The FINE Trial. BMJ ARTICLE. Nurse led, home based self help treatment for patients in primary care

[Dolphin]

Well, maybe it's not very 'exciting', but it's very useful, so thanku. (I've read it now.).

Thanks Bob. :Retro smile:

Yes, at 70 weeks, all measures show no improvement in the patients...
But it would be extremely valuable for our community if we had the stats for the different patient cohorts (patients diagnosed using different diagnostic criteria).
If 'pragmatic rehabilitation' (in other words: CBT/GET) was shown to make patients with a CDC diagnosis worse, in a one-million-pound medical trial, then this would be a very useful weapon against the psychological establishment for us.

Yes, such information would be useful.

You or others could always re-inforce my questions with another rapid response making that point.

The BMJ puts up most responses.

Best to make it look like a letter to a journal by having at least one reference at the end - even if it's only a website or even the paper itself[1]. The paper itself and something else is probably better - but in this case it could just be the protocol paper[2]. Just showing how easy it is to make something look official. As one can see on the BMJ site, lots of people don't do this.

I might be able to give a quick bit of help if somebody wants to send something in.

References:

[1] Wearden AJ, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK, Peters S, Riste L, Richardson G, Lovell K, Dunn G; Fatigue Intervention by Nurses Evaluation (FINE) trial writing group and the FINE trial group. Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial. BMJ. 2010 Apr 23;340:c1777.

[2] Wearden AJ, Riste L, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK, Peters S, Dunn G, Richardson G, Lovell K, Powell P. Fatigue Intervention by Nurses Evaluation--the FINE Trial. A randomised controlled trial of nurse led self-help treatment for patients in primary care with chronic fatigue syndrome: study protocol. [ISRCTN74156610]. BMC Med. 2006 Apr 7;4:9.

 

[Bob]

Yes, such information would be useful.

You or others could always re-inforce my questions with another rapid response making that point.

We might also be able to make a freedom of information request... as it was a government funded project.
Suzy (ME agenda) seems to be our resident expert at these (she's very good at them), so maybe Suzy can help us get that done.

 

[PoetInSF]

Which is why the FINE trial was allowed, or designed, to fail... The PACE trial won't fail... we can all be absolutely sure of that!

Well, I don't have such prejudice or suspicion. If they were really conspiratorial, it wouldn't make sense for them to set up FINE to fail and PACE not to.

I don't expect PACE to fail either given past trial results. What's interesting about PACE, however, is that it measures the disability as well as fatigue and symptoms. Other trials done up to date mostly measured fatigue and symptoms improvements as far as I know. But the disability is the true brick wall that hardly moves, and I'm keenly interested on what PACE will find in that department. If they truly select patients from all spectrum, I'd expect some to show improvement since stabilized later-stage patients are more likely to improve in my experience. If not, I'll be disappointed.

 

[bananaman]

http://www.meassociation.org.uk/ind...urprise-mea-responds&catid=30:news&Itemid=161

'Failure of FINE trial comes as no surprise' - MEA responds to study results in British Medical Journal

Tuesday, 11 May 2010 11:49

Published by BMJ.com, 11 May 2010

Editor

Having apparently spent 1,147,000 of Medical Research Council funding on a clinical trial to assess whether 'pragmatic rehabilitation and supportive listening' carried out by 'specially trained general nurses' would lead to significant improvements in the health of people with ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome), the results are disappointing but not surprising [1].
When we learnt of the FINE Trial, The ME Association felt that it was unlikely to contribute to our understanding of the illness, or to its management. For example, it included a number of flaws identified in previous trials, such as the lack of objective measures to confirm compliance with the exercise programme and the use of the bimodal scoring method for the Chalder Fatigue Scale, a measure with a low ceiling that does not permit those with maximal or near-maximal scores at baseline to record an exacerbation after treatment [2]. And from a theoretical perspective, we questioned the cognitive behavioural model underpinning the intervention. Studies had already shown that improvements were not dependent on changing somatic attributions and indeed, research first published in 2001 alerted us to the fact that positive outcomes cannot be attributed to increases in activity [3].

Since the start of the FINE Trial, studies of more individualised programmes have been shown to be as effective as those focused largely on increasing activity and improving sleep [4]. At present, the only form of activity management that meets with widespread approval and positive patient evidence of benefit is an approach known as pacing [5]. The strategy requires people to live within the limits imposed by the illness and avoid post-exertional fatigue. There are various versions and it is noteworthy that a randomized controlled trial of various interventions found that pacing was associated with a positive outcome across the groups [6]. However, we accept that there are scenarios where a trial of gentle, graded increases in activity would be more appropriate.

The really important message from this study is that while lifestyle advice can improve coping, it is not enough. In our view, lifestyle advice should be one element of a multi-component, multi-disciplinary approach. The time has come to abandon research which ignores the heterogeneity of the ME/CFS population, the complexity of this condition, the evidence of ongoing pathology in subsets, and the mistakes of the past.

Dr Charles Shepherd
Hon Medical Adviser, ME Association

Dr Ellen Goudsmit FBPsS
Hon Adviser, Psychology, ME Association

The ME Association, 7 Apollo Office Court, Radclive Road, Gawcott, Buckingham RM7 OAG

http://www.meassociation.org.uk

References:

[1] Wearden AJ, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK, Peters S, Riste L, Richardson G, Lovell K, Dunn G; Fatigue Intervention by Nurses Evaluation (FINE) trial writing group and the FINE trial group. Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial. BMJ 2010 Apr 23;340:c1777.

[2] Stouten B. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Serv Res 2005, 5:37. doi:10.1186/1472-6963-5-37

[3] Van Essen M, de Winter, LJM. Cognitieve gedragstherapie by het chronisch vermoeidheidssyndroom (cognitive behavior therapy for chronic fatigue syndrome). (Report No. 02/111, Appendix B). Amstelveen, Netherlands: College voor Zorgverzekeringen (CVZ). 2002.

[4] Goudsmit EM, Ho-Yen DO, Dancey, CP. Learning to cope with chronic illness. Efficacy of a multi-component treatment for people with chronic fatigue syndrome. Patient Educ Couns 2009;77:231-36.

[5] Report: ME Association questionnaire to assess current management options for ME/CFS. ME Association May 2010.

[6] Jason LA, Benton M, Torres-Harding S, Mudowny K. The impact of energy modulation on physical functioning and fatigue severity among patients with ME/CFS. Patient Educ Couns 2009;77:237-41.

Competing interests: Both authors act as unpaid advisers to The ME Association - a charity that funds biomedical research into ME/CFS.

 

[Bob]

Well, I don't have such prejudice or suspicion. If they were really conspiratorial, it wouldn't make sense for them to set up FINE to fail and PACE not to.

I don't expect PACE to fail either given past trial results. What's interesting about PACE, however, is that it measures the disability as well as fatigue and symptoms. Other trials done up to date mostly measured fatigue and symptoms improvements as far as I know. But the disability is the true brick wall that hardly moves, and I'm keenly interested on what PACE will find in that department. If they truly select patients from all spectrum, I'd expect some to show improvement since stabilized later-stage patients are more likely to improve in my experience. If not, I'll be disappointed.

Hi Poet,

I don't understand why you have so much confidence in the PACE trial...

First of all, the patients were selected using the Oxford criteria, which probably diagnoses a collection of disease processes under the CFS umbrella term, but it doesn't diagnose a single disease known as ME. So the trial is confused and muddle before it begins. Oxford doesn't diagnose 'ME' as recognised by a more exclusive diagnostic criteria such as the Canadian criteria and, as far as I understand, the Oxford criteria are not used in any official medical capacity, so the whole project was irrelevant to our community before it even began.

Many other questions hang over the study as well, and it is well known that some of the people who organised the study have vested interests in CFS/ME being seen as a psychological illness.

I'm not sure why you would be disappointed if CBT or GET were proven not to improve symptoms in ME... surely the science, rather than any preconceived prejudices, should be allowed to determine the facts. Many people with ME report being made worse by GET and CBT... In a member survey for Action for ME, a majority of respondents reported that GET had made their symptoms worse.

And I'm not sure why you would think that CBT or GET would improve symptoms in ME anyway... if we are talking about ME (i.e. as diagnosed by the Canadian criteria) rather than some vague illness as defined by Oxford criteria, then why would CBT or GET significantly improve a complex physical illness with a multitude of different symptoms? And why on earth would CBT or GET improve the symptoms of a physical illness which has 'post exertional malaise' as one of its main symptoms?

There seem to be more holes in the PACE trial than in a Swiss cheese... in my opinion.

Bob

 

[Dolphin]

I don't expect PACE to fail either given past trial results. What's interesting about PACE, however, is that it measures the disability as well as fatigue and symptoms. Other trials done up to date mostly measured fatigue and symptoms improvements as far as I know. But the disability is the true brick wall that hardly moves, and I'm keenly interested on what PACE will find in that department. If they truly select patients from all spectrum, I'd expect some to show improvement since stabilized later-stage patients are more likely to improve in my experience. If not, I'll be disappointed.

They are primarily measuring disability using the SF-36 physical functioning scale (a questionnaire) http://www.biomedcentral.com/1471-2377/7/6 . That has been done several times before. But Fred Friedberg and Dutch researchers have found that while patients have reported improvements in physical functioning on the SF-36, these patients weren't doing any more activity across the day - I think the latter is a much better measure of the true status of people.

Initially, the PACE trial was going to use actometers both before the trial and then at the end. Somewhere along the way, they decided to drop actometers at the end, so we don't know if people will be doing more activity or not.

Don't forget that these people have done some work with insurance companies and like to suggest that the existing evidence suggests CBT or GET restore the ability to work!

Symptoms apart from fatigue have generally not been measured in CBT and GET trials. The main symptom measure they're using is a fatigue scale.

 

[Robin]

Initially, the PACE trial was going to use actometers both before the trial and then at the end. Somewhere along the way, they decided to drop actometers at the end, so we don't know if people will be doing more activity or not.

Self-reportage studies are notoriously unreliable; look at all of the troubles researchers have with diet studies -- poor memory and discipline about reportage, and dishonesty, and the outcomes are often conflicting.

Did they say why they dropped the actometers? Surely not cost! ;-)

Also, is it true that the FINE participants were homebound more ill? Having been at various parts of the disability spectrum with ME/CFS, I can firmly say that walking on treadmills is not difficult for the less ill but horribly dangerous for the severely ill. I wonder if the level of incapacitation will be factored in?

 

[Dolphin]

Self-reportage studies are notoriously unreliable; look at all of the troubles researchers have with diet studies -- poor memory and discipline about reportage, and dishonesty, and the outcomes are often conflicting.

That's interesting. Any more information/general information on diet studies/the diet area welcomed.

You have brought up a couple of issues.
The is self-reportage in terms of the outcome measures.
A comparison I might make with regard to dropping the actometers, is measuring cholesterol at the start of testing a cholesterol-lowering drug but not at the end.
Or weighing people at the start of a weight loss trial, but not at the end but instead asking them did they think they lost weight e.g. are their clothes looser!

But then there is the treatment adherence point which hasn't really been brought up in the CFS literature much.

(Here is something I just posted in another thread)
A major problem is that we don't have good data that proves the patients in the trials do what the advice says. So the advice in the White/Fulcher GET trial is to endure 7 days of symptoms before reducing the amount of exercise (basically they don't want you to decrease exercise). But did all the patients actually stick to this? So the advice to not reduce can look safe to outsiders as there weren't adverse reactions but that's because many people probably didn't stick to it. If people actually do what the advice actually says, it isn't necessarily safe.

In the PACE trial, I came across one person who was counting minutes of her housework in the exercise she was supposed to be doing. But much of the information is that the exercise program is supposed to be exercise on top of other activities. And housework is stop-start. So again, not really treatment compliant.

Did they say why they dropped the actometers? Surely not cost! ;-)

They it was too much of a burden on the patients (ref: "we decided that a test that required participants to wear an actometer around their ankle for a week was too great a burden at the end of the trial." http://www.biomedcentral.com/1471-2377/7/6/comments)
They are still going to get them to wear the actometers before the trial but they said it would be too much of a burden at the end of the trial.
Of course, they didn't drop any of the other outcome measures that I'm aware - lots and lots and lots of questionnaires.
And the patient will have to do two short exercise tests at the end (where, I think, the GET patients will try to push themselves while the pacing-type group would be more inclined to pace). There will be no blood or gas testing so it's not really a very good exercise test.

But as I said, they dropped the actometers at the end even though the patients would likely be curious whether there was a change or not. There was no mention that there was a call to drop any of the outcome measures.

You would think for a trial that is costing UK5m (nearly US$7.5m), good outcome measures should be used.

Also, is it true that the FINE participants were homebound more ill? Having been at various parts of the disability spectrum with ME/CFS, I can firmly say that walking on treadmills is not difficult for the less ill but horribly dangerous for the severely ill. I wonder if the level of incapacitation will be factored in?

In the FINE Trial, they were supposed to report the results of the step test: “time to take 20 steps, (or number of steps taken, if this is not achieved) and maximum heart rate reached on a step- test” but didn't!

It was initially presented as a trial that would test a treatment for the housebound.
But it became clear, everyone was being let in.
In the end, this is what we were told: "Thirty three patients (11%) were non-ambulatory".

 

[PoetInSF]

Sorry for the late reply, Bob. I'm trying to stick to my online schedule...

First of all, the patients were selected using the Oxford criteria, ... so the whole project was irrelevant to our community before it even began.

Strangely enough, I don't share concern about various different definitions of CFS. This disease called CFS is still unknown and we are all blinds who are trying to describe the elephant. How do we know Canadian definition is the truth and not Fukuda or Oxford? We don't, yet. And this requirement of PEM for CFS goes on too often without challenge. I used to be on that boat too. But I'm starting to question now that my post-exertional malaise are becoming more like post-exercise fatigue while the brick wall of disability still remains. Just who am I to say that those who don't get really sick after an exertion do not have CFS?

Still, I agree they should tell us how many of the participants also qualify under Canadian. If nothing, that will help dispel doubts about the criteria used.

I'm not sure why you would be disappointed if CBT or GET were proven not to improve symptoms in ME...

Not symptoms, but disability. My exercise program did help me improve my QOL/symptoms. Now I'm hoping that it'll also improve my disability, eventually. Right now I'm finally seeing some signs after a year and a half into my program. But if the study shows that GET doesn't improve the disability, then it means that the improvement is only a coincidence. I'd be disappointed, but it'll still be good to know either way.

Many people with ME report being made worse by GET and CBT... In a member survey for Action for ME, a majority of respondents reported that GET had made their symptoms worse.

I understand that. But a patient survey is not a scientific study. I also understand that previous GET studies did not include serverely affected patients, but they still say something. Namely, "for moderately ill patients, GET holds promise". Therefore, I think it's worth investing in further studies. PACE, in particular, includes pacing that the patients think is most effective for them. If it is proven to be more effective than CBT/GET, then I think the policy will change for better for those who are against CBT/GET.

There seem to be more holes in the PACE trial than in a Swiss cheese... in my opinion.

Your opinion dully noted. That's what we are here for.

 

[PoetInSF]

They are primarily measuring disability using the SF-36 physical functioning scale (a questionnaire) http://www.biomedcentral.com/1471-2377/7/6 . That has been done several times before. But Fred Friedberg and Dutch researchers have found that while patients have reported improvements in physical functioning on the SF-36, these patients weren't doing any more activity across the day - I think the latter is a much better measure of the true status of people.

OK. But I'd be more interested in the outcome of the 6 min walk tests that I think is a more objective measure of physical capacity. It's probably true that the total activity is what really counts in practical terms. But it's also interesting to know how much one could do before getting exhausted and how soon he can recover from it. And I think that gets more important as you improve enough to take care of the activities of daily living without crashing.

Symptoms apart from fatigue have generally not been measured in CBT and GET trials. The main symptom measure they're using is a fatigue scale.

And that's probably for a good reason. Fatigue seems to be the only universal symptom in all CFS patients. That, of course, depends on how you define CFS. (Too bad fatigue is also a universal symptom for several other illness.)

 

[Esther12]

OK. But I'd be more interested in the outcome of the 6 min walk tests that I think is a more objective measure of physical capacity. It's probably true that the total activity is what really counts in practical terms. But it's also interesting to know how much one could do before getting exhausted and how soon he can recover from it. And I think that gets more important as you improve enough to take care of the activities of daily living without crashing.

It's interesting to know, but doesn't do that much to help us decide if CBT and GET is useful for CFS patients. If the program was heavily focused upon encouraging peope to do the sorts of activities that would better prepare their body for a 6 minute walking test, in lieu of other activities, then you'd expect the test to show an imporovement even if overall levels of disability had not improved.

I'm a bit sceptical of my own scepticism here. CFS is genuinely difficult to study, and I may be especially critical of those studies which claim GET and CBT successfully treat CFS, due to the history and origins of the ideas which surround these treatments (as well as my own personal experiences with them) - but even so, with the money being spent on PACE I really think we should be able to expect more than what it looks like we're going to get.

 

[Sam Carter]

PoetInSF wrote:

"""""""""""""""""""""
... I'd be more interested in the outcome of the 6 min walk tests that I think is a more objective measure of physical capacity. It's probably true that the total activity is what really counts in practical terms. But it's also interesting to know how much one could do before getting exhausted and how soon he can recover from it.
"""""""""""""""""""""

I'm not sure how a single, six-minute walk test can be described as an objective measure of physical capacity given that the cardinal symptom of ME is post-exertional malaise / worsening of symptoms [1]. A one-off test cannot capture this - what does it mean to say you walked X metres in six minutes but spent the next two weeks in bed? Only serial / longitudinal testing can provide a meaningful measure of physical capacity in ME.

The kindest thing one can say about Professors White, Chalder, Sharpe and Wessely is that they do not understand the scientific process. The decision to replace post-treatment actigraphy with a single, six-minute walk test means that no empirically reliable data can be obtained from the PACE Trial.

[1] A report of the CFS/ME Working Group:
Report to the Chief Medical Officer of an independent working group

http://www.dh.gov.uk/prod_consum_dh...@dh/@en/documents/digitalasset/dh_4064945.pdf

""""""""""""""""""
p47
...

Perhaps the prime indicator of the condition is the way in which symptoms behave after activity is increased beyond what the patient can tolerate. Such activity, whether physical or mental, has a characteristically delayed impact, which may be felt later the same day, the next day, or even later. ... In some instances, the patient can sustain a level of activity for some time, but a cumulative impact is seen, with a setback after several weeks or more.
"""""""""""""""""""""

 

[biophile]

Dropping the actigraphy could be damage control. Burdening patients, are the benefits of CBT/GET that fragile? The same Professor White who doesn't want to burden patients with "unethical" tilt-table tests? I suspect at some stage the PACE trial designers dropped actigraphy after becoming aware of the lack of objective improvements using this measurement, possibly from Nijmegen before their meta-analysis of 3 old CBT studies was published.

 

[Dolphin]

Symptoms apart from fatigue have generally not been measured in CBT and GET trials. The main symptom measure they're using is a fatigue scale.

And that's probably for a good reason. Fatigue seems to be the only universal symptom in all CFS patients. That, of course, depends on how you define CFS. (Too bad fatigue is also a universal symptom for several other illness.)

One can measure symptoms even if not everyone has them. It wouldn't take long to measure symptoms using visual analogue scales (i.e. one end is 0, one end is 100 and a patient puts a line down for the level they are at).

In particular, I don't find it very acceptable that pain isn't measured.
What tends to happen is that clinicians will claim exercise is good for pain in CFS but we really don't have the evidence that it is. But we do have evidence that pain even more than fatigue is worsened by exercise testing.

Other extrapolations are also often made. Exercise is claimed to work for CFS (based on fatigue measures - which may not mean much if somebody isn't do more steps in total) and then lots of claims follow (from how exercise helps the general population).

 

[biophile]

Nijmegen has published one study on the effects of CBT on pain in CFS.

http://www.ncbi.nlm.nih.gov/pubmed/17451642

 

[Dolphin]

Nijmegen has published one study on the effects of CBT on pain in CFS.

http://www.ncbi.nlm.nih.gov/pubmed/17451642

I'd be interested in seeing this. They don't seem to be comparing to controls. If on average, there is no change, with half improving and half being made worse, you could have such a result so it doesn't tell us too much by itself.

Also, doesn't suggest it is necessarily good for people (well adults anyway) with significant pain:

In adult patients, a higher pain severity at baseline was associated with a negative treatment outcome.

It's odd they don't publish this data when publishing the studies. Makes me think that overall there wasn't a good result but with a bit of "processing", one can get a good result.

Non-pharmacologic Interventions for CFS: A Randomized Trial
Journal Journal of Clinical Psychology in Medical Settings
Issue Volume 14, Number 4 / December, 2007
DOI 10.1007/s10880-007-9090-7
Pages 275-296
Leonard A. Jason1 , Susan Torres-Harding2, Fred Friedberg3, Katrina Corradi1, Mary Gloria Njoku1, Julie Donalek1, Nadia Reynolds1, Molly Brown1, Bing Bing Weitner4, Alfred Rademaker4 and Morris Papernik5

This compared 4 interventions COG (involving pacing), CBT (based on graded activity/exercise model), ACT (exercise) and RELAX (relaxation, stretching, yoga, etc):

The present study found few differential results among the
non-pharmacologic interventions, although the COG condition
appeared to have more positive change than the other
conditions. On only three variables was one intervention
clearly and significantly different from all of the other three
conditions (depression and pain in joints for COG, and
muscle pain for RELAX).

 

[biophile]

In particular, I don't find it very acceptable that pain isn't measured.

I agree. "There is no consensus in defining chronic widespread pain in CFS, and although there is little or no strong proof for the exact prevalence, chronic pain is strongly disabling in CFS." - Chronic musculoskeletal pain in patients with the chronic fatigue syndrome: a systematic review. (Meeus & Nijs & Meirleir 2007) http://www.ncbi.nlm.nih.gov/pubmed/16843021

It's odd they don't publish this data when publishing the studies. Makes me think that overall there wasn't a good result but with a bit of "processing", one can get a good result.

I have similar suspicions. It is unfortunate when "trust" becomes an issue in research.

The present study found few differential results among the non-pharmacologic interventions, although the COG condition appeared to have more positive change than the other conditions. On only three variables was one intervention clearly and significantly different from all of the other three conditions (depression and pain in joints for COG, and muscle pain for RELAX).

I wonder if CBT proponents have responded with suggestions Jason et al cannot conduct CBT properly?

 

[wdb]

I'm curious how they justify calling the FINE trial single blind, as far as I can see those administering the treatments must have known which treatment they were administering and those receiving treatment must have known which treatment they were receiving.

I would also be interested how medical professionals would react to a study of GET and CBT for weight loss - with the only outcome measures being questionnaires asking the subjects how much weight they felt they had lost.

 

[xanadu]

I'm curious how they justify calling the FINE trial single blind, as far as I can see those administering the treatments must have known which treatment they were administering and those receiving treatment must have known which treatment they were receiving.

I would also be interested how medical professionals would react to a study of GET and CBT for weight loss - with the only outcome measures being questionnaires asking the subjects how much weight they felt they had lost.

Medical professionals are trained not to ask questions about ME.

They are using single blind here to mean the data were collected blindly. From the protocol:

To reduce observer bias in assessment, all assessment data are collected by research assistants not involved in, and blind to, treatment; in addition, the research assistants are accommodated in different locations from the therapists.

But I can't see any mention whether the statistical analysis was blinded, which ought to be the case.

 

[wdb]

Oh, I see, thanks. So it's basically..

Placebo effect due to nurse's expectations - present
Placebo effect due to subject's expectations - present
Placebo effect due to statistician's expectations - not present

Still seems to me enough placebo in there to explain any less than dramatic outcomes.