PACE Trial and PACE Trial Protocol

[Dolphin]

The correspondents also mention the PACE trial and state that "No data on recovery rates and positive outcomes have been released.." The results of positive (and negative) outcomes were published in the Lancet medical journal early in 2011. The results of recovery rates are due to be published in the medical journal Psychological Medicine within the next three weeks.

This journal takes letters to the editor, which is good.
No word limit mentioned in instructions: http://assets.cambridge.org/PSM/PSM_ifc.pdf .
However, my impression is that the standard of English will have to be reasonably good e.g. one or two big/fancy/"jargony" words would help, "tight letter" e.g. avoiding repeating words if possible, concise, etc.

 

[WillowJ]

Yes, agreed. APT may not have been a suitable control for a variety of reasons. But if we are ever making a reference to the number of sessions of SMC being less than CBT and GET, then I think it might be worth remembering that APT was also proposed as a control.

APT was supposed to be testing 'pacing' as 'championed' by the patients, so it was not really envisioned as a control (apologies if someone mentioned this already; I am kind of behind).

However there are all kinds of problems with APT as traditional pacing. It supposedly used a model of 'undiscovered illness' causing symptoms (therefore pacing to ameliorate possible effects of said mystery illness, opaque to research), but patients were told that symptoms were caused by, for example, 'overbreathing' (disproved by research; CBT intrusion as hyperventilation would go along with anxiety/fear), poor sleep hygiene (CBT intrusion; this is an issue traditionally explored by CBT-type interventions and not solely caused by physiological disease) and, iirc, possibly by reconditioning (GET intrusion). Furthermore most patients' pacing doesn't involve extensive planning; this tends to wear us out. While we do have an idea of stopping activity before we wear ourselves out, the notion of 70% threshold in particular is novel AFAIK.

I think the notion of 'create the best conditions for natural recovery' is a bit weak of a plan compared to the promises of CBT and GET (basically, we have done this before and this can truly cure you, wasn't it?).

Also there is a lot of confusion in the APT module, between the official APT model and the intrusion of the preferred models of the manual authors. I think this confusion could have reduced efficacy. Plus the idea of an illness which nobody has any idea of any substantial physical pathology for, despite conducting research, is not exactly encouraging. It's too bad some researchers (and government agencies) do not seem to know how to read anything more complicated than the Daily Mail.

 

[WillowJ]

a little diversion:
http://www.columbia.edu/~to166/hiawatha.html

 

[WillowJ]

I've found a specific reference...

White’s letter - PACE - Response to the complaint to The Lancet of March 2011

http://www.forward-me.org.uk/Reports/White to Lancet re Hooper complaint (2).pdf

6. Failure to “control” (page 24)
A control condition in an experiment or trial means an appropriate comparator.
Both the paper and protocol explain that this trial was designed to compare
effectiveness across treatment arms, with particular comparisons being
prespecified; for each comparison of two treatments, one functioned as the
control.

that's odd

 

[Dolphin]

Not sure if this has been highlighted before. I know one of their studies was mentioned somewhere.

In
----

Implementing a minimal intervention for chronic fatigue syndrome in a mental health centre: a randomized controlled trial.
Psychol Med. 2012 Oct;42(10):2205-15. doi: 10.1017/S0033291712000232. Epub 2012 Feb 21.
Tummers M, Knoop H, van Dam A, Bleijenberg G.
Source
Expert Centre for Chronic Fatigue, Radboud University Nijmegen Medical Centre, The Netherlands. m.tummers@nkcv.umcn.nl

----

SF-36 physical functioning <=70 represented "patients with physical disabilities at baseline"

plus, from the full text:

All referred patients, aged between 18 and 65 years, received a baseline assessment. In accordance with the CDC criteria for CFS, patients were eligible to enter the study if they (1) were severely fatigued, operationalized as scoring >=35 on the subscale fatigue severity of the Checklist Individual Strength (CIS; Vercoulen et al. 1994), (2) were fatigued for 6 months or longer, (3) were severely disabled, operationalized as scoring <=70 on the physical and/or social functioning subscale of the Medical Outcomes Survey Short Form-36 (SF-36; Stewart et al. 1988)

Contrast that with:

In the PACE Trial editorial, Knoop & Bleijenberg described a SF-36 physical functioning >=60 plus Chalder Fatigue Questionnaire score (Likert) <=18 as a "strict criterion (sic) for recovery"

(Higher scores equal better functioning on this scale)

 

[Andrew]

I skimmed (not read) the PACE trial manual for patients. The instructions to patients didn't look like graded exercise to me. But I'd have to read more.

 

[Dolphin]

I skimmed (not read) the PACE trial manual for patients. The instructions to patients didn't look like graded exercise to me. But I'd have to read more.

There were different arms of the trial. I presume you were reading the graded exercise manual (apologies if this is a stupid question/point).

 

[Dolphin]

Not sure if this has been highlighted before. I know one of their studies was mentioned somewhere.

Two more papers involving Gijs Bleijenberg somebody has drawn my attention to are:

“Severe fatigue and severe functional impairment were defined as a score of 40 or more on the fatigue severity subscale of the checklist individual strength4 and a weighted score of 65 or less on the SF-36 physical functioning subscale.”
Stulemeijer M, de Jong LW, Fiselier TJ, Hoogveld SW, Bleijenberg G. Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: randomised controlled trial. BMJ. 2005 Jan 1;330(7481):14. Epub 2004 Dec 7.

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“Rand 36 Physical functioning (Cronbach's-α: 0.92):28,29 A 10-item subscale, transformed to a 0–100 score, where higher scores mean better physical function. A cut-off of ≤65 was considered to reflect severe problems with physical functioning.”
van't Leven M, Zielhuis GA, van der Meer JW, Verbeek AL, Bleijenberg G. Fatigue and chronic fatigue syndrome-like complaints in the general population. Eur J Public Health. 2010 Jun;20(3):251-7. Epub 2009 Aug 18. http://eurpub.oxfordjournals.org/content/20/3/251.long

 

[Andrew]

There were different arms of the trial. I presume you were reading the graded exercise manual (apologies if this is a stupid question/point).

Yes, I was reading the GET manual.

 

[Dolphin]

I skimmed (not read) the PACE trial manual for patients. The instructions to patients didn't look like graded exercise to me. But I'd have to read more.

The GET process is summarised on page 32 of this http://www.pacetrial.org/docs/get-participant-manual.pdf

 

[Dolphin]

Somebody has just drawn my attention to the following:

The future strategy for the management of mental health in the UK

Presentation by Professor Simon Wessely FRCP FRCPsych FMedSci

http://www.foundation.org.uk/events/audios/audiopdf.htm?e=440&s=1200

There is sound to go along with the slides. Not sure when it is from but includes some slides on the PACE Trial i.e. from the Lancet paper so is from the last two years.

 

[Valentijn]

http://www.foundation.org.uk/events/audios/audiopdf.htm?e=440&s=1200

There is sound to go along with the slides. Not sure when it is from but includes some slides on the PACE Trial i.e. from the Lancet paper so is from the last two years.

Haven't listened to the audio yet, but will. Here's some excerpts from the slides:

CFS: What do we know? ... • Perpetuated by behavioural and psychological factors;

• What doesn’t work – antidepressants, anti viral agents, immune modulators, diets, allergy treatments, vitamins, being told to pull yourself together etc. etc.
•What might work - understanding what you think about your illness and what you do about it.

Edit: It looks like the audio and slides match up with an article from December 2011 in http://www.foundation.org.uk/journal/pdf/fst_20_07.pdf

Edit #2: It looks like the articles are pretty much transcripts of the meetings for the Foundation for Science and Technology. The speaker immediately before Wessely was a "Richard", and the article preceding Wessely's is by a "Richard Leyard". Richard Leyard's article is introduced as being from "a meeting of the Foundation for Science and Technology on 4 May 2011." Thus it seems likely that's the date for the audio of Wessely's presentation.

 

[Esther12]

re PACE and recovery paper: I wonder if they will spin it in a different way than we are expecting.

Maybe they'll come up with a very tight definition for 'recovery', but then go on to argue that it is unrealistic for patients to expect this, but that treatments can successfully lead to a remission of symptoms. With 'remission' not meaning anything like what most people would expect (eg: A remission is a temporary end to the medical signs and symptoms of an incurable disease), so it's definition would include patients still suffering from symptoms which seriously restrict them (I expect that 'remission' will be defined in a way which requires only a very minor change in questionnaire scores). This would allow them to spin the media and public perception of treatment in a way that is more easily defensible imo. "Oh they thought we meant 'remission' as in a temporary relief of abnormal symptoms?... what a misunderstanding. The media are bad at reporting on science, aren't they? They love to make it sound so dramatic and impressive."

Just a thought. It's easy to assume that they'll go on making really exaggerated claims about recovery, but it is possible that they'll dramatically change tactics. I think that the data from PACE is so bad for them that they're going to have to come up with a new way of spinning it.

 

[Dolphin]

re PACE and recovery paper: I wonder if they will spin it in a different way than we are expecting.

Maybe they'll come up with a very tight definition for 'recovery', but then go on to argue that it is unrealistic for patients to expect this, but that treatments can successfully lead to a remission of symptoms. With 'remission' not meaning anything like what most people would expect (eg: A remission is a temporary end to the medical signs and symptoms of an incurable disease), so it's definition would include patients still suffering from symptoms which seriously restrict them (I expect that 'remission' will be defined in a way which requires only a very minor change in questionnaire scores). This would allow them to spin the media and public perception of treatment in a way that is more easily defensible imo. "Oh they thought we meant 'remission' as in a temporary relief of abnormal symptoms?... what a misunderstanding. The media are bad at reporting on science, aren't they? They love to make it sound so dramatic and impressive."

Just a thought. It's easy to assume that they'll go on making really exaggerated claims about recovery, but it is possible that they'll dramatically change tactics. I think that the data from PACE is so bad for them that they're going to have to come up with a new way of spinning it.

Who knows. One of their previous comments suggested there would be various definitions reported on.

However, I want to know the numbers for the secondary outcome measure, "recovery". Recovery has been mentioned in brochure for KCL clinic, Barts clinics and in some papers. Also, when the first PACE Trial paper came out, as you know, the 28%/30% figures were portrayed in some contexts as like recovery. So I want the figure for the definition they used which I expect will be low and suggests that the illness isn't simply due to factors that can be overcome by CBT or GET. It's the most useful in terms of proof-of-concept.

 

[Graham]

I remember reading somewhere recently about a group of psychologists defining "recovery" as a process. So it may be that they take that approach. In which case it is the flattening out of the graphs which would be relevant.

 

[Dolphin]

I hope they get quite a few letters. For the FITNET Trial, the Lancet published two and I heard from one other person whose letter wasn't published.

 

[Esther12]

Who knows. One of their previous comments suggested there would be various definitions reported on.

However, I want to know the numbers for the secondary outcome measure, "recovery". Recovery has been mentioned in brochure for KCL clinic, Barts clinics and in some papers. Also, as the first PACE Trial paper came out, as you know, the 28%/30% figures were protrayed in some contexts as like recovery. So I want the figure for the definition they used which I expect will be low and suggests that the illness isn't simply due to factors that can be overcome by CBT or GET. It's the most useful in terms of proof-of-concept.

I somehow doubt they're going to come with the 'honest apology and correction' spin.

I certainly think that they owe it to patients to provide access to data for this outcome as it was laid out in their protocol.

I remember reading somewhere recently about a group of psychologists defining "recovery" as a process. So it may be that they take that approach. In which case it is the flattening out of the graphs which would be relevant.

Yeah. I saw someone defending a crazy re-definition of recovery on the grounds that it would help mental health staff feel as if they were achieving more! As if claims made about recovery were intended to act as motivational tools for manipulating people, rather than just providing access to information which will help people make decisions about what different treatments were worthwhile.

Paternalism and pragmatism seem to be used to justify all sorts of disdainful quackery.

 

[Simon]

... However, I want to know the numbers for the secondary outcome measure, "recovery". Recovery has been mentioned in brochure for KCL clinic, Barts clinics and in some papers. Also, as the first PACE Trial paper came out, as you know, the 28%/30% figures were protrayed in some contexts as like recovery. So I want the figure for the definition they used which I expect will be low and suggests that the illness isn't simply due to factors that can be overcome by CBT or GET. It's the most useful in terms of proof-of-concept.

Good point.

I got the impression from one of their previous comments that 'Recovery' might have been redefined pre-unblinding, at the same time the primary outcome measures were redefined. That might explain why they still haven't released the Analyses Strategy [whatever], even though it must have been agreed and finalised prior to unblinding in spring 2010. I guess we will know soon enough.

 

[Dolphin]

Good point.

Thanks

I got the impression from one of their previous comments that 'Recovery' might have been redefined pre-unblinding, at the same time the primary outcome measures were redefined. That might explain why they still haven't released the Analyses Strategy [whatever], even though it must have been agreed and finalised prior to unblinding in spring 2010. I guess we will know soon enough.

Why would that cause a delay in releasing the Analysis Strategy?

 

[Dolphin]

At least there isn't the rush there was with the Lancet in terms of writing letters.