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

Is the only reason we think MAGENTA is ready to be published that a Bath employee discussed the results?

 

Yes, I think I set off this flurry of activity.

Good to be prepared though!

 

So yes accelerometers have been dropped between feasibility and full protocol. @dave30th.

Interestingly, Reviewer 1states on p17 of her Review of Version 2

https://bmjopen.bmj.com/content/bmjopen/6/7/e011255.reviewer-comments.pdf

"In summary, the authors have made major amendments but the GET section still needs work, as it should be very clear to readers who are exercise therapists, physiologists and physiotherapists what sort of exercise programs/activities can be utilised as GET. Vague statements that therapists will administer GET as they would in the NHS settings means nothing to exercise professionals/allied health clinicians who are a) not working in NHS; and 2) work outside the UK but are interested in this project. The many references to the PACE trial may be inappropriate for this project, as the PACE trial has been highly criticised for fundamental flaws in its design and reporting of GET/APT and other outcomes."

 

Thanks so much to @Amw66 for retrieving the PR threads. I have taken some screen shots of relevant bits.
Don't know if DT or some of the S4ME founders will be able to look at them.

There were lots of useful comments, incuding our lovely "Bob" at #87, Keith G starting at #104, and @Dolphin did a fair bit of quoting/analysing as well. So did @Jenny TipsforME, but she's already on this thread.

I am going away for the w/e and should have been packing etc this morning.....so will probably not contribute to thois much in the next couple of days apart from next post.

 

You' re welcome. I don' t know if there are others. These were the most active results from simple search

 

@MEMarge was the person you spoke to a researcher on the project?

 

The PR thread I remember is https://forums.phoenixrising.me/index.php?threads/junior-version-of-pace-funded-pi-dr-crawley.42685/

 

Reviewer 1 is Suzanne Broadbent (Aus) who is a Dr following her PhD in Exercise studies.

The final Review I can access is dated 3 May 2016 as above. It also includes:
"REVIEWER RESPONSES TO AUTHOR RESPONSES Manuscript ID bmjopen-2016-011255.R1, entitled "The Managed Activity Graded Exercise iN Teenagers and pre-Adolescents (MAGENTA) feasibility randomised controlled trial: Study Protocol.." May 3rd 2016. Firstly, I thank the authors for their hard work on the manuscript, which reads much better and is certainly much clearer. I am happy with most of the amendments. The only issue I still have is with the lack of clarity and description of the graded exercise program itself, and some of my previous comments have not really been addressed. This is a protocol paper and as such needs to be clear enough to replicate – the current version still needs work.

In particular, I highlight the author responses below and my concerns with those responses.
1This sentence still makes no sense.
I think the authors are trying to say that participants will be doing up to 30 minutes of play and low intensity recreational physical activity (not planned exercise), and once this is established, participants may be able to move onto more structured aerobic exercise at a higher intensity.

By definition, aerobic exercise is any exercise that noticeably increases heart rate, last for more than 10 minutes, and that uses the larger muscle groups (see Heyward and Gibson 2014 or ACSM guidelines), therefore relying on aerobic metabolism.

So the authors need to be a lot clearer in their description of what the children will be doing BEFORE they incorporate aerobic activity and then what kind of aerobic exercise they may be doing (e.g. walking, sports involving running, swimming etc). The NICE definition is “any activity that increases pulse” which is not really correct as strength training also increases heart rate.

The PACE trial results were very sketchy about what participants did and only mentioned walking as the most common example of aerobic activity undertaken (White et al, 2011))
“Once participants are doing 30 minutes of daily exercise within the low intensity heart rate limits, the exercise will increase in intensity such that participants start doing aerobic exercise”."!!!!!

 

Above extract continued:

"This sentence still makes no sense. I think the authors are trying to say that participants will be doing up to 30 minutes of play and low intensity recreational physical activity (not planned exercise), and once this is established, participants may be able to move onto more structured aerobic exercise at a higher intensity.

By definition, aerobic exercise is any exercise that noticeably increases heart rate, last for more than 10 minutes, and that uses the larger muscle groups (see Heyward and Gibson 2014 or ACSM guidelines), therefore relying on aerobic metabolism. So the authors need to be a lot clearer in their description of what the children will be doing BEFORE they incorporate aerobic activity and then what kind of aerobic exercise they may be doing (e.g. walking, sports involving running, swimming etc).

The NICE definition is “any activity that increases pulse” which is not really correct as strength training also increases heart rate. The PACE trial results were very sketchy about what participants did and only mentioned walking as the most common example of aerobic activity undertaken (White et al, 2011)"

 

From Reviewer 1's comments on the first draft, she warns about high rates of increase of exercise, given that subjects have ME/CFS!
https://bmjopen.bmj.com/content/bmjopen/6/7/e011255.reviewer-comments.pdf Page 2

"P 8, Lines 4 and 29-30: A progression of 10-20% per week in physical activity is regarded as standard for healthy adults. Other CFS research suggests that progression for CFS patients should be a lot less or at least self-paced with periods of no progression if symptomatic. Can the authors explain why the 10-20% progression was chosen and support this with references from CFS literature?"

Crawley et al's response is:
"2) A progression of up to 20% is the guidance provided by the National Institute of Clinical Excellence1 and is standard practice in the UK. This is also consistent with the PACE trial, the largest trial done to date. We have now included a reference to NICE guidelines and the PACE trial, the protocol now reads: “The intervention will encourage children and adolescents to find a baseline level of exercise which will be increased slowly (by 10-20% a week, as per NICE guidance1 and the PACE trial2)”.

 

Reviewer 1 replies:
"The NICE guidelines state that a progression of up to 20% is deemed appropriate for CFS/ME clients. There is no reference in any of the published PACE articles, that I can find, that defines the actual progression. This was one of the many faults of the reporting of this trial. I suggest removing the reference to PACE and using the NICE guideline."

Then in 3) Reviewer 1 recommends using RPE (rate of perceived exertion) as it is also recommended in the NICE guidelines...

Then in 4) Rev 1 includes:
"The referencing of the PACE trial is not appropriate as nowhere in the PACE protocol paper (2007) or the main results paper (2011) can I find any description of what sort of graded exercise the participants actually did. Only the 2011 paper mentions that walking was the most popular choice. "

Have not had time to follow this through to the final ?June 2016 protocol.

Hope you all have some good stuff over the w/e

 

Can anyone remember the source for children cheating with accelerometers? This does ring a bell, but do we have evidence from the research team?

 

A therapist who now works in Bath paediatric CFS service. No idea how long she's been there or her involvement with the trial.
I will message her name next week.

 

FITNET-NHS is also full of PACE references.

this bit on how Crawley and her team proposed to differentiate between the two treatment arms:

"Fidelity of GET and activity management: we will monitor protocol adherence and evaluate whether the two interventions are distinct and being delivered in a consistent manner across centres.

Two clinicians, from centres other than that in which the session was delivered, will listen to a random sample (∼10%) of the audio-recorded sessions in a blinded fashion and rate them on a five-point Likert scale as being GET or activity management or a mixture of the two using the mandatory, prohibited and flexible elements for each intervention.

We will estimate intervention fidelity as the percentage of sessions in each intervention arm which were correctly identified by the clinicians assessing recordings."

good grief.

eta: "audio-recorded sessions", how on earth can you know what is going on if you can't see it?

 

In one of EC's talks she said something about youngsters not wanting to wear things that made them look different.
In something I've accessed re Magenta in the last day or so it mentions the accelerometer as being a box you wear round your hips?waist...Does not sound that cool.

 

"Prof Crawley (paediatrician who is a fan of GET) shared the results of various randomised trials. This included such gems as the SMILE trial investigating the Lightening process. Most of the trials she discussed, SMILE, GETSET, FITNET, etc use subjective, patient report outcome measures. I asked her if there was a trend in future trials that will incorporate objective measures to ensure that the small, modest improvements seen in such trials are not due to the placebo effect. She really didn't like that at all. She did manage to tell me that using accelerometers is not that objective and her young patients cheat."
https://www.s4me.info/threads/hello-everyone.4253/

I think she said it on one of her talks, or radio interviews as well

 

I'm going through my Crawley catalogue and found this one which was actually about FITNET-NHS;
interesting that they also have a group doing 'Activity Management' delivered by SKYPE.

 

That certainly sounds like it needs understanding better. What was going on in the period 15/01/2013 to 10/09/2015? And why was the trial's start date retrospectively shifted, in June this year, back more than 2 1/2 years to Jan 2013! Did they not know when it was starting at the time it was starting?! Were any participants recruited prior to 10/09/2015, and just "rolled into" the main study? Could be legit reasons, but given the track record, definitely needs understanding.

 

Just been having another look at ECs Eventbrite talk:

Re Magenta EC says:
"Recruited ahead of target.
Independent DSMC and TSC review.
Children loved both treatments."

Generally about her research she says:
"I preregister my trials, I publish protocols, I publish analysis plans, well before we do the analysis".

hmm.
eta: thread on the talk here
https://www.s4me.info/threads/bette...ter-data-25th-october-2017-esther-crawley.75/

so she 'knew' in oct 2017 that it was 'going great'.

 

Here’s a thought. Bear with me. . .

My background is biology, and as a student, when surveying plants in the wild, we always used quadrats that were placed in very precise predetermined locations. So if surveying a transition from wood to grass land for example the quadrat positions could not be selected once you were in the field. As young students we always wanted the best results, and we’re always tempted to reposition our quadrats to include the plants that fitted our notion of what we thought we should see.

Of course we had it drummed into us, that biasing results like this by reselecting where our sample boundaries lay was NOT science, no matter how much tidier it made the results appear.

So, could these date switches be means a means of shifting the sample boundaries (a bit like repositioning a quadrat) to give a sample that gave the “best” (in their view) results?

It all seems a little weird