The second half of the IOM public meeting was dominated by patients and advocates, which meant presentations were intelligent, cogent, well-organized, and comprehensible. The patient groups had divided up their presentations so that each
focused on a specific point, which was illustrated with slides, documented, and referenced.
Unfortunately, the IOM committee (non-expert members) showed virtually no interest in any of the presentations, in spite of the fact that they had been submitted well in advance. This should have given committee members ample time to examine the documents and materials, and to come up with questions.
There was only one question posed by a non-expert panel member. In response to Charmian Proskauer's presentation on children and adolescents, Dr. Theodore Ganiats,
Executive Director of the UCSD Health Services Research Center, said, "I am intrigued by the idea of trying to diagnose children earlier. But
whenever you start diagnosing earlier, you'll have some false diagnoses. If you take it to the extreme, and
have it
be only one day instead of six months, then you're going to have
problems. If you wait six months you're going to have problems. So, the
question is if you have any data, or know of any data, on length of time
of symptoms, and how well that is correlated with a final true
diagnosis."
Aside from the fact that Charmian had only two minutes earlier stated in her summary, "You should add the
existing clinical definition for Pediatric ME/CFS to your scope of study" [in reference to Leonard Jason, et al.
A Pediatric Case Definition for Myalgic Encephalomyelitis and Chronic Fatigue Syndrome, 2006], it is mind-boggling that a committee formed months ago with the charge of evaluating all existing case definitions for ME/CFS has not yet read them.
Dr. Ganiats' flippant proposal that a diagnosis of ME/CFS could be made after one day not only points to a lack of preparation on the part of the committee, it indicates an underlying attitude: This committee is not going to take us, or the illness, seriously.
That was the attitude also expressed by Dr. Clayton's announcement that "we'll be hearing from ...
gosh ... patients." Why should it be remarkable for patients to provide input on a process that will have such a profound impact on their lives? Shouldn't patients have the opportunity to speak to that process? And shouldn't their input be welcome?
In a
recent blog post, Valerie Eliot Smith observed that "the atmosphere in the room felt sterile, devoid of empathy and compassion... [patients] seemed to be unwelcome and unheard." Astutely, Ms. Smith pointed out that such rigidly imposed restrictions on the amount of time allotted to each presenter acted contrary to First Amendment right to freedom of speech. She asks, "Does a constitutional right to freedom of expression have any meaning in
the absence of a subsidiary right to be listened to by the state which
should be upholding those rights?"
It is the denial of that right which has led so many patients to boycott the IOM process.
There is an alternative, however:
speak louder.
________________________________________________
This article originally appeared on ProHealth.
Note: You can read a summary of Part 1 of the meeting here.
Part 2 can be found here.
By Erica Verrillo
The
second half of the public meeting concerning the IOM’s review of
diagnostic criteria for ME/CFS was devoted to presentations by FDA and
ME/CFS associations.
Presenters included:
- Sara Eggers, FDA, Voice of the Patient Report
- Lori Chapo-Kroger, PANDORA Org , Let’s Get It Right group
- Mary Schweitzer, for Pat Fero, Wisconsin ME/CFS Association, Inc., Let’s Get It Right group
- Carol Head, CFIDS Association of America, Let’s Get It Right group
- Pat LaRosa, New Jersey Chronic Fatigue Syndrome Association, Inc., Let’s Get It Right group
- Gabby Klein, Phoenix Rising
- Charmian Proskauer, Massachusetts CFIDS/ME & FM Association, Let’s Get It Right group
- Jennie Spotila, OccupyCFS
You can read the meeting agenda
HERE.
You can watch presentations
HERE.
You can read information about the committee members
HERE.
It is not too late to submit comments to the IOM Committee. Send your comments to:
mecfs@nas.edu
Sara Eggers,
FDA Office of Program and Strategic Analysis/Office of Strategic
Programs, Center for Drug Evaluation and Research (the office which is
coordinating the Patient Focused Drug Development Initiative) (
Video) (
Transcript courtesy ME/CFS Forums)
Key message: The key to success is meaningful engagement and valuable input by the patients and the patient community.
Ms.
Eggers began by saying that FDA recognizes that CFS and ME is a serious
disease, or set of diseases, for which there are no currently approved
FDA therapies. “We share in the commitment to facilitate the development
of safe and effective drug therapies for CFS and ME,” she stated.
In
April of 2013, there was a public meeting to hear perspectives from
patients with CFS and ME and patient representatives, and those who care for
people with CFS and ME or advocate on behalf of those patients. This
was the first meeting conducted as part of the FDA’s Patient Focused
Drug Development Program (PFDD). The meeting was part of a larger
workshop to explore important issues related to CFS and ME drug
development.
Some background on the PFDD initiative
To provide background, Ms. Eggers explained that when the FDA reviews drugs for pre-market approval, it performs a risk/benefit
assessment that takes into account a number of factors.
The key decision factors are:
- The analysis of the condition
- The current treatment options
- Benefit, risk, and risk management
The
first two provide therapeutic context for weighing benefits and risks.
Assessing benefits and risks depends on how bad the condition is, how
serious the condition is, what’s available for patients, and how well
those current therapies are meeting patients’ needs.
FDA
typically focuses on obtaining patient input when a specific application
is under review. In contrast, PFDD offers a more systematic way of
providing patient input on their conditions and treatment options in a
broad context.
How FDA chose CFS and ME
In
2012 FDA started the process by nominating disease areas. They got
public input through a meeting, through a federal docket, and a federal
register notice. Over 4500 comments addressing 90 different diseases
were nominated, of which 16 were selected for the first three years of
the program. In 2015, they will start another
process for the final two years.
The PFDD focused on diseases
that are chronic, symptomatic, have few or no effective therapies, etc.
CFS and ME fit in many of these categories.
At the meeting for CFS and ME, there was a patient panel for
different discussion topics to provide some comments. That was followed
with facilitated discussion with the patients in the audience. FDA also
had a federal docket that allowed people who could not attend to submit
comments.
The meeting resulted in a report that will help FDA
staff as they review drugs, as well as when FDA advises drug sponsors in
their development program.
Questions posed to patients
- What are the most significant symptoms that you have?
- What impact do they have on daily life?
What are patients’ perspectives on current approaches to treating CFS and ME?
There
were 70 patients and patient representatives at the meeting, many on
the web. FDA received 228 docket comments, which were detailed and
informative.
The report was posted in September of 2013. It is a
snapshot of the story that patients collectively told FDA. Though FDA believes
the report reflects the content of the meeting and the docket
submissions, they stress that the report is not meant to be reflective of the
entire patient population.
Key themes
- Abrupt onset, after a specific illness or just waking up one day and not feeling good
- CFS
and ME is much more than simply feeling fatigued. More than 50 symptoms
were reported, both cognitive and physical manifestations
- Post-exertional malaise or a crash
The
meeting reiterated the devastating toll that the disease can take on
patients and families. Some reported still being able to function in
society, or go to
work,
but that’s about all they could do. Others reported that they were
virtually housebound or bedbound. Many described themselves as being
successful professionals or students before, but said they now struggle
with many aspects of day-to-day living.
Patients use a complex
regimen of drug and non-drug therapies to treat their disease and manage
their symptoms. Over a hundred therapies were mentioned in the meeting
or on the docket comments.
They also mentioned a range of
diagnostic tools and biomarkers that their clinicians use to help treat
their condition. They talked about the varying degree of effectiveness
of their treatments, and how their treatments are often associated with
bothersome side effects which can exacerbate other aspects of their
disease, making treatment a very complex endeavor.
They are
desperate for research and development of CFS and ME treatments, at a
minimum to relieve their most significant symptoms, but ideally to
address the underlying cause or causes of their disease.
Specifics
Cognitive impairment:
Impaired executive functioning, or “brain fog,” was frequently
mentioned, as were disorientation, inability to process information,
slowed reaction times, word-finding difficulties, etc.
Fatigue:
This symptom encompassed lack of energy, weakness, exhaustion, feeling
drained or difficulty recovering their strength, feeling tired but
wired, and feeling extreme bone-crushing fatigue.
Sleep dysfunction:
Insomnia, sleep disruptions, having difficulty staying asleep or waking
up feeling unrefreshed or not rested can exacerbate their other
symptoms, but even with 10,12, or more hours of sleep patients still
wake up feeling unrefreshed. Sleep medications often exacerbate fatigue.
Chronic pain:
Muscle pain, burning muscles, muscle spasms, joint pain, pain in the
eyes, pain behind the eyes, neck pain, nerve pain, neuropathy, headaches
and migraines, and whole body pain were mentioned. Patients expressed
concern about the lack of knowledge about the fundamental causes of
their pain. A few commented that they have fibromyalgia, but they didn’t
attribute all of their pain to that. They commented again on the
challenge of finding the right treatments for their pain.
Sensitivity to light, sound, and temperature and other stimuli:
For some patients, this is their most debilitating set of symptoms. It
limits their ability to engage in social interactions or go outside.
Other symptoms
included sore throat, flu-like symptoms, orthostatic intolerance, other
issues related to blood pressure drops, susceptibility to viral and
other infections, GI and vision problems.
PEM:
The “crash” is the incapacitating exacerbation of all symptoms that can
occur with even minimal exertion and without warning. There is a
difference between a physical crash and a cognitive crash. The physical
crash is your body feeling like you can’t move. The cognitive crash
where your mind feels like you can’t think.
Patients described
best days and worst days in great detail. One of the surveys submitted
to our docket reported that on “best days” 67 percent of the survey
respondents could do light housework or could work part-time on some
household tasks, versus 6 percent who could not. On the worst days, 61%
reported being bedbound.
In conclusion, this meeting demonstrated
that CFS and ME is a debilitating disease that can have a devastating
impact on patients’ lives. Patient input strengthens understanding of
the specific symptoms that matter most to patients, the burden that this
disease has on patients and their families, the range of treatments
that are currently being used, and how well those treatments are
currently meeting their needs.
Ms. Eggers described the key to
success as being “meaningful engagement and valuable input by the
patients and the patient community.”
Q&A
Ellen Clayton: Do you have the primary data that the committee can have access to as well?
Ms. Eggers:
The primary data is in the form of a transcript, which is available,
and public docket comments. One challenge is that not all of the public
docket comments were actually put on the website. So I would have to
look into seeing how we can make those accessible. That’s the raw data.
Lily Chu:
I just have a comment. Dr. Eggers gave some of the results of a survey
regarding best and worst days. And if the committee wants that data, Dr.
Jason and I conducted that survey, and we can share it with the
committee.
Ms. Eggers: Two of the submissions
to the docket comments were surveys that were conducted by patient
stakeholders and submitted to us through the docket, and we treated them
as a piece of input, like the docket comments.
Nancy Klimas:
Another comment that came up at the FDA meeting is that the
PatientsLikeMe site also has a huge data set on symptoms and even
outcomes. There are more than seven thousand patients, I think, right
now.
Rick Erdtmann: I just have one quick
question. You mentioned at the beginning of your presentation that there
was a second report more technical that was in process. When will that
be done and will it be publicly available?
Ms. Eggers:
That report will be a summary report of the second day of our workshop,
which covered technical discussions. That should be posted as soon as
it’s available.
Remarks from ME/CFS Advocates and Associations
Lori Chapo-Kroger, PANDORA Org (Video)
PANDORA
Org submitted two written comments to the IOM committee for the public
meeting. 1) The Needs of the Severely Ill has pictures to show how
people suffer with this illness, and 2) Critique of the NICE Guidelines.
(Transcripts
HERE.)
Key
message: The IOM study is important, because until we have a
universally accepted biomarker, the clinical definition will be the
front-line diagnostic tool that determines the course of clinical care
and treatment management for patients with ME.
We
are all concerned that this process will further set back patient care,
and we are concerned that history will repeat itself and patients will
end up in a worse position. In the real world, ME/CFS is used as a
wastebasket diagnosis. It’s time to take us out of the wastebasket.
Fatigue is a symptom, not an illness. Fatigue is the 7
th
most common symptom reported to doctors. Fatigue is also experienced by
healthy people, and it can result from virtually every physical or
psychological illness. These conditions are not under one big “chronic
fatigue umbrella,” because fatigue is a symptom of so many diseases.
The
main problem in a clinical setting of a fatigue-based definition is
that doctors confuse chronic fatigue with chronic fatigue syndrome. They
diagnose patients who have primary psychiatric disorders with CFS, and
are not educated in illness severity. They prescribe physical therapy
and exercise that worsen patient outcomes. They don’t have specialists
to send patients to, and they fail to diagnose the disease.
There
are some case definitions that are very broad, where the only criteria
is that patients have six months of fatigue and a few other symptoms,
and others, like the Canadian Consensus Criteria that are concise. But
the multiple definitions and the overly broad definitions are causing
clinician and researcher confusion.
When looking at
research in your study we recommend that you reject all research that
focuses on, or only requires, chronic fatigue. Those studies do not inform you on our illness. They inform you on a symptom of many diseases.
Some
of you may think that a broad definition would be better for patients,
because a more focused definition would limit treatment. This isn’t true
for ME/CFS because some of the treatments that are prescribed for
idiopathic fatigue are harmful for patients. For example, someone who
has depression should be exercising more to release endorphins, but
someone with ME/CFS will need to be careful to not exacerbate symptoms
by exercising.
We need you to develop a definition that
distinguishes between primary depression, idiopathic fatigue, and other
organic diseases. Why? Because we want the right treatment. We
need a definition narrower than Fukuda and Oxford to eliminate
idiopathic fatigue and primary depression, but balanced enough to
include patients that represent a proper cohort.
The case
definition drives correct diagnosis, drug trials, classification,
disability assessment, research, and will lead to a proper name.
Q&A
No Questions
Mary M. Schweitzer, Ph.D., Wisconsin ME/CFS Association, Inc. (
Video) (
Transcript)
Key message:
This is a national public health catastrophe. We need to address it
with urgency, not by going back to the drawing board 30 years ago.
Thank
you for allowing the Wisconsin ME/CFS Association time to speak; Pat
Fero is not here but we worked on this presentation together.
We
have known about Myalgic Encephalomyelitis since 1934 (when it was
called atypical polio); it was classified as a neurological illness by
WHO in 1969.
In the mid-1980s, a series of mysterious cluster
outbreaks of the disease occurred around the nation. At first, because
many cases seemed to start with a bout of EBV, they called it “Chronic
Epstein-Barr Virus,” or CEBV. But common thinking at the time was that
you had an acute case of a virus, and then you were immune to it.
Barring something like AIDS, there could be no chronic EBV. NIH decided
this had nothing to do with the immune system - and that it had nothing
to do with EBV.
NIAID's EBV specialist, Stephen Straus, who
coined the name CFS in 1986, decided that the disease was somatic (the
physical expression of a psychiatric problem) – the result of depression
and/or stress. For the next three decades, what little funding NIH
allocated went to fatigue studies or studies of stress hormones. As for
cluster outbreaks, it was decided they were outbreaks of friendly
diagnoses.
At CDC, the first demographic efforts came up with a
figure of 10-50,000 patients with CFS, all white upper middle class
women. Critics noted that the method CDC used was to ask physicians for
information about patients they saw with CFS, which heavily tilted the
data set towards those with the means and determination to find someone
who could diagnose and treat them.
In 1999, Leonard Jason and a
team at DePaul estimated that roughly 800,000 American adults probably
had the disease, and the disease affected all income groups and all
ethnicities. This estimate has been in use ever since – today, the
DePaul estimate would put the number of patients closer to 1.3 million.
In
2003, Canada adopted its version of ICD-10, which included CFS, along
with M.E., in neurology. A committee was convened of clinician experts,
including several from the US. The result is called the Canadian
Consensus Criteria and it does an admirable job of capturing the
complexity of this illness.
In 2004, CFSAC recommended to the
Secretary of HHS that the US adopt the Canadian Consensus Criteria - and
that's when we found out that money allocated to CDC to study young
people had been misused.
The money had been spent on closed
annual meetings at a resort. According to Dr. Reeves, they had created a
new definition for CFS (the “New International Definition”). Comparing
the Canadian criteria with Reeves' questionnaires, Jason found that
Reeves lost the bottom 30% of patients, while inappropriately including
patients with primary mood disorders
Researchers never used the Reeves questionnaires. The funds and the time spent were wasted.
M.E.
experts desperately need funding to replicate and further new research
on exercise physiology, immunology, virology, genomics, and intricate
metabolic research
. Please do not repeat the errors of the past – do not waste money on something that researchers do not want and will not use.
A
study published in PLoS ONE just over a week ago showed that 3/4 of CFS
patients had a deficient EBV-specific B and T-cell response. It appears
the dismissal of EBV as having a role in the disease was premature.
Recent
research has also shown that 80% or more of CFS patients suffer from
chronic infections of CMV, HHV-6, and/or HHV-7. There are new studies on
Coxsackie B.
Patients have been found to have abnormal natural
killer cell function, abnormal 37kDa Rnase-L, and abnormal cytokine
functions. They have abnormal SPECT scans and CPET tests
With so
many ongoing research projects, is it any wonder that 50 experts signed
a letter asking HHS not to spend one million on this study? If you
create a new, more heterogeneous definition and name - let's say,
"Multi-system disorder," will applications for NIH research funds and
NDA applications require that the researcher meet the new definition?
That would set research back terribly.
Now that scientists are
again making great breakthroughs, we do not need to descend yet again
into a name that implies this is a poorly understood and vague illness
having something to do with pain, fatigue, and sleep. We did not need
the detour into CFS, and we do not now need a new detour into something
like Multi-symptom Disorder.
We need CDC to come out against
efforts to portray this illness as psychosomatic, or“factitious
illness,” or “factitious illness by proxy,” a euphemism for the
discredited Munchausen’s Syndrome by Proxy.” We need CDC to stop
suggesting exercise programs.
The government needs to work WITH the experts to find ways to use the biomarkers that have been found,
to explain to the world the scientific discoveries that have been made,
to fund large studies to confirm or deny the smaller ones. M.E. is NOT
a mysterious disease. There is a great deal that is known about it.
Listen to the experts.
This is a national public health
catastrophe. We need to address it with urgency, not by going back to
the drawing board 30 years ago.
Q&A
No questions.
Carol Head, CFIDS Association of America, President and CEO of the CFIDS Association of America (
Video) (
Transcript)
Key
message: Patients wait for years, and see many doctors, before they
obtain a diagnosis. We believe that the Canadian Consensus Criteria can
be optimized as a clinical case definition by applying a standardized
methodology, validation of criteria, and nationwide dissemination to
health professionals.
Our involvement in this IOM
process stems from our desire to inform the regulatory framework and to
accelerate approval of ME/CFS therapies. The development of safe and
effective treatments for ME/CFS requires strengthened,
uniformly-accepted criteria that can be used consistently by
researchers, clinicians and patients. The lack of uniformly-accepted
clinical diagnostic criteria is one of many reasons for the slow
progress against this illness.
The FDA has stated that, “When
there is confusion, lack of consensus and no progress, go back the
Core.” The “core” regulatory framework for any disease is: core signs,
symptoms or decreases in specific functioning. The FDA recognizes that
for ME/CFS, we are still at the very beginning of understanding the
core.
We applaud HHS’s effort to address this critically
important issue. And at the same time, we anticipate that your work will
be extremely difficult, despite your best efforts, as the available
research is more limited than any of us would want.
Despite
disagreement about the best way forward, we all acknowledge the need for
evidence-based, broadly-accepted clinical and research tools that can
accurately include or identify all subsets of the heterogeneous group
that presents under any of the case definitions of ME/CFS. We believe
that the Canadian Consensus Criteria can be optimized as a clinical case
definition by applying a standardized methodology, validation of
criteria, and nationwide dissemination to health professionals.
This
month, the CFIDS Association conducted a survey to understand the
patients’ journey with ME/CFS. Of the 256 people who responded, 88% have
been diagnosed with ME/CFS by a physician. 32% indicated it took 1 year
or less to get a diagnosis, while 36% said it took between 1-5 years,
21% stated it took 5-10 years and nearly 12% waited more than 10 years
to be diagnosed. This is a desperately long time to live with pain and
impairment, without validation.
The
majority of patients saw more than 4 doctors to get that ME/CFS
diagnosis. This implies time lost, quality of life lost, demoralization
and precious dollars spent.
Further, the longer it takes to get
a diagnosis, the worse a patient gets and becomes more difficult to
treat. One of this panel’s charges – to get good diagnostic criteria
into the hands of all physicians - is imperative for faster diagnosis
and, therefore, better care.
Over and over again, patients told
us stories of delayed diagnosis, lack of treatment, a need to educate
the doctor, increased disability and even hostility due to physician
lack of knowledge and empathy. Patients spoke of the unfortunate
ignorance of some in the medical community.
This panel has an opportunity to rewrite that story.
(
Read the full survey results HERE.)
And
while it’s imperative to develop and disseminate consistent diagnostic
criteria, we know that time has not stood still. The few clinicians who
specialize in ME/CFS have developed solid intuition and are now treating
a few patients to mitigate their symptoms in some cases. This is far
from a cure and the situation is not ideal, but treatment is occurring
and should not be ignored. Wanting to better understand ME/CFS
clinicians’ intuition, in 2012 we conducted a survey asking 25
physicians – all ME/CFS experts – how they treated their patients’
symptoms. [Ms. Head showed a chart of some of the CFIDS Association’s
survey results.]
And going even further, good clinical
diagnostic criteria will lead to biomarker discovery. [Ms. Head showed a
slide of blood samples from the SolveCFS BioBank; the samples were
selected using the Canadian Consensus Criteria. The horizontal axis
showed 100 different genes and the vertical axis showed whether the
sample was from an ME/CFS patient or a control. The majority of ME/CFS
patients above the line were distinct from the majority of the controls
below. It’s noteworthy that these samples came from patients being cared
for by expert ME/CFS physicians – who use current clinical definitions
and diagnostic criteria – again demonstrating that clinical diagnostic
criteria is possible for ME/CFS.]
The credibility and authority
of this IOM committee is important to making ME/CFS widely recognized
and diagnosed throughout our nation’s medical community. And that will
help the one million Americans who struggle with this serious illness.
The success of this committee is of great importance; you have an
unprecedented opportunity in the history of ME/CFS.
Q&A
Lily Chu:
I wondered if you have any information about duration of illness, and
if people who have been sick for a longer period of time had more
difficulty getting diagnosed in the past than in recent times.
Ms. Head:
I am happy to provide you with the full results of the study, but I
don't think it will answer the question you asked. The survey is not
longitudinal and we did not explore how long an individual has had the
illness.
Pat LaRosa, New Jersey Chronic Fatigue Syndrome Association, Inc. (
Video)
(Transcript)
Key
message: We urge you to adopt the name Myalgic Encephalomyelitis (ME) -
a name that is appropriate to the severity of the disease. The name CFS
discourages proper coding, and creates numerous obstacles for patients.
Outside
the US, the name Myalgic Encephalomyelitis (ME) is accepted
internationally, including the World Health Organization (WHO.) In
recent years, ME has been accepted by US government agencies, using
ME/CFS as the name. Some references might be needed for a time to
redirect people to ME, but it is now time to make the change to the
single factual name.
In 2011, the name “Chronic Fatigue Syndrome”
was rejected by the international panel that wrote Myalgic
Encephalomyelitis: International Consensus Criteria. In this document,
ME is declared the appropriate name based on "research and clinical
experience that strongly points to widespread inflammation and
multisystemic neuropathology." It further states, “Using ‘fatigue’ as a
name of a disease gives it exclusive emphasis and has been the most
confusing and misused criterion.” No other disease adds fatigue to its
name.
We urge you to adopt the name Myalgic Encephalomyelitis (ME) - a name that is appropriate to the severity of the disease.
The
CDC defined and named CFS in 1988. At that time, the ICD-9 included ME
under “Diseases of the Brain.” There was no listing for CFS until 1991,
when it was added under “Symptoms and Signs/Malaise and Fatigue.”
Diagnostic
codes affect medical care and insurance benefits. The release of the
ICD-10-CM raises many concerns. The issue of psychiatric diagnosis for
ME/CFS may be even more likely with the publication of the Psychiatric
Diagnostic Manual 5 (DSM-5) which introduces a new psychiatric
diagnosis, Somatic Symptom Disorder (SSD).
In the ICD-10-CM, there two places that ME/CFS might be classified.
- G93.3 ME, CFS, PVFS – "Other Disorders of the Brain", "Diseases of the Nervous System Disorders
- R53.82
CFS - "Symptoms, signs, and abnormal clinical and laboratory findings,
not elsewhere classified": "Malaise and Fatigue" "Chronic Fatigue
Syndrome, unspecified"
The ICD-10-CM will perpetuate the
failure to properly classify this very real, organic illness. ME/CFS
will remain, at least partially, classified under "Malaise and Fatigue"
in the R code area. This vague and uncertain classification is
detrimental to patients, since it may encourage physicians and insurance
companies to misdiagnose and classify the illness as psychiatric.
G93.3
- acknowledges neurological pathologies, viral triggers and the
relationship of ME, CFS and PVFS. Studies have shown differences between
brains of people with CFS, healthy controls and those with
psychological disorders. These brain changes justify ME/CFS as a disease
of the neurological system. This G code enables patients to receive
proper diagnosis, treatment, and disability benefits.
Unfortunately,
it is not very well known to physicians and a patient may be coded as
having CFS in the R code, instead of ME/CFS in the G code.
The
ICD-10-CM is coordinated with the Centers for Medicare and Medicaid
Services (CMS) and electronic record keeping. Improper diagnosis can
negatively affect the response of doctors reviewing patients' records.
Social
Security disability programs use the name “CFS.” Many private long-term
disability (LTD) providers follow the SS guidelines and also use “CFS.”
Some LTD plans have two-year limits for "mental impairment." A
physician using the R code for the vague illness of malaise and fatigue
may possibly create an obstacle to obtaining LTD benefits. A diagnosis
of ME under the G code would be a definite improvement. The coding issue
circles around to the name issue.
These aspects, “name” and “coding,” are of major importance. Please consider these comments as you proceed.
Charmian Proskauer, Massachusetts CFIDS/ME & FM Association, president of the Massachusetts CFIDS/ME & FM Association (
Video) (
Transcript)
Key
message: A separate clinical definition for pediatric ME/CFS has been
developed and should be added to the list of clinical definitions that
you consider in your study.
I am here to speak on behalf of children and adolescents with this illness.
Children and adolescents are an important group to consider separately, not merely as a “sub-group” of the adult illness.
- The
clinical presentation, while variable, fits into patterns that are
described by the existing case definition for pediatric ME/CFS.
- The illness often follows mononucleosis — 13% of mono cases develop into ME/CFS.
As
in adult ME/CFS, symptoms can wax and wane. A child who arrives at
school and seems OK may need to go home by lunchtime. A pattern of
variable symptoms over time may be an indication of ME/CFS.
ME/CFS
is the most frequent cause of prolonged absence from school, and it is
this prolonged absence that often leads school officials down the wrong
path of falsely labeling ill children with “school phobia” or taking the
parents to court for Medical Child Abuse. Children with ME/CFS want to
go to school — and will tell you that if you ask them!
The adult
definition is not appropriate for children and youth, as the initial
presentation of symptoms may be quite different from that of adults.
Also it may not be appropriate to ask an ill child to wait until the
symptoms have persisted for six months (most of a school year) before
receiving a diagnosis which will allow helpful management and treatments
to be put in place.
While the onset, symptoms and course of the
illness in youth can be quite different from that in adults, as with
adults the symptoms vary in nature and intensity on any given day. This
variability can cause providers and others uninformed about the illness
to believe the symptoms are psychological.
Also as with adults,
the illness is usually prolonged, lasting from several years to 10 or
more. When a child changes schools, often the process of educating
school officials has to start all over again.
The range of
issues needing to be dealt with is also different — important aspects
for a child include educational needs and social development as well as
physical health. Addressing these issues involves the school, the
family, and the community, as well as providers of health care.
Families
with a chronically ill child already face many challenges. Caring for
an ill child who does not have a recognized diagnosis, or with a
diagnosis that family, friends, and school officials do not understand,
is especially difficult. Without a diagnosis, the more severely ill a
child is, the more likely the family will be under pressure from the
school and the threat of legal action against them.
Pediatricians,
at least in our state, have little knowledge of ME/CFS. When a school
nurse recognizes a child with symptoms suggestive of ME/CFS, it is
usually very difficult or impossible to find a pediatrician who can make
the diagnosis which would allow the child to receive needed educational
accommodations and begin appropriate treatment. Lacking a correct
diagnosis, there is a significant risk, especially in the case of a
severely ill child, that an incorrect diagnosis of Medical Child Abuse
or Munchausen Syndrome by Proxy may be given, and the situation may
escalate to the point where the child could be removed from the home or
legally required to undergo an inappropriate treatment.
On the
positive side, outcomes for youth, if good information, treatments, and
social and educational support are provided promptly, seem to be better
than outcomes for adults. However it should be noted that these studies
do not include the most severely ill children, so we do not know the
outcomes for them.
In summary:
- We urge this committee to give pediatric ME/CFS sufficient attention during your review.
- You should add the existing clinical definition for Pediatric ME/CFS to your scope of study.
- Your
plan to educate physicians should explicitly address pediatricians and
school nurses, as well as the providers of adult care. Pediatricians
need to be confident in diagnosing this illness as a physical, not
psychological, one.
- Please do not defer this; great harm is done every day to children and families due to this lack of knowledge.
There are three brief but very important points concerning your review of the research literature.
- Reviewers
need to focus carefully on the case definition used to select patients
for the study, since this greatly influences the results of the study. A
study group that is overly broad or heterogeneous will lead researchers
to incorrect conclusions.
- In any research which
discusses psychiatric symptoms (such as depression) in the study group, a
careful distinction must be made between pre-existing and post-illness
manifestations of the condition. Depression following the onset of
ME/CFS often occurs, as it does in many chronic illnesses. Any paper which does not clearly make this distinction is suspect and should be disregarded.
Such flawed “research” is responsible for much of the misinformation
about ME/CFS being a psychiatric illness, not a medical illness, leading
to recommendations of psychiatric care as the primary treatment instead
of attempts to treat the underlying medical condition.
- In
closing I want to point out that over the years at least some
mainstream journals have refused to even consider publishing papers on
ME/CFS, regardless of their merit. This has forced ME/CFS researchers to
sometimes seek less traditional avenues to publish their work,
especially in years past. Please do not overlook these contributions
just because they do not appear in the journals you may usually read.
Q&A
Nancy Klimas:
As someone who has dealt with a number of "Munchausen by Proxy" cases
in my clinical practice, I can't underscore how devastating it is to a
family to see their child literally seized from them. I had one child
who was forced into a foster care situation where they did morning
calisthenics before he was shipped to school, with devastating
consequences.
Theodore Ganiats:
I am intrigued by the idea of trying to diagnose children earlier. But
whenever you start diagnosing earlier, you'll have some false diagnoses.
Because, I'm .. obviously, if you take it to the extreme, and have it
be only one day instead of six months, then you're going to have
problems. If you wait six months you're going to have problems. So, the
question is if you have any data, or know of any data, on length of time
of symptoms, and.. uh.. how well that is correlated with a final true
diagnosis.
[Note:
Ms. Proskauer mentioned the existing pediatric definition in both her
written comments, as well as those made only a few minutes earlier in her
presentation.]
Ms. Proskauer: The existing pediatric definition, which was published by Lenny Jason and colleagues, suggests a three-month waiting period.
Gabby Klein, Phoenix Rising (Video) (
Transcript)
Key
message: ME is an organic, complex, seriously disabling disease, which
needs a definition at least as strict as the CCC or ICC. Myalgic Encephalomyelitis. (ME) should be the term used for the disease.
Thank
you for the invitation to speak on behalf of Phoenix Rising. We are a
non-profit patient-led organization which hosts the largest online forum
for ME/CFS patients.
We have enlisted our members to comment on
the question posed by the IOM in their study to recommend clinical
diagnostic criteria for ME/CFS:
“What is the most important aspect or information that this committee should consider throughout the course of the study?”
Phoenix Rising members have identified several points of focus:
- ME is an organic, complex, seriously disabling disease
- ME needs a definition at least as strict as the CCC or ICC
- ME is not a psychogenic somatoform illness
- Myalgic Encephalomyelitis (ME) should be the term used for the disease
ME is an organic, complex, seriously disabling disease
ME
is a complex, severely disabling disease involving multiple systems in
the body. It involves extreme muscle weakness, drastic loss of stamina,
cognitive dysfunction and viral symptomatology along with neurological
and endocrine dysfunction. Fatigue is only a small part and not
necessarily the most prominent symptom.
ME
renders half of the patients unable to work. A quarter of the patients
are left bedbound, some unable to feed themselves. Others have died due
to complications of ME. In the U.S. estimates show that there are
800,000 adults and children suffering from ME/CFS. This would mean that
200,000 patients might be listening to us from their beds. In addition,
this large group of disabled patients is a great strain on the U.S
economy. You might be surprised then to hear that in each of the past
ten years the NIH has spent less on ME than on hay fever.
ME needs a definition at least as tight as the CCC or ICC
Most
of the experts treating and researching ME have endorsed and are
currently using the Canadian Consensus Criteria (CCC). They have
recognized that by using post exertional malaise (PEM) as a hallmark of
the disease and mandating neurological and immune dysfunction, the CCC
best captures the patients who are suffering from this particular
disease.
Any new definition for ME must include PEM as a minimal prerequisite for the diagnosis of ME.
The
CCC were created to distinguish ME patients from those diagnosed using
broad CFS definitions such as the Oxford Criteria of 1991 and the Fukuda
Criteria of 1994. These definitions selected many who suffered from
vaguely defined idiopathic fatiguing illnesses. These broad definitions
have impeded serious research into the complex disease and have held the
disease hostage without a chance of effective recognition and
advancement.
Studies on the disease have shown that there are
testable biomarkers, such as the two-day cardio-pulmonary exercise
testing (CPET), which show remarkable abnormalities in ME patients. The
fact that PEM/PENE is a hallmark of the disease is no longer debatable.
Immune dysfunction has been shown, with multiple studies uncovering
defects in natural killer cells in ME patients. Neurological/cognitive
dysfunction has been shown by abnormalities in cerebrospinal fluid and
structural MRIs.
We therefore ask the panel that the population
of severely ill and disabled ME patients should be separated out from
the broad fatigue-based definitions, using a definition at least as
'strict' as the CCC or ICC.
ME is not a psychogenic somatoform illness
Terms
previously used to describe the syndrome CFS, such as “depressive
mood”, “deconditioning”, “somatoform”, “personality disorder”,
“childhood abuse”, “hypochondria”, “laziness”, “malingering” or
“unwellness” do not apply to the organic disease of ME.
Other
illnesses such as Asthma, Stomach Ulcers, Multiple Sclerosis, and
Inflammatory Bowel Disease were thought as ‘psychosomatic’ until a known
and identifiable physical element was discovered.
Any research into ME as a psychological, psychogenic or functional disorder should be disregarded.
Attempts to give a psychiatric or somatization explanation for our
illness have utterly failed to explain the realities of the condition,
and are incompatible with the details of its progression.
Myalgic Encephalomyelitis (ME) should be the term used for the disease
The term “Chronic Fatigue Syndrome” (“CFS”) is not appropriate for this disease.
No disease should be characterized by a symptom shared by many healthy people.
Patients with different illnesses and different clinical needs are
mixed together under a single ‘CFS’ label. CFS as defined by Fukuda may
include people suffering from depression and idiopathic fatiguing
illnesses. This leads to confusion in clinical settings often leading to
chronic neglect.
ME, as described by the CCC, has a distinct and
definable nature. It best describes our members’ complex and specific
symptoms of muscular and neurological dysfunctions.
We
would like you to know that our members have expressed many concerns
about this study, especially the fact that many members of the panel, as
currently constituted, lack appropriate expertise in the treatment or
diagnosis of this disease.
In addition, there is a
large group of stakeholders, experts, advocates and patients who are
calling for a cancellation of this study and the adoption of the CCC
now. Their concerns are due to the fact that they believe that a new
definition can come only from a panel of knowledgeable experts. Some
have questioned the legality of the contract as well as the lack of
transparency in the actions of HHS. These feelings have resulted in
their boycotting these proceedings and choosing not to take part.
Please
keep in mind that the recommendations that this study will produce will
directly affect the lives of millions of patients worldwide. We hope
that you will take the patients’ voice to heart and that you will
continue to invite us to be part of the process.
Q&A
No questions.
Jennie Spotila, OccupyCFS (
Video) (
Transcript courtesy ME/CFS Forums)
Key message: The definition of ME/CFS must be both accurate and precise.
You
are facing an enormous challenge, the result of decades of inaccuracy
and imprecision in the definition and diagnosis of our disease. I
believe the one thing you must keep in mind throughout this study is to
be as accurate and precise as you can in order to create sensitive and
specific diagnostic criteria.
Multiple names and definitions have
been used in the last 30 years, and you should go back as far as the
1950’s to examine the descriptions and definitions of ME. Each
definition carries with it a rationale, an associated description of the
disease, and a set of limitations. Prevalence rates vary because each
definition draws a different circle around – or within – a patient
population.
Another challenge is that there are no gold standard
biomarkers for the heterogeneous Fukuda population. Despite that, we are
very close to establishing one or more diagnostic markers, and a number
of you have been responsible for that important research. But the
breadth and weaknesses of the case definitions have been a huge obstacle
to achieving this.
Finally, as you no doubt realize already,
there are competing schools of thought on case definition. Does the
mixed bag of definitions describe one disease or more than one disease?
How do we identify a more homogenous cohort? What should we call it? Who
is competent to diagnose it? We do not agree on the answers to those
questions because there are no easy answers.
Potential Pitfalls
As in any controversial subject, there are potential pitfalls that could complicate your work.
First and foremost is the fatigue paradigm.
Severe fatigue lasting longer than six months is an extremely common
symptom experienced by 4-5% of the general population. One study of
newly diagnosed MS patients found that nearly 30% had been diagnosed
with severe fatigue or CFS in the three years prior to the MS diagnosis.
Because it is based on fatigue, the Fukuda definition has been used as a
wastebasket for people with unexplained fatigue, consigning them to
medical purgatory when they may have more treatable conditions.
It
might help to draw a comparison to chronic pain. While pain conditions
are researched across diseases to identify common mechanisms and
treatments, we do not define and diagnose them that way. We do not
diagnose fibromyalgia, vulvodynia, and migraines as one disease that is
subtyped based on where the pain is located in the body because chronic
pain is simply too common a symptom. I believe the same is true for the
fatigue paradigm. Severe fatigue is simply too common a problem to form
the basis of an accurate and precise case definition, regardless of how
you try to slice it into subtypes.
Second, it is imperative to recognize which definitions and exclusionary conditions were used in each research study. If you do not take this into account, you will not be able to sort through the evidence with any resulting clarity.
Third, I believe it would be a mistake to lose sight of the impact your report will have in the real world.
As Lori and Pat have said, you will have an impact on research and
clinical trials. You will have an impact on policy. You will have an
impact on clinical care. The stakes are very high, but there is a
solution.
Accurate and Precise
I believe
it is possible to create diagnostic criteria that are both sensitive and
specific for ME/CFS. To do so, you will need to be as accurate and
precise as possible.
Start by setting aside the fatigue umbrella,
because severe chronic fatigue is common to many diseases, and should
not be used as the foundation of a precise case definition. Instead,
focus on the core symptoms of disease. Across multiple studies and
surveys, post-exertional malaise – not fatigue – has emerged as the key
and most disabling feature of this disease. PEM is an exacerbation of
multiple symptoms after mental or physical activity, and can be measured
through both self-report instruments and objective biological tests. It
is also notable for its use in distinguishing between people with
ME/CFS and those with major depressive disorder and other illnesses with
a fatigue component. Another core symptom identified in the research is
cognitive impairment, particularly memory and concentration problems.
Unrefreshing sleep and autonomic symptoms also rise to the top. There
are many other symptoms as well, but your diagnostic criteria will be
more meaningful if you focus on the core features.
Another
approach that will help you succeed is to use frequency and severity
thresholds, in addition to a list of symptoms, to identify a more
precisely defined patient population. In one study, 34% of healthy
controls reported at least 4 out of 8 Fukuda secondary symptoms. When
higher cutoff thresholds for frequency and severity measures were used,
that number dropped to 5%. If you combine a core symptom set with
thresholds for frequency and severity of those symptoms, I believe you
will be able to establish accurate diagnostic criteria that have high
sensitivity and specificity.
Precision is the most important tool
at your disposal, and yet it will not remove all ambiguity and
uncertainty because there is so much we do not know about this disease.
Three hundred years ago, cancer could only be diagnosed when it advanced
to externally palpable tumors. The definition of cancer has evolved
from the most severe and easily detected form of the disease to the
sophisticated detection and subtyping methods of today. Precision based
on what we know is the first step.
Conclusion
In
summary, you face the enormous challenge of creating diagnostic
criteria for a disease with conflicting case definitions, no gold
standard biomarkers, and competing views about how to define the
problem. You must avoid multiple pitfalls, including the high prevalence
of the symptom of chronic fatigue in the general population and the
effects of those competing case definitions on research results, and
never lose sight of the very high stakes we face. But there is a way for
you to overcome all of these challenges, and that is by being accurate
and precise.
If you set aside the fatigue umbrella and focus on
the core symptoms of this disease, if you establish frequency and
severity threshold requirements, and if you recognize that your
diagnostic criteria will be part of an iterative process of refinement,
then I believe you can create diagnostic criteria that will advance
clinical care and research, instead of putting us further behind: a
definition that is sensitive and specific to ME/CFS.
