Measures of outcome for trials and other studies

[duncan]

Ok, my difficulty in seeing if you appreciate my point - or if I am missing yours - may be a case in point. So excuse me if this is obvious to everyone else.

My point is, how can that objective measure be relied on if it varies from day to day, or even hour to hour, other than as a data point that is unreliable in the broader context of a meaningful assessment?

So, these neuro-cognitive tests are expensive and time-consuming. It's not like we can take them, or have someone administer them, on a regular basis. As objective qualifiers, if the values captured through these tests are so fickle, can we really use those results as reliable qualifiers, i.e., objective results, outside of snapshot assessments?

 

[user9876]

Ok, my difficulty in seeing if you appreciate my point - or if I am missing yours - may be a case in point. So excuse me if this is obvious to everyone else.

My point is, how can that objective measure be relied on if it varies from day to day, or even hour to hour, other that a data point that is unreliable in the broader context of a meaningful assessment?

So, these neuro-cognitive tests are expensive and time-consuming. As objective qualifiers, if the values captured through these tests are so fickle, can we really use those results as reliable qualifiers, i.e., objective results, outside of snapshot assessments?

I think I get your point. I think the technical term is aliasing where two different signals appear the same as they are not sampled at a high enough rate. That is why I was suggesting the idea of breaking tests up and spreading them over time so that each acts as a sample and an overall trend can be derived.

 

[duncan]

user9876, yes, that would do it, I think. Trending. I'd wager many of us would demonstrate a downward trend, a precipitous one perhaps, early on, then more of a plateauing, then....I'm not sure.

But that's data I'd like to see.

 

[Jonathan Edwards]

Ok, my difficulty in seeing if you appreciate my point - or if I am missing yours - may be a case in point. So excuse me if this is obvious to everyone else.

My point is, how can that objective measure be relied on if it varies from day to day, or even hour to hour, other than as a data point that is unreliable in the broader context of a meaningful assessment?

So, these neuro-cognitive tests are expensive and time-consuming. It's not like we can take them, or have someone administer them, on a regular basis. As objective qualifiers, if the values captured through these tests are so fickle, can we really use those results as reliable qualifiers, i.e., objective results, outside of snapshot assessments?

Variability is a different issue from subjectivity/objectivity. Swelling of joints in RA varies from day to day and hour to hour. I you measure it with a tape measure it is pretty objective but if an assessor just looks there can be subjectivity on the assessor's part - which is a big problem if the assessor knows which treatment the person is on. The problem with subjectivity is not variation but the fact that it depends on somebody's opinion (patient or therapist) in a way that can be biased by what they want to believe. Certainly there are advantages in picking measures that do not vary too much but if the thing that is important - whether feeling lousy with ME or having a swollen joint with RA - varies it may still be the primary outcome of interest and everything else may be unreliable because it does not correlate well enough with what really matters.

As user9876 is suggesting, it seems that a good way to reduce the problem is to measure repeatedly and take some sort of average.

 

[Marco]

In addtion to the points made by @user9876 I was wondering about the possibility of some modification of the (dreaded) UK Work Capability Assessment and Disability Living Allowance forms.

Leaving aside the controversies and unavoidable motivational biases on both sides they do have the advantage of identifying problems with carrying out real world tasks which in terms of recovery is really what we should be aiming to eliminate.

The DLA form is probably more relevant as it isn't aimed specifically at capability to work although I admit I'm not familiar with it. Perhaps a cut down (electronic?) version could be used on a daily basis?

 

[Sasha]

In addtion to the points made by @user9876 I was wondering about the possibility of some modification of the (dreaded) UK Work Capability Assessment and Disability Living Allowance forms.

Leaving aside the controversies and unavoidable motivational biases on both sides they do have the advantage of identifying problems with carrying out real world tasks which in terms of recovery is really what we should be aiming to eliminate.

The DLA form is probably more relevant as it isn't aimed specifically at capability to work although I admit I'm not familiar with it. Perhaps a cut down (electronic?) version could be used on a daily basis?

I don't think so - the questions are, for, example, can you take a pencil out of your pocket, can you lift a 1kg bag of potatoes, can you walk 50 yards, and so on - and the issue of course is really 'how many times can you do that?' and the answer will depend in part on what else you've been doing.

 

[Marco]

I don't think so - the questions are, for, example, can you take a pencil out of your pocket, can you lift a 1kg bag of potatoes, can you walk 50 yards, and so on - and the issue of course is really 'how many times can you do that?' and the answer will depend in part on what else you've been doing.

I'm not suggesting that either of those forms would be useful as they stand in fact I looked up the DLA/PIP form and it was pretty sparse in areas that would be relevant to PWME. I was more concerned with the principle of the ability to carry out everyday tasks (including social/leisure) being more important than abstract symptoms. Although of course it would be nice to be able to do these things repeatedly and in the absence of pain/fatigue etc.

 

[Sasha]

I'm not suggesting that either of those forms would be useful as they stand in fact I looked up the DLA/PIP form and it was pretty sparse in areas that would be relevant to PWME. I was more concerned with the principle of the ability to carry out everyday tasks (including social/leisure) being more important than abstract symptoms. Although of course it would be nice to be able to do these things repeatedly and in the absence of pain/fatigue etc.

I agree that some real-world measure would be extremely important but I think that if we put our heads together we could come up with something infinitely more meaningful than any DWP thing.

I think a basic list of what anyone needs to do in terms of tasks of everyday living would be a good start. For example, a question such as:

'In a normal day, a healthy person can take a shower, wash their hair, clean their teeth, dress themselves and prepare their own meals without difficulty. Can you do all of those things without difficulty or ill-effect every day, even if there are other normal activities that you cannot do?'​

would be infinitely more real-world than the DWP approach. So that would be a question identifying who is capable of self-care. And one could add at each stage to that list to see who can do all that AND sit in a chair all day, and then who can do all that AND walk around up to a mile outside each day, and then who can do all that AND could work half-time at a desk job if they wanted, and so on upwards. The additions would represent the order in which most people would add things on as they recovered more function.

I'm sure people could come up with something better than what I've just suggested but I think the principle of not isolating a single activity is important.

 

[user9876]

I'm not suggesting that either of those forms would be useful as they stand in fact I looked up the DLA/PIP form and it was pretty sparse in areas that would be relevant to PWME. I was more concerned with the principle of the ability to carry out everyday tasks (including social/leisure) being more important than abstract symptoms. Although of course it would be nice to be able to do these things repeatedly and in the absence of pain/fatigue etc.

I was thinking questions around general activities of daily living would be good and what someone has managed in a day. Its the type of area OT assessments may cover and they might be a good source of information.

 

[Marco]

I was thinking questions around general activities of daily living would be good and what someone has managed in a day. Its the type of area OT assessments may cover and they might be a good source of information.

Yep. There's got to be something around that assesses everyday activities and a graduated approach from basic self-care through to leisure etc would be a bonus.

 

[Seven7]

Here is the tricky part: they ask me can you work full time, Yes I can but I have a recliner and work from home laying down as much as I can. so My answer might not very truth since I am always ask only can u work full time.
2) the often question I get: can you go up a flight of staris: Yes I can but I go up as a doggy (on hands and feets) I have learnt not to fight gravety while I do activity......

 

[lansbergen]

can you go up a flight of staris: Yes I can but I go up as a doggy (on hands and feets)

I did that too but now I can go up the normal way and more important go down on my feet instead of on my prat.

 

[voner]

So we want evidence that the person says they feel better because their physiology has changed in a way we might have predicted.

it seems to me that the ability/functionality of a person is evidence that the person says they feel better.

i agree with Marco:

There's got to be something around that assesses everyday activities and a graduated approach from basic self-care through to leisure etc would be a bonus.

As I said before, Dr. David Bells "ME/CFS Ability Scale" is an example of a place to start... it certainly could be improved upon.

it also seems that with today's technology, a person's movements can be tracked. – You can tell if a person is able go outside of the house, go shopping. this tracking of movement might even be able to detect some of the postexertional malaise that might happen from somebody overdoing it. For example, somebody might go out for a "long" walk and then spend the next few days inside their house recovering from it. I do think finding a way to measure the severity of the PEM is fundamental to a measurement.

here is Dr Bells Scale (i'm not setting the scale is it by any means perfect or even usable. I'm just using it as an example someplace to start the conversation):

100: Patient has no symptoms at rest, no symptoms with exercise; has
normal overall activity; is able to work full-time without difficulty.

90: Patient has no symptoms at rest, has mild symptoms with activity;
has a normal overall activity level. The patient is able to work
full-time without difficulty.

80: Patient has mild symptoms at rest, symptoms worsened by exertion.
Patient has minimal activity restriction noted for exertion activities
only; patient is able to work full-time with difficulty in jobs
which require exertion.

70: Patient has mild symptoms at rest. Patient clearly notes some
daily activity limitation. Overall, the patient functions close
to 90% of expected, except for activities requiring exertion.
Ability to work full-time with difficulty.

60: Patient has mild to moderate symptoms at rest, with daily activity
limitation clearly noted. Overall functions 70-90%. Patient is
unable to work full-time in jobs which require physical labor,
but has the ability to work full-time in light activity if hours
are flexible.

50: Patient has moderate symptoms at rest, and moderate to severe
symptoms with exercise or activity. An overall activity level
is 70% of expected. Patient is unable to perform strenuous duties,
but can perform light duty, or desk-work 4-5 hours per day, requires
rest periods.

40: Patient has moderate symptoms at rest, and moderate to severe
symptoms with exercise activity. The patient has an overall activity
level of 50-70% of expected. Patient is not confined to house;
is unable to perform strenuous duties, but can perform light duty/desk
work 3-4 hours/day, but requires rest periods.

30: Patient has moderate to severe symptoms at rest, and severe symptoms
with any exercise. Patient has an overall activity level reduced
to 50% of expected; is usually confined to house. Patient is unable
to perform any strenuous tasks; is able to perform 2-3 hours of
desk work per day, but requires rest periods.

20: Patient has moderate to severe symptoms at rest; is unable to
perform strenuous activity. Overall, activity levels are 30-50%
of expected. Patient is unable to leave house except rarely, is
confined to bed most of the day, is unable to concentrate for
more than 1 hour/day.

10: Patient has severe symptoms at rest, is bedridden the majority
of the time. Patient has no travel outside of house. Patient
has marked cognitive symptoms preventing concentration.

0: Patient has severe symptoms on a continuous basis, is bedridden
constantly, and is unable to care for him/her self.

 

[Sasha]

Here is the tricky part: they ask me can you work full time, Yes I can but I have a recliner and work from home laying down as much as I can. so My answer might not very truth since I am always ask only can u work full time.
2) the often question I get: can you go up a flight of staris: Yes I can but I go up as a doggy (on hands and feets) I have learnt not to fight gravety while I do activity......

Then I think we need to have a qualifier in there along similar 'without any problems, like a healthy person would do' lines as in my question about basic self-care.

I think it would be good to specify a few examples, such as 'without special adaptations being made for you such as recliner chairs, ground-floor working, home-working, rest breaks, your needing to crawl rather than walk, and so on that a healthy person wouldn't require' so that people are clear we're looking for indications of health, not of how well we manage to adapt. We forget the tricks we use to adapt, because they're so instilled in us after so many years.

 

[Sasha]

I think the Bell scale needs operationalising in terms of activities. Hard to say what 30% of normal is, when one person's normal might have been running marathons and another's being a couch potato. And is it 30% of energy, 30% of hours awake being able to do moderate stuff... I don't know what it means.

 

[Sasha]

Here is the tricky part: they ask me can you work full time, Yes I can but I have a recliner and work from home laying down as much as I can. so My answer might not very truth since I am always ask only can u work full time.
2) the often question I get: can you go up a flight of staris: Yes I can but I go up as a doggy (on hands and feets) I have learnt not to fight gravety while I do activity......

Then I think we need to have a qualifier in there along similar 'without any problems, like a healthy person would do' lines as in my question about basic self-care.

BTW, this is why I think it's important to get away from what the DWP ask. They're interested in whether we can work, if we use adaptations. But for clinical trials, we want to know if our health is improving in real ways that allow us to take part in real-world activities in the same way that healthy people do, without adaptations.

 

[MeSci]

Finally read all the messages so far!

My thoughts:

A lot of good suggestions already.

Is there any symptom or measurable sign (e.g. biochemical abnormality) that we all have in common? For example, do we all over-produce lactic acid/lactate from physical and/or mental exertion? If so, perhaps that could be a measure, but in the case of mental exertion might that require lumbar puncture (potentially hazardous)? There are several threads on lactate/lactic acid, and I think there may be papers on the subject that suggest that lumbar puncture can be avoided because brain lactate levels tend to equilibrate to some degree with blood lactate. Would have to check. Or might low lactate levels also be interpreted as 'deconditioning' or lack of fitness due to our mythical lack of motivation?

Improvement in resting heart rate might be useful, but again can also be interpreted as simple improvement in physical fitness.

Do we all have mineral depletion, or deficiency in any other nutrients, e.g. certain vitamins, that can be measured? (Of course, when people know they have this they usually try to correct it!) I seem to lose a lot of minerals and fluid after exertion, as I think many of us do, but maybe not all?

I agree with those who say that many measurements are needed, and that they need to be repeated over time - over a year at least, I think. Do we need to differentiate remission from recovery? People sometimes relapse after apparent recovery - a year later or even longer. Seasonal variation has been mentioned, and I think I get this too.

Re tilt table testing, I think that different studies have found very different percentages of orthostatic intolerance in people with ME, perhaps due to differing diagnostic criteria? Also, as @Kati has already mentioned, medication/self-treatment (e.g. hydration with electrolyte solutions) would probably have to be discontinued prior to such tests, which might or might not be problematic.

 

[Marco]

Improvement in resting heart rate might be useful, but again can also be interpreted as simple improvement in physical fitness.

Given the pretty consistent findings of autonomic dysfunction (whether a a central or secondary problem) I wonder would heart rate variability be useful? It can certainly be reasonably unobtrusively measured (small devices, apps etc) but interpretation may be more difficult (e;g. I've just read that dengue virus infection appears to improve (increase) heart rate variability??).

 

[user9876]

Given the pretty consistent findings of autonomic dysfunction (whether a a central or secondary problem) I wonder would heart rate variability be useful? It can certainly be reasonably unobtrusively measured (small devices, apps etc) but interpretation may be more difficult (e;g. I've just read that dengue virus infection appears to improve (increase) heart rate variability??).

It may depend on the reliability you want. I read that apple were going to add a heart monitor to their smart watch but didn't in the end because it didn't meet medical standards. This made me wonder about the accuracy of small devices but that may not matter for the type of readings necessary for this type of monitoring. I have read about efforts to use accelerometers to detect heart beats and to be used in non-medical applications as well where I would have thought accuracy was necessary.

What may be interesting is to tie heart beat into other accelerometer data

 

[RWP (Rest without Peace)]

There is a subsection on the forums page on rituximab issues I think - under treatments. The threads used most recently relate to the Haukeland studies but general discussion of rituximab would work there I think.

@Jonathan Edwards,

I went ahead and started another thread. Here is the link:
A quick question about low CD19 and Rituximab