PACE Trial and PACE Trial Protocol

[Sean]

Fair point, Aurator. We live in a world of imperfect compromises.

[resigned shrug icon]

 

[Graham]

Not even sure that a serious peer-review journal should use a Like button system at all. Don't really see the point.

I ticked "Like" on Sean's comment. Would that mean that we aren't serious?

 

[Sean]

Nah, those rules don't apply to us. We're special.

 

[Tom Kindlon]

Another substantial BMJ e-letter on the UK£5 million PACE Trial, this time from Alem Matthees.

He highlights various changes to the protocol.

He also highlights how the recovery criteria are much easier than planned (and there was an error in the justification given for changing them).

http://www.bmj.com/content/350/bmj.h227/rr-16

 

[Dolphin]

Giving Science a Bad Name: unethical psychiatric research into ME
Wednesday January 21 2015
https://guj30.wordpress.com/2015/01...-name-unethical-psychiatric-research-into-me/

Extract:

The appearance of yet another somewhat rehashed publication, based on the absurd PACE trial from 2011[7], in The Lancet Psychiatry is no guarantee of scientific rigour. As a published academic I have reason to suspect that the peer review process within certain academic journals has become a questionable praxis. In small, narrow fields of research there are few experts available to peer review submitted drafts for publication. Peer review is supposed to be blind but even I, coming from the much wider field of education research, have been given texts in the past whose author(s) I identified by their writing style and the more specific research questions posed. Any ‘blind’ peer review conducted on a text from Professor Chalder et al would and could not be blind, as any reviewer would recognise the author. This is what happens when a tight-knit group of researchers repeat themselves and milk their own research to such an extent they no longer produce anything original. As the reviewers themselves are members of a tight-knit community of, in this case psychiatrists and psychotherapists, they would be reluctant to criticise let alone reject a paper on grounds of its lacking scientific rigour (even if they were to find the methodology lacking); never mind how biased the research questions or how skewed the selection criteria. Scientific editorial boards will always at least try to allocate sympathetic peer-reviewers/scientists who know the literature and field of research.

 

[Dolphin]

I posted this last week in another thread. I thought I'd also post it here.


We have new 6-minute walking test data in the supplement. These are the scores at 24 weeks.

n (%) complete for walk test data

APT: 113 (71)
CBT: 122 (76)
GET: 119 (74)
SMC: 118 (74)

Metres walked

Baseline
APT: 322 (306 to 338)
CBT: 336 (320 to351)
GET: 321 (308 to 335)
SMC: 332 (316 to 347)

24 weeks

APT: 342 (322 to 361)
CBT: 361 (345 to 377)
GET: 381 (366 to 395)
SMC: 350 (333 to 368)

Here are the results at 52 weeks:

APT: 334 (117) i.e. -8m compared to 24 weeks
CBT: 354 (106) i.e. -7m compared to 24 weeks
GET: 379 (100) i.e. -2m compared to 24 weeks
SMC: 348 (108) i.e. -2m compared to 24 weeks

So doesn't look like one can conclude that they are gradually getting better after an initial slight improvement all around

They have data at baseline and 52 weeks for:

APT: 111 (70%) i.e. -1% compared to baseline/24 weeks
CBT: 123 (76%) i.e. no percentage change compared to baseline/24 weeks
GET: 110 (69%) i.e. -5% compared to baseline/24 weeks
SMC: 118 (74%) i.e. -1% compared to baseline/24 weeks

The 5% drop off (8 people) for GET makes me wonder whether people in GET were more likely to overpush themselves at 24 weeks and then have payback and so decide not to do the test at 52 weeks.

Knoop and Wiborg themselves speculated this might be happening:

"In the present study, no increase in fitness after GET was noted. An increase in distance walked during a test situation without an increased fitness suggests that patients walk more because of a change in cognitive processes (eg, daring to do more or an increased self-efficacy with respect to activity), not because of a change in physiological capacity."

 

[Min]

http://www.sciencemediacentre.org/e...reatments-for-chronic-fatigue-syndromeme-2-2/

A number of doctors, including Dr Miller, Action for ME's medical advisor, expressed their admiration and support for PACE here in 2011. Of most particular concern is paediatrician Dr Crawley's statment that she intends to do a PACE style study on children.

 

[Bob]

http://www.sciencemediacentre.org/e...reatments-for-chronic-fatigue-syndromeme-2-2/

A number of doctors, including Dr Miller, Action for ME's medical advisor, expressed their admiration and support for PACE here in 2011.

Yes, it's worth reminding ourselves of the propaganda that the SMC promotes on behalf of their friends...
I've highlighted some of the more shocking untruths below...

This trial represents the highest grade of clinical evidence – a large randomized clinical trial, carefully designed, rigorously conducted and scrupulously analysed and reported. It provides convincing evidence that GET and CBT are safe and effective and should be widely available for our patients with CFS/ME.

The trial design in this study was very good, and means that the conclusions drawn can be drawn with confidence.

The study suggests that everyone with the condition should be offered the treatment, and every patient who wishes to be helped should be willing to try one or both of the treatments.

At least half of patients improved with CBT or GET. The study also allays fears that CBT or GET may be harmful. There are a minority of patients who didn’t see improvement so the next step must try and find treatments to help them.

It was extremely rigorous. It was large and it was randomised. The study was carefully conducted in the manner of a drug intervention study to not only establish the superiority of one treatment over the other but also to carefully report any side effects or harm from those treatments.

 

[Min]

"Propaganda" is the right word for it Bob, it's certainly nothing to do with science.

 

[Dolphin]

More good responses to the PACE Trial piece in the BMJ posted today:

(i) "The cognitive-behavioural model of illness for chronic fatigue syndrome and myalgic encephalomyelitis is not supported by the outcomes of the PACE trial" - by Robert Courtney

(ii) "Rightly outraged" by Greg Crowhurst (Stonebird) (a carer) & Simon Lawrence (25% ME Group)

(iii) Re: Tackling fears about exercise is important for ME treatment, analysis indicates by Ian McIllroy (who lists various studies which found abnormal responses to exercise in ME and CFS)


http://www.bmj.com/content/350/bmj.h227/rapid-responses

 

[Ecoclimber]

Just wait a minute. I believe there are two salient points not emphasized enough in comments refuting the PACE Trial. First of all, within the biomedical field, all the data on which the researchers based their conclusions must be revealed within the four corners of their scientific research papers so other researchers can reproduce their findings. Secondly, before it is accepted as a matter of scientific fact, the evidence for the research must be replicated by other scientists with no competing interest. If the research cannot be replicated or if there is missing data for researchers, then the paper must be retracted. The most recent prominent example to date is the XMRV research paper in Science.

The fact that the authors of the PACE Trial refuse to release the data on which their research paper was based even under the FOIA, then summarily this research paper should be retracted. In addition, since results and conclusions stated in the PACE Trial have not been replicated by any other researcher outside of the UK, then the PACE Trial itself should not be considered as objective verifiable evidence until replicated. The same standard of scientific rigor and criteria required of research papers within the biomedical field must be applied within the behavior field. Otherwise, it is mere hypotheses, theories, and conjectures within a small contingency of powerful researchers of which many in the psychiatric profession fear to oppose.

We have an historical record where scientific technology has proven psychological theories obsolete and false. The most recent case is MS with the advancement of MRI technology. The results leave a vulnerable ME/CFS patient population suffering needlessly because of scientific turf wars among egotistical scientists. When you have a group of medical professionals blaming and vilifying the patient population for their illness instead of treating them, you wonder who really needs to have their heads examined.

 

[Graham]

There is a long, long history of the medical world failing to respect scientific methods. Think back to John Snow and his statistics proving that cholera was caused through fouled drinking water. The medics of the day ignored that and stuck to their belief in miasmas. The most recent example was with stomach ulcers, which the medical profession knew was caused by stress, knowing that bacteria could not survive in the stomach, until two Australians proved them wrong. We could fill the gap between them with all sorts of examples.

What really irritates me is that the two basic guesses of what lies behind ME, fear and deconditioning, have never been examined rigorously by other psychiatrists. In science, any hypothesis undergoes extensive debate, and is required to predict something that can be measured. There is enough evidence to debunk the deconditioning belief, but why hasn't there been any attempt to test the fear belief: surely a simple analysis of how people with ME respond to additional illnesses or conditions would make the point? When I broke my hip 5 years ago, if my life has been so restricted by fear it would have been evident in my recovery.

As you say, Ecoclimber, the XMRV claims were greeted with great suspicion and immediately efforts were made to replicate the results (as it should be in science), but with PACE we didn't even get an open debate.

 

[Dolphin]

Response to Lancet article from Prof. Betsy Keller, Ph.D., Ithaca College
https://theothersideofthestretcher....e-from-prof-betsy-keller-ph-d-ithaca-college/

 

[Daisymay]

Oh I hope she posts that as a BMJ rapid response for more people to see.

 

[Bob]

This is a quote from the PACE CBT manual for therapists:

"The essence of CBT is helping the participant to change their interpretation of symptoms..."

I think that says it all really! Shame it doesn't improve outcomes.

 

[MeSci]

This is a quote from the PACE CBT manual for therapists:

"The essence of CBT is helping the participant to change their interpretation of symptoms..."

I think that says it all really! Shame it doesn't improve outcomes.

What does CBT stand for again...was it Complete Bl**dy Trash?

 

[Tom Kindlon]

Another substantial BMJ e-letter on the UK£5 million PACE Trial, this time from Alem Matthees.

He highlights various changes to the protocol.

He also highlights how the recovery criteria are much easier than planned (and there was an error in the justification given for changing them).

http://www.bmj.com/content/350/bmj.h227/rr-16

Erica Verrillo has done a new (Jan 30) piece on this:

Australian Researcher Challenges Measures of "Recovery" in PACE Trial:
http://cfstreatment.blogspot.ie/201...challenges.html#sthash.bmmt0iZc.e2e3nZ3D.dpuf

 

[Simon]

Six minute walking test 'no longer a measure of physical function'

The PACE team have redefined the 6MWT, which was originally included as their chosen objective measure of physical function (a secondary outcome specificied in the protocol), as instead a measure of 'behaviour change' or exercise tolerance.

From the 2015 mediation paper: (you will need to register (free) to access fulll text and the appendix)

APPENDIX

Six-Minute Walk Test Participants were asked to walk as far as possible in six minutes, and the distance walked in metres was recorded. This is a measure of exercise tolerance (14). Due to concerns about patients with CFS coping with physical exertion, no encouragement was given to participants as they performed the test, in contrast to the way this test is usually applied (15, 16). Rather than provide encouragement, we told participants, “You should walk continuously if possible, but can slow down or stop if you need to.” Furthermore we had as little as 10 metres of walking corridor space available in centres rather than the 30 to 50 metres of space used in other studies (15-17); this meant that participants had to stop and turn around more frequently. Due to the modifications and the associated measurement error we considered this test as an internally referenced measure of behaviour change or exercise tolerance, not a measure of physical fitness.

PAPER
We also postulated that timed walking distance as a measure of exercise tolerance, but also as a more objective measure of activity engagement, would mediate change in both outcomes for CBT and GET.

ie no longer even a secondary measure of physical function.

 

[Dolphin]

Six minute walking test 'no longer a measure of physical function'

The PACE team have redefined the 6MWT, which was originally included as their chosen objective measure of physical function (a secondary outcome specificied in the protocol), as instead a measure of 'behaviour change' or exercise tolerance.

From the 2015 mediation paper: (you will need to register (free) to access fulll text and the appendix)

ie no longer even a secondary measure of physical function.

After they have the results they can try to disown results that were not good; that doesn't mean their interpretation should be accepted.

We saw with the cost effectiveness paper, they said they would look at valuing informal care in three different ways in the statistical plan: zero, minimum wage, average wage. Then in the paper itself, measuring it at zero wasn't mentioned. They only reported it using "average wage" and said the sensitivity analyses showed similar results, which was not what happened as the therapies were not cost effective at minimum wage (and so wouldn't have been if informal care was measured at zero). In discussion (i.e. following being challenged on this), they tried to disown the zero pricing method saying it was controversial. But they were the people who chose it.

 

[Dolphin]

I wonder whether these e-letters have been highlighted before?

http://pb.rcpsych.org/content/early/2014/07/14/pb.bp.113.045005.abstract/reply#pbrcpsych_el_21069

Rectification to ensure balance

• Ellen M Goudsmit, Health Psychologist (Retired.)
• Re: Response to Dr Goudsmit
• • Peter D White, Professor of Psychological Medicine Trudie Chalder, Michael Sharpe QMUL, KCL & University of Oxford