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Quality and acceptability of patient-reported outcome measures used in CFS/ME

Dolphin

Senior Member
Messages
17,567
I don't promise to say interesting at all in this thread. Add that to the fact that the topic itself might only have a minority appeal and people might find other threads of more interest...

Qual Life Res. 2011 May 18. [Epub ahead of print]

Quality and acceptability of patient-reported outcome measures used in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review.

Haywood KL, Staniszewska S, Chapman S.

Source: Royal College of Nursing Research Institute, School of Health and Social Studies, University of Warwick, Coventry, CV4 7AL, UK, k.l.haywood@warwick.ac.uk.

Abstract
PURPOSE: To review the quality and acceptability of condition-specific, domain-specific and generic multi-item patient-reported outcome measures (PROMs) used in the assessment of adults with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

METHODS: Systematic literature searches were made to identify PROMs. Quality and acceptability was assessed against an appraisal framework, which captured evidence of both the thoroughness and results of evaluations: evidence of measurement (reliability, validity, responsiveness, interpretability, data quality/precision) and practical properties (feasibility, patient acceptability), and the extent of active patient involvement was sought.

RESULTS: A total of 11 CFS/ME-specific, 55 domain-specific and 11 generic measures were reviewed. With the exception of the generic SF-36, all measures had mostly limited evidence of measurement and/or practical properties. Patient involvement was poorly reported and often cursory.

CONCLUSIONS: The quality and acceptability of reviewed PROMs is limited, and recommendations for patient-reported assessment are difficult. Significant methodological and quality issues in PROM development/evaluation were identified by the appraisal framework, which must be addressed in future research. Clear discrepancies exist between what is measured in research and how patients define their experience of CFS/ME. Future PROM development/evaluation must seek to involve patients more collaboratively to measure outcomes of importance using relevant and credible methods of assessment.

PMID:21590511[PubMed - as supplied by publisher]
 

Dolphin

Senior Member
Messages
17,567
I was hoping for more specific criticisms of questionnaires. In some ways, there are criticisms in the tables - but they are generally about more "factual" aspects. They generally don't talk about how particular items [i.e. questions] on particular questionnaires may be problematic e.g. the effect of confounding with measures of mood i.e. some symptoms that might be part of CFS rather than evidence of depression, etc. (I think on this specific point they make a vague reference to two papers but don't spell out the possible problem).

Anyway, it's quite a long paper so perhaps some people may find the bits I've underlined (and am now posting) of more interest than reading it all. Or they might not find what I post of interest as I'm tired now so am not promising to editorialise or put explanatory notes.
 

Dolphin

Senior Member
Messages
17,567
From abstract (more information explaining this is given at the end)
Clear discrepancies exist between what is measured in research and how patients
define their experience of CFS/ME. Future PROM development/
evaluation must seek to involve patients more collaboratively
to measure outcomes of importance using
relevant and credible methods of assessment.

Underlined bits are bits I'm interested in:
Background

[..]

A patients experience and expertise regarding their health and associated
health care is an essential resource that should be
actively utilized to communicate the relevant outcomes of
care, and it is incumbent upon all stakeholders within
health care to ensure that methods adopted to capture and
measure the patients voice are credible
. Well-developed
patient-reported outcome measures (PROMs), often multiitem
questionnaires, aim to provide a systematic and
structured assessment of the patients perspective across a
range of health-related concerns from symptoms and
physical functioning to well-being and quality of life [8].
However, many have been developed using patients as
sources of information rather than in the more collaborative
way, which is now supported in other areas of research
[5, 9].

They didn't search the Journal of Chronic Fatigue Syndrome which I think is a major omission.

Inclusion/exclusion criteria

[..]

Measures without evidence of reliability or
validity were excluded. Clinician-assessed, single-item and
mobility measures, radiographic and imaging techniques
were excluded.

Results

Although the expected association was not defined, a
head-to-head comparison of the ChalderFS (index and
domain scores) and FSS following completion by a large
patient group (n = 166) reported very low correlations
between the two measures, suggesting that they measure
different aspects of fatigue [100]. The FSS had stronger
correlations with variables reflecting CFS severity and the
generic Short-Form 36-item Health Survey (SF-36) [101],
leading the authors to suggest that the FSS provides a more
comprehensive reflection of fatigue-related severity,
symptomology and functional disability than the ChFS.

100. Taylor, R. R., Jason, L. A., & Torres, A. (2000). Fatigue rating
scales: An empirical comparison. Psychological Medicine, 30,
849856.
101. Ware, J. E. (1997). SF-36 health survey. Manual and interpretation
guide, 2nd edn. The Health Institute, New England
Medical Centre, Boston, MA, Nimrod Press.

Evidence of ceiling effects was reported for 6/14 items
of the ChalderFS following completion by a large group of
CFS/ME patients [99]. There was no evidence of precision
for other fatigue measures.

99. Morriss, R. K., Wearden, A. J., et al. (1998). Exploring the
validity of the Chalder Fatigue scale in chronic fatigue syndrome.
Journal of Psychosomatic Research, 45(5), 411417.

A concurrent evaluation of the SF-36 (v1) and EuroQoL
EQ-5D reported ceiling effects for the EQ-5D [111]. With
the exception of floor effects reported for the PF domain,
the SF-36 had acceptable measurement properties. A single
study provided limited evidence in support of the validity
of the SF-36 (Version 2), but did not describe the precision
of the revised PF domain [112]. Evidence of precision was
not found for other generic measures.

111. Myers, C., & Wilks, D. (1999). Comparison of Euroqol EQ-5D
and SF-36 in patients with chronic fatigue syndrome. Quality of
Life Research, 8(12), 916.
112. Lowry, T. J., & Pakenham, K. I. (2008). Health-related quality
of life in chronic fatigue syndrome: Predictors of physical
functioning and psychological distress. Psychology, Health and
Medicine, 13(2), 222238.

Discussion

[..]

Moreover, several authors have suggested that
the BDI may be an inadequate measure of depression in
CFS/ME [44, 115].

44. Short, K., McCabe, M., & Tooley, G. (2002). Cognitive functioning
in Chronic Fatigue Syndrome and the role of depression,
anxiety, and fatigue. Journal of Psychosomatic Research, 52(6),
475483.

115. Johnson, S. K., DeLuca, J., & Natelson, B. H. (1996). Depression
in fatiguing illness: Comparing patients with chronic fatigue
syndrome, multiple sclerosis and depression. Journal of
Affective Disorders, 39(1), 2130.

Underlined bit is bit I'm interested in:

Although limited evidence suggests that the FSS may
provide a more comprehensive assessment of fatigue in
CFS/ME patients when compared to the ChalderFS [100], it
lacks evidence of reliability and responsiveness. Moreover,
with the exception of the PFRS, patient views of PROM
relevance and acceptability have not been sought. Although
the ChalderFS has been more widely applied in CFS/ME
than the PFRS, both have comparable levels of evidence in
support of essential measurement properties. However, the
PFRS was developed specifically for patients with CFS/ME,
defining fatigue across four conceptually distinct domains
and, in contrast to the ChalderFS, has good evidence of
content validity in this group
.

There was limited evidence for the alternative generic measures, but the poor
data quality of the EQ-5D suggests that it should be used
with caution

The content validity of all PROMs, including CFS/MEspecific,
was poorly evaluated. Although recently highlighted
as an important aspect of validity [117], there was
no evidence of domain-specific or generic PROMs being
assessed for relevance in the CFS/ME populationthat is,
in a population other than the original target population in
which it was developed. Where evidence of active patient
involvement was identified, this was poorly reported, largely
cursory and only at the consultative level. Rarely do
developers work collaboratively with patients to develop
and evaluate PROMs to ensure their relevance, acceptability
and appropriateness [118, 119]: there was no
example of such active collaboration in this review

Evidence of construct validity is limited for all measures
by the failure of the majority of authors to test hypothetical
associations between variables: there was a striking lack of
justification for the selection of variables or indication of
the expected strength and direction of association. Often,
simply the statistical significance of a correlation or between
groups difference was reported. Guidance suggests that
formal hypothesis testing should state the expected magnitude
of correlations and differences, and not simply the
P-value [117]. The paucity of evidence describing responsiveness
and complete absence of score interpretation for all
measures is a significant concern and is complicated by the
limited evidence about which interventions may improve
health and quality of life in CFS/ME [121].

Moreover, in the absence of any specific
guidance, the number of studies chosen to reflect limited/
moderate/good evidence reflects a pragmatic assessment of
what may be considered a reasonable level of evidence
underpinned by the understanding that a measure can
perform differently across different populations and settings
[15].
 

Dolphin

Senior Member
Messages
17,567
Last two paragraphs of discussion section

These are the last two paragraphs of discussion section - I have a lot underlined here so thought I'd include them all:

Dominance of the assessment of emotional well-being
and the symptomatic impact of CFS/ME illustrated in this
review, and the lack of CFS/ME-specific measure that
captures the broad-ranging experience of the condition
highlights the discrepancies that exist between outcomes
assessed in research and those identified by patients as
significant to their experience of living with CFS/ME,
including social well-being and physical function [6]. The
poor quality of reviewed PROMs combined with the failure
to measure genuinely important patient outcomes suggests
that high quality and relevant information about treatment
effect is lacking [123]. Such dilemmas have been reported
in other conditions, for example, Diabetes [124, 125].
Exemplified in rheumatology [126], resources are required
to drive consensus between patients with CFS/ME and
health professionals towards the standardization of
assessment practice, identification of important and
appropriate health outcomes and selection of good quality,
acceptable measures. The resulting availability of relevant
and credible information about treatment effect will support
informed decision-making and patient choice [127].

A more scientific focus towards the collaborative
development and ongoing evaluation of PROMs in CFS/
ME is essential to the future of evidence-based health care.
Without investment in appropriate and rigorous measurement
of health, the true burden of CFS/ME and the relative
success of health care will not be fully understood and
communicated. This investment should include the development
of a patient-derived assessment that includes
detailed descriptions of CFS/ME-specific health and quality
of life across the range of domains considered important
by patients with CFS/ME. Such a measure should be
developed collaboratively with the full involvement of
people with CFS/ME as partners in the process. The lack of
such a measure is an important omission from the battery
of assessment approaches in CFS/ME and must be
addressed as a matter of urgency.
 

wdb

Senior Member
Messages
1,392
Location
London
Very interesting paper, lots of stuff to think over. I'm so glad some researchers at least are taking this issue seriously. I can't see how we can make any real progress until we have the means to actually measure it reliably.

I think Malcolm Hooper hit the hail on the head with this paragraph:

Instead of using actometers, the PIs relied largely on participants subjective responses to questionnaires, which are notoriously unreliable. Subjective data is just that it lacks objectivity and is prone to influences such as participant deference, motivation, gratitude, placebo effect and interpretation. Subjective data is not evidence-based and should be considered unreliable in remitting/relapsing disorders such as ME/CFS. Furthermore, to rely on subjective data in a trial that intentionally set out to modify participants own subjective beliefs cannot be classed as a scientific study.
 

Enid

Senior Member
Messages
3,309
Location
UK
He always gets things right - Prof Hooper - definately "nail on the head" for me too wdb. Must add that my own personal observations/descriptions to my own medics were met with disbelief so often anyway despite obvious difficulties. Even at that stage much prone to Prof Hooper's "influences" - deference gratitude for investigations etc.
 

Simon

Senior Member
Messages
3,789
Location
Monmouth, UK
Thanks for posting this Dolphin. Thought I'd summarise a few key points, which repeats some of yours

1. Central importance of properly meauring outcomes that are important to patients
study abstract said:
Clear discrepancies exist between what is measured in research and how patients define their experience of CFS/ME. Future PROM development/ evaluation must seek to involve patients more collaboratively to measure outcomes of importance using relevant and credible methods of assessment .
This isn't some wishy-washy point about consultation, it's about good science: if you are going to use self-reported outcomes as a measure then the patient view is everything. So if your fatigue scale, developed without checking with patients, fails to meaningfully and accurately describes fatigue then its a lousy measure from a scientific as well as a patient perspective.

Many scales are 'validated' basically on their 'psychometric' properties, which usually means checking things like their being plausible statistical relationships between individual questions on the questionnaires. But if the questions themselves are wrong, or unbalanced, the questionnaire can still be a poor measure of fatigue (or whatever) -however impressive its statistical qualities.

2. Failure to show outcome scales actually measure what they claim to measure
Linked to the first point

the remaining studies evaluating PROM validity fail to evaluate hypothesized associations between variables and evidence should be interpreted with caution...
One way to show as questionnaire does what it claims is to compare how it's results with an external measure that should measure the same underlying thing. Comparing, say, questionnaire results of reported activity against an objective measure of activity such as actomters is one way of doing this. Comparing reported activity levels against employment rates or benefit rates of the same people would be another way of doing this. This sort of thing is also covered by various types of 'validity'. And it hasn't been done for CFS measures.

Here's one example:
Although the expected association was not defined, a head-to-head comparison of the ChalderFS (index and domain scores) and FSS [Fatigue Severity Scale] following completion by a large patient group (n = 166) reported very low correlations between the two measures, suggesting that they measure different aspects of fatigue [100]. The FSS had stronger correlations with variables reflecting CFS severity and the generic Short-Form 36-item Health Survey (SF-36) [101], leading the authors to suggest that the FSS provides a more comprehensive reflection of fatigue-related severity, symptomology and functional disability than the ChFS.
In this case the fatigue measured by the FSS correlates better with other measures of CFS, CFS severity, and SF36 scores (both also questionnaires) than the Chalder Fatigue Scale. However, it is still comparing the results of one questionnaire with the results of another.


With the exception of the IMQ, evaluation of content validity is limited or not reported; conceptual base, methods of item generation, relevance and comprehensiveness of items to patients with CFS/ME was generally not reported.
Similar to above, and makes the point that asking patients what matters is important. A great example of this sort of problem is the Chalder Fatigue scale, which was largely invented by Simon Wessely
There was no instrument available to measure subjective fatigue, so I simply invented one, which would later get modified into the Chalder Fatigue Scale, which also became a citation ‘hit’. And basically that was that.
Note he didn't ask patients what they thought was the best way to describe fatigue, he decided he knew himself - there is no sign he even consulted patients once he had 'invented' the scale. The scale was then psychometrically assessed and found to be 'acceptably valid', but this didn't involved looking for anything outside the original questions.

As far as I know, this is how most 'patient-reported outcome measures' are invented, without any direct input from paitents.

3. Failure to show "clinically significant changes" are actually significant to patients.
.There is no evidence of score interpretation for any fatigue measure.
Another key point this review highlights is that none of the PROMS reviewed include any evidence on interpretation of changes in scores. So if average Questionnaire scores improve by 3 points during a trial - how do we know that matters to the patients involved? Given it's such an important question, it's amazing that dozens of CFS trials, and no doubt thousands of trials in other areas are done without showing that any gains are meaningful.

One way used to deterimine 'Clinically Significant Improvement' it to use statistics. Eg the PACE trial decided that a gain of 0.5 Standard Deviation (SD) was a 'clincally useful difference' - though they would have been better to call it a 'Statisically Significant Difference' since patients were not consulted on whether or not they thought this was a worthwhile gain. (For the Chalder scale, a gain of 2 points (=0.5 baseline SD) on a 0-33 scale was declared significant). Given the problems already covered that the Chalder scale might not even be a very good way of measuring CFS fatigue, the use of statistics to decide what is 'clinically useful' - instead of asking patients (which could be a way to check the statistically-dervied threshold) is worrying.
The majority of studies reported statistically significant change in scores, or correlation of change scores over time; few studies reported evidence of distribution-based or anchor-based assessment. No study described, or tested, a hypothetical relationship between an intervention, or external criterion, and proposed change in score over time [117]. Evidence of measurement responsiveness is an essential requirement for PROMs used in evaluative settings; the lack of appropriate evidence to inform both responsiveness and interpretation of score change must be addressed by future research.


Summary: if patient measures are unreliable you can't measure the benefit of any treatment properly
.. the failure to measure genuinely important patient outcomes suggests that high quality and relevant information about treatment effect is lacking [123].

Exemplified in rheumatology [126], resources are required to drive consensus between patients with CFS/ME and health professionals towards the standardization of assessment practice, identification of important and appropriate health outcomes and selection of good quality, acceptable measures. The resulting availability of relevant and credible information about treatment effect will support informed decision-making and patient choice [127].
 
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One way to show as questionnaire does what it claims is to compare how it's results with an external measure that should measure the same underlying thing. Comparing, say, questionnaire results of reported activity against an objective measure of activity such as actomters is one way of doing this. Comparing reported activity levels against employment rates or benefit rates of the same people would be another way of doing this. This sort of thing is also covered by various types of 'validity'. And it hasn't been done for CFS measures.
Actually studies have used objective measurements, in addition to the usual questionnaires. And they've shown that reporting less disability on questionnaires isn't supported by increased activity levels. Does this mean that those questionnaires have been proven invalid in certain circumstances, such as after an extended course of brain-washing/CBT?
 

peggy-sue

Senior Member
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Location
Scotland
Going back to Hooper's paragraph (which should read as follows - I've bolded the grammar correction)


Instead of using actometers, the PIs relied largely on participants subjective responses to questionnaires, which are notoriously unreliable.
Subjective data is just that. It lacks objectivity and is prone to influences such as participant deference, motivation, gratitude, placebo effect and interpretation. Subjective data is not evidence-based and should be considered unreliable in remitting/relapsing disorders such as ME/CFS. Furthermore, to rely on subjective data in a trial that intentionally set out to modify participants own subjective beliefs cannot be classed as a scientific study.


It strikes me that subjective evidence has been USED as objective evidence in PACE.
It is described as an evidence-based study, it touts itself as the best available evidence

but it's all subjective in the first place - none of the skewing even matters - it's simply not evidence.
 

Simon

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Location
Monmouth, UK
Actually studies have used objective measurements, in addition to the usual questionnaires. And they've shown that reporting less disability on questionnaires isn't supported by increased activity levels. Does this mean that those questionnaires have been proven invalid in certain circumstances, such as after an extended course of brain-washing/CBT?
Thought it might be worth putting some numbers on this by comparing gains in fatigue, with gains overall (both self-rated) and with the 6MWT - all for PACE, of course. I've given data for CBT, and also for the control SMC group ( :) brain-washing free). All results at 52 weeks vs baseline

% with fatigue improving by a 'clinically useful difference': CBT=79%; SMC=65%
% with physical function (sf36) improving by a 'clinically useful difference': CBT=71%; SMC=58%
% with positive 'Clinical Global Impression' score: CBT=41%; SMC=25%
Mean gain in 6 min walking difference: CBT=+21m (6%); SMC= +22m (6%)

Far more people show clinically significant improvements in fatigue or function than report an overall improvement in their health, which should in itself be cause for concern. If patients don't think they have improved overall but the researchers say they have made a 'clinically useful' gain, something is up. More than twice as may in the control group were classified as clinically improved in fatigue than said they were improved overall. Also, the two measures may not even correlate well, eg some of those saying they have improved overall may not have improved 'clinically' at all.

And of course the average gain in distance walked was tiny (and not statistically significant) for both CBT and SMC despite large gains in self-rated physical function.

peggy-sue - not sure I would wholly agree with that: there is no objective measure of fatigue and generally I think patient-reported outcomes are important. However, objective measures are important too, and as a matter of course authors should, in my opinion, check that objective measures back up the subjective measures. If they don't then the authors need to explain why not.

Looking at the figures above, I think the authors should have at least attempted to explain the large discrepancy.
 

peggy-sue

Senior Member
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Location
Scotland
I'm very bad in terms of brain function, I'm afraid. Simon.
Can't hold many ideas in my head at one time, and can't follow details, I'm just grabbing and kind of clinging to little twigs here and there. :redface:

I want to be simplistic and shout;

"Why can't they jolly well measure lactic acid production in my muscles if they want physical proof (and an objective measure) of my so-called "fatigue".

But I was thinking of the gaslighting really - regarding the use of subjective reports within the study, but then CALLING the results of the trial "evidence".
 

Simon

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Location
Monmouth, UK
I'm very bad in terms of brain function, I'm afraid. Simon.
Can't hold many ideas in my head at one time, and can't follow details, I'm just grabbing and kind of clinging to little twigs here and there. :redface:

I want to be simplistic and shout;

"Why can't they jolly well measure lactic acid production in my muscles if they want physical proof (and an objective measure) of my so-called "fatigue".

But I was thinking of the gaslighting really - regarding the use of subjective reports within the study, but then CALLING the results of the trial "evidence".
Most studies on CFS patients don't find differences in lactic acid production, despite greater levels of fatigue - that may well not be the issue (and believe me, I've slogged through a lot of papers to find this out).

But also if I was in a Trial and reported my fatigue levels, or overall levels of health I wouldn't want that dismissed as 'not evidence' by anyone. It's a subjective report and should be treated as such, but that doesn't make it unimportant. A lot of people arguing for meaningful patient self-reports are patients themselves. The problem with any subjective report, though, is that there may be self-report bias, especially in clinical trials. That doesn't mean, in my opinion, that patient reports pre se are meaningless.

Actually, there is a whole debate about patient involvement in research, arguing about moving from studies about patients to studies with or by patients. Not all researchers are very keen on this as it involves a loss of power.
 

peggy-sue

Senior Member
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Location
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I do believe you have slogged... and slogged... and slogged. :thumbsup:
But I do not get fatigue.
I do get horrendous lactic acid pain, very rapidly.

For example, in my legs if the pavement starts a small incline, or I manage to get half-way up the stairs.
My problem is energy production.
I cannot do anything that recruits aerobic metabolism, I am stuck in anaerobic mode. But if I stay there, I can achieve a few things.


Lactic acid was found to be produced at 20 times the normal rate, in cultured muscle cells from sufferers, by Prof. Julia Newton, published earlier on this year.

My suspicion about many publications which say they "found nothing" is that they did not look in the right places, or use the correct patient population, and they get published because the "powers that be" want that sort of "nothing to be found" stuff out there.

Studies which did find things, earlier on, had a nasty habit of going awol, Elaine de Freitas, for example...

Done a bit of googling on her for accurate info:-

(copied and pasted the relevant bit from this link. Article by Margaret Williams)

http://meagenda.wordpress.com/?s=Elaine de


"
In 1991, using polymerase chain reaction and in situ hybridisation, Dr Elaine De Freitas, a virologist at the Wistar Institute, Philadelphia (which is America’s oldest independent institution devoted to biological research) and Drs Daniel Peterson, Paul Cheney, David Bell et al found such an association (Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome. Proc Natl Acad Sci USA 1991:88:2922-2926). It is notable that co-author Hilary Koprowski is a distinguished virologist and Professor Laureate who was Director of the Wistar Institute from 1957-1991; he is a member of the US National Academy of Sciences and is Director of the Centre for Neurovirology at Thomas Jefferson University.
Before publication, the findings were presented on 4th September 1990 by Elaine De Freitas at the 11th International Congress of Neuropathology in Kyoto, Japan.
Ten days later, on 14th September 1990 Dr Peter White (as he then was) and other members of the Wessely School dismissed the findings: “in the vast majority of CFS cases there is a psychological component. About 75% of CFS sufferers are clinically depressed, according to Peter White, senior lecturer in the department of psychiatric medicine at St Bartholomew’s Hospital in London. White said he believes depression is often a cause, rather than a consequence, of CFS…Les Borysiewicz, a clinical virologist at Addenbrookes Hospital in Cambridge (now Chief Executive of the MRC, having succeeded Professor Colin Blakemore) (said) ‘Whatever causes CFS, it isn’t the virus itself’…Anthony Clare, psychiatrist and medical director of St Patrick’s Hospital in Dublin (now deceased), pointed out that…there have been many ‘fatigue’ diseases with shifting causes: ’Neurasthenia, food allergies, now viruses. Some people would always rather have a disease that might kill them than a syndrome they have to live with’ ” (Science 1990:249:4974:1240).
In their PNAS article that was published in April 1991, De Freitas et al noted that chronic fatigue immune dysfunction syndrome (CFIDS) “may be related or identical to myalgic encephalomyelitis” and examined adult and paediatric CFIDS patients for evidence of human retroviruses (HTLV types I and II). As the CFIDS Chronicle article noted, the Wistar team looked at the peripheral blood DNA to see if they could find messenger RNA (mRNA) encoding for a viral segment of the HTLV-II virus.
At that time, known human retroviruses were the human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2) which are known to cause AIDS, and human T-lymphotropic viruses HTLV-I which causes lymphoma and HTLV-II which causes leukaemia (Hunter-Hopkins ME-Letter, October 2009). The four segments of the HTLV-II virus are referred to as the env, gag, pol and tax.
After a two year study, De Freitas et al provided evidence for HTLV-II-like infection of blood cells from CFIDS patients (and also to a lesser extent from people closely associated with them). This evidence was further substantiated by patient reactivity to proteins with the molecular weights reported for HTLV-I and HTLV-II antigens.
In their article, De Freitas et al said: “The frequency of these antibodies in CFIDS patients compared with healthy non-contact controls suggests exposure / infection with an HTLV-like agent rare in healthy non-contact people”.
Following the Wistar findings, researchers at the US Centres for Disease Control (CDC) allegedly attempted to replicate De Freitas’ work but failed to do so; this was suggested to be because certain scientists appeared eager to discount any possibility of a retroviral association with CFIDS. De Freitas defended her work and insisted that the CDC investigators had modified her assays, with the result that her work could not be replicated by the CDC.
De Freitas was publicly discredited; her research funding was discontinued and her research abandoned; she was subjected to what appeared to be attempts to destroy her professional reputation. Commenting on the subsequent discovery of XMRV (see below), ME/CFS expert Dr Paul Cheney of The Cheney Clinic was unambiguous: “Her work was unfortunately assaulted by the CDC. Her proposal to fly to the CDC in Atlanta to physically run the assays side by side with the CDC scientists was dismissed by the CDC” (http://cheneyclinic.com/a-retrovirus-called-xmrv-is-linked-to-cfs/538 ).
Read full article here:
http://www.meactionuk.org.uk/The-role-of-viruses-in-ME.htm
http://tinyurl.com/ykjveep
http://www.meactionuk.org.uk/The-role-of-viruses-in-ME.pdf
http://tinyurl.com/y8m8s8h
 
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13,774
Thanks D and Simon.

re validity:

Many scales are 'validated' basically on their 'psychometric' properties, which usually means checking things like their being plausible statistical relationships between individual questions on the questionnaires. But if the questions themselves are wrong, or unbalanced, the questionnaire can still be a poor measure of fatigue (or whatever) -however impressive its statistical qualities.

It always pisses me off when they talk of fatigue questionnaires as being 'validated', without there being any good evidence that they are valid measures of what people (and particularly that patients being studied) mean by 'fatigue'. It's invalid 'validity'!
 

Snow Leopard

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Location
South Australia
I want to be simplistic and shout;

"Why can't they jolly well measure lactic acid production in my muscles if they want physical proof (and an objective measure) of my so-called "fatigue".

There is no simple measure for fatigue, unfortunately.

Lots of things have been proposed, from specific cytokines, to a build up of free fatty acids, to oxidative stress, even elevated levels of serotonin. (which by the way, three different groups which investigated this did in fact find evidence of elevated serotonin activity)

That's why I suggest using objective measures of activity and cognitive function at the same time as self-report questionnaires.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Going back to Hooper's paragraph (which should read as follows - I've bolded the grammar correction)


Instead of using actometers, the PIs relied largely on participants subjective responses to questionnaires, which are notoriously unreliable.
Subjective data is just that. It lacks objectivity and is prone to influences such as participant deference, motivation, gratitude, placebo effect and interpretation. Subjective data is not evidence-based and should be considered unreliable in remitting/relapsing disorders such as ME/CFS. Furthermore, to rely on subjective data in a trial that intentionally set out to modify participants own subjective beliefs cannot be classed as a scientific study.


It strikes me that subjective evidence has been USED as objective evidence in PACE.
It is described as an evidence-based study, it touts itself as the best available evidence

but it's all subjective in the first place - none of the skewing even matters - it's simply not evidence.

More to the point, claiming that subjective data is objective is misleading. Whether this is deliberate or just really bad science is a matter of debate.
 

alex3619

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There is no simple measure for fatigue, unfortunately.

Lots of things have been proposed, from specific cytokines, to a build up of free fatty acids, to oxidative stress, even elevated levels of serotonin. (which by the way, three different groups which investigated this did in fact find evidence of elevated serotonin activity)

That's why I suggest using objective measures of activity and cognitive function at the same time as self-report questionnaires.

You can objectively measure activity. You can objectively measure oxygen use, and the AT threshold. You can objectively measure failure to recover from activity by repeat CPET. You can objectively measure cognitive function in various ways using extensive automated cognitive testing batteries. Somehow those who like subjective testing don't want to use any of these.

In my view the 6 minute walking test is also invalid, based upon published physiology of ME. Only repeat exercise testing has validity now. The same criticism does not appear to apply to actometers. This measures sustained activity over a large period of time. What the science does suggest though is that actometers should be worn over extended periods of time, in part to compensate for the fluctuation in activity - perhaps over weeks.
 

Firestormm

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How to you measure someone who says they are 'fatigued' to the extent that it effects their life; but who is able to 'push through' if necessary?

Isn't this something else that needs to be taken into account somewhere? I mean we do need to listen to patients - of course we do - and it is subjective: but measuring biologically cannot account for everything.

There will ever be the 'human factor'. Be it someone who is healthy, someone with significant cancer, someone being treated for cancer, someone with acute ME or someone with chronic ME.

We are all different - at least at some level.
 

alex3619

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Firestormm, that is why I suggested long periods with actometers. People pushing through will find they spend time doing less. That should show, most of the time, in prolonged actometer data.

Where its unclear is with misdiagnosed patients, or patients at the extreme mild end. These might not show up the same, but then we need to see that in the data in order to begin addressing the issue.