Review ‘Pacing’ for management of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review and meta-analysis, 2024, Sanal-Hayes

[Dolphin]

https://www.tandfonline.com/doi/full/10.1080/21641846.2024.2433390

Review Article
‘Pacing’ for management of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review and meta-analysis

Nilihan E.M. Sanal-Hayes1, Marie Mclaughlin2, Jacqueline L. Mair3,4, Jane Ormerod5,David Carless6, Rachel Meach7, Natalie Hilliard8, Joanne Ingram9, NicholasF. Sculthorpe6 and Lawrence D. Hayes 10

1 School of Health and Society, University of Salford, Salford, UK; 2Physical Activity for Health Research Centre, Institute for Sport, P.E. and Health Sciences, University of Edinburgh, Moray House School of Education and Sport, Edinburgh, UK; 3Future Health Technologies, Singapore-ETH Centre, Campus for Research Excellence and Technological Enterprise (CREATE), Singapore; 4 Saw Swee Hock School of Public Health, National University of Singapore, Singapore; 5 Long COVID Scotland, Aberdeen, UK; 6School of Health and Life Sciences, Sport and Physical Activity Research Institute, University of the West of Scotland, Glasgow, UK; 7 Department of Earth Sciences, University of Durham, Durham, UK; 8 Physios for ME, London, UK; 9 School of Education and Social Sciences, University of the West of Scotland, Glasgow, UK; 10Lancaster Medical School, Lancaster University, Lancaster, UK

ABSTRACT
Background
Pacing typically comprises regulating activity to avoid post-exertional neuroimmune exhaustion, the worsening of symptoms after an activity. Yet, the efficacy of pacing to improve symptomology is unclear.

Objective
We aimed to undertake a PRISMA-accordant meta-analysis concerning the effect of pacing on ME/CFS patients’ symptoms.

Data sources
Six electronic databases (PubMed, Scholar, ScienceDirect, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials [CENTRAL]) were searched; and websites MEPedia, Action for ME, and ME Action were also searched for grey literature.

Study selection
Studies (k = 5) selected from the 210 identified included randomised controlled trials (RCTs; k = 2), uncontrolled trials (UCTs; k = 1), intervention case series (k = 1), and sub-analysis of the PACE trial (k = 1), all of which had a pacing component, and an outcome measure reported pre- and post-pacing.

Study appraisal and methods
Three separate meta-analyses were conducted on changes in symptoms using standardised mean differences (SMDs) and random-effects models.

Results
The overall SMD showed pacing improved physical function (k = 4, SMD = 0.15 [95% CI = −0.39, 0.68], p = 0.5951). Pacing improved pain (k = 4, SMD = −0.11 [95% CI = −0.32, 0.10], p = 0.3090). Pacing improved fatigue (k = 4, SMD = −1.09 [95% CI = −2.38, 0.21], p = 0.0998).

Conclusions
Pacing exerted a trivial beneficial effect on physical function and pain. Fatigue was improved with a large effect, which did reach the p < 0.05 level. We cautiously conclude pacing likely exerts some beneficial effects on symptomology, particularly, fatigue, in people with ME/CFS. However, the level of empirical research is insufficient, and more high-quality RCTs are essential to support the NICE guidelines.


Sanal-Hayes, N. E. M., Mclaughlin, M., Mair, J. L., Ormerod, J., Carless, D., Meach, R., … Hayes, L. D. (2024). ‘Pacing’ for management of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review and meta-analysis. Fatigue: Biomedicine, Health &amp; Behavior, 1–18. https://doi.org/10.1080/21641846.2024.2433390

https://twitter.com/user/status/1862865806708682998

 

[Trish]

Pacing improved fatigue (k = 4, SMD = −1.09 [95% CI = −2.38, 0.21], p = 0.0998).

Fatigue was improved with a large effect, which did reach the p < 0.05 level.

These appear to be contradictory. I haven't read the whole paper.

 

[John Mac]

Six electronic databases (PubMed, Scholar, ScienceDirect, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials [CENTRAL]) were searched; and websites MEPedia, Action for ME, and ME Action were also searched for grey literature.

Science for ME would have been a better source

 

[Nightsong]

The statement in the abstract for pain, too:

Pacing improved pain (k = 4, SMD = −0.11 [95% CI = −0.32, 0.10], p = 0.3090)

I've only read the abstract but how can you say there is an improvement when the confidence interval includes 0 and there is a p-value of 0.3090?

I also quickly searched to see if the authors included the PACE trial; they do - but the APT arm was not pacing as patients typically practice it.

 

[Creekside]

Pacing exerted a trivial beneficial effect on physical function and pain. Fatigue was improved with a large effect,

Are they completely clueless about PEM and pacing? AFAIK, pacing is intended to avoid PEM, and avoiding PEM has far more than a trivial effect on symptoms. Does anyone with ME pace to reduce fatigue?

Pacing to maximize what little exercise PWME can do would probably have a trivial beneficial effect on "fatigue" and well-being compared to avoiding physical activity completely, but I don't think that deserves professional coaching or whatever some "expert" would want to get paid for.

 

[Hutan]

The overall SMD showed pacing improved physical function (k = 4, SMD = 0.15 [95% CI = −0.39, 0.68], p = 0.5951). Pacing improved pain (k = 4, SMD = −0.11 [95% CI = −0.32, 0.10], p = 0.3090). Pacing improved fatigue (k = 4, SMD = −1.09 [95% CI = −2.38, 0.21], p = 0.0998).

Others have already commented about the results given for pain and fatigue. The result for physical function also seems to be a problem (non-significant p-value, confidence interval includes 0).

Another problem, previously mentioned in relation to the PACE trial, is that most people with ME/CFS start working out a version of pacing soon after they develop the illness. So, over time, they may reduce working hours, change employment to something less demanding, give up work altogether, give up on study. They may move back in with parents, move to a smaller house. They may give up sports, give up other hobbies, reduce the amount of time they spend socialising, stop going away for holidays. They may adapt their food preparation, pay for people to do jobs around the house and garden, get groceries delivered. They may rest before a big event, they will try not to schedule demanding activities on two consecutive days. They may lie down for a bit after a shower, they may only shower once a week.

So, pretty much anyone who has had ME/CFS for some months will be pacing - they will have adjusted their activity level to fit the constraints of their illness. Any study that attempts to assess the effect of pacing on people who have had the illness for 6 months or more is going to be flawed because all the participants will be pacing already. The effect of any study intervention is really only going to be playing around the edges, after major and many minor changes in lifestyle have been made. I don't know how the impact of pacing can be properly and ethically studied; I very much doubt that any study so far has effectively done it.

 

[Trish]

Also they seem to be saying pacing needs to lead to improvement to be classed as effective. But pacing has only ever been claimed to be a management strategy aimed at avoiding deterioration. Just like some drug treatments for incurable diseases, avoiding or delaying deterioration is a win when the alternative, in this case not pacing, and pushing through repeatedly beyond the PEM threshold instead, generally leads to deterioration.

 

[poetinsf]

These appear to be contradictory. I haven't read the whole paper.

I'm guessing that the first number (p=0.0998) is for the population of studies (k=4) and the second number (p<0.05) is for the population of patients?

Results
The overall SMD showed pacing improved physical function (k = 4, SMD = 0.15 [95% CI = −0.39, 0.68], p = 0.5951). Pacing improved pain (k = 4, SMD = −0.11 [95% CI = −0.32, 0.10], p = 0.3090). Pacing improved fatigue (k = 4, SMD = −1.09 [95% CI = −2.38, 0.21], p = 0.0998)

These results seem to make sense to me. Pacing is about minimizing the fatigue/symptoms by avoiding PEM. It's not a treatment to improve the functioning. Whatever the little improvement in physical function they saw probably was incidental from being in PEM less often: it was small and statistically less significant.

 

[forestglip]

These appear to be contradictory. I haven't read the whole paper.

Good catch. I contacted the author who confirmed that the statement in the abstract is a typo. It should say "which did not reach the p < 0.05 level". He is going to contact the journal to correct it.

 

[Trish]

Good catch. I contacted the author who confirmed that the statement in the abstract is a typo. It should say "which did not reach the p < 0.05 level". He is going to contact the journal to correct it.

Thanks, well done.
Surely that means their conclusion is wrong too. They can't claim real effect when it didn't even reach statistical significance.

 

[Medfeb]

Thanks, well done.
Surely that means their conclusion is wrong too. They can't claim real effect when it didn't even reach statistical significance.

I wondered about that also. But at least according to ChatGPT, this can happen for various reasons including when there's a small sample size or high variability in the data. So technically, that seems possible.
But to your point, it seems dicey to imply that that is a real effect

 

[ME/CFS Skeptic]

I don't think these estimates are useful.

The authors have thrown 2 case studies with less than 10 participants and no control group in the mix. This entirely messes up the meta-analysis. The only 2 randomized studies are the PACE trial and this small Belgian study:
https://pubmed.ncbi.nlm.nih.gov/26356665/

In the effect for fatigue, for example you can see that the Antcliff study with only 6 participants reported an effect size bigger than 3.5 standard deviations which seems pretty unreliable. The group of Antcliff also has a different interpretation of pacing, coming from the chronic pain tradition, they see it more like a gentle form of GET.


The review doesn't include this Norwegian RCT (Pinxsterhuis et al. 2015) which tested a 'self-management program based on a self-efficacy theory and the ‘energy envelope’ theory (pacing)'. Unfortunately, it also did not show a favourable effect.
https://journals.sagepub.com/doi/abs/10.1177/0269215515621362

People will probably use this to argue that pacing might be effective but then when critics will look closer it will all fall apart...

 

[Dolphin]

Some official corrections have been posted:
https://www.tandfonline.com/doi/full/10.1080/21641846.2024.2447181

 

[Mij]

A Digital Platform with Activity Tracking for Energy Management Support for Long Covid: A Randomized Control Trial

People with long COVID (LC) report worsening symptoms after activity, like post-exertional malaise (PEM) in chronic fatigue syndrome (CFS). The National Institute for Health and Care Excellence (NICE) recommends ‘energy management’ for CFS, but at the time of writing, how people with LC would respond to energy management was unknown.

In a 6-month pragmatic decentralised randomised controlled trial (RCT), we compared a just-in-time intervention to support energy management in adults with LC to standard care. Participants were randomised to receive either the ‘Pace Me’ app and a wearable activity tracker (intervention) or an app only with data entry screens (control). The intervention group received just-in-time messages on PEM management when they reached 50%, 75%, and 100% of their daily ‘activity allowance’. The primary outcome was PEM measured by the DePaul Symptom Questionnaire-Post-Exertional Malaise (DSQ-PEM).

Of 368 participants assessed for eligibility, 250 participants were randomised 1:1, but 36 control and eight intervention participants were lost to follow-up. 12 control and 24 intervention participants were excluded from analysis due to missing data. 84 intervention participants and 77 control participants were analysed. There was no time by group interaction for the DSQ-PEM. The intervention group value was 48 (95% CI 44–53) pre-intervention and 46 (95% CI 41–51) post-intervention (arbitrary units). The control group value was 47 (95% CI 42–52) pre-intervention and 44 (95% CI 39–49) post-intervention (interaction effect p = 0.614, η²p = 0.002; trivial). No individual question exhibited an interaction effect (P > 0.05).

Digitally supported energy management in people with LC had no effect on PEM compared to standard care. Although the intervention had no additional effect compared to control, the substantial recovery rate in LC may have masked intervention effects. Therefore, future studies should consider this energy management framework in conditions without such recovery rates, such as CFS.