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PACE Trial and PACE Trial Protocol

Messages
2,158
Got to page 15 and gave up. Basically it's a tutorial on a sophisticated statistical method for working out whether particular parts of a treatment process over time contribute most to the results. I think (I may well be wrong) they are saying that the CBT/GET arms had the most improvement in the first 12 weeks, and put this down to changing false illness beliefs (ha ha).

I can see that such analyses might be useful in assessing a treatment protocol where objective linear data is collected and that involved a series of steps over time, to help work out which steps were the most effective, but surely that can be seen simply visually by drawing a graph of outcomes against time, and marking which time periods involved which treatment. But then I'm just a simple ex-maths teacher...

Basically it's same old same old. Garbage in, garbage out.

I'd love to see the psychs on the team trying to explain sentences like this from page 36:

(warning, concentrated jargon soup coming up. May cause foggy brains to implode):

'The models partition the true score and residual from one another using a decomposition of covariances (Kline, 2011). These models then usually postulate a first-order autoregressive structure among the true scores where a variable is a function of that variable at the previous time point, resulting in the correlation between measurements decreasing the further apart they are in time. For longitudinal mediation, the simplex structure is fitted to each of the mediator measures and outcome measures and then the processes are joined through b paths between the latent variables (Figures 1 and 2).'

Though I did like this bit near the end:

'We note in the case where there is no effect of the treatment on the outcome, terms like total effect, indirect effect, partial mediation and so on, become rather obsolete'

Ha ha, obsolete indeed.
 
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lilpink

Senior Member
Messages
988
Location
UK
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RogerBlack

Senior Member
Messages
902
Page 10:

'In order to avoid bias in estimating a mediated effect, several other assumptions must hold. We assume (a) reliably and validly measured variables, (b) linear relationships between variables,'

So that excludes PACE at the starting line.

Doesn't b) miss out that those variables need to be linear, not just the relationships between them - I.E. not SF36.
 
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13,774
Seems like they don't want us to know after all. "This page could not be found": https://kclpure.kcl.ac.uk/portal/en...me(a50c287c-17da-4f9b-94f4-2d3ec0851eea).html

Hope someone cached it. I tend to think the things they don't want you to see are the things we really should be seeing ;)

Still worked for me. Thanks for the comments from people... sounds like this stats heavy paper may not be for me. I had struggled through the other ones, but I'm not sure how much I got from them. From what others have already pulled out, maybe this paper could be handy for providing quotes to compare what PACE should have done with what they actually did though.
 

lilpink

Senior Member
Messages
988
Location
UK
quote-the-true-definition-of-madness-is-repeating-the-same-action-over-and-over-hoping-for-albert-einstein-81-23-99.jpg
 
Messages
2,158
Still worked for me. Thanks for the comments from people... sounds like this stats heavy paper may not be for me. I had struggled through the other ones, but I'm not sure how much I got from them. From what others have already pulled out, maybe this paper could be handy for providing quotes to compare what PACE should have done with what they actually did though.

You're right, it's basically a stats paper. Don't waste your time on it.
 
Messages
2,391
Location
UK
Doesn't b) miss out that those variables need to be linear, not just the relationships between them - I.E. not SF36.
Depends exactly what variables they mean. Linearity/non-linearity only makes any sense if talking about one thing relative to another. But either way I agree with you - subjectivity is highly likely to exhibit non-linearity, and would at least be very hard to prove it was linear. Maybe the subject of another study?
 

user9876

Senior Member
Messages
4,556
Depends exactly what variables they mean. Linearity/non-linearity only makes any sense if talking about one thing relative to another. But either way I agree with you - subjectivity is highly likely to exhibit non-linearity, and would at least be very hard to prove it was linear. Maybe the subject of another study?
They add up the question answers and give a score. Then they give a mean of scores in trials or a mean difference. But if you have one set of answers then a change to add in an additional answer may be small but is counted as the same improvement as when the change is big. So for example the difference between being able or struggling to walk a block (in the US version) is the same as being able to or struggling to walk a mile.
 
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13,774
Not sure how noteworth this is, but my google searching just turned up this response from QMUL to an FOI:

https://www.whatdotheyknow.com/request/cfs_misleading_and_poor_quality#incoming-972957

https://www.whatdotheyknow.com/requ...CE sponsorship and indemnity letters.pdf.html

I've been thinking that I would like to make an official complaint to QMUL about hte problems with PACE, but I've always been a bit unsure how to do this. Maybe some of the info there will help? tbh, my mind has gone for the day, so will leave this for now.
 

user9876

Senior Member
Messages
4,556
Not sure how noteworth this is, but my google searching just turned up this response from QMUL to an FOI:

https://www.whatdotheyknow.com/request/cfs_misleading_and_poor_quality#incoming-972957

https://www.whatdotheyknow.com/request/398301/response/972957/attach/html/3/PACE sponsorship and indemnity letters.pdf.html

I've been thinking that I would like to make an official complaint to QMUL about hte problems with PACE, but I've always been a bit unsure how to do this. Maybe some of the info there will help? tbh, my mind has gone for the day, so will leave this for now.

I think they are avoiding the issue of who approved what and when and what information they were presented with. I have a theory that the changes were not explicitly approved but they got the stats plan approved which slipped in the changes without mentioning them. To me their refusal to release records saying the changes were approved only adds to my belief.

One thing that I find strange is that they push blame onto others who seem happy to quietly take it. I wonder if at some point someone on the ethics committee will realize their professional judgement is being questioned and say not of course we didn't approve recovery outcomes that were below the trial entry criteria. But I can't see that happening until they feel people are questioning their judgement due to the decisions that they are being blamed for.
 

Dolphin

Senior Member
Messages
17,567
I think they are avoiding the issue of who approved what and when and what information they were presented with. I have a theory that the changes were not explicitly approved but they got the stats plan approved which slipped in the changes without mentioning them. To me their refusal to release records saying the changes were approved only adds to my belief.
Perhaps that is true for some changes but the recovery criteria and the normal ranges are not discussed in the statistical analysis plan:
https://trialsjournal.biomedcentral.com/articles/10.1186/1745-6215-14-386
 
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2,125
Good website:
ANGLIA ME ACTION (AMEA) is a UK-based medico-political campaign. The AMEA website is designed to encourage and assist medical professionals, politicians, journalists and public to press for genuine evidence-based research, care and treatment, based upon genuine science-based patient selection criteria, for the WHO-ICD-10-recognised biomedical multi-system illness known as Myalgic Encephalomyelitis/ME.

http://www.angliameaction.org.uk/
 

RogerBlack

Senior Member
Messages
902
Is there a list of everyone connected to the PACE trial ie not just the authors?
eg J.Bavington who devised the GET.

A larger set consisting of people who have commented positively in a professional capacity on PACE might also be useful.
Everyone from SMC staff to uncritical journalists, to ...
 

Dolphin

Senior Member
Messages
17,567
Is there a list of everyone connected to the PACE trial ie not just the authors?
eg J.Bavington who devised the GET.
Lancet. 2011 Mar 5;377(9768):823-36. doi: 10.1016/S0140-6736(11)60096-2. Epub 2011 Feb 18.
Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial.
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.
Collaborators (19)
Darbyshire J, Butler J, Doherty P, Law S, Llewelyn M, Sensky T, Aylward M, Spencer P, Clark C, Stansfeld S, Wearden A, Dieppe P, Fletcher A, Feinmann C, Akagi H, Miller A, Spickett G, Bowman B, Fleetwood D.

*Authors contributed equally †Members listed at end of paper Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine, Queen Mary University of London, London, UK (Prof P D White MD, J C DeCesare BSc, H L Baber BSc, L V Clark PhD); Mental Health and Neuroscience Clinical Trials Unit, Institute of Psychiatry, King’s College London, London, UK (K A Goldsmith MPH, L Potts MSc, R Walwyn MSc); Medical Research Council Biostatistics Unit, Institute of Public Health, University of Cambridge, UK (A L Johnson PhD); Medical Research Council Clinical Trials Unit, London, UK (A L Johnson); South London and Maudsley NHS Foundation Trust, London, UK (M Burgess PhD); Faculty of Health and Well Being, University of Cumbria, Lancaster, UK (D L Cox PhD); Nuffi eld Department of Medicine, University of Oxford, The John Radcliff e Hospital, Oxford, UK (B J Angus MD); Royal Free Hospital NHS Trust, London, UK (G Murphy MSc); Barts and the London NHS Trust, London, UK (J Bavinton BSc, M Murphy FRCP); Frenchay Hospital NHS Trust, Bristol, UK (H O’Dowd PhD); Western General Hospital, Edinburgh, UK (D Wilks FRCP[Ed]); Centre for the Economics of Mental Health Service and Population, King’s College London, London, UK (Prof P McCrone PhD); Academic Department of Psychological Medicine, King’s College London, London, UK (Prof T Chalder PhD); and Psychological Medicine Research, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, UK (Prof M Sharpe MD)

PACE trial group Trial Steering Committee (independent members)—Janet Darbyshire (Chair), Jenny Butler, Patrick Doherty, Stella Law, M Llewelyn, and Tom Sensky. Observers—Sir Mansel Aylward (Department for Work and Pensions, London, UK), Sir Peter Spencer and Chris Clark (Action for ME, Bristol, UK), Stephen Stansfeld (Queen Mary University of London, London, UK), Alison Wearden (Fatigue Intervention by Nurses Evaluation trial), and members of analysis strategy group and writing and publication oversight committee. Data Monitoring and Ethics Committee—Paul Dieppe (initial Chair), Astrid Fletcher (fi nal Chair), and Charlotte Feinmann. Independent assessors of the trial safety data— Hiroko Akagi, Alastair Miller, and Gavin Spickett. Independent assessors of therapy—Barbara Bowman and Deborah Fleetwood.

Contributors

The principal investigators (PDW, TC, and MS) designed the study and obtained funding. Design of the trial was further developed by the trial management group, trial steering committee, data monitoring and ethics committee, and the patients’ organisation, Action for ME. The trial management group, chaired by PDW, included all the authors of this report and Chris Clark, Eleanor Feldman, Tim Peto, and Sir Peter Spencer. The analysis strategy group, chaired by MS, consisted of HLB, TC, JCD, KAG, ALJ, LP, PDW, and RW. The statistical analysis plan was written by the analysis strategy group and approved by the trial steering committee and data monitoring and ethics committee before the analysis was started. The trial analysis team, chaired by ALJ, consisted of HLB, TC, KAG, MS, PDW, and RW. ALJ, LP, and RW were trial statisticians who participated in the design of the study, with RW being the lead writer of the analysis plan. KAG did the main statistical analysis. TC designed and undertook the analysis of therapy diff erentiation, integrity, and alliance. The writing and publication oversight committee, chaired by MS, consisted of HLB, TC, KAG, ALJ, PM, LP, PDW, and RW. The trial managers were JCD initially, then HLB. The treatment leaders were JB, MB, DLC, LVC, and GM (JB and LVC in sequence for one treatment group), who designed the treatment manuals in collaboration with the principal investigators and trained and supervised the trial therapists and doctors. The centre leaders were BA, TC, Eleanor Feldman, GM, MM, HO, Tim Peto, MS, PDW, DW, and Simon Wessely. The centres were at St Bartholomew’s Hospital, London; Western General Hospital, Edinburgh; King’s College Hospital, London; John Radcliff e Hospital, Oxford; Royal Free Hospital, London and the Frenchay Hospital, Bristol (all UK).

Acknowledgments

The PACE trial was funded by the UK Medical Research Council (MRC G0200434), the Department of Health for England, the UK Department for Work and Pensions, and the Chief Scientist Offi ce of the Scottish Government Health Directorates. The Department of Health and the Chief Scientist Offi ce provided excess treatment and service support costs for the trial therapists and doctors. We thank the participants who took part in the PACE trial, staff from all the centres (including all PACE research nurses or assistants: Susan Begg, Matteo Cella, Sally Cregeen, Sarah Horne, Chris James, Julie Richards, Joanna Smee, and Vicky Toghill; data managers: Victoria Bates, Ann M Doust, Emma Hartley, Kate Lievesley, Sandy Smith, and Olga Zielona; therapists: Mary Barker, Jen Bobrow, Laura Butler, Nathan Butler, Richard-John Chippindall, Ruth Cowlishaw, Vincent Deary, Caroline J Heading, Lindsey Hume, Vicky Johnson, Sally Ludlam, Lorraine Maher-Edwards, Louise Mason, Christina Michailidou, Stacey Millet-Clay, Karen Shute, C M Simpson, Sheena E Spence, Valerie Suarez, Brendan Thomas, Tracey Turner, Rebecca Van Klinken, S M Wagner, Sue Wilkins, Giselle Withers, Fiona Wright, and Daniel Zahl; and specialist medical care doctors: Janet Andrews, Michael Broughton, Frauke Fehse, Eleanor Feldman, Janet Gray, Michael E Jones, Tara Lawn, Brian Marien, Tim Peto, Angharad Ruttley, Alastair Santhouse, Adrian Vos, and Simon Wessely. Kathy Fulcher, Tom Meade, C L Murphy, Anthony J Pinching, and Rajesh Shah contributed and provided advice about the study, and Kurt Kroenke, Jan Scott, Peter Tyrer, and Simon Wessely commented on an early draft of the report.