MAGENTA (Managed Activity Graded Exercise iN Teenagers and pre-Adolescents) - Esther Crawley

Alvin said:
Who is paying for this study?
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  • Contributors EC conceived the initial trial concept and obtained the funding as part of her NIHR Senior Research Fellowship. All authors contributed to the development of the trial design and protocol. All authors have read and approved the manuscript.

  • Funding This trial is supported by the National Institute for Health Research (Senior Research Fellowship, EC, SRF-2013-06-013). This study was delivered in collaboration with the Bristol Randomised Trials Collaboration (BRTC), a UKCRC Registered Clinical Trials Unit in receipt of National Institute for Health Research CTU Support Funding. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.
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https://bmjopen.bmj.com/content/6/7/e011255
 
I don't have time to read the thread at present but just in case it hasn't been highlighted, the prepublication peer review history is here:
https://bmjopen.bmj.com/content/bmjopen/6/7/e011255.reviewer-comments.pdf

It involves Lucy Clark, who has worked on graded exercise therapy trials in CFS in the UK, and Suzanne Broadbent who has trialled exercise programmes for CFS in Australia. The latter is part of the Australian medical research council's committee on CFS/ME
 
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Dolphin said:
I don't have time to read the thread at present but just in case it hasn't been highlighted, the prepublication peer review history is here:
https://bmjopen.bmj.com/content/bmjopen/6/7/e011255.reviewer-comments.pdf

It involves Lucy Clark, who has worked on graded exercise therapy trials in CFS in the UK and Suzanne Broadbent who has trialled exercise programmes for CFS in Australia. The latter is part of the Australian medical research council's committee on CFS/ME
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One for @dave30th perhaps given recent Australia trip
 
I have skimmed reviewers comments from the link posted by @Dolphin- notable difference between UK and Australian reviewer. Looks like the difference between someone who knows what they are talking about and someone who dosn' t / someone who is on a defined career path/ cognitive dissonance.

Someone with more time will no doubt find significant issues . This is for children!

Significant concerns re exclusion criteria ( only those severely affected enough to require wheelchairs and not be able to do daily tasks). This risks harm.

No definition of exercise therefore no delivery consistency if being rolled out to multi centred. Very vague.( In fact whole thing pretty vague given numbers of points elicited by reviewer 1 - how can this be termed remotely scientific)

Why on earth are they targeting aerobic exercise?

Someone with better knowledge than I should pick this apart.

Charities should read the reviewers comments as no doubt it will be part of NICE review documentation , and there seems much to be concerned about.
@Russell Fleming ,@Action for M.E. , @JenB
 
the Bristol Uni site on Magenta
http://www.bristol.ac.uk/ccah/research/childdevelopmentdisability/chronic-fatigue/magenta-trial/

recruitment finished in March and according to @MEMarge they have started analysis(?)

I watched the Trust me I'm doctor prog on BBC this week where they featured an unconnected trial on exercise for older people called REACT
( https://www.bath.ac.uk/projects/retirement-in-action-react-study/ ).
It was based on the LIFE study done in the US (https://www.thelifestudy.org/public/index.cfm ).

What I found interesting was the difference in approach.

"In these studies, people will be asked to wear physical activity monitors, complete food diaries over three days, and attend a lab at the University where the researchers will measure leg strength, balance, and undertake detailed scans of body composition."

http://www.bath.ac.uk/news/2017/01/26/muscles/

In comparison to MAGENTA this appears to be a well designed and organised trial with clear and well measured objectives.
and, the person leading the project:
"Oly Perkin, a PhD student in the Department for Health who is leading the research".....

(just thinking of Michael Sharpes comments about people who had signed the letter to the Lancet not being RCT experts). ie if a phd student can design a good trial.....
 
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The info on Magenta was from chatting to a therapist during the NICE Scoping mtg in May. She works with the Bath paediatric CFS service.

Not wanting to be too confrontational or scathing I asked something like: "Oh, how are things going down there?".
Her reply was along the lines of :It's exciting we're getting the Magenta results thro, and then confirmed that they were positive.

I have no idea whether that means all the data is in or whether they have finished collecting it...

Just think we need to be prepared for when it is. Maybe someone more informed than me could do a "Main reasons why Magenta results are meaningless summary for CS and an MEA press release"

I suspect that @dave30th has already done a fair bit of groundwork on his virology blog response.
 
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Sly Saint said:
the Bristol Uni site on Magenta
http://www.bristol.ac.uk/ccah/research/childdevelopmentdisability/chronic-fatigue/magenta-trial/

recruitment finished in March and according to @MEMarge they have started analysis(?)
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Looking at this website I was reminded of that the ethics information is available (I think we have discussed it before)

http://www.bristol.ac.uk/ccah/resea...ability/chronic-fatigue/magenta-trial/ethics/

Including a letter they wrote to the ethics committee dismissing concerns about PACE. I feel its misleading the ethics committee in that it doesn't represent the issues raised or really address them.

http://www.bristol.ac.uk/media-library/sites/ccah/cfsme/study-docs/Ethics Letter 31.10.16.pdf

It certainly doesn't give a neutral version for the ethics committee to decide on. You couldn't accuse Bristol University of providing all necessary evidence for the ethics committee to use to make a judgement. But then the ethics committee should realize that and dig further. They seem to have done some sort of re-review
http://www.bristol.ac.uk/media-libr...mation of favourable opinion 24.11.16 (1).pdf

They seem to heavily rely on Cochranes meta analysis in support of doing GET and for arguments of safety. Of course Bristol university doesn't mention to the ethics committee the issues with the Cochrane review and the unreliability of the evidence base that they are using.
 
MEMarge said:
The info on Magenta was from chatting to a therapist during the NICE Scoping mtg in May. She works with the Bath paediatric CFS service.

Not wanting to be too confrontational or scathing I asked something like: "Oh, how are things going down there?".
Her reply was along the lines of :It's exciting we're getting the Magenta results thro, and then confirmed that they were positive.

I have no idea whether that means all the data is in or whether they have finished collecting it...

Just think we need to be prepared for when it is. Maybe someone more informed than me could do a "Main reasons why Magenta results are meaningless summary for CS and an MEA press release"

I suspect that @dave30th has already done a fair bit of groundwork on his virilogy blog response.
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I'm wondering if that indicates something dodgy is going on. Are they doing an early assessment of results in case they need to tweak the protocol. But they if I remember correctly they didn't bother with any objective measures.
 
Adrian said:
I'm wondering if that indicates something dodgy is going on. Are they doing an early assessment of results in case they need to tweak the protocol. But they if I remember correctly they didn't bother with any objective measures.
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If they are indicating positive results before all the data is in and been analysed, that would fly contrary to the argument used (albeit speciously) in PACE.
 
Barry said:
If they are indicating positive results before all the data is in and been analysed, that would fly contrary to the argument used (albeit speciously) in PACE.
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It seems to me that they cannot then claim that analysis happened before data was unblinded (to the stats team) it also suggests any deviations from the protocol outcome measures could come as a result of knowledge of the data. If they were doing this all the way through it could be dodgy but I can't remember what was happening in terms of protocol changes and upgrades from a feasibility study.
 
Jonathan Edwards said:
In my own experience feasibility studies have been open trials of no more than six cases, which allow you to see if treating is feasible. 100 patients in a feasibility study looks very odd to me.
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I agree with @Jonathan Edwards that a feasibility study of a hundred sounds a lot.

My own experience was that no matter how well you think you have designed the trial there are always practical issues irrelevant to the purpose of the trial that need to be sorted out, be it if venues are appropriate, do the transport links work, have you included items in a questionnaire that people consistently interpret differently to the original intention, etc. To answer these questions only a handful of subjects are required.

If you a run a feasibility study of a hundred or more subjects, some 50% of the total number suggests you are asking very different questions about how the study works in relation to the research questions. The only way to answer these questions would be to look at the results. This then either results in bias either by changing the design (eg outcomes switching) or through deciding whether to continue or not. If neither, then why undertake the feasibility study in the first place?

Do we have any examples of Crawley conducting such a large feasibility study and then abandoning that data, either abandoning the research completely or starting a new redesigned investigation? If not then surely these are not feasibility studies. In that case these are single studies where the data is collected in two stages, but for some reason Crawley wishes to mislead about their nature.
 
Am I missing something, like the protocol for the final study?

Under the AIMS AND OBJECTIVES section response to Reviewer 1 (Dr Suzanne Broadbent) is the following:

Reviewer has said:
" AIMS AND OBJECTIVES
One of the aims is to assess the effectiveness of GET compared to AM. You could include an aim that states exactly how you will assess “effectiveness” e.g. adherence, exercise compliance, evaluation of exercise performance."
https://bmjopen.bmj.com/content/bmjopen/6/7/e011255.reviewer-comments.pdf p2 & 7

Authors respond:
"Within the aims we state: “To ascertain the feasibility and acceptability of conducting an RCT to investigate the effectiveness and cost-effectiveness of GET compared to Activity Management for the treatment of CFS/ME in children. We will use the information to inform the design of a full-scale, adequately powered trial.” If it is feasible to recruit into MAGENTA, we will detail how we will define effectiveness in the full trial, which will be to investigate the effectiveness of GET compared to AM."
https://bmjopen.bmj.com/content/bmjopen/6/7/e011255.reviewer-comments.pdf p7

So presumably it has been possible to recruit and they have detailed how they havedefined effectiveness in the full trial protocol.

I've probably missed a whole thread on this
 
Outcome measures:
"
Primary outcome measure
Feasibility trial:
Feasibility and acceptability of investigating GET in a randomised controlled trial measured after 1 year.

Full trial:
Physical function is measured with the 36-Item Short Form Health Survey (SF36, physical function sub scale), collected at the 6 month time point.

Secondary outcome measures
Feasibility trial:
No secondary outcome measures.

Full trial:
1. School attendance is measured as percentage attendance of expected sessions
2. Fatigue is measured using the Chalder Fatigue score
3. Pain is measured using the visual analogue scale
4. Depression and anxiety are measured using the Spence Children’s Anxiety Scale (SCAS) and the Hospital Anxiety and Depression Scale (HADS, if they are 12-17 years old)
5. Health related quality of life is measured using the EQ-5D-Y

All of the above outcomes will be measured via child self-completed questionnaires at baseline, 6 and 12 months as well as a measure of physical function the SF36-PFS at 12 months."

http://www.isrctn.com/ISRCTN2396280...36&page=1&pageSize=10&searchType=basic-search
 
Sly Saint said:
Outcome measures:
"
Primary outcome measure
Feasibility trial:
Feasibility and acceptability of investigating GET in a randomised controlled trial measured after 1 year.

Full trial:
Physical function is measured with the 36-Item Short Form Health Survey (SF36, physical function sub scale), collected at the 6 month time point.

Secondary outcome measures
Feasibility trial:
No secondary outcome measures.

Full trial:
1. School attendance is measured as percentage attendance of expected sessions
2. Fatigue is measured using the Chalder Fatigue score
3. Pain is measured using the visual analogue scale
4. Depression and anxiety are measured using the Spence Children’s Anxiety Scale (SCAS) and the Hospital Anxiety and Depression Scale (HADS, if they are 12-17 years old)
5. Health related quality of life is measured using the EQ-5D-Y

All of the above outcomes will be measured via child self-completed questionnaires at baseline, 6 and 12 months as well as a measure of physical function the SF36-PFS at 12 months."

http://www.isrctn.com/ISRCTN23962803?q=&filters=conditionCategory:Nervous System Diseases&sort=&offset=6&totalResults=536&page=1&pageSize=10&searchType=basic-search
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So basically questionnaires, questionnaires and more questionnaires?
 
Sly Saint said:
not sure if this is for the full trial it's version 3, and from 14/06/2016
https://www.whatdotheyknow.com/request/368381/response/902419/attach/html/3/MAGENTA Protocol.pdf.html

eta: have checked and this is the only version I can find; it was published in the BMJ in July 2016.
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Thanks @Sly this still refers to a feasibility:

"If MAGENTA is shown to be feasible, the study will continue as a full trial. We anticipate that
we will be able to use the data obtained in the feasibility phase for the full trial and plan to
recruit participants for a further 18 months with an additional 15 months follow up.

Aims and objectives:
The overall aim of this study is to investigate the feasibility and acceptability of conducting a
Randomised Controlled Trial (RCT) to investigate the effectiveness and cost-effectiveness of
Graded Exercise Therapy compared to Activity Management for the treatment of CFS/ME in
children and adolescents. The specific objectives will inform the design of a full-scale,
adequately powered trial which will follow the feasibility study. "
 
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