OK so we are looking for a compound set of measures (cross validating and should correlate) that capture the key features of ME/CFS; are robust enough to be used in blinded and unblinded trials; would ideally include an element of personalisation and would also ideally be comparable to previous studies.
Physical function (subjective)
SF36 PF does seems to be reasonably robust at capturing limitations in physical function and is well known, understood and comparable to previous studies/norms. But as a subjective measure is subject to bias.
Somewhat contradicting my earlier statement that functionality is more important to patients than symptoms, anecdotally I spent 7 years working full time when the severity of my symptoms was such that I really shouldn't have been working at all. You can only carry on like that so long but it does suggest that there can be an apparent disconnect between the symptoms experienced and apparent functionality. I'm sure this is a familiar scenario to many PWME.
So a measure of symptoms would be desirable - but which symptoms from the myriad possiblities?
Symptoms (subjective)
Both the
IOM and Lenny Jason agree that a short list of symptoms is sufficient for
diagnostic purposes.
Jason suggests that just three core symptom domains —
post-exertional malaise, sleep and cognitive functioning — are necessary to discriminate between ME/CFS and other disorders
The SEID criteria require :
A substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities, that persists for more than 6 months and is
accompanied by fatigue;
post-exertional malaise, and
unrefreshing sleep. At least one of the two following manifestations is also required :
cognitive impairment OR
orthostatic intolerance
Both the IOM and Jason recommend that frequency and severity are measured.
Some fatigue scales suffer from ceiling effects and it could be argued that 'fatigue' is already adequately measured by the reduction in physical function measured by SF36 PF (if it covers occupational, educational, social, personal activities etc).
That leaves just
PEM, unrefreshing
sleep and either
cognitive impairment or
orthostatic intolerance.
Tailored measures
One frequent criticism of the SEID criteria was that 'it doesn't describe my illness'. Many common and often disabling symptoms don't feature as key symptoms. I can sympathise to an extent. Temperature regulation is a major issue for me and for much of the year is the major limitation on my activities/symptoms. So in addtion to the 'core' symptoms individuals could nominate another symptom which they feel has a major impact on their health.
Objective measures
The absence of physiological abnormalities is the issue. Objective performance measures can and have been used including the 6MWT, CPET, 2 day CPET etc. Ethical/safety issues aside these are snapshots and also cumbersome an unsuitable for continuous measurement. Actimeter/fitbit type measures of activity could be used for extended periods. As discussed their accuracy varies but as long as its a constant error that shouldn't preclude measuring relative change (everyone would need to use the same model I suspect).
The SEID criteria propose orthostatic intolerance as an optional symptom and there's quite a collection of studies suggesting impaired autonomic function. I'm not convinced there's an easy way to measure this outside of the lab so any objective measures would again have to be periodic.
Cognitive impairment is included as a subjective symptoms but should also be measurable in 'real world' challenges that involve processing speed and multi-tasking (that increases 'cognitive loading').
An ME/CFS battery?
What we could end up with is a battery of subjective and onjective tests measuring function/activity and symptoms periodically and continuously. Something like :
- SF36-PF at start, middle and end points (subjective)
- Cognitive measures at start, middle and end points (objective)
- Autonomic function start, middle and end points (objective)
- Continuous (daily?) monitoring of a short list of key symptoms including one individual choice (subjective)
- Continuous, or perhaps over discrete 1 week periods, activity monitoring (objective).
Of course some thought would have to be given to how these are scaled and score to produce thresholds amenable to construct a single composite outcome measure.
