Graded exercise therapy compared to activity management for paediatric [CFS/ME]: pragmatic randomized controlled trial, 2024, Gaunt, Crawley et al.

[SNT Gatchaman]

Graded exercise therapy compared to activity management for paediatric chronic fatigue syndrome/myalgic encephalomyelitis: pragmatic randomized controlled trial
Gaunt, Daisy M.; Brigden, Amberly; Harris, Shaun R. S.; Hollingworth, William; Jago, Russell; Solomon-Moore, Emma; Beasant, Lucy; Mills, Nicola; Sinai, Parisa; Crawley, Esther; Metcalfe, Chris

The MAGENTA pragmatic parallel groups randomized controlled trial compared graded exercise therapy (GET) with activity management (AM) in treating paediatric myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). Children aged 8-17 years with mild/moderate ME/CFS and presenting to NHS specialist paediatric services were allocated at random to either individualised flexible treatment focussing on physical activity (GET, 123 participants) or on managing cognitive, school and social activity (AM, 118 participants) delivered by NHS therapists.

The primary outcome was the self-reported short-form 36 physical function subscale (SF-36-PFS) after 6 months, with higher scores indicating better functioning. After 6 months, data were available for 201 (83%) participants who received a mean of 3.9 (GET) or 4.6 (AM) treatment sessions.

Comparing participants with measured outcomes in their allocated groups, the mean SF-36-PFS score changed from 54.8 (standard deviation 23.7) to 55.7 (23.3) for GET and from 55.5 (23.1) to 57.7 (26.0) for AM giving an adjusted difference in means of −2.02 (95% confidence interval −7.75, 2.70). One hundred thirty-five participants completed the mean SF-36-PFS at 12 months, and whilst further improvement was observed, the difference between the study groups remained consistent with chance. The two study groups showed similar changes on most of the secondary outcome measures: Chalder Fatigue, Hospital Anxiety and Depression Scale: Depression, proportion of full-time school attended, a visual analogue pain scale, participant-rated change and accelerometer measured physical activity, whether at the 6-month or 12-month assessment.

There was an isolated finding of some evidence of an improvement in anxiety in those allocated to GET, as measured by the Hospital Anxiety and Depression Scale at 6 months, with the 12-month assessment, and the Spence Children’s Anxiety scale being aligned with that finding. There was weak evidence of a greater risk of deterioration with GET (27%) than with AM (17%; p = 0.069). At conventional UK cost per QALY thresholds, the probability that GET is more cost-effective than AM ranged from 18 to 21%. Whilst completion of the SF-36-PFS, Chalder Fatigue Scale and EQ-5D-Y was good at the 6-month assessment point, it was less satisfactory for other measures, and for all measures at the 12-month assessment.

CONCLUSIONS
There was no evidence that GET was more effective or cost-effective than AM in this setting, with very limited improvement in either study group evident by the 6-month or 12-month assessment points.

TRIAL REGISTRATION
The study protocol was registered at www. isrctn.com (3rd September 2015; ISRCTN 23962803) before the start of enrolment to the initial feasibility phase.

Link | PDF (European Journal of Pediatrics) [Open Access]

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

 

[SNT Gatchaman]

The lack of improvement in self-reported physical function in either group was unexpected, contrasting with the findings of adult treatment trials using the SF-36-PFS measure and our earlier SMILE RCT of interventions for paediatric ME/CFS.

Only cautious conclusions can be drawn from those secondary outcome measures with poor completion rates. Whilst we registered MAGENTA before starting recruitment during the feasibility phase, we did not confirm the primary outcome measure until the first full trial protocol (Appendices 1 and 5); we recognise this invites the accusation that we used the data collected during the feasibility phase to select the primary outcome.

@dave30th: improving science one blog post and letter at a time.

 

[SNT Gatchaman]

Finally, in October 2021, NICE revised its ME/CFS diagnostic criteria for technology appraisal [12]. We cannot retrospectively determine if the MAGENTA participants meet these new diagnostic criteria, which have been criticised [36].

[36] Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis (2023)

 

[Hutan]

I groaned when I saw this - Crawley, I thought, why can't she just leave vulnerable children alone and go skiing?

But:

CONCLUSIONS
There was no evidence that GET was more effective or cost-effective than AM in this setting, with very limited improvement in either study group evident by the 6-month or 12-month assessment points.

So, blow me down with a feather.

GET, even a lovely 'individualised flexible' version of GET, wasn't better than activity management. And neither produced any meaningful improvement in the medium term. Even with considerable loss to followup. Even with the vague and easily manipulated Chalder Fatigue Scale. Even with no controls to identify natural rates of recovery (I'm really surprised that the results of both therapies didn't look better than they did, just due to natural recovery with time).

Is it possible that the scales are falling from the eyes of some of these people who have believed that they were doing something useful when pushing GET and various other sorts of 'get out of bed and off the couch and stop thinking about your symptoms' approaches?

This feels like another major hit to the BPS crowd, just after the NICE rebuttal came out.

There was weak evidence of a greater risk of deterioration with GET (27%) than with AM (17%; p = 0.069).

A little bit of acknowledgement of harm, although, with a mean of 3.9 sessions and the significant loss to followup, it sounds as if many young people may have given up rather than continue to push on and get worse.

There was an isolated finding of some evidence of an improvement in anxiety in those allocated to GET, as measured by the Hospital Anxiety and Depression Scale at 6 months, with the 12-month assessment, and the Spence Children’s Anxiety scale being aligned with that finding.

Of course there's some clutching at straws, can't expect complete miracles.

Surely this result requires the NHS to fundamentally change its clinical services for children with ME/CFS?

 

[Jonathan Edwards]

There was weak evidence of a greater risk of deterioration with GET (27%) than with AM (17%; p = 0.069).

That is pretty strong evidence. The chances that the difference is purely due to chance is one in fourteen. So the chance that it is real is thirteen fourteenths. That isn't good enough to be sure of a beneficial result but it is perfectly good enough to conclude that GET most likely makes people worse.

the probability that GET is more cost-effective than AM ranged from 18 to 21%.

So again a bit back to front. What they mean is that we can be more than 80% confident that it isn't cost-effective.

 

[Jonathan Edwards]

Surely this result requires the NHS to fundamentally change its clinical services for children with ME/CFS?

Maybe to activity management in the form of 'pacing up' - two legs good and all that?

 

[Hutan]

They are still hanging on to the idea that CBT works, and the activity management is supposedly pacing.

Cognitive behavioural therapy (CBT) improves fatigue, disability and school attendance compared to waiting list or usual medical care [7,8,9,10,11]. However, at least 37% of children have not recovered at 6 months [9]. Alternative approaches, but with limited evidence of effectiveness in the paediatric setting, include graded exercise therapy (GET) and activity management (AM) (also called energy management [12] or pacing).

Their GET was symptom contingent. Their activity management does include 'pacing up', it is probably more accurately called graded activity therapy.

GET was delivered by specialist therapists as a personalised approach, initially establishing a baseline level of physical activity (walking, sport, etc.) estimated as the median amount of daily physical activity over a week. Children were asked to avoid peaks in exercise, to be able to do the same every day. Participants were offered a detailed assessment of their physical activity at baseline. Once that baseline was established, participants were asked to slowly increase (by 10–20% a week) their physical activity when they felt able to. Participants were asked to monitor exercise and were taught how to stay within 50–70% of their maximum heart rate [13, 14]. If symptoms increased, participants were advised to stabilise or reduce their physical activity.

Activity management (AM) was provided as a personalised approach that established a baseline (similar every day) level of cognitive (e.g. schoolwork, social activities) and physical activity (walking, any exercise) using diaries. This usually required a reduction in activity on some days. Both physical activity and cognitive activity were then gradually increased as participants were able. If participants’ symptoms increased, they were advised to keep activity constant or reduce activity (cognitive and physical). Sessions were delivered by health professionals including specialist doctors, psychologists, physiotherapists, occupational therapists and nurses.

Follow-up sessions were offered to participants in both groups [16]. In this pragmatic trial, the total number and frequency of sessions were agreed between participants and clinicians. From previous paediatric RCTs, we expected between eight and 12 sessions [7, 13, 17].

They expected to provide 8 to 12 sessions. The mean number completed for the participants who made it to the 6 month followup was only 3.9 and 4.6.

 

[Jonathan Edwards]

Maybe it just shows the expected - when you compare two therapy programmes the results always look the same, because they don't reflect any particular therapy.

 

[dave30th]

I groaned when I saw this - Crawley, I thought, why can't she just leave vulnerable children alone and go skiing?

Let's hope this was her last hurrah and she is no longer the grant magnet she's been for years. Someone with her record of corrections and controversy at this point should really not be conducting research.

 

[dave30th]

Poor Esther. She and her colleagues must be pulling their hair out. Although surely they must have realized long ago they weren't getting the results they wanted. I hope this puts a cork in her ability to attract so much funding. Maybe after this people will stop believing the nonsense she tells everyone.

 

[dave30th]

@dave30th: improving science one blog post and letter at a time.

I'll have to see exactly what they did here. I can't remember--in this case did they also fold the feasibility trial subjects into the full trial?

 

[Jonathan Edwards]

She and her colleagues must be pulling their hair out.

Must they?
New Clinical Guidelines favour activity management, not GET.
Trial shows activity management as good as GET. Spot on. Jobs for the girls continue.

 

[Dolphin]

https://twitter.com/user/status/1764060587602956688

 

[Dolphin]

(1st column is GET; 2nd AM)

https://twitter.com/user/status/1764063088427286555

 

[Sean]

Is it possible that the scales are falling from the eyes of some of these people who have believed that they were doing something useful when pushing GET and various other sorts of 'get out of bed and off the couch and stop thinking about your symptoms' approaches?

Or they have merely realised that they cannot keep being so brazen in their persistent pattern of egregious misrepresentation of results from their own studies.

In other words, a tactical retreat, not an admission of fundamental error and appropriate change of direction and views.

 

[Hutan]

Maybe it just shows the expected - when you compare two therapy programmes the results always look the same, because they don't reflect any particular therapy.

Poor Esther. She and her colleagues must be pulling their hair out.

Must they?
New Clinical Guidelines favour activity management, not GET.
Trial shows activity management as good as GET. Spot on. Jobs for the girls continue.

Yes, the two therapy groups weren't really different in terms of improvements over time. But also, relative to baseline, nothing useful happened as a result of either therapy.

CONCLUSIONS
There was no evidence that GET was more effective or cost-effective than AM in this setting, with very limited improvement in either study group evident by the 6-month or 12-month assessment points.

 

[Lucibee]

It feels like we've been waiting for this trial for at least a decade... (2015ish?).

Anyway. I thought it might be useful to tie together a few older threads:

MAGENTA (Managed Activity Graded Exercise iN Teenagers and pre-Adolescents) - Esther Crawley
https://www.s4me.info/threads/magen...gers-and-pre-adolescents-esther-crawley.4808/

Esther Crawley (2019) Physical activity patterns among children and adolescents with mild-to-moderate CFS / ME [baseline accelerometer MAGENTA data]
https://www.s4me.info/threads/esthe...-me-baseline-accelerometer-magenta-data.9141/

David Tuller: Trial By Error: So What's Happening with the MAGENTA Trial?
https://www.s4me.info/threads/david...-whats-happening-with-the-magenta-trial.5788/

 

[Amw66]

View attachment 21284
(1st column is GET; 2nd AM)

Am I reading this wrongly ?
The baseline figures for school attendance show ACM group as potentially being " more well " in that school attendance is much higher 74 v 56 . The difference at baseline is striking .
At the end of the trial this has tanked to 42 ( GET has 47).

There are lots of factors as to why school attendance is not a brilliant metric , but to have attendance almost halved seems to me to indicate the same problems GET invoked.

How many drop outs ?

ETA I agree with @Jonathan Edwards .
This keeps the money flowing , and with long COVID likely coming under existing " specialists" umbrellas , this is justification for continuance .

The queen is dead, long live the queen

 

[Trish]

Am I reading this wrongly ?
The baseline figures for school attendance show ACM group as potentially being " more well " in that school attendance is much higher 74 v 56 . The difference at baseline is striking .
At the end of the trial this has tanked to 42 ( GET has 47).

Isn't that just the numbers of participants they had data for?

 

[Hutan]

The baseline figures for school attendance show ACM group as potentially being " more well " in that school attendance is much higher 74 v 56 . The difference at baseline is striking .
At the end of the trial this has tanked to 42 ( GET has 47).

The numbers are the mean proportion of school attendance (e.g. 0.5 = 50% school attendance per week), then standard deviation.
The double digit numbers are the numbers reporting school attendance. Young people who reported 'not applicable' are not included in the average calculation.

So, no change from baseline, but the numbers of young people reporting school attendance decreases with time.