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

Sly Saint

Sly Saint

Senior Member (Voting Rights)
https://bmjopen.bmj.com/content/6/7/e011255

"
Study design
This study started in September 2015 and recruitment is expected to finish in August 2016. This is a feasibility RCT with integrated qualitative methods."

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Ethical considerations
GET, CBT and activity management are recommended as treatments in NICE guidance for CFS/ME;5 however, there is no evidence that GET is effective or safe in children and adolescents."

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At 12 months, we will assess whether the trial should continue to a full trial. The full trial is unlikely to be feasible in the format considered here if any of the following apply:

  1. Less than 70 children and adolescents have been recruited (∼70% of the target) and if the qualitative data collected suggest that recruitment cannot be improved any further.

  2. The 6-month follow-up is <80% and if the qualitative data suggest that follow-up rates cannot be improved any further.

  3. Data suggest the interventions are not acceptable to children and/or their parents.

  4. If the Data and Safety Monitoring Committee (DSMC) and the Trial Steering Committee (TSC) recommend the trial is stopped for safety reasons."
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Public and patient involvement
A Patient Advisory Group (PAG) has been involved throughout the development of this protocol and will remain involved throughout the running of the trial, with PAG meetings being held every 6 months. Minutes from the PAG group will be disseminated to the Study Steering Committee and the Trial Management Group."

Anyone know anything about the PAG on this trial?

Has this been turned into a full trial ?

eta: OK I guess it has
http://www.isrctn.com/ISRCTN23962803?q=&filters=conditionCategory:Nervous System Diseases&sort=&offset=6&totalResults=536&page=1&pageSize=10&searchType=basic-search

When is the study starting and how long is it expected to run for?
September 2015 to March 2019

does this mean the feasibility study has been rolled into the full one?

eta2:
yes
Favourable ethical opinion to amend from feasibility to full trial: NRES Committee South West - Frenchay, 06/03/2017, ref: 15/SW/0124

The overall trial end date has been updated from 31/12/2018 to 31/03/2019 3. The target number of participants has been updated from 100 to 222 (this includes the 100 participants from the feasibility trial).

eta3:
Have the MPs who took part in the Westminster debate been made aware of this trial?

MAGENTA website:
http://www.bristol.ac.uk/ccah/research/childdevelopmentdisability/chronic-fatigue/magenta-trial/

eta4:
The version of the feasibility study I posted in the OP first link was updated in July 2016.
The previous version is here:
https://bmjopen.bmj.com/content/bmjopen/6/7/e011255.draft-revisions.pdf
and the reviewer (just the one) comments here:
https://bmjopen.bmj.com/content/bmjopen/6/7/e011255.reviewer-comments.pdf
 
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I've been looking at these two arms of the trial and I am bemused.

Arm 1: activity management
This arm will be delivered by CFS/ME specialists. As activity management is currently being delivered in all three services, clinicians will not require further training; however, they will receive guidance on the mandatory, prohibited and flexible components (see online supplementary appendix 1). Clinicians therefore have flexibility in delivering the intervention within their National Health Service (NHS) setting.

Activity management aims to convert a ‘boom–bust’ pattern of activity (lots 1 day and little the next) to a baseline with the same daily amount before increasing the daily amount by 10–20% each week. For children and adolescents with CFS/ME, these are mostly cognitive activities: school, schoolwork, reading, socialising and screen time (phone, laptop, TV, games). Those allocated to this arm will receive advice about the total amount of daily activity, including physical activity, but will not receive specific advice about their use of exercise, increasing exercise or timed physical exercise.
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Arm 2: graded exercise therapy (GET)
This arm will be delivered by referral to a GET-trained CFS/ME specialist who will receive guidance on the mandatory, prohibited and flexible components (see online supplementary appendix 1). They will be encouraged to deliver GET as they would in their NHS setting.20 Those allocated to this arm will be offered advice that is focused on exercise with detailed assessment of current physical activity, advice about exercise and a programme including timed daily exercise.

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 guidance5 and the Pacing, graded Activity and Cognitive behaviour therapy – a randomised Evaluation (PACE)12 ,21). This will be the median amount of daily exercise done during the week. Children and adolescents will also be taught to use a heart rate monitor to avoid overexertion. Participants will be advised to stay within the target heart rate zones of 50–70% of their maximum heart rate.5 ,7
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So they are actually both GET, but with the one labelled as GET more carefully monitored using timing and heart rate monitoring.
 
Sly Saint said:
recruitment is expected to finish in August 2016
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Sly Saint said:
At 12 months, we will assess whether the trial should continue to a full trial
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August 2017(?)
Sly Saint said:
Favourable ethical opinion to amend from feasibility to full trial: NRES Committee South West - Frenchay, 06/03/2017
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so did the feasibility trial start early? ie March 2016?

eta:
or did EC go for full trial permission after 6 months? (ie the first follow-up of the feasibility trial, therefore it did not run for a year as initially intended?)

eta2:
for full study it says
Recruitment end date
07/03/2018
 
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I can't believe that, after all, there is a GET trial again, this time they are destroying childrens' lives. This really touches me in a negative sense. :( It's incredible. Can't there nothing be done to stop this lunacy?
 
This trial design is a win-win for Crawley either way - the outcome measures are likely to be questionnaires, so whichever group persuades the most kids to fill them in to say they are better she promotes as successful treatment. They are both GET, so GET wins either way. That's ridiculous. Where's the control group?
 
Trish said:
This trial design is a win-win for Crawley either way - the outcome measures are likely to be questionnaires, so whichever group persuades the most kids to fill them in to say they are better she promotes as successful treatment. They are both GET, so GET wins either way. That's ridiculous. Where's the control group?
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And don’t forget the GET arm is “by referral” so presumably that means they can cherry pick the sample
 
I don' t know how genuine volunteers are. From the other place there were posts indicating that parents were being " hassled" to join the trial. Phonecalls every 30 mins.
With ever present PRS diagnosis should your child slip backwards it' s Hobson's choice.

Somehow this Kafkaesque nightmare has no traction here - we protest at refugees and Trump separating parents and children, yet have no mainstream knowledge of what goes on behind twitching curtains here ..
 
Some thoughts on this

http://www.bristol.ac.uk/ccah/research/childdevelopmentdisability/chronic-fatigue/magenta-trial/

Activity Management
Participants in this group will have a detailed assessment of the activity they do. This includes thinking activity such as school work, homework, time on the computer and screens, reading and hobbies that require concentration and physical activity such as walking or PE. We call this high energy activity. We will ask participants to record their activity on paper or our iPhone app “ActiveME”. We will then help them find their “baseline” activity which is the average amount of activity that they can do each day. When they have found their baseline activity, they will help them increase this by 10-20% each week. This is called activity management.
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Graded exercise therapy
Participants in this group will receive a detailed physical assessment including how far they can walk in 2 minutes and how many times they can move from sitting to standing in one minute. This will help us set a safe exercise programme. Participants will be asked about the exercise they do each day and will be helped to find their exercise baseline. The baseline is the average amount of exercise they do each day. It will be less than they do on a good day. When they have found their baseline, we will ask participants to slowly increase their exercise. When they are able to do 30 minutes each day, we will increase the intensity of exercise. participants will be asked to record exercise using either charts or the iPhone app ActiveME. They will not be asked to record other activities, only exercise. To make sure participants do not over do their exercise, we will ask them to use a heart rate monitor.
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Ineffective treatments appear effective mainly due to reporting biases and regression to the mean. This study fails to control both of these factors.

The design of the GET intervention is also susceptible to activity displacement (sacrificing activity in one area to increase activity in another area).

A target of thirty minutes of exercise a day makes me question the CFS diagnosis.

Accelerometers will be used to record activity at 0, 3, 6 months. The primary outcome is self reported physical function however, so in my view the study still fails to control for biased self reporting. It will be interesting to see whether the accelerometer data supports or contradicts self reported measures.

Since regression to the mean isn't controlled for, it will be technically impossible to attribute any improvement to the interventions. The study authors are probably operating under he assumption that the efficacy of the intervention has already been proven in previous studies. My memory is hazy on this but I doubt that this is really the case, most likely, previous studied based claims of efficacy on weak design susceptible to bias.

Due to failing to control for regression to the mean, a positive outcome is very likely. Crawley's clinic probably offers both kinds of treatments, or could easily switch to whichever comes out on top. As usual with CBT/GET, it's about defending business interests rather than finding out what treatments really work.
 
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Sly Saint said:
yes
Favourable ethical opinion to amend from feasibility to full trial: NRES Committee South West - Frenchay, 06/03/2017, ref: 15/SW/0124
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It does look like the ethics committee has extended it from a feasibility study to a full trial. Which seems to me very dodgy. From the Smile trial we learned that this approval goes through a sub committee rather than the full committee and hence she is avoiding a full ethical examination of whether to carry out a new trial.
 
Reading all this is so disheartening. I had begun to think that we might be moving beyond this. And then here she comes again. How are they getting the young people for this study. I feel sorry for them, their parents and for all of us. There is huge manipulation going on and it is very intentional... A kafkaesque nightmare is an apt description.
 
I have not studied this in detail but from what I can see this is another unblinded trial with subjective outcome measures that will provide no useful information.

Additional serious concerns have been identified with the SMILE study. Bristol University legal department is well aware of the fact that people have concerns, as is the BMJ. These studies on children have been generated on the back of adult studies like PACE using similarly flawed methods. There may be some hope that the message may be finally getting through that studies like this are not justified. If not I am not sure quite what more should be done to shift opinion but on the other hand it will be increasingly difficult for bristol to maintain the credibility of these studies as PACE collapses.

The whole business of doing feasibility studies that are rolled into full studies looks to me problematic and against the basic rule that you set things up prospectively and do not fiddle with them half way through. There is a strong suspicion that it is perceived that 'feasibility studies' are easier to get ethical approval for.

I would be interested to know if Dr Crawley is the only person worldwide to be doing studies of therapist-delivered treatments in childhood ME. And whether the rest of the world is following her results.
 
Jonathan Edwards said:
I have not studied this in detail but from what I can see this is anounblinded trial with subjective outcome measures that will provide no useful information.

Additional serious concerns have been identified with the SMILE study. Bristol University legal department is well aware of the fact that people have concerns, as is the BMJ. These studies on children have been generated on the back of adult studies like PACE using similarly flawed methods. There may be some hope that the message may be finally getting through that studies like this are not justified. If not I am not sure quite what more should be done to shift opinion but on the other hand it will be increasingly difficult for bristol to maintain the credibility of these studies as PACE collapses.

The whole business of doing feasibility studies that are rolled into full studies looks to me problematic and against the basic rule that you set things up prospectively and do not fiddle with them half way through. There is a strong suspicion that it is perceived that 'feasibility studies' are easier to get ethical approval for.

I would be interested to know if Dr Crawley is the only person worldwide to be doing studies of therapist-delivered treatments in childhood ME. And whether the rest of the world is following her results.
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As FITNET is a follow up of a Dutch study ( taken apart by @Docsimsim & Vink ) , I suspect that where the BPS model is alive and well, that you will find paediatric research.
 
I don't think extending a feasibility trial into a full trial is a problem per se--the problem in SMILE was that the two-person subcommittee responding to the request to extend it also allowed Professor Crawley to swap primary sound secondary outcome measures at the same time--a move virtually guaranteed to create bias. I do think the concerns that have been raised about SMILE and about the school absence study have put Bristol and Professor Crawley on notice that people are now aware of this sort of data manipulation--ok, let's call it research misconduct. MAGENTA was set up and approved before all the recent PACE/CBT/GET debunking.
 
Sly Saint said:
could someone else have a look at the dates as something doesn't seem to be right
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Sept 2015 - Recruitment to feasibility trial starts.
Sept 2016 - Recruitment to feasibility trial planned completion. 100 patients.
March 2017 - Approval given for conversion to full trial.
Sept 2017 - Planned 12 month assessment of feasibility and conversion to full trial.
March 2019 - expected completion of full trial. Total 220 patients including 100 from feasibility trial.

From that it looks like they got approval for conversion to a full trial 6 months earlier than planned.
 
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