• Phoenix Rising needs funds to operate: please consider donating to support PR

"News" 8 Sep 2016: PACE trial team analyse main outcome measures according to the original protocol

Tom Kindlon

Senior Member
Messages
1,648
Likes
8,694
The results don't look nearly so good according to the protocol

View attachment 17186



Note the Lancet paper and the protocol use very different definitions of improver, but I guess that's the whole point.
I thought I would explain exactly what is being discussed as some people have said they are confused (elsewhere).

The PACE Trial investigators published a protocol in which they described how they would report their results.

See below for their primary outcome measures (the most important results of a trial). Note that the 3rd one is called "overall improvers".

However when they came to publish the results, they decided to alter these and not publish the original results alongside so people could make their own decisions about whether the changes made a difference or not.

They also decided to make up a new definition for improvement. They said this was a post-hoc analysis i.e. performed after they had seen the data.

This led to them to say in the Lancet that 61% improved overall (i.e. on fatigue and self-reported physical functioning) with GET and 59% improved overall with CBT.

Today they have now released the data showing that if one used the original definition for overall improvers that they commited to publish in the 2007 protocol paper, 21% were overall improvers with GET and 20% were overall improvers with CBT i.e. approximately one 3rd of the rate of improvement they reported in the Lancet.

Note that today they never mentioned the 61%/59% improvement rates so readers won't see or be made aware of the stark difference.

2007 Protocol paper said:
Primary outcome measures – Primary efficacy measures

Since we are interested in changes in both symptoms and disability we have chosen to designate both the symptoms of fatigue and physical function as primary outcomes. This is because it is possible that a specific treatment may relieve symptoms without reducing disability, or vice versa. Both these measures will be self-rated.

The 11 item Chalder Fatigue Questionnaire measures the severity of symptomatic fatigue [27], and has been the most frequently used measure of fatigue in most previous trials of these interventions. We will use the 0,0,1,1 item scores to allow a possible score of between 0 and 11. A positive outcome will be a 50% reduction in fatigue score, or a score of 3 or less, this threshold having been previously shown to indicate normal fatigue [27].

The SF-36 physical function sub-scale [29] measures physical function, and has often been used as a primary outcome measure in trials of CBT and GET. We will count a score of 75 (out of a maximum of 100) or more, or a 50% increase from baseline in SF-36 sub-scale score as a positive outcome. A score of 70 is about one standard deviation below the mean score (about 85, depending on the study) for the UK adult population [51, 52].

Those participants who improve in both primary outcome measures will be regarded as overall improvers.
From:
White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; PACE trial group. 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. BMC Neurol. 2007 Mar 8;7:6.

http://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-7-6
2011 Lancet paper said:
A clinically useful difference between the means of the primary outcomes was defined as 0・5 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.
from

White PD1, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, Baber HL, Burgess M, Clark LV, Cox DL, Bavinton J, Angus BJ, Murphy G, Murphy M, O'Dowd H, Wilks D, McCrone P, Chalder T, Sharpe M; PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011 Mar 5;377(9768):823-36. doi: 10.1016/S0140-6736(11)60096-2. Epub 2011 Feb 18.
Cr2dWflWIAAYOqg.jpg
 
Last edited:

daisybell

Senior Member
Messages
1,613
Likes
7,387
Location
New Zealand
I think strictly speaking, what you are describing is response bias, ie people changing their scores as opposed to really improving. There's now good evidence that the placebo effect doesn't really amount to much - almost nothing doing on objective measures of improvement (across many illnesses), hardly any better on self-reported outcomes.

Placebo interventions for all clinical conditions. - PubMed - NCBI
Is the placebo powerless? Update of a systematic review with 52 new randomized trials comparing placebo with no treatment. - PubMed - NCBI
Yes - of course, you're right!
 

Research 1st

Severe ME, POTS & MCAS.
Messages
762
Likes
2,537
I would like to know how many patiënts where fully recovered. They said 22% in 2013. I think no one is recovered now.
Good point, but that would still only be an alleged recovery from F48.0 Psychiatric criteria CFS as this criteria was used in PACE. (The established research in CFS science, does not use F48.0 criteria, as this is psychiatric, and CFS is not classified as psychiatric disorder). A very important when considering PACE data.

This is where the ME denial lobby are screwed, by foolishly inventing their own criteria (Oxford CFS), in order to rig the game against patients with Myalgic Encephalomyelitis (Organic CFS in USA) believing the situation would never change as they called the shots.

PACE was meant to keep UK patients with organic disease ME hostage for at least another 20 years, it's lasted about 7 though.

Even if PACE had 'won' by denying ME (ME as psych CFS F48.0) this lie only remains, as long as biomedical ME research is blocked and psychiatry is massively over presented in research journals, health services, and in the eyes of the public who see ME patients as inferior. Time ran out for that. Science has moved on even if the politics hasn't.

Bogus Science and Government are always joyously linked, but that doesn't consider Independent Honest Scientists, changing the Status Quo. This is happening, not just in America. Too many studies are now published to propose ME doesn't exist and CFS is psych F48.0.
 

Research 1st

Severe ME, POTS & MCAS.
Messages
762
Likes
2,537
Thanks for that Kati.
Peter Tatchell is an incredible guy, he always stands up for freedom and an end to Xenophobia for all people irrespective of sexuality.

The treatment of ME CFS (via disease denial) is a form of Xenophobia.

It's great to see Peter Tatchell can see this and is supporting us. Perhaps this heralds the first signs of equality?
 

Daisymay

Senior Member
Messages
754
Likes
4,060
Just looking at some of the wording of this:

http://www.wolfson.qmul.ac.uk/images/pdfs/pace/PACE_bimodal_CFQ_analysis_final_8_Sept_2016.pdf

"PACE was a randomised controlled trial"

No, it wasn't an RCT, as they know only too well, it was merely a randomised trial, as is clearly stated in the PACE title:

"Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial"

"Interpretation - The pattern of trial outcomes observed when the Chalder Fatigue scale was bimodally scored was very similar to that seen in the main PACE results paper (White et al 2011) for the Likert scored CFQ i.e. there was a greater improvement in fatigue in those allocated to CBT and GET groups compared with those allocated to APT and SMC with these differences being of moderate size."

So have I got this right.....they're saying it's OK because whichever method they used they found "very similar" patterns????

"In summary, these results support our initial interpretation that “CBT and GET can safely be added to
SMC to moderately improve outcomes for chronic fatigue syndrome, but APT is not an effective
addition.”


No, these new results give no information at all on the safety or otherwise of CBT/GET, the issue of safety shouldn't be mentioned here.

How can they call 10% better than SMC alone moderate improvement?
 

Research 1st

Severe ME, POTS & MCAS.
Messages
762
Likes
2,537
If I'm reading this correctly, the bottom line is that 10% of people improve naturally over time (SMC). If you focus on exercise and tell people this will help, an extra 11% will report some improvement. If you give people CBT and tell them they will feel better, 10% say they do to some extent. Those figures are dreadful considering the power of the placebo effect!
Exactly, CBT is a placebo effect as nothing has to exist for the 'effect' to alter the disease, as no test is used to verify that anything is wrong with the person with F48.0 CFS in the first place. With Oxford criteria CFS, existing or prior history of mental illness, is permitted in the CF patient (unlike Fukuda CFS/CCC-CFS/ME-ICC/IOM SEID).

It wouldn't be hard to enroll people with 'perhaps' MS in a study (with active depression or prior mental illness) to walk 6 mins a day, for 3 months whilst giving them magic pills, convincing them there is a potential cure for MS if they take it.

And then answering a questionnaire, do you feel less fatigue?

The results would be irrelevant to Science and nothing to do with MS, as the criteria with MS weren't met in the first place, before the placebo effect was given!
 

Hutan

Senior Member
Messages
1,086
Likes
6,445
Location
New Zealand
So pleased the PACE investigators were presumably able to scrape up a statistician to retrieve the data for this analysis - given one of their reasons for not releasing the raw data was that they would have to hire and train a statistician and that was all just too onerous.

Interesting changes but frankly it is all just wobble on the way to a null result at 2.5 years for a group of people that may well not even have had ME/CFS.
 

Dolphin

Senior Member
Messages
17,555
Likes
28,242
So pleased the PACE investigators were presumably able to scrape up a statistician to retrieve the data for this analysis - given one of their reasons for not releasing the raw data was that they would have to hire and train a statistician and that was all just too onerous.

Interesting changes but frankly it is all just wobble on the way to a null result at 2.5 years for a group of people that may well not even have had ME/CFS.
One effect that comes to mind is that the medical textbook entry, I think written by Peter White, which said that around 60% improved in the PACE Trial with CBT or GET would need to be significantly altered.
 
Last edited:

Esther12

Senior Member
Messages
13,774
Likes
28,356
Ok so the data released was not the raw data we expected? But another reanalisys?
Yes. This was the results for the primary outcomes laid out in the trial protocol.

It's really good to have these. They provide more realistic information on efficacy for those patients who are unconcerned by things like response bias, and are happy to try poorly evidenced interventions like homeopathy, that may be no more than placebo. These figures also provide more realistic information to doctors, and is likely to reduce the danger them being misled with exaggerated claims about the likelihood of significant improvement.
 

Dolphin

Senior Member
Messages
17,555
Likes
28,242
For this analysis, the primary outcomes were recoded to define dichotomous improvement versus non-improvement as outlined in the PACE protocol (White, Sharpe, Chalder, DeCesare, & Walwyn, 2007). This coding was as follows: for physical functioning, participants were coded as improvers if they had either a score of 75 or more (out of 100) at 52 weeks post-randomisation, or a 50% increase from the baseline score at that time point. For fatigue, participants were coded as improvers if they had either a score of 3 or less (out of 11) at 52 weeks post-randomisation, or a 50% decrease from the baseline score on the bimodal scored Chalder fatigue scale at this time point. We used prorated outcomes, as described in the main paper (White et al, 2011).

An additional composite outcome of overall improvement in which participants were coded as improved or not improved in both physical functioning and fatigue was created.
Don't know if I'm being too picky or not, but after reading this last sentence one could be forgiven for thinking that the composite outcome was not one of the prespecified primary outcomes in the protocol and instead they had just come up with it now to be transparent.
 

eastcoast12

Senior Member
Messages
136
Likes
399
Location
Long Island ny
So just thinking about this from a different angle. They used the Oxford criteria for entry into the trial which is just 6 months of fatigue ( did they even describe the type of fatigue? Was the 6 months of fatigue even documented in medical records? I'm thinking the word fatigue wouldn't be the word we use to describe that no lifeblood feeling we feel).
So if it's just fatigue then it's pretty safe to bet that some people who were entered may have just been experiencing life. You know, work, kids, family etc. Before I got sick when I was working and tutoring and going to the gym and cooking and cleaning and going out with friends/family a lot, I would have considered myself fatigued specially if it was near the holidays. That's why you see in comments sections people saying things like I'm tired too stop being lazy.

Second, because of the Oxford criteria used for entrance, it's also a pretty safe assumption that a significant portion of those entered had/have another health issue (psych/bio) causing fatigue.

Three, with this in mind it's not only safe to say but it's definitive that we have no idea how many people in this study actually had cfs/me.

Ok. So taking those things into consideration what I'm taking away from PACE is not only does GET/CBT/BPS not work for people with cfs/me it barely works for anything that may have been wrong with people in this trial. To me the bigger picture is that this study provides little evidence that they're GET/CBT/BPS model has any scientific legitimacy at all.
If I'm overlooking anything or misinterpreting anything please let me know.
 

Dolphin

Senior Member
Messages
17,555
Likes
28,242
Interpretation
All three of these outcomes are very similar to those reported in the main PACE results paper (White et al, 2011); physical functioning and fatigue improved significantly more with CBT and GET when compared to APT and SMC. One difference was found however; in this analysis with CBT compared to SMC, the difference for physical functioning was no longer statistically significant at p = 0.20.
I don't find a 20% overall improvement for CBT and 21% overall improvement for GET to be very similar to the 59% overall improvement rate for CBT and 61% overall improvement rate for GET reported in the main PACE results paper.