PACE Trial and PACE Trial Protocol

[Esther12]

He says "Two other conditions, CBT and GET, were associated with better symptom outcomes than the other two." He is taking that....e, never questioning whether they actually had better symptom outcomes, and does not seem to recognize the problem with it being a subjective outcome itself.

He's making an unfounded assumption that (CFS) patients' perceptions are wrong compared to the presumed trustworthy answers on a different questionnaire. It's nonsensical to see that two sets of answers on different questionnaires don't match up, and assume that patients' perceptions about one topic are correct, but the ones on a different topic are faulty.

I suppose having my perceptions questioned based on crappy research is a bit of a sore spot for me And I'm REALLY tired of people not doing their homework before "analyzing" these sorts of things.

I see what you're saying but I'm just so used to people assuming that questionnaire results accurately reflect symptoms that I barely consider it a sin. It's a problem, but one which is so normal that neuroskeptic probably shouldn't be singled out for it (although obviously still fair to criticise)

 

[Dolphin]

Do You Know What’s Good For You?

By Neuroskeptic | July 9, 2013 5:16 pm

6 comments under this at the moment.

 

[biophile]

On the University of Maryland Medical Center's webpage for CFS:

http://umm.edu/health/medical/reports/articles/chronic-fatigue-syndrome

"Although CBT doesn't bring patients completely back to normal, research has found that people who use the therapy have higher mental health scores, and are able to walk faster and with less fatigue than those who do not use CBT."

The reference for this statement is not entirely clear because there are a list of references at the end of the article but no inline citations. Is anyone aware of any CBT studies for CFS which demonstrated improved walking speed? Otherwise it appears to me to be referring to the PACE Trial, in which such a statement would be incorrect.

 

[Dolphin]

On the University of Maryland Medical Center's webpage for CFS:

http://umm.edu/health/medical/reports/articles/chronic-fatigue-syndrome

"Although CBT doesn't bring patients completely back to normal, research has found that people who use the therapy have higher mental health scores, and are able to walk faster and with less fatigue than those who do not use CBT."

The reference for this statement is not entirely clear because there are a list of references at the end of the article but no no inline citations. Is anyone aware of any CBT studies for CFS which demonstrated improved walking speed? Otherwise it appears to me to be referring to the PACE Trial, in which such a statement would be incorrect.

Can't think of anything.
I imagine there is a good chance "physical functioning" was misinterpreted here and/or is regularly misinterpreted (when CBT is said to improve physical functioning in CFS studies what invariably is being referred to are questionnaire measurements, usually the SF-36 physical functioning subscale).

 

[biophile]

I just came across this potentially interesting article. It is about the lack of adequate placebo control in the video-game-training research literature, but it touches upon the problem in general too. Many of the statements could also apply to CBT/GET and the PACE Trial:

The Pervasive Problem With Placebos in Psychology: Why Active Control Groups Are Not Sufficient to Rule Out Placebo Effects.

Walter R. Boot, Daniel J. Simons, Cary Stothart, Cassie Stutts

Perspectives on Psychological Science

July 2013 vol. 8 no. 4 445-454

doi: 10.1177/1745691613491271

http://pps.sagepub.com/content/8/4/445

http://pps.sagepub.com/content/8/4/445.full

http://pps.sagepub.com/content/8/4/445.full.pdf

Abstract: To draw causal conclusions about the efficacy of a psychological intervention, researchers must compare the treatment condition with a control group that accounts for improvements caused by factors other than the treatment. Using an active control helps to control for the possibility that improvement by the experimental group resulted from a placebo
effect. Although active control groups are superior to “no-contact” controls, only when the active control group has
the same expectation of improvement as the experimental group can we attribute differential improvements to the
potency of the treatment. Despite the need to match expectations between treatment and control groups, almost no
psychological interventions do so. This failure to control for expectations is not a minor omission—it is a fundamental
design flaw that potentially undermines any causal inference. We illustrate these principles with a detailed example
from the video-game-training literature showing how the use of an active control group does not eliminate expectation
differences. The problem permeates other interventions as well, including those targeting mental health, cognition,
and educational achievement. Fortunately, measuring expectations and adopting alternative experimental designs
makes it possible to control for placebo effects, thereby increasing confidence in the causal efficacy of psychological
interventions.

 

[Graham]

Hi all

Those of you who helped to produce the analysis of the PACE trial that we did on Phoenix Rising may be pleased to hear that I just got a very nice email from a member of the Hampshire ME support group. They decided to print the whole of our ten point conclusion / summary in their magazine (with attributes), and she wanted to thank us all for "taking an objective, careful, expert view". She had been a psychiatrist herself until the ME forced her to retire, and commented that psychiatrists are very divided over the "Wessely school" of thought.

By a weird coincidence, her last job was in the town where Kathy and I met, married and had Ian, which was in my "had a hairstyle" days.

Give yourselves a pat on the back!

 

[Esther12]

Good work Graham. I've seen a few people around the internet referring to your videos as a helpful way of understanding/explaining the problems around PACE.

I just came across this potentially interesting article. It is about the lack of adequate placebo control in the video-game-training research literature, but it touches upon the problem in general too. Many of the statements could also apply to CBT/GET and the PACE Trial:

The Pervasive Problem With Placebos in Psychology: Why Active Control Groups Are Not Sufficient to Rule Out Placebo Effects.

Walter R. Boot, Daniel J. Simons, Cary Stothart, Cassie Stutts

.

In case you're interested, I'd posted a thread on another article covering this here: http://forums.phoenixrising.me/inde...in-psych-trials-some-interesting-links.24145/

 

[Shell]

I haven't gone back over the thread, sorry. So if this is merely a repeat ignore me.

It's not just patient responses on questionnaires that can be biased either to make the questioner feel better or because the patient wants to believe all that work was for something.
The question design can be done to ensure a certain answer. A kind of pressure can be put on the answerer to say or tick the "right" answer that the questionnaire designer is pushing for.
There's often not extra space on these things to clarify a point because it would mess up the desired stats.

Not to mention the fact that during the mainly English fight with the Govt over home education, some stats were simply made up and others were lied about.

And even where deliberate dishonesty isn't at play it seems massive gaps in stats can be given.
Take Lupus for example. As I'm in the process of being tested and seen for this I've been doing some reading. (ignorance has not been bliss over the last ten years to I am, to use my dh term rectum-frying this)
Lupus websites - showing medical evidence - report the following; 80% of Lupus patients have +ANA results. Another site; between 90 and 95% have +ANA another site 95% have +ANA and finally nearly all Lupus patients have +ANA.
That's a massive discrepancy and almost every document admits that Lupus is complicated, difficult to dx and blah blah...

I'm not good on stats. I have only ever written one essay on them and the poor tutor wrote at the bottom "You really didn't understand this at all did you?"

 

[Sean]

Thanks for that, Graham.

••••••••••••••••••••••••

RE: The Pervasive Problem With Placebos in Psychology...

Although active control groups are superior to “no-contact” controls, only when the active control group has the same expectation of improvement as the experimental group can we attribute differential improvements to the potency of the treatment. Despite the need to match expectations between treatment and control groups, almost no psychological interventions do so. This failure to control for expectations is not a minor omission—it is a fundamental design flaw that potentially undermines any causal inference.

[Highlighting mine. Sean]

Compare and contrast with PACE, et al, which was blatantly biased in this regard. That methodological weakness could easily explain the very modest 'positive' result they got.

The phrase

Always properly control for placebo effect.

should be tattooed on the forehead of every psych researcher in the world.

 

[biophile]

Re the framing issue, here are the questions and answers for fatigue and physical function as used in the PACE Trial:

Chalder fatigue questionnaire, 11 questions and 4 choices of answer:

• Do you have problems with tiredness?
• Do you need to rest more?
• Do you feel sleepy or drowsy?
• Do you have problems starting things?
• Do you lack energy?
• Do you have less strength in your muscles?
• Do you feel weak?
• Do you have difficulty concentrating?
• Do you make slips of the tongue when speaking?
• Do you find it more difficult to find the correct word?
• How is your memory?

Less than usual (bimodal score is 0, Likert score is 0).

No more than usual (bimodal score is 0, Likert score is 1).

More than usual (bimodal score is 1, Likert score is 2).

Much more than usual (bimodal score is 1, Likert score is 3).

The total bimodal score (0,0,1,1) range is 0-11 and the total Likert score (0,1,2,3) range is 0-33 where 11 is neutral.

Physical function subscale of the SF-36 health survey, 10 questions and 3 choices of answer:

Does your health limit you doing activities that you might do during a typical day? If so, how much? ...

• Vigorous activities, such as running, lifting heavy objects, participating in strenuous sports;
• Moderate activities such as moving a table, pushing a vacuum cleaner, bowling or playing golf;
• Lifting or carrying groceries;
• Climbing several flights of stairs;
• Climbing one flight of stairs;
• Bending, kneeling or stooping;
• Walking more than a mile;
• Walking several hundred yards;
• Walking one hundred yards;
• Bathing or dressing yourself;

Yes, limited a lot (score 10/10).

Yes, limited a little (score 5/10).

No, not limited at (score 0/10).

[Edit: In the PACE Trial, the score range was 0-100]. The total physical function score is usually out of 100 (technically it is out of 20 with each questioning scoring 0 or 1 or 2 rather than 0 or 5 or 10, but these are usually multiplied by 5). Sometimes the scores are "normalized" so that 50 is the average of the group with a standard deviation of 10, IIRC.

 

[user9876]

The total physical function score is usually out of 100 (technically it is out of 20 with each questioning scoring 1 or 2 rather than 5 or 10, but these are usually multiplied by 5). Sometimes the scores are "normalized" so that 50 is the average of the group with a standard deviation of 10, IIRC.

Its slightly more complex in that if their are (upto 3?) answers missing then the remaining answers are scaled to a 0..100 scale. I'm not sure if this was done in PACE but it is certainly done with the Bowling paper which they use to define 'healthy'

 

[Dolphin]

Its slightly more complex in that if their are (upto 3?) answers missing then the remaining answers are scaled to a 0..100 scale. I'm not sure if this was done in PACE but it is certainly done with the Bowling paper which they use to define 'healthy'

Scaling would be the same thing: both are the percentages out of 100 of the questions answered.

What was done in the PACE Trial wasn't normalised scoring. That's SF36v2.

 

[Dolphin]

This trial:

Non-pharmacologic interventions for CFS: A randomized trial.
Jason, Leonard A.; Torres-Harding, Susan; Friedberg, Fred; Corradi, Katrina; Njoku, Mary Gloria; Donalek, Julie; Reynolds, Nadia; Brown, Molly; Weitner, Bing Bing; Rademaker, Alfred; Papernik, Morris
Journal of Clinical Psychology in Medical Settings, Vol 14(4), Dec 2007, 275-296. doi: 10.1007/s10880-007-9090-7 Free at: http://www.researchgate.net/publica..._Randomized_Trial/file/79e415092d1f0967a1.pdf

contains:

It should be mentioned that the changes in the present trial were relatively modest and few participants experienced remission of illness.

(one of the interventions was KCL-style CBT).

I'm not sure whether this refers to data given in the paper or not.

It may be the following:

Clinical Significance White, Sharpe, Chalder, DeCesare, and Walwyn (2007) have recommended using the Physical Functioning subscale of the Medical Outcomes Survey-SF-36 as a primary outcome measure for CFS trials. In addition, Ferguson, Robinson, and Splaine (2002) have recommended using the Reliable Change Index (RCI), which evaluates the magnitude of change scores necessary for a measure to be considered statistically reliable. To determine clinical significance of the Physical Functioning subscale, the baseline minus 12-month follow-up change scores need to exceed the age adjusted RCI and the 12-month follow-up scores must fall within the normative value (defined for this study as being within one standard deviation of the mean). Using these two criteria, the CBT*, COG*, ACT, and RELAX groups achieved clinically significant improvements for physical functioning in 18.2%, 30.4%, 11.1%, and 21.7% of participants, but there were no significant differences among conditions [v2 (3, N = 86) = 2.41, p = .49].

Anyone know how this RCI and age adjusted RCI might apply to the PACE Trial?

*COG was an intervention that involved pacing plus some elements of non-CFS CBT (paper gives the details - this is a rough description from memory). CBT was the type of CBT in the PACE Trial

 

[Dolphin]

I wonder had he the PACE Trial in mind?

From Co-Cure: https://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind1307c&L=co-cure&F=&S=&P=9540

Q. Do you notice a changing attitude among physicians?

Prof. Dr. Kenny De Meirleir: A very gradual and slow shift is taking place because publications continue to appear on the subject of the psychological model of the disease continuing to create confusion.

There is a lot of criticism of the studies and about how they were performed, of their statistics, withholding of data, etc. But these publications are written by persons with influence and they continue to cause a stir in the medical world.

It's really difficult for people who focus on the biological basis of this disease to obtain and maintain credibility, when there are people who continue to make statements based on bad and unreliable studies.

----------------

Full video available at:

5 minutes 39 seconds

Six answers of Prof. Dr. K. De Meirleir about remedies and hope.

00.13 Is it possible for patients to recover just through their own powers? And in that case should they be above a certain limit with regard to the severity of ME?

00.53 What kind of research do you think will have the best chance of producing a biomarker for ME, following a successful replication study?

01.40 Could you describe a few recent discoveries?

02.24 Do you notice a changing attitude among physicians?

03.28 There are patients who recover overnight. Does this mean that they didn't have ME?

04.23 Is there consensus among scientists, who, for example, are specialized in Lyme and ME-comorbidities, on the existence and criteria of ME?

This web seminar is part of the project 'Wetenschap voor Patiënten' or in English 'Science for Patients'. This project is realized through a collaboration between Science Alliance and the Dutch ME/cvs Vereniging. There will be 20 web seminars with Prof. Dr. Kenny De Meirleir. Other ME/cfs scientists will follow. Not all seminars are available with English subtitles yet. We are working hard to produce them for you. Sign up to this Youtube channels to see the latest video's.


This video does not contain any diagnostic or therapeutic information about your own medical condition. It can never replace a personal consult. Notify your attending doctor in time about any question, complaint or sympom you might have.

 

[Bob]

Here we see a conflict of interest in action, as Peter White provides advice to Swiss Re insurance about CFS/ME treatment and diagnosis. It covers the PACE Trial. Brace yourself, take a deep breath, and hold your nose, before reading (it's the usual nonsense)...

Swiss Re: Managing claims for chronic fatigue the active way
http://www.swissre.com/clients/newsletters/Managing_claims_for_chronic_fatigue_the_active_way.html

I've started a separate thread to discuss the non-PACE aspects of the webpage. which seem quite revealing and interesting:
http://forums.phoenixrising.me/inde...e-from-peter-white-diagnosis-treatment.24394/

 

[Dolphin]

This was posted elsewhere.

Thought I'd post although we don't have information on what exactly was said about the PACE Trial:

http://www.southampton.ac.uk/populationhealth/news/events/2013/07/professorpeterwhite.page

Population Health

What does the PACE trial tell us about how to treat chronic fatigue syndrome (CFS), when CFS seems to be heterogeneous

13:00 - 14:00, 18 July 2013

How to treat chronic fatigue syndrome (CFS)

Speaker information

Professor Peter White, Centre for Psychiatry, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, What does the PACE trial tell us about how to treat chronic fatigue syndrome (CFS), when CFS seems to be heterogeneous?

Venue

1st Floor, Aldermoor Health Centre, Seminar Room

SO16 5ST
Contact for more information

Name: Lisa Sturdy

Phone: 023 8024 1050

E-mail: ls @ soton.ac.uk

~~~~~~~~~~~~~~~~~

http://www.swissre.com/clients/newsletters/Managing_claims_for_chronic_fatigue_t\
he_active_way.html

http://www.swissre.com/clients/newsletters/Managing_subjective_claims.html

http://ifdm2012.rsm.ac.uk/sponsors.html

International Forum on Disability Management

IFDM

Principal Sponsors

serco - Shaw Trust - Remploy - irwinmitchellsolicitors - spring - unum

http://ifdm2012.rsm.ac.uk/downloads/presentations/

peter-white-deleted.pdf 25-Sep-2012 10:17 452K

http://ifdm2012.rsm.ac.uk/downloads/presentations/peter-white-deleted.pdf

~~~~~~~~~~~~~~~~~~~

Cognitive and behavioural treatments for functional somatic syndromes

ifdm

International Forum on Disability Management 10-12 September 2012 London England
UK

Peter White & Kate Harri

London 2012

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
About Kate Harri - BMI makes sense of complex claims. What can we do for you? http://www.behavioralmedical.com/
http://www.behavioralmedical.com/news/

Thursday, June 27th, 2013

Beginning this quarter, we will be featuring one of our clinicians to help advertise not only our panels expertise, but also the fun side that we know each of our clinicians have. This month we spotlight: Kate Harri, MA, LP. Her current role is the VP of Behavioral Products for BMI. Click here to learn more about Kate and who she thinks would play her in a movie!
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

What moderates response to behavioural treatments?

~~~~~~~~~~~~~~~~~~~~~~~

Moderators of non-response to GET or CBT for CFS

Membership of a self-help group

Severity of fatigue

Sickness benefit

High combined mood score

Involvement in legal proceedings to achieve
disability benefits

Not duration of illness!

R Bentall et al, 2002
J Prins et al. 2003

~~~~~~~~~~~~~~~~~~~~~~~

 

[biophile]

Moderators of non-response to GET or CBT for CFS

Membership of a self-help group

Severity of fatigue

Sickness benefit

High combined mood score

Involvement in legal proceedings to achieve disability benefits

R Bentall et al, 2002
J Prins et al. 2003

Why do I get the feeling that if we looked at these studies, direction of causation would not be shown?

Re "Not duration of illness!" Yes, perhaps the placebo response is not susceptible to duration of illness.

 

[Esther12]

re moderators - that they've not released the data from PACE, or referenced it even though the above presentation released unpublished PACE data on 'remissions' (which was then sold as 'recovery'), makes me suspect that they're having trouble spinning it in a way which supports their conclusions.

 

[Graham]

I see once again that membership of a self-help group is branded as a problem. With PACE the biggest subjective improvements came in the first few weeks, presumably as patients came to terms with their diagnosis and understanding of the illness, so why is it beyond their wit to understand that if people who are members of a self-help group show less improvement, it might be that the group has already helped that patient part-way along that route?

 

[Firestormm]

Re the framing issue, here are the questions and answers for fatigue and physical function as used in the PACE Trial:

Chalder fatigue questionnaire, 11 questions and 4 choices of answer:

• Do you have problems with tiredness?
• Do you need to rest more?
• Do you feel sleepy or drowsy?
• Do you have problems starting things?
• Do you lack energy?
• Do you have less strength in your muscles?
• Do you feel weak?
• Do you have difficulty concentrating?
• Do you make slips of the tongue when speaking?
• Do you find it more difficult to find the correct word?
• How is your memory?

Less than usual (bimodal score is 0, Likert score is 0).

No more than usual (bimodal score is 0, Likert score is 1).

More than usual (bimodal score is 1, Likert score is 2).

Much more than usual (bimodal score is 1, Likert score is 3).

The total bimodal score (0,0,1,1) range is 0-11 and the total Likert score (0,1,2,3) range is 0-33 where 11 is neutral.

Do they amend these in say a Trial to take into account circumstance? For example, what is 'usual' in the Chalder fatigue questionnaire may be very relevant to circumstance and to whether a person is newly diagnosed or not. Unless this is specifically related to time and the individual then it's pretty weak when used across a cohort I would think unless there are specifics established.