Exploring Symptom Fluctuations and Triggers in ME/CFS Using N-of-1 Observational Designs: Protocol for a Feasibility Study, 2021, McDonald et al

Exploring Symptom Fluctuations and Triggers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Novel Patient-Centred N-of-1 Observational Designs: A Protocol for a Feasibility and Acceptability Study

Suzanne McDonald 1 , Samuel X Tan 2 , Shamima Banu 2 3 , Mieke van Driel 3 , James M McGree 4 , Geoffrey Mitchell 2 3 , Jane Nikles 2

Abstract
Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic condition of unknown aetiology associated with a range of disabling symptoms, including post-exertional malaise, chronic fatigue, musculoskeletal pain, orthostatic intolerance, unrefreshing sleep, and cognitive dysfunction. ME/CFS is a heterogeneous disorder, with significant variation in symptom type and severity between individuals, as well as within individuals over time. The diversity of ME/CFS symptom presentation makes management challenging; treatments supported by data from randomised controlled trials may not work for all individuals due to the variability in experienced symptoms. Studies using quantitative N-of-1 observational designs involve repeated outcome measurements in an individual over time and can generate rigorous individual-specific conclusions about symptom patterns and triggers in individuals with ME/CFS. This study aims to explore the feasibility and acceptability of using novel patient-centred N-of-1 observational designs to explore symptom fluctuations and triggers in ME/CFS at the individual level.

Methods and analysis: Individuals with a medical diagnosis of ME/CFS will be recruited through ME/CFS patient organisations to participate in a series of patient-centred N-of-1 observational studies. Using a wrist-worn electronic diary, participants will complete ecological momentary assessments of fatigue, stress, mood, and cognitive demand, three times per day for a period of 6-12 weeks. Personally relevant symptoms and triggers will also be incorporated into the questionnaire design. Physical activity will be objectively measured via an integrated accelerometer. Feasibility and acceptability outcomes will be assessed including the percentage of diary entries completed, as well as recruitment and retention rate, feasibility of analysing and interpreting the data collected, and participant views about participation elicited via a post-study semi-structured interview.

Discussion: This study will assess the feasibility and acceptability of patient-centred N-of-1 observational studies to assess diseases with complex presentations such as ME/CFS, as well as provide individual-level evidence about fluctuations and triggers of ME/CFS symptoms that may aid self-management.

Trial registration: Australian and New Zealand Clinical Trials Registry: ACTRN12618001898246. Registered on 22 November 2018.

https://link.springer.com/article/10.1007/s40271-021-00540-0
https://pubmed.ncbi.nlm.nih.gov/34368926/

Online ahead of print

 

This is a study seeking to assess whether something can be assessed. OK. Missed opportunity to call it the ASSES study.

I can't see any point to this, however. What could possibly be learned from this?

 

Paid work for the researchers? It seems unlikely that it will benefit patients more than just telling them to pay attention to changes in symptoms and keep a food/activity/symptoms journal. We all differ too much in our symptoms and responses to factors for any general findings.

 

just how are severely effected people going to keep up with the burden of note taking three times a day . this is really not feasible.

 

There has been a correction to this paper published, but there are no details on what that might be. PubMed shows no information, https://pubmed.ncbi.nlm.nih.gov/34562227/, and the journal link, at time of posting, doesn't work (for me), https://link.springer.com/10.1007/s40271-021-00549-5

 

I don't know if this study is any good or not but one of the key symptoms for ME was variability and I believe that is the reason why it has been so difficult to find out what is going on.

Some things affect us all the time but in my experience things go wrong but settle down with rest.

I have been trying to sort out our bedroom drawers for weeks, a little bit at a time. I am almost finished and last week I did a bit when I was not feeling too good. After a few minutes I felt my heart rate go up then I could hardly stand. My husband helped me lie down and used an oxygen monitor to see if anything showed up. My heart rate had dropped to 65 (it's usually 85 - 90) and my blood oxygen was 91.

I have seen this happen since I started using a heart rate monitor and I believe what is going on is that I do not have enough available energy to push up my heart rate and increase my oxygen (like a healthy person running for a bus) Over the course of fifteen minutes my heart rate went up to normal and my blood oxygen increased to my normal 95.

Anyway, the point is that the chances of that sort of thing being picked up in research is almost nil. Other problems we get could be not producing hormones at the right time or a dozens of other body processes so what can we do about it?

If doctors believed this variability nowadays that would be a big help though Wessely said that if it can be normal sometimes it could be normal all the time so it is not a sign of damage. Hardly helpful.

I don't know what the answer is.

 

Unfortunately variability is one of the aspects of ME that some regard as evidence for it being a psychogenic condition.

 

Yes, it is one of the things about BPS theory I find very simplistic. We obviously have an underlying deficit which expresses itself in different ways. If we lack the means to produce lots of ATP it will only be obvious at a point where demand for ATP is high.

It is frustrating when they class us as MUS because they dismiss all explanations. Many disease are still diagnosed by a collection of unexplained symptoms, migraine for instance, but they refuse to see it and confirm their beliefs by doing the wrong tests.