A core outcome set - What core set of relevant health outcome measures should be used for trials of treatments for, and managing symptoms of, ME/CFS?

I've taken the title of this thread from the draft NICE guideline for ME/CFS, where it highlights the topic as one where research is required, and I thought it would be a good subject for general discussion.

It's been suggested to that the ACR (American College of Rheumatology) score may be a good model.

ACR Score: How Do You Measure Rheumatoid Arthritis with ACR Scores?

The ACR score has a primary measure of, I assume self-reported, improvement in tender and painful joints, as well as five other parameters:

• Inflammation
• Patient assessment
• Physician assessment
• Pain scale
• Disability/functionality questionnaire

All quotes from https://www.rheumatoidarthritis.org/treatment/acr-score/

So, if we were to have something similar for ME, what measures and parameters would we want to see used.

 

Sleep score measured by a wearable
HRV (I use App and phone camera)
Hours of upright activity (can also be measured with a wearable)
Cognitive challenge test

The first two I track and do seem to correlate with my better/worse days and are not open to bias or require lengthy questionnaires.

 

This is a big topic that we have spent some time on before I think.

Just to note that the account of the ACR criteria by Dr Duckworth at rheumatoidarthritis.org is garbled and fails to point out the reason why it is a useful score. It is useful because it takes key subjective measures and also objective measures (like CRP) that can corroborate the significance of the subjective measures and combines them using a multiple threshold system rather than addition. So there is no bogus arithmetic like in a Chalder score. ACR20 is not 20% improvement in anything. It is a level you pass if you are 20% better on at least several things - which is something different and more stringent.

I don't think the logic of the ACR grading was ever openly discussed by those inventing it. The reason why it is a good system is common sense but a fairly subtle sort of common sense and it takes some time to work out why it is common sense. The Europeans subsequently devised something called DAS that lacks this common sense and adds things up by bogus arithmetic. Unfortunately people who like sitting on committees tend to prefer tidiness to common sense.

Another important point is that ACR is only appropriate for certain types of treatment. What you want to measure depends on what you think your treatment is trying to do.

And of course criteria for trials are not likely to be of good for looking after individuals.

 

@Andy it would probably be worth asking Caroline Kingdon of the U.K. ME/CFS Biobank (or one of the other trained nurses, because of course Caroline is on the Panel!) to assist with information on the use of their ‘usual protocol’ of taking measurements at participant appts at the Biobank.

Nothing is invasive (well, obviously blood samples are taken)
the measurements taken on the Tanita machine must be valuable info
Hand grip strength.


It would also be worth adding on some form of easy cognitive testing at the beginning, middle and end of to show how standing, or sitting up in a chair, has affected a patient.
With “my sort of O.I.” (i .e. absolutely no PoTS but severely affected by standing still/can ‘work’ longer if legs are raised) the cognitive testing would be a valuable marker as to how OI affects me.

 

Maybe to have a useful set of outcomes there first need to be some more work done on better definitions of signs and symptoms of ME?

Apologies for mixing up different purposes, but for research in general, I think it would be good to have a clearer picture of the specific symptom cluster of ME and whether there are specific symptom cluster subsets.

I have been pottering at this comment for some days, and from skimming other threads realize some points might have become redundant.

Can't find the individual threads now, though (and think there is no thread on the NICE draft guidelines' section on research recommendations?), so just leave this here:

There are some odd symptoms that I think warrant a closer look and precise description, even if not all pwME seem to have all of them.

Could it make sense to do a representative survey how these odd symptoms are distributed among pwME?

The most obvious is delayed PEM. As people discussed in a recent thread, PEM is not clearly defined, even though the CCC list it as a mandatory symptom.

So how about doing a well-designed survey based on the discussion of the paper and Trish's letter,
and ask pwME whether they have a delayed onset of PEM, whether all their symptoms they experience durig or immediately after exertion differ from symptoms with delayed onset etc.?

Also, I think there could be a more precise description how muscle fatigability and cognitive fatigability in pwME look like. Apparently, tests and clinical examination that are designed to assess signs and symptoms in other illnesses with symptoms that sound similar, can't assess those symptoms in pwME. (Perhaps the hand-grip test is an exception?)

So other tests and examinations are needed and I think these should be based on an open-minded, precise observation and monitoring.

Regarding muscle fatigability, see e.g.:
https://www.s4me.info/threads/objec...gue-and-fatiguability.4241/page-2#post-184216

And also maybe a large enough replication study of the hand-grip test?

Regarding cognitive fatigability, see e.g.:
https://www.s4me.info/threads/javascript-advice-needed.12430/

 

(This is off-topic to the thread's question but connected to what I wrote in the previous post so don't know whether it should be put anywhere else.)

Other symptoms I'm thinking of are sore throat, tender lymph nodes and alcohol intolerance. I have all three so I'm biased, but could it be helpful to know how many pwME have one or more of those symptoms and how they are associated with other symptoms, including more specific PEM symptoms?

Also, could it be helpful to get a clearer picture of the sore throat and alcohol intolerance pwME have?

E.g. sore throat: permanent, fluctuating (triggered?), does it burn or feel rough or swollen, is it associated with difficulties in swallowing, redness, tender lymph nodes etc.?

Another one of the 'odd' symptoms that I think are often too readily ascribed to more common physiological phenomena could be orthostatic intolerance.

Would it make sense to described more precisely hoe pwME experience OI, e.g. differentiate between more common reactions like getting dizzy when standing up or POTS from other reactions. (I experience OI rather as somethin like orthostatic fatigability that happens not only when standing, but also when sitting upright and especially when sitting without a back rest; does not happen immediately but builds up slowly during 15-30 minutes.)

Maybe a survey that captures a more precise description of the mentioned symptoms could also help strengthen the further application of only one of the case definitions / consensus criteria for ME (I think the CCC are the most appropriate), that could then be amended or revised, but the name could be kept in order to reduce confusion among clinicians and researchers.

 

Again a personal account, but the measurable signs of being in PEM or just being a poor state generally include:

Resting heart rate
Goes up from 55 to 60 in PEM.

Steps
I'm more active in PEM than when in good shape and pacing well. I need to visit the toilet three times more often than usual; I can't sit still because I feel wired; and my memory is so shot that I can't do the most basic things efficiently. (E.g., get up to fetch a drink, but then remember hearing something come through the letterbox, so go and fetch that instead. Sit down, remember about the drink, get up again, but then realise I need the toilet, so do that instead. Ditto until I literally can't get up again.)

Disrupted sleep
Frequent waking, short overall duration, and little or no 'deep sleep' recorded. (I realise wrist-worn consumer devices can't actually determine sleep stages, but as they apply the same measurements and algorithms consistently, they probably are showing real changes in pattern.)



When in a better state, I sleep for longer and wake up during the night less, my overall resting heart rate is lower, and there are longer period of sitting with no steps recorded and no increases in heart rate. And when I am active, it's continuous rather than the extremely fragmented pattern in PEM – e.g. 50 minutes of pottering around feeding the cat, getting my own meal, and then clearing away afterwards. Heart rate is appropriate for the activity, rather than shooting around everywhere.

So – if an intervention had worked to improve my energy and reduce PEM, I'd either record far fewer days over a year with a PEM pattern, or the same level of PEM but much more activity.

I realise the above signs wouldn't necessarily show up for people who're pacing well, but the need to maintain a level of physical activity in order to manage my arthritis means that I inevitably have days with mild or moderate PEM.

For this reason, studies probably need to separate patients into 'activity profile' groups as well as trying to categorise the severity of their illness. I would probably be placed into the same group as patients who – for instance – have responsibilities (e.g. caring for someone else) that are not optional no matter how unwell they are themselves, or who live alone and don't have a car or powered wheelchair to fetch shopping and attend appointments.

 

I would really need to be grouped away from HR monitors due to difficulties caused by other conditions.

Disrupted sleep is definitely a warning sign for me as is the wired but tired phenomenon.

Interesting and it's made me think. When put under pressure and in the initial stages of PEM my cognitive performance can actually improve quite noticeably - a bit like in the days when I would take break and have a coffee and a smoke but without external stimulants. Inevitably this is followed by a corresponding crash. It does mean that under certain circumstances my performance in early PEM is better than when I am pacing and managing my condition well.

 

Yes, that's true for me too – I have much more of a sense of energy, muscle power, and (occasionally) feeling of wellness right at the outset, and not all the activity I do is forced by loo trips and memory lapses. But it does disintegrate into a downward spiral of ever more disorganised, inarticulate, clumsy, and forgetful attempts to get through whatever I can't avoid doing that day.