PACE Trial and PACE Trial Protocol

[Bob]

Does anyone have any links to any informal or off-the-cuff comments or discussion by White (or even Wessely) about the PACE Trial?
Thank you for any info.

 

[Esther12]

Does anyone have any links to any informal or off-the-cuff comments or discussion by White (or even Wessely) about the PACE Trial?
Thank you for any info.

Michael Sharpe: "Chronic fatigue syndrome: Neurological, mental or both" incl. PACE

http://forums.phoenixrising.me/show...tal-or-both-quot-incl.-PACE&highlight=wessely

ABC radio interview:

http://forums.phoenixrising.me/show...eatments-for-CFS-PACE-trial&highlight=wessely

There was that recent Wessely presentation where he mentioned Pace... but I can't find it now. A collection of slides, and audio of him speaking. He describes it as 'beautiful and elegant', or something like that.

 

[oceanblue]

Does anyone have any links to any informal or off-the-cuff comments or discussion by White (or even Wessely) about the PACE Trial?

try this Wessely talk:

"Health in mind and body: bridging the gap"
http://www.foundation.org.uk/events/audios/audiopdf.htm?e=440&s=1200

20 minute audio and slides, PACE bit starts about 10 mins in.

 

[Angela Kennedy]

Just thought I'd re-post this correspondence sent to Angela from the Lancet, in case people aren't aware that the Lancet has an 'independent' Ombudsman to make complaints to.

But people need also to be aware that Warlow has a conflict of interest in that he is a co-author with Sharpe, and promotes psychogenic explanations for difficult to diagnose somatic (meaning bodily) illnesses.

 

[Enid]

What a tangled web it all is Angela. One feels bound to ask this lot about the basis of their "difficult to diagnose" patients for which the psychogenic "model" is deemed the treatment. I hear we have very basic blood tests here and yet all the likely viruses etc. (or combinations of) are found widely with accurate testing - as all on PR. What may be difficult to them is apparently not for Docs outside the UK. Perhaps they should update their diagnostic "tools" first - and find a lot less difficult to diagnose !.

 

[Bob]

But people need also to be aware that Warlow has a conflict of interest in that he is a co-author with Sharpe, and promotes psychogenic explanations for difficult to diagnose somatic (meaning bodily) illnesses.

*sigh*

Is there no escape from these people?!?

I did wonder about the word 'independent'!

I'm guessing that the Lancet have to pay them to be their 'independent' ombudsman (that's a guess), in which case, they are not entirely independent.

 

[Bob]

Thanks for the links Esther and ocean.
Much appreciated.

 

[Jenny]

The letter on PACE that Ocean Blue and I wrote for The Psychologist has been published in the June edition (both on-line and print editions).

It was unedited, but oddly it was under the heading 'In defence of PACE' and coupled with another letter that was somewhat positive about the trial.

Here is the text of our letter:

Your summary of the findings of the PACE trial (White et al., 2011), which evaluated the effectiveness of CBT and graded exercise therapy as treatments for ME/CFS (Fatigue evidence gathers PACE, April 2011), gave a somewhat misleading impression of the outcomes of this study. You said that self-reports on measures of fatigue and physical function showed that 30% of CBT patients and 28% of exercise patients had returned to normal function. This suggests that nearly one-third had recovered with these treatments. Unfortunately this is far from the case.

First, the thresholds for normal were set so low they could include those with considerable disability. The authors defined within the normal range as a Short Form-36 Physical Function (SF-36) score of 60 or more (0-100 scale), yet the problems with physical functioning that characterise CFS were defined by a SF-36 score of up to 65 - which overlaps with normality. The situation with fatigue scores is similar, so that a participant may have met the trial fatigue criteria for CFS yet simultaneously have met the criteria for normal. Consequently the figures you quoted tell us little meaningful about the PACE trials effectiveness.

Secondly, it is of some concern that the authors inexplicably changed the criteria for positive primary outcomes originally proposed by them in the protocol for the study
(White et al., 2007). On the Chalder Fatigue Scale, for example, they stated that a positive outcome would be a 50% reduction in self-reported fatigue, or a score of 3 or less. And on the SF-36 scale of physical function a score of 75 or more, or a 50% increase from baseline would be required. So the figures you reported are misleading.

Thirdly, you omitted to mention the disappointing outcomes on more objective measures of functioning. For example, after a year of treatment, patients receiving graded exercise therapy had on average increased the distance they were able to walk in 6 minutes from 312 to 379 metres. Even patients suffering from serious chronic cardiopulmonary diseases can manage more than this (in a sample of over 1,000 such patients the mean distance walked was 393 metres [Ross, Murthy, Wollak, & Jackson, 2010]), and at normal walking speed people typically cover around 500 metres. CBT treatment had no significant effect on walking distance.

Perhaps these results are unsurprising, given that the treatments focused on reducing patients assumed fear of engaging in activity, and completely failed to acknowledge the complexity of this illness. We are much concerned that exaggerated claims for these treatments will create a false impression of the effectiveness of PACE amongst psychologists, and will continue to divert scarce resources away from effective medical treatments for this devastating condition.

References
Ross, R.M., Murthy, J.N., Wollak, I.D., & Jackson, A.J. (2010). The six-minute walk test accurately estimates mean peak oxygen uptake. BMC Pulmonary Medicine, 10.31. http://www.biomedcentral.com/1471-2466/10/31

White P.D., Sharpe M.C., Chalder T., DeCesare J.C., Walwyn R., and the PACE Trial Group (2007). Protocol for the PACE trial: A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BioMed Central Neurology, 2007;7:6. http://www.biomedcentralcom/1471-2377/71/6

White, P.D., Goldsmith, K.A., Johnson, A.L, Potts, L., Walwyn, R., DeCesare, J.C, Baber, H.L., Burgess, M., Clark, L.V., Cox, D.L., Bavinton, J., Angus, B.J., Murphy, G., Murphy, M., ODowd, H., Wilks, D., McCrone, P., Chalder, T., Sharpe, M.C., on behalf of the PACE trial management group (2011). Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE). The Lancet, published online February 2011. DOI:10.1016/So140-6736(11)60006-2.
Edit Report .Results 1 to 1 of 1

 

[ukxmrv]

Congratulations Jenny and Oceanblue, for writing such a fine letter, getting through their exhausting process and having it printed

Thank you!

:victory:

 

[Dolphin]

Congratulations Jenny and Oceanblue, for writing such a fine letter, getting through their exhausting process and having it printed

Thank you!

:victory:

Yes well done, Jenny & Oceanblue. Good you were on the ball that there are/were other places to post criticisms.

 

[Dolphin]

FWIW, the letters are in the print edition of the Lancet today. The pdfs can be downloaded for free: http://www.thelancet.com/journals/lancet/issue/current

 

[Bob]

Congratulations Jenny and oceanblue. And thank you.

And a big thank you to everyone else who has been working so hard on this issue over the past few months, for representing our community so brilliantly.

 

[Bob]

From the Action for ME website:

Reports of PACE results are far from accurate
In a letter to the editor, sports psychologist Phil Johnson points out that a previous articles summary about the PACE trial was misleading. Mr Johnson, who has CFS, says the results it reported that nearly a third of patients recovered using GET or CBT are actually far from accurate, because a form of pacing underlies all treatments and its difficult for researchers to pin this down.

In another letter, Jennifer Kidd and Simon McGrath voice their concerns that exaggerated claims for the effectiveness of GET and CBT will divert resources away from effective medical treatment of M.E.

The Psychologist, p 400-401
01/06/11

http://www.afme.org.uk/news.asp?newsid=1217

The comment about pacing is interesting... I hadn't thought of that angle before.

Pacing is an extension of what people do naturally when they are tired or exhausted... They slow down and rest.
It's a natural, inbuilt, human survival mechanism.
It's very natural, and not at all contrived, and so it is very easy for patients to understand.
(But according to Horton on the abc radio interview, scientists are 'sceptical' about it!)

So, yes, participants in all groups in the PACE Trial would have been employing a form of pacing, whether they knew it or not.
When we feel exhausted, we slow down or stop. It's as simple as that.

 

[Dolphin]

PACE press conference audio and transcript

PACE press conference audio and transcript

This might be better discussed on the thread specifically for it:
http://forums.phoenixrising.me/showthread.php?12043-PACE-press-conference-audio-and-transcript

Permission to repost:

Lancet podcast, February 18th 2011: Authors discuss the results of the PACE trial concerning treatment strategies for chronic fatigue syndrome.

This podcast was part of the PACE Trial Press Conference held at the Science Media Centre on the 17th February 2011


http://www.meactionuk.org.uk/pacepressconf.html

The audio takes a wee while to download.

 

[Andrew]

I've been reading the comments here and I have questions, so I hope someone can help me out.

Would it be reasonable for me to say to a doctor:

The study was not CFS as we know it in the U.S, but rather a group of unexplained fatigue causes, some of which might have been what we call CFS in the U.S. and elsewhere. Most subjects had no improvement. The minority that did improve had increase that was so slight they did not reach a normal range. As for the question of no harm, the study included inadequate information about people who could not complete the study. This is the group that is most likely to contain people who had bad reactions and could not continue. So we don't have a clear picture of safety. Also, the protocol mentions the use of actimeters, but the data was not reported. In a previous study where mild improvement was reported, the actimeters showed no increase in activity. Because the current researchers withheld this data from their report, this leaves a big hole in the analysis. And because we don't know the outcome of subjects would fit the Fukuda or Canadian Consensus diagnosis for CFS. no conclusions about CFS can be drawn.

If any of this is wrong or overstated, please let me know.

 

[Esther12]

Hi Andrew. I'm not sure about all this, but will add my comments in bold, and see if anyone corrects me.

A lot depends, imo, on how your doctor raises it.

I've been reading the comments here and I have questions, so I hope someone can help me out.

Would it be reasonable for me to say to a doctor:

The study was not CFS as we know it in the U.S, but rather a group of unexplained fatigue causes, some of which might have been what we call CFS in the U.S. and elsewhere. Difficult to say if this is true. It's likely that many of the patients were less seriously ill, and for less long, than the typical US CFS patient. I suppose that it partly depends upon how your doctor diagnoses CFS.Most subjects had no improvement. I don't think we've got data on that yet.The minority that did improve had increase that was so slight they did not reach a normal range. They defined 'normal range' in a funny way, so that it included patients more seriously ill than those classed as suffering from 'sever and disabling fatigue' at the start of the trial - certainly not what most would consider 'normal'. It would be fair to say that the average improvement was really minor.As for the question of no harm, the study included inadequate information about people who could not complete the study. This is the group that is most likely to contain people who had bad reactions and could not continue. So we don't have a clear picture of safety. Weren't completion rates pretty good (by the standards of studies of this sort). More of a problem is that we don't really have a good idea as to the rate at which , for example, activity levels were expected to be increased with GET. From their data, it looks like the average increase was much smaller than that promoted in past conceptions of GET. It could be this more cautious approach avoided the problems of the past, but will now be used to justify a less cautious approach on the front-line.Also, the protocol mentions the use of actimeters, but the data was not reported. Actometers were purchased and used at baseline, but dropped prior to the publication of the protocol. In a previous study where mild improvement was reported, the actimeters showed no increase in activity. True. Because the current researchers withheld this data from their report, this leaves a big hole in the analysis. It leaves a big hole, but they didn't collect the data, rather than withholding it. There is still lots more data that was collected for Pace, and hopefully we'll get it all soon. And because we don't know the outcome of subjects would fit the Fukuda or Canadian Consensus diagnosis for CFS. no conclusions about CFS can be drawn. Only limited conclusions anyway.

Hopefully that will get the ball rolling.

 

[Snow Leopard]

I posted a reply to Andrew's post about 30 minutes ago, but it doesn't seem to have turned up. (it might have been due to connection problems on my end)

I think you need to use different language for medical practitioners..

The issue with the Oxford criteria is because it only requires unexplained fatigue for 6 months, it has much lower specificity than Fukuda or CCC and is much more likely to produce a heterogeneous group, including many with mild depression related fatigue and these cases are much more common than moderate-severe CCC CFS.

Secondly, the authors previously published a fairly rigorous protocol with thresholds for 'clinical significance' and 'recovery'. But in the Lancet paper, they did not report outcomes according to the protocol. No data was published on how many subjects reached these thresholds. So the clinical significance is uncertain and likely to be small since these thresholds were not reached in most subjects.

Secondly, no objective data on activity levels were reported (as you suggest), such as hours spent employed (paid/volunteer) or in study/training. In a review of the outcomes of the Belgian rehabilitation programme (combined GET, CBT, physiotherapy, referrals to employment assistance etc), with a total of 593 adults, they found that paid employment decreased and activity levels did not change (volunteer work/study increased while paid employment decreased).

 

[Graham]

I'd like to think of the PACE report in a different way. The problem to me with there being so many faults with the study, that we can miss the big picture.

Everything was set up in such a way that the bias was towards success with GET and CBT. Despite all the many dissatisfactions that we have with it and its lack of scientific rigour, it is pretty conclusive in showing that the absolute best we can expect from CBT and GET is that perhaps 2 in 15 people, after a whole year, will show some progress, but not good progress (if I am wrong and some do show good progress, then the proportion drops to much less than 1 in 15). The rest, at the very best, will make minimal progress or get worse. (Bob and I set up a little blog to illustrate that - meanalysis ) That is the most that GET or CBT can achieve for a very large group of patients, and this is a trial that was set up by GET and CBT "experts" and proponents. Of course the truth is likely to be much worse than that, due to the errors in the trial, and there may well be people who, to my intense frustration, are harmed, but in a scientific sense, that is irrelevant because there is now strong evidence that there is no justification for expecting GET or CBT to help with CFS under any set of criteria. The small number of individuals that may be helped clearly fill some other criteria, yet to be determined, but not relevant to CFS (it may, for example, turn out to be a subset of people with depression).

I think that, viewed dispassionately, the study provides a very strong case for abolishing CBT or GET for CFS of any form, and in doing that, it totally undermines the psychological assumptions about CFS that underpin it. It will just take a long time for the logic to sink in.

 

[Bob]

Could somebody help me with something that's been puzzling me please...
When Sharpe says the following in the abc radio interview:

Michael Sharpe: We have a number needed to treat; I think it's about seven to get a clinically important treatment benefit with CBT and GET. What this trial isn't able to answer is how much better are these treatments than really not having very much treatment at all.

Is he basing that 'one in seven' figure (to get a clinically important treatment benefit) on the results for the 'normal range'?

Normal Range at 52 weeks:
SMC 22 of 152 participants (15%)
GET 43 of 154 participants (28%) (This is 13% more than the SMC group)
CBT 44 of 148 participants (30%) (This is 15% more than the SMC group)

'One in seven' is 14.3%, which is nearly 13% and 15%, as per the net values for GET and CBT.



By the way, I think that's a very useful quote to remember:

Michael Sharpe: "What this trial isn't able to answer is how much better are these treatments than really not having very much treatment at all." http://www.abc.net.au/rn/healthreport/stories/2011/3192571.htm#transcript

What an admission! Doesn't this make our case for us?!? (or am i missing something?)

 

[Dolphin]

Could somebody help me with something that's been puzzling me please...
When Sharpe says the following in the abc radio interview:

Michael Sharpe: We have a number needed to treat; I think it's about seven to get a clinically important treatment benefit with CBT and GET. What this trial isn't able to answer is how much better are these treatments than really not having very much treatment at all.

Is he basing that 'one in seven' figure (to get a clinically important treatment benefit) on the results for the 'normal range'?

Normal Range at 52 weeks:
SMC 22 of 152 participants (15%)
GET 43 of 154 participants (28%) (This is 13% more than the SMC group)
CBT 44 of 148 participants (30%) (This is 15% more than the SMC group)

'One in seven' is 14.3%, which is nearly 13% and 15%, as per the net values for GET and CBT.



By the way, I think that's a very useful quote to remember:
Sharpe: "What this trial isn't able to answer is how much better are these treatments than really not having very much treatment at all."
What an admission! Isn't this all we need to make our case?!? (or am i missing something?)

I think it's more likely "clinically important treatment benefit" refers to the following:

A clinically useful difference between the means of
the primary outcomes was defi ned as 05 of the SD of
these measures at baseline,31 equating to 2 points for
Chalder fatigue questionnaire and 8 points for short
form-36. A secondary post-hoc analysis compared the
proportions of participants who had improved between
baseline and 52 weeks by 2 or more points of the Chalder
fatigue questionnaire, 8 or more points of the short
form-36, and improved on both.

64 (42%) of 153 participants in the APT group improved
by at least 2 points for fatigue and at least 8 points for
physical function at 52 weeks, compared with 87 (59%) of
148 participants for CBT, 94 (61%) of 154 participants for
GET, and 68 (45%) of 152 participants for SMC. More
participants improved after CBT compared with APT
(p=00033) or SMC (p=00149), and more improved with
GET compared with APT (p=00008) or SMC (p=00043);
APT did not diff er from SMC (p=061; webappendix p 2).

So 61% (GET) - 45% (SMC) = 16%

59% (CBT) - 45% (SMC) = 14%.