' or 'To restore to useful life'.

There's also political rehabilitation, but that's probably not relevant, unless we consider CBT to be a small 'p' political tool, which I suppose it is.

Thanks signore. I was thinking about my reply and came back to say that although someone who has lost their legs might be helped to walk again - they still face life with no legs and that can be I would imagine as hard to cope with as learning to walk again on prosthetics. So I don't really consider rehabilitation to always have an end point. And I don't regard any management process to be effective within the kind of time-frame that the NHS for example consider able to provide - not that I am asking for more - but I think the amount offered to those who might need it e.g. at a point closer to their diagnosis is too little. Generally though a multi-disciplinary rehabilitative approach is all that we can hope for at the moment. However my opinion remains that the emphasis is placed too much on the non-pharmacological approaches.

 

[Graham]

Thanks Bob.
Although you also make a useful general point: the Oxford criteria only needs not to be satisfied at one moment in time. So if a person got a CFQ score of less than 6 (bimodal) or a SF-36 PF of greater than 65 on one questionnaire at one time, they would no longer satisfy the Oxford criteria.

I think recovery should require more than one timepoint.

Are you talking about the Oxford criteria, or simply the PACE version of it? Surely the original Oxford criteria had nothing to do with scores on Chalder and sf-36? That's one of the very many things that irritates me about the PACE trial: the ease with which they redefine things on the fly.

 

[Dolphin]

Thanks Bob.
Although you also make a useful general point: the Oxford criteria only needs not to be satisfied at one moment in time. So if a person got a CFQ score of less than 6 (bimodal) or a SF-36 PF of greater than 65 on one questionnaire at one time, they would no longer satisfy the Oxford criteria.

I think recovery should require more than one timepoint.

Are you talking about the Oxford criteria, or simply the PACE version of it? Surely the original Oxford criteria had nothing to do with scores on Chalder and sf-36? That's one of the very many things that irritates me about the PACE trial: the ease with which they redefine things on the fly.

I'm talking about how the Oxford criteria were operationalised for the PACE Trial.

 

[Simon]

Thanks Bob.
Although you also make a useful general point: the Oxford criteria only needs not to be satisfied at one moment in time. So if a person got a CFQ score of less than 6 (bimodal) or a SF-36 PF of greater than 65 on one questionnaire at one time, they would no longer satisfy the Oxford criteria.

I think recovery should require more than one timepoint.

Are you sure that's right?i thought the other measures were at 12 and 24 weeks ie more than 6 months before endpoint evaluation.

 

[Dolphin]

Thanks Bob.
Although you also make a useful general point: the Oxford criteria only needs not to be satisfied at one moment in time. So if a person got a CFQ score of less than 6 (bimodal) or a SF-36 PF of greater than 65 on one questionnaire at one time, they would no longer satisfy the Oxford criteria.

I think recovery should require more than one timepoint.

Are you sure that's right?i thought the other measures were at 12 and 24 weeks ie more than 6 months before endpoint evaluation.

Not sure whether we are talking about different things. Recovery just used the data from the measurements taken at the 52-week timepoint.

 

[biophile]

Further commentary on the 6MWD issue:

Second, and importantly, there were practical limitations to our conduct of the walking test. Due to concerns about patients with CFS coping with physical exertion, no encouragement was given to participants as they performed the test, by contrast to the way this test is usually applied (Guyatt et al. 1984; American Thoracic Society, 2002). Rather than encouragement, we told participants, 'You should walk continuously if possible, but can slow down or stop if you need to.' Furthermore we had only 10 metres of walking corridor space available, rather than the 30-50 metres of space used in other studies; this meant that participants had to stop and turn around more frequently (Guyatt et al. 1984; Troosters et al. 1999; American Thoracic Society, 2002), slowing them down and thereby vitiating comparison with other studies. Finally, we had follow-up data on 72% of participants for this test, which was less than for the self- report measures (White et al. 2011).

American Thoracic Society (2002). ATS Statement: Guidelines for the six-minute walk test. American Journal of Respiratory and Critical Care Medicine 166, 111-117 http://www.thoracic.org/statements/resources/pfet/sixminute.pdf

Encouragement

Only the standardized phrases for encouragement (as specified previously here*) must be used during the test.

Rationale: Encouragement significantly increases the distance walked (42). Reproducibility for tests with and without encouragement is similar. Some studies have used encouragement every 30 seconds, every minute, or every 2 minutes. We have chosen every minute and standard phrases. Some studies (53) have instructed patients to walk as fast as possible. Although larger mean 6MWDs may be obtained thereby, we recommend that such phrases not be used, as they emphasize initial speed at the expense of earlier fatigue and possible excessive cardiac stress in some patients with heart disease.

* These are "you are doing well" and "keep up the good work", but it also states earlier, "Do not use other words of encouragement (or body language to speed up)."

42. Guyatt GH, Pugsley SO, Sullivan MJ, Thompson PJ, Berman LB, Jones NL, Fallen EL, Taylor DW. Effect of encouragement on walking test performance. Thorax 1984;39:818–822

53. Troosters T, Gosselink R, Decramer M. Six minute walking distance in healthy elderly subjects. Eur Respir J 1999;14:270–274.

A low 6MWD is nonspecific and nondiagnostic. When the 6MWD is reduced, a thorough search for the cause of the impairment is warranted. The following tests may then be helpful: pulmonary function, cardiac function, ankle–arm index, muscle strength, nutritional status, orthopedic function, and cognitive function.

PACE have not demonstrated any concern about the cause of the impairment i.e. low 6MWD, probably dismissing it as fear-avoidance and deconditioning while simultaneously denying that the scores are much lower than average for healthy people because encouragement was lacking and short walking spaces were used? As I mentioned before, I doubted lack of encouragement cited above can explain the low scores in the PACE Trial participants, and in the sources White et al use, encouragement only accounted for about 30m on average (not 250-300m), as explored below:

White et al and the American Thoracic Society (2002) both cite Guyatt et al 1984, so I had a closer look at this small study of 43 patients, but I wonder if there are more recent and better conducted research on encouragement:

Guyatt GH, Pugsley SO, Sullivan MJ, Thompson PJ, Berman L, Jones NL, Fallen EL, Taylor DW. Effect of encouragement on walking test performance. Thorax. 1984 Nov;39(11):818-22. PMID: 6505988
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC459930/pdf/thorax00227-0020.pdf

Figure 1 shows that encouragement and repeated testing makes a difference (but not big enough to explain the similar PACE scores). Also, I wonder if patients may need more encouragement than healthy controls anyway.

Interestingly, Guyatt et al wrote that "The difference between corrected scores in the E+ and E- groups constituted the encouragement effect and averaged 30.5m." In other words, coincidently, the average effect of encouragement on 6MWD scores was about the same as the GET advantage after 52 weeks.

According to page 53 of the PACE Trial complete protocol, the 6MWT was conducted at baseline, 24 weeks (end of therapy), 52 weeks (trial end), and also in the situation of "treatment discontinuation". GET specifically encourages increased activity, and walking was the most commonly chosen activity, so others on this forum have stated previously that the minor improvement in 6MWD for the GET group could have merely been a learning effect.

The 6MWT is far from perfect, I have come across research before which suggests it is often not a particularly good indicator, and whether or not it correlates with other domains may be illness specific. But the reason it has become a prominent issue with the PACE Trial is because it was the closest to an objective measurement of physical fitness used.

From the abridged PACE Trial protocol, White et al even assured us that, "The six-minute walking test will give an objective outcome measure of physical capacity." Yet they did not conduct the test properly and continue to show disregard for the importance and implications of objective measurements in an illness which is known to have objectively measured impairments. At the same time, White et al want to use the minor improvement in the GET group to support the effectiveness of GET. Not very impressive for a large "definitive" trial costing 5 million pounds that supposedly, according to its supporters, settled the ongoing CBT/GET controversy about effectiveness and safety.

Proponents are still downplaying objective measures while still promoting CBT/GET as evidence-based therapies which significantly improve symptoms and function, despite no objective evidence demonstrating clinically significant improvements in function, and the evidence available actually suggesting no such improvement. At the same time, potential sources of bias present when measuring patients' perceptions about illness after researchers have actively attempted to alter these same perceptions, are also being conveniently ignored.