Article: A Hitch in its Step: PACE Trial Indicates CBT/GET No Cure For CFS, 60% of Patients Show No

Article: A Hitch in its Step: PACE Trial Indicates CBT/GET No Cure For CFS: 60% of Pa

You can view the page at http://forums.aboutmecfs.org/content.php?369-A-Hitch-in-its-Step

 

Hi Dolphin, I am not a huge fan of the CAA but you raised a very good point. Kim McCleary was probably ambushed by reporters who had more information than she did. We have to be careful about jumping to conclusions without the facts. It would really help if she posted a personal press release detailing the issues, and explaining what happened. Bye, Alex

The press also prints the sections of interview that they want to - which makes some people who have been bitten by out of context remarks - wary of participating with them. I imagine she said much more - and that was left on the cutting floor because it did fit in the journalists 'story'.

 

Mark - I won't have the numbers exactly right here, but they seem to stack up something like this: "providing you're in the 25% subset of patients diagnosed with ME/CFS who we looked at, then after a year of this therapy you have a 40% chance of a 9% improvement in fatigue levels (ignoring those who dropped out of the treatment of course),

Well done!

As you noted in your post CBT is moving into MS and post-cancer fatigue...and a study on heart disease recently came out (it was successful in reducing the # of cardiac events, I think.). Natelson, as I remember, thinks CBT should be taught to everyone in medical school - I guess because it is a stress reducer...It is still mostly used in mood disorders but there are some exceptions.

I plugged 'cognitive behavioral therapy' into the NIH clincal trials database

http://projectreporter.nih.gov/reporter_searchresults.cfm?&new=1&icde=7151550&loc=2&CFID=34433770&CFTOKEN=49016940

and it came up with 238 ongoing studies. Most are on mood disorders but it is reaching into other areas. Here is one on chronic obstructive pulmonary disease and its not all about QOL - they want to see if their program effects mortality and medical costs.

The study will examine the short- and longer- term impact of CST on psychological distress and quality of life as well as the effects of the intervention on morbidity, mortality, and medical costs over a follow-up period of up to 4 years. The ultimate goal of this research program is to develop more effective ways to help patients with chronic lung disease and their caregivers cope more effectively with problematic symptoms, reduce distress, improve quality of life, enhance physical functioning, and increase survival.

Check out this one on MS - the primary effect or outcome is the # of lesions at the end of the study (!).

he purpose of this study is to determine the efficacy of cognitive behavioral therapy for MS (CBT. MS), a stress management program we have developed specifically for MS, in reducing the occurrence of new brain lesions in people with relapsing-remitting multiple sclerosis (RRMS). RRMS was selected over other types, because it is the most common form of MS and it is more likely than other types to be associated with clinical exacerbation and Gd+ MRI. One hundred and twelve patients will be enrolled for 2 years. To ensure equivalent medical treatment across patients and treatment arms, all patients will receive neurological care through the University of California, San Francisco (UCSF) MS Center. Patients will be randomly assigned to either CBT-MS or treatment as usual (TAU). The stress management program will consist of 26 weekly group stress management training sessions followed by 12 monthly booster sessions to encourage maintenance of behavioral changes,

Consistent with Phase II clinical trials in MS, the primary outcome will be Gd+ MRI brain lesions acquired at screening, and months 3, 6, 12, 18, and 24. Secondary neuroimaging outcomes will include T2-weighted MRI and brain parenchymal fraction (BPF). Secondary clinical outcomes will include MS exacerbation rate, progression of disability, and neuropsychological impairment. Quality of life will be examined as a secondary outcome to evaluate clinical utility. We also wilt enhance our understanding of mechanisms by examining potential psychosocial, immune, and endocrine mediators of the relationship betweenSLEs and clinical and neuroimaging markers of MS inflammation.

Here's one on Lupus - the secondary outcome is measuring inflammation and biomarkers associated with the disease

In this project, entitled, Reducing Depressive Symptoms in SLE, we will investigate the efficacy of an innovative non-pharmacologic intervention, Mind-Body Skills Training (MBST) for improving mental and physical health outcomes in SLE in a randomized controlled trial (RCT). MBST is a novel approach that combines cognitive-behavioral therapy methods, mind-body relaxation skills, and mindfulness components, each of which is beneficial for reducing pain and/or distress in other inflammatory conditions.

The primary specific aims of the project are to evaluate the effects of the 8-session MBST program on 1) mental health (depression) and 2) physical health (pain, fatigue, and health-related quality of life). Additionally we will explore the effects of the MBST intervention on 1) novel SLE biomarkers of inflammation and immune function: cell-bound complement activation products, developed at our site, 2) measures of SLE disease activity, and we will explore 3) potential treatment modifiers and mediators: baseline pain and socioeconomic status, and self-efficacy and perceived stress. We will evaluate health outcomes after the interventions and at 6- and 12-months follow-up.

SLE is one of the most complex autoimmune diseases, with one of the highest rates of depression. The MBST intervention has strong potential for addressing the unique physical manifestations and mental suffering in this patient group, and may have broad impact on distressed patients with other debilitating chronic diseases.

 

I'm not sure if this has already been posted...

It's Professor Hooper’s Initial Response to the MRC PACE Trial Press Release...

http://www.meactionuk.org.uk/Hooper-response-to-PACE-Trial-Press-Release.htm

It's not an analysis of the data in the paper though. It's just a very initial response, and I think it's repeating some of his earlier analysis of the project.

 

Acer2000 said:


YES! This was my thought too (see comment #8). Their analysis of the study was helpful, but had NO EFFECT ON HOW THE STORY WAS TOLD! That is what their job is (or maybe it isn't; they do seem to have completely abdicated any public relations activity and that may be just as well given their effectiveness at it). Cort is certainly welcome to write a letter to the NY Times, but that's closing the door after the proverbial horse has left the barn. It's too late. Every doctor in the English-speaking world and beyond has been told that exercise will cure ME/CFS and as patients, we have very little ability to change their minds.

CAA needed to have made sure to have sent their press release to all the media outlets the White et al group sent theirs to and laid out exactly what Cort and many of the commenters have said here about how flawed this study was. They need to give the journalists the headline. The quotes. The main narrative. Journalists, whether because they have no time or are just lazy (or both), are not going to read the study. They are not going to do much beyond read the press release, maybe call two quotes, and then write it up in their own words in the space of maybe an hour TOPS before moving on to their next assignment(s) for the day.

PR is not an arena for "inside voices." It's the loudest and most manipulative voice that wins. Always.

100% agreed. Its always harder to do damage control rather than to be proactive. The CAA should have sent out a press release pointing out the problems with this study and how it, more than anything, indicates the need to move past studies on behavioral approaches and go whole hog into funding research to find the biological cause.

 

There is a Spanish study on GET and CBT for MECFS patients based on the Fukuda criteria: "Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up."

http://www.ncbi.nlm.nih.gov/pubmed/21234629

Unfortunately, it has no press-release that journalists can copy/paste into their articles. Anyone can send this to David Tuller or Amy Dockser Markus?
Can someone get hold of the complete article?

This is a great idea! Have them do an article on this study, which comes to the opposite conclusions as the PACE study, and uses better metric and longer follow up! Even better, before someone contacts them, lets line up links to all of the papers that re-inforce this point. It would be good to have that as a sticky post anyways.

 

Loads of illuminating stuff since I posted, thanks everyone.

Cort, one thing that seemed missing from the numbers analysis in your article, was the part discussed here somewhere about how about some of those who weren't eligible for inclusion - you mentioned those who were told they were told they weren't eligible but the breakdown of that, I thought, revealed that a large proportion of them were rejected for having - effectively - ME symptoms, like neurological or immune symptoms. I may be a little foggy on all that, but that was one of the few details pulled out from the analysis here that I didn't notice in your article.

Its always harder to do damage control rather than to be proactive. The CAA should have sent out a press release pointing out the problems with this study and how it, more than anything, indicates the need to move past studies on behavioral approaches and go whole hog into funding research to find the biological cause.

Key point. Everyone should have been prepared with press releases ready to go based on what we did already know, and response teams ready to maximise that, and got them all sent out alongside the study's press release. Immediate reaction from opponents is really, really tough, when the thing is so deviously timed and embargoed, but at least a pre-emptive press release priming journalists on all the flaws, expected flaws, disputed methodology, etc, could have been ready to go.

ME Action did a great job there, I thought, releasing its own patient survey results alongside the PACE results, and at least getting a little bit of counter-information out there right near the beginning of the race. That was a smart move. Patient surveys can't be seen to be comparable to peer-reviewed science, one can't expect that, but it's still information worth reporting, it's about as much as could be expected, and it did get out there, a bit. Good job!

 

The CAA have put out a statement now:

Too Big to Fail - Commentary on the PACE Trial
http://www.cfids.org/cfidslink/2011/lancet-study.asp

And they've published a 'detailed analysis' here:

Falling Off the PACE
http://www.cfids.org/pdf/lancet-analysis.pdf

 

I plugged 'cognitive behavioral therapy' into the NIH clincal trials database


Check out this one on MS - the primary effect or outcome is the # of lesions at the end of the study (!).

he purpose of this study is to determine the efficacy of cognitive behavioral therapy for MS (CBT. MS), a stress management program we have developed specifically for MS

The CBT in the PACE Trial wasn't a a stress management program. That's more like the Lopez et al. study from Florida published recently.

 

Light Speed

After one year of 'treatment', the reported improvement for the GET group of patients, was to walk an extra 67 meters in a 6 minute period, as compared to what they could do at the beginning of the study.

If we were to assume that the rate of improvement would be continuous, then I've worked out that it would only take approximately 1,661,538,500 years of GET training in order to be able to walk at the speed of light for a 6 minute period (If only we would put our minds to it and stop malingering!) (Light travels 108,000,000,000 metres in a six minute period.)

The study indicates that we'd only be able to travel at Light Speed for 6 minutes though, and with the depth of the relapse afterwards, I don't think it would be worth it really, just for a six minute joy-ride!

Stupid study!

(Sorry, it's late at night, and I should be in bed!)

 

The most recent NIH workshop on chronic fatigue syndrome was the one on neuroimmune mechanisms held in June, 2003. Dr. Peter White was one of the invited speakers, and he spoke on graded exercise therapy. During the audience question period, I asked him whether he was concerned that exercise produces oxidizing free radicals, and that they might further deplete glutathione. His response was "I'm not a biochemist."

Rich

 

The most recent NIH workshop on chronic fatigue syndrome was the one on neuroimmune mechanisms held in June, 2003. Dr. Peter White was one of the invited speakers, and he spoke on graded exercise therapy. During the audience question period, I asked him whether he was concerned that exercise produces oxidizing free radicals, and that they might further deplete glutathione. His response was "I'm not a biochemist."

Rich

Peter White writes letters to journals if people suggest there might be risks with GET (barely writes about anything else, except in reply to the Lombardi et al. study even though they (he and colleagues) didn't say too much of substance, they just wanted to throw general dirt in the direction - there are plenty of worse studies out there that are much more clearly flawed). His line is that their GET program is safe. Even if that is the case (which I'm not convinced), he never (to my knowledge) admits there could be problems with other exercise programs or that people or doctors hearing exercising could help might lead to people with ME/CFS using exercise in other ways. I don't trust him as an unbiased person on the issue of safety. It reminds me very much of somebody associated with a pharmaceutical product. I could give more evidence but have a lot on.

The insurance company(s) he does work for I'm sure like his opinion when he is denying people their claims until the person does a GET program (somebody showed information they got on their case which was shocking ).

 

Peter White writes letters to journals if people suggest there might be risks with GET (barely writes about anything else, except in reply to the Lombardi et al. study even though they (he and colleagues) didn't say too much of substance, they just wanted to throw general dirt in the direction - there are plenty of worse studies out there that are much more clearly flawed). His line is that their GET program is safe. Even if that is the case (which I'm not convinced), he never (to my knowledge) admits there could be problems with other exercise programs or that people or doctors hearing exercising could help might lead to people with ME/CFS using exercise in other ways. I don't trust him as an unbiased person on the issue of safety. It reminds me very much of somebody associated with a pharmaceutical product. I could give more evidence but have a lot on.

The insurance company(s) he does work for I'm sure like his opinion when he is denying people their claims until the person does a GET program (somebody showed information they got on their case which was shocking).

Hi, Dolphin.

Note that on the "crowd-sourced" site http://www.curetogether.com/chronic-fatigue-syndrome/treatments/ GET is running in next to last place in the "average effectiveness" ranking, just above drinking alcohol. Rest breaks and resting are running first and second.

Rich

 

Hi, Dolphin.

Note that on the "crowd-sourced" site http://www.curetogether.com/chronic-fatigue-syndrome/treatments/ GET is running in next to last place in the "average effectiveness" ranking, just above drinking alcohol.

Rich

Thanks.
Then one have the surveys mentioned in my .sig:

11 surveys which found high rates of adverse reactions with GET
http://bit.ly/4nH5Wi

 

The CAA have put out a statement now:

Too Big to Fail - Commentary on the PACE Trial
http://www.cfids.org/cfidslink/2011/lancet-study.asp

And they've published a 'detailed analysis' here:

Falling Off the PACE
http://www.cfids.org/pdf/lancet-analysis.pdf

Yeah while this is much better than the quote she gave to CNN and NPR, it still stops short pointing out how this study actually proves the opposite of what the authors claimed in their press release. Namely, that the data actually show that CBT/GET are pretty much useless as far as impact on the symptoms of ME/CFS and that future research should focus exclusively on biomedical causes and treatments.

 

Loads of illuminating stuff since I posted, thanks everyone.

Cort, one thing that seemed missing from the numbers analysis in your article, was the part discussed here somewhere about how about some of those who weren't eligible for inclusion - you mentioned those who were told they were told they weren't eligible but the breakdown of that, I thought, revealed that a large proportion of them were rejected for having - effectively - ME symptoms, like neurological or immune symptoms. I may be a little foggy on all that, but that was one of the few details pulled out from the analysis here that I didn't notice in your article.

I did miss that (completely)... It sounds like a good point. Looking at the news article we really lost the spin battle. I did notice this the SF rag

"Even with the best therapies we have, four out of 10 people don't improve," said Peter White, a professor of psychological medicine at the Queen Mary University of London, who led the study. "This is a genuinely disabling condition, and we need to do more to determine how to enhance current therapies."

Its just a frigging shame that they newspapers don't have a clue what 'improve' means.....And here's Peter White saying what we need to do is 'enhance the current therapies' not find new ones.

 

Hi Cort,
This is my first post on your site.
Thanks for the great summary of the study and for the enlightening comments by others.
Has anybody found answers to some questions I have:

1. What was the definition of 'serious adverse reaction'? I note there were very few of these. I gather it does not mean PEM which is pretty serious for me.
2. Does anybody know how the 30% 'recovery rate' quoted by Bleijenberg in the Lancet was arrived at? the statistical explanation does not mean much. From this though it would seem to mean an average of 30% improvement among all the participants. This would mean that quite a few would have got worse than a 30% improvement.
BBC News has already interpreted this vague statement to mean that 30% of patients returned to normal.
3. Is it apparent form the report what 'other' symptoms were taken into account? Besides fatigue I guess. I have numerous'other' symptoms in accordance with ME.

Thanks,
acacia

 

Concise Statement

Cort

I'm going to quote myself from another thread to present my most compact statement of what I believe the study achieved:

These data support the hypothesis that a substantial proportion of patients in this cohort, approaching half, suffer from undetected organic disease which is as unresponsive to psychological treatment as multiple sclerosis.

I can't fault either the resources that went into the study or the expressed intent of those running it for lack of belief in psychological etiology. This brings up a question of British sporting etiquette. Should you congratulate a group for cheering an own goal?

 

Not much attention has yet been given to the fact that all four groups received 'standard medical care'. What we see is e.g. not the effect of CBT, but the effect of the combination of 'standard medical care' and CBT.

But this SMC was not the same for every individual patient, and since the researchers knew which patients followed which regime, they had much opportunity to influence the outcome.

Also, the statistical method used to calculate the significancy of the results does not take any dependencies into account. There is no justification for that, since antidepressants, antihypnotics and painkillers will most certainly influence how the participants (half of them psychiatric patients) perceive the effects of CBT, GET and 'adaptive pacing'. As a consequence, the reported significancy is biased and likely overestimated.

Regards,

Guido den Broeder
www.me-cvsvereniging.nl

 

All music to our ears here in the UK. Thanks to you all for thorough analysis/reasoning. And putting PACE where it belongs.

 

Distinguishing Nonresponders

Following a previous line of argument further, the most striking result of the study is a complete failure to distinguish responders who might benefit from proposed treatments from nonresponders except by overall failure. This is a powerful argument against scaling up. It also resurrects the cohort question.

My succinct summary now looks like this:

These data support the hypothesis that a substantial proportion of patients in this cohort, approaching half, suffer from undetected organic disease which is as unresponsive to psychological treatment as multiple sclerosis. Psychological means of distinguishing nonresponders appear limited to failure of a full-scale trial. Without falsifiability of hypotheses of etiology within psychology, we must seek physiological data to distinguish responders from nonresponders.