
Analysis of chronic fatigue syndrome study casts doubt on published results - rch
https://www.statnews.com/2016/09/21/chronic-fatigue-syndrome-pace-trial
======
philipkglass
I had a sibling who struggled with CFS for years. Even before this bad study
came out the usual reaction from doctors was _you 're suffering from mental
illness/try exercising/you're faking_. It sounds almost like this study was
constructed for the convenience of doctors so they could point to the
publication and keep suggesting what they had already suggested.

It's hard living with a debilitating medical condition that doesn't have good
treatments or a clear cause. It's even harder when the doctor says "I think
it's all in your head" instead of "sorry, we really don't know how to treat
this yet." That sort of consistent dismissal/borderline victim-blaming from
real doctors is what I think pushed my mom toward bogus alternative health
practices. There appears to be nothing medically valid about chiropractors but
at least they don't call you crazy just for telling them about the experiences
you've been having.

~~~
wpietri
That sounds awful.

There's a phenomenon that I wish I had a name for. Or even a good description
of. It's when people imagine that your issue is just something they've
experienced, even when the magnitude is very different. E.g., when people who
have been sad at some point tell clinically depressed people that they should
just cheer up. When they tell somebody with an anxiety disorder that they
should calm down. Or, as with your sibling and CFS sufferers that they should
just get a little exercise and it'll all be fine.

I can sort of forgive that in regular folk. But in doctors? It's shameful.

~~~
wott
My folks are like that too. They never experienced any psychic or physic
trouble at any point in their 70 years long life, so they cannot fathom that
people may strongly suffer from any of these problems, which are in their
opinion not real problems and can be solved with cheering up and _making an
effort_ , because that's how they solved their own 5-minute 'problems'.

~~~
BerislavLopac
> They never experienced any psychic or physic trouble at any point in their
> 70 years long life

How can you tell?

------
j374
As a near 10-year sufferer of severe ME/CFS, I can confirm this study has done
unbelievable damage to the cause and should absolutely be retracted in full.
Recent research has identified unquestionable, tangible and severe
abnormalities in immune and metabolic function that are unique and consistent
to ME/CFS sufferers, and this is no longer realistically up for debate. Most
doctors though still dismiss the condition as psychological, and because of
this (and even though the burden has been shown worse than other immune
disorders like AIDS in many cases) funding is virtually non-existent. This
study has been so widely disseminated and taught to medical professionals, the
damage will take some time to undo unfortunately.

~~~
cpncrunch
A couple of points:

\- the study hasn't done "unbelievable damage", unless you're firmly in the
camp that CFS must be organic.

\- "severe abnormalities in immune and metabolic function" doesn't rule out
psychosomatic causation (as the stress system also controls the immune system
and mitochondria, for example).

\- there is no "unique and consistent to ME/CFS sufferers" dysfunction, except
perhaps in HPA axis (the main stress system) responsiveness (but even this is
somewhat up for debate).

\- Saying it is psychological is not "dismissing" it. From what I can tell
(having suffered from it, and researched it), psychosomatic causation does
seem the most plausible. The symptoms, abnormalities, triggers and cures match
perfectly with what you would expect from exhaustion due to chronic stress.

~~~
jsjohns2
> \- there is no "unique and consistent to ME/CFS sufferers" dysfunction,
> except perhaps in HPA axis (the main stress system) responsiveness (but even
> this is somewhat up for debate).

This is at odds with the current scientific consensus. Table 1 of "Myalgic
encephalomyelitis: International Consensus Criteria" (2011) describes one
primary dysfunction (postexertional neuroimmune exhaustion) and several
secondary dysfunctions [1].

Furthermore, post-exertional malaise, which is similar to postexertional
neuroimmune exhaustion, has been described as a "hallmark" symptom of ME/CFS
at least as far back as 2007 [2].

[1]
[http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011....](http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02428.x/full)

[2]
[http://www.tandfonline.com/doi/abs/10.1300/J092v14n02_07](http://www.tandfonline.com/doi/abs/10.1300/J092v14n02_07)

~~~
cpncrunch
The OP specifically mentioned "immune" and "metabolic" dysfunction, not
symptoms. You are correct that postexertional is likely common to all CFS
sufferers, although even that isn't fully agreed on and there is no way of
objectively measuring it (repeat CPET might be an objective measure, but that
needs more research).

Neuroimmune exhaustion has not been objectively defined. The ICC says "rapid"
malaise, but it's typically 24 or 48 hours later.

~~~
jsjohns2
> The OP specifically mentioned "immune" and "metabolic" dysfunction, not
> symptoms.

Fair enough.

> The symptoms, abnormalities, triggers and cures match perfectly with what
> you would expect from exhaustion due to chronic stress.

Based on your research, what are the cures for "chronic stress"? The
treatments discussed in the PACE paper (CBT, GET, etc.)? I'm genuinely
interested -- my sister was diagnosed with CFS over a year ago and has made
little progress since then.

~~~
cpncrunch
>Based on your research, what are the cures for "chronic stress"?

Well the first thing is to obviously get rid of the chronic negative stress.
However even then, many people don't recover (hence the fact that they have
long-term CFS, rather than a temporary burnout which they then recover from
after removing the stress).

As for why people don't always recover after removing the negative stresses? I
think there are a couple of possibilities:

[1] Negative stress from the illness itself (a vicious circle).

[2] The brain gets stuck in the fatigued state, until it gets a "kick" out of
it, in the form of a positive stressor. (Basically the fatigue state is a
protection mechanism against negative stress that the organism can't cope
with, and it requires evidence of a positive development in the future outlook
in order to remove the "brakes").

Even though I suffered from CFS, it's hard to pin down exactly which one makes
most sense. However the effective cures seem to address both (i.e. getting the
patient to do a positive activity). (I should clarify that there are no truly
effective "official" cures, only unofficial ones that people like me and
others figure out by ourselves).

The problem is that CBT and GET aren't based on valid etiologies of the
illness, so at best they might be a placebo that just happens to kick the
person out of the exhaustion state on some occasions. The problem is that CBT
and GET can be inherently stressful (especially if the person is convinced of
an organic etiology), which will likely just make things worse.

~~~
eukaryote
I suffered from ME many years ago, and I was looking for something - anything
- to help me cope with the continual fatigue, muscle pain, insomnia, night
sweats, tinnitus etc. I went to learn meditation, and the instructor told me
that for many chronic illnesses, the stress of being ill can slow down
recovery.

Once I started practicing meditation, I felt a slow improvement in my
condition, and most of the symptoms had sufficiently eased after 10 months
that I was living a fairly normal life again. I did experience a couple of
mild relapses years later (both times by not easing up on intense exercise
when suffering a throat infection), but the symptoms were more mild and I
recovered each time after about 4 months.

I an not advocating meditation as a cure, but it did make living with ME more
bearable.

------
TazeTSchnitzel
It saddens me how bad science will be so quickly defended if it confirms
preconceived notions that a marginalised group should be dismissed, and then
whoever protests this will be slurred as opposing science, as if there could
not possibly be a scientific basis to object to it.

This is hardly the first time it has happened.

~~~
tremon
This, very much. The attitudes described in the paper really make my blood
boil. From refusing to share research data on bogus grounds to dismissing
patients as "unhinged", then publishing its own "revised research" just before
being forced to release the raw data.

The proper response from the scientific community should be to disqualify
every study from Queen Mary University of London until the university owns up
to its mistakes, instead of digging in.

------
cpncrunch
Just be aware that the author of this article is a writer who is basically
"out to get" the PACE trial, and she has some slightly strange ideas about CFS
([http://www.healthrising.org/blog/2014/05/02/constant-
vigilan...](http://www.healthrising.org/blog/2014/05/02/constant-vigilance-
julie-rehmeyers-mecfs-recovery-story/)).

From what I can see from the reanalysis released by QMUL
([http://www.wolfson.qmul.ac.uk/images/pdfs/pace/PACE_bimodal_...](http://www.wolfson.qmul.ac.uk/images/pdfs/pace/PACE_bimodal_CFQ_analysis_final_8_Sept_2016.pdf)
and
[http://www.wolfson.qmul.ac.uk/images/pdfs/pace/PACE_publishe...](http://www.wolfson.qmul.ac.uk/images/pdfs/pace/PACE_published_protocol_based_analysis_final_8th_Sept_2016.pdf)),
the main difference from the original trial was the "recovery" measure, which
is a pretty arbitrary value anyway (as recovery can mean various things).
However the average fatigue scores don't seem to be much changed from the
original trial as far as I can see, and that is the more important result.

A lot of people are out to kill PACE, but releasing lots of frothy press
releases with the worst possible interpretation isn't terribly useful for
anyone.

~~~
sirmarglar
First, the article in STAT is not a press release...it's a reported
commentary/opinion piece where the author has clearly done a lot of reporting.

Second, setting a functional level on measure you're talking about is
arbitrary. But the the PACE authors picked a very lo value for "recovery." And
they dropped that level after beginning the trial - a very poor practice known
as outcome switching. At the end, they defined "recovery" below the physical
functioning level for most heart failure patients - and below their entry
criteria. That is, a CFS patient could enter the trial, _get worse_ , and get
called recovered - all while functioning worse than a heart failure patient.
Pretty shady stuff.

~~~
cpncrunch
>Second, setting a functional level on measure you're talking about is
arbitrary

Yes, and the PACE recovery paper does say this.

>But the the PACE authors picked a very lo value for "recovery."

How exactly is 1sd below the mean of the general population "lo"?

>At the end, they defined "recovery" below the physical functioning level for
most heart failure patients

Again, it's 1sd below the mean of the general population. Congestive heart
failure has a _mean_ value of physical functioning around 1sd below the mean
for the general population. The person who first threw out this "congestive
heart failure" meme probably didn't understand statistics.

>That is, a CFS patient could enter the trial, get worse, and get called
recovered

The point is that the entry criteria was an upper limit and the recovery
criteria was a lower limit, so it makes sense that they're different. I don't
think you can have patients who didn't improve being classed as "recovered" as
recovery also included various other measures (e.g. not meeting Oxford
criteria). The main point of the study was to show the differences in recovery
between the treatment groups.

The other point is that the recovery results weren't even in the PACE trial,
they was in a second paper. The paper does mention that there is no agreed
definition of recovery, and they were just trying to get a handle on it using
various measures.

Overall, apart from the recovery results (which are somewhat arbitrary) the
PACE trial results are in line with all the other CBT trials.

There are certainly problems with the PACE trial (the main one being that CBT
and GET are based on dubious etiologies), so I think CFS advocates would be
better off actually delving into the real problems with the treatments, rather
than putting up these strawmen.

------
lutusp
Apart from the article's importance in exposing some bad science, its author
is skilled in narrative, in making an essay readable. A worthwhile read.

------
tomcam
Western medicine is AWESOME for traumatic injuries. The state of the art moves
forward at an impressively steady clip. But our grasp of chronic conditions
like this is pathetic, and worse, physicians are usually very uninterested in
exploring these conditions with patients.

~~~
dhimes
Indeed. "Syndromes" are very hard because there's no real way to test for
them. Once there is, the condition can be classified as a disease (or
whatever) and progress can be made. It's very hard to make progress without
being able to test well. And that is true across disciplines (I'm looking at
you, Education).

I think in the _early_ days there was a lot of initial skepticism because, if
there were real cases they were diluted by people complaining to their
(chronically tired, overworked and stressed) doctors that they were tired.
Doctors thoughts were, "welcome to the club." And there is a certain subset of
the population who complain constantly about medical conditions- indeed it is
the foundation of most conversation it seems- so with no good way to
conclusively test for the condition it was often dismissed.

