The following is the written testimony of Dr. Joan Grobstein for the upcoming CSFAC meeting this week in Washington DC. Dr. Grobstein will be offering her verbal testimony on Wednesday June 13, 2012. Dr. Grobstein has testified in front of this committee for a number of years now. A video of her testimony in 2010 can be found
here. Please note that there is a disclaimer at the end of her written testimony.
CFSAC June 2012 Written Testimony
Joan Grobstein, M.D.
This is a very hopeful time in the history of Myalgic
Encephalomyelitis and the mis-named Chronic Fatigue Syndrome. I will call this disease ME/CFS, for
lack of a better term. Despite
many obstacles, we have come a long way in the past few years, and the way
forward is beginning to become clearer.
We now have most of what we need
to make significant and rapid progress. We have a workable definition. Thanks to researchers at the Pacific Fatigue Laboratory and
the University of Utah, we have two measures of the most characteristic and
disabling symptom, post-exertional malaise and exhaustion. We have information about several
treatments that are not only effective in at least some patients, but also help
to clarify the etiology or etiologies of the disease. Rituximab and antivirals as well as less well-studied but
effective treatments have changed the game. We can begin to imagine a future very different from our
past, a future where patients will be quickly diagnosed and presented with a
choice of therapies based on solid evidence of efficacy.
What
is holding us back from this brighter future? What we are lacking is
support from the scientific and medical communities and from our government. We need to change our current
reality. In order to do this we
must step back from gazing at our bright future and re-enter the darkness of
our past. We need to examine the
scientific and medical arms of our government and challenge them to make
necessary changes based on the information that is now available.
What
is our current reality and what could be our future? It is best to examine our current obstacles agency by
agency, acknowledge the past reality and look for a way forward.
CDC
The
CDC has created two definitions for this disease which effectively make it
impossible to study. The empiric
(2005) definition has been shown to be so flawed that even the CDC appears to
have abandoned it, although they are still spending scarce research dollars to
try to justify it. Briefly, that
definition is overly broad; it
includes many people who do not have ME/CFS, so any research is unlikely to
come up with significant conclusions about people who do have ME/CFS. The more commonly used Fukuda (1994)
definition also has at least two significant flaws: it does not make the cardinal symptom, post-exertional
malaise, mandatory for the diagnosis, and it requires patients to be sick for
at least six months before diagnosis.
This is like an insurance company sending an adjustor to the scene of an
accident six months after the accident occurred. There will be no evidence that the accident occurred, so it
will be easy to deny coverage for an accident that never occurred. Because of the Fukuda definition it is
unlikely that a single pathogen, if it exists, will ever be found. It is also unlikely that a toxic cause
for an immune deficiency could ever be found, because a toxin will likely
disburse in six months. The
Canadian Consensus definition and the International Consensus definition are
both acceptable definitions. The empiric and Fukuda definitions are not
acceptable definitions.
The
CDC has recently arranged a series of phone conversations with advocates. One of the stated goals of these
conversations was to increase a sense of trust between the CDC and the patient
community. There are many reasons
that patients do not trust the CDC, not the least of which is their failure to
adequately investigate past outbreaks.
If the CDC continues to use the empiric or the Fukuda definitions it is
highly unlikely that any outbreaks will be reported or investigated. There is evidence that outbreaks are
continuing to occur, at least in families but probably also in communities. However, because of inaccurate definitions,
people are not getting diagnosed with ME/CFS for at least six months, if at
all. By the time they are
diagnosed any chance of finding the original pathogen or toxic exposure (the
most likely causes of geographic outbreaks) is gone. If the CDC wishes to
regain the trust of the patient community they must abandon the Fukuda and
empiric definitions. We cannot
“agree to disagree” on this issue, as Dr. Unger has suggested. The CDC is still spending our tax
dollars on studies to justify these definitions.
Another
way for the CDC to regain the trust and respect of the patient community is to
adopt the Canadian Consensus definition of ME/CFS (or the similar International
Consensus definition) and to use it to begin doing the epidemiological,
longitudinal and laboratory research that is necessary to address the massive
personal and financial cost of this disease to the American economy.
The
CDC is also spending very scarce research dollars on studies that have no
possibility of helping patients or protecting communities from this
disease. Rather than working to
discover what is helping patients to recover or where the sickest patients are,
the CDC is spending money to document that people who feel very sick are not
particularly interested in card games. This would be laughable, if we could ignore the people with
ME/CFS who are unable to leave their homes and are receiving no medical care at
all and no help from CDC research.
The CDC should be spending its
money (our taxpayer money) on epidemiological and longitudinal studies that can
lead to diagnostic tests and therapies and that can protect our communities
against this disease. That is
their mission.
What can the CFSAC do to facilitate more
effective research at the CDC?
It can ask for semiannual reports of what projects are ongoing at the
CDC and what are the budgets for each.
In 2009 one of its recommendations stated that “the CFSAC rejects the
empirical case definition”. It is
vitally important that it repeat this
recommendation and emphasize to the Secretary that the Canadian and Consensus
definitions are far better definitions than either the empiric or Fukuda
definitions. There is no time
to waste continuing to use faulty definitions. These definitions are damaging to patients. Finally, it can ask to have input into
a new 5 year plan for the CDC which includes epidemiological and longitudinal
studies.
In
addition, the CDC website continues to disseminate false and misleading
information to physicians and the general public. CFSAC should ask that
the Toolkit be removed from the website immediately.
NIH
The
NIH funding level for this disease is 5 percent of the funding level for
multiple sclerosis, a disease which affects half as many people as ME/CFS. There
should be a Request for Proposals with a dollar amount attached that is at
least equivalent to the amount spent on MS. There are several obvious studies that need to be done right
away. The Lights have received
funding to continue their study of gene expression changes associated with
post-exertional malaise. Other
laboratories should be funded to attempt to reproduce their findings, with the
goal to develop and validate a diagnostic test. In addition, money should be available to the Pacific
Fatigue Laboratory to validate a second diagnostic test, and there should be an
additional study to see if these two modalities correlate. Dr. Lipkin is funded to look for a
single pathogen, but funding should be made available to examine the possibility
that more than one pathogen may act synergistically to initiate this
disease. We also need studies to
see how orthostasis is associated with post-exertional malaise. Can the Lights gene expression changes
be seen after prolonged standing rather than exercise? Following the success of rituximab
therapy in some patients, it is also obvious to look again at the immune system
and try to figure out why rituximab works. In addition, cognitive dysfunction is one of the most
disabling aspects of ME/CFS. Can
cognitive dysfunction be correlated with orthostasis, post-exertional malaise
&/or viral infection? These
possibilities are only the beginning.
There are numerous other questions that must be studied, remembering
that results will only be interpretable
if the patient population is appropriately defined.
The grant review process for ME/CFS at the
NIH needs to be improved. It
is hard for anyone outside the scientific community to fully appreciate the
problems in this area. However, it
is clear from comments made at CFSAC meetings by multiple researchers, many
very experienced, that the process is not functioning well. An inquiry by the leaders of the NIH
into why this is happening and how to make improvements is necessary.
ME/CFS
does not belong in OWRH. It is not
a “woman’s disease”. It should be
housed in one of the Institutes, probably NIAID or NIND. Again, direction and involvement are
needed from Dr. Collins and the leaders of the Institutes to find the best
place for ME/CFS research to be centered.
There are certainly other multi-system diseases studied at the NIH that
can serve as examples.
Accountability
for funding of ME/CFS projects at the NIH needs to be improved. Pat Fero and Charlotte von Salis have
found evidence that somel money allocated for ME/CFS is actually being used to
study other diseases. Of course,
this is not acceptable, especially given the relatively small amount allocated
to ME/CFS research.
What can CFSAC do to promote a more
effective program for ME/CFS at the NIH? Ask for reports at every meeting on the number of grants,
the amount of money allocated and the topics studied. Convene a panel of people who have experience with the NIH
grant process to make recommendations about the ME/CFS grant process and make
sure that the recommendations are implemented. Make sure that the NIH has a process in place to ensure that
funding for ME/CFS is actually being used for ME/CFS projects. Ask
for a specific, appropriate allocation of funds. Insist that responsibility for ME/CFS be housed in one of
the Institutes, and that the highest officials at NIH be involved in and
committed to the decision about which Institute is appropriate. Finally, the NIH must insist that all
funded studies use the Canadian Consensus or International Consensus
definition.
FDA
There
is apparently only one drug currently under consideration for the treatment of
ME/CFS at the FDA, and it has been under consideration for several years. Part of the problem has been the
definition of the disease, which has made it difficult to demonstrate positive
benefits from drugs. It is
important that the FDA insists that the
Canadian or International Consensus definitions be used in drug trials. It is also important that the FDA
expedite approval for diagnostic tests as they are developed with NIH funding.
One
of the obvious problems at the FDA is that ME/CFS has been placed in six
different divisions over the past several years. This has meant that no division has developed the expertise
to properly evaluate therapies, diagnostic tests or devices for ME/CFS. Like at the NIH, involvement at the
highest levels of FDA is needed to find an appropriate, permanent place for
issues related to ME/CFS.
FDA
action is dependent on the activity of researchers funded by the NIH, CDC and
other groups who find possible therapeutic agents and diagnostic tests relevant
to this disease. FDA needs to be
prepared to handle requests for evaluate them. CFSAC can encourage
preparation by insisting that the FDA use an appropriate definition in its
evaluations and have a process to expedite evaluations. ME/CFS patients have been waiting for a
very long time.
Other Issues
It
is very important that the CFSAC provide input about the new DSM-5
criteria. I am no expert on this
matter and cannot speak about it in any informed way. I I refer you to Mary Dimmock and Suzy Chapman, who
understand this issue . I urge
CFSAC to formulate an appropriate
comment about the DSM-5 as one of your recommendations at this June, 2012
meeting. This is very
important to patients.
It
is important to note that CFSAC itself has significant problems at this
time. According to the website there are four vacant seats on the
Committee, including the post of Chairman. This is a huge problem. Without a Chairman who is communicating with the Secretary
and with Dr. Koh? How can there be
any continuity or institutional memory of all that patients and other experts
have taken the trouble to communicate to the Committee if seats are
unfulfilled? There could be four
additional experts providing input to the Committee? Who is responsible for ensuring that there are a full
complement of members. At this
point, it is hard to believe that there is any commitment on the part of our
Government to provide or listen to advice about ME/CFS.
In
addition, it is important to note that the process involved in attending
meetings and submitting testimony is getting more opaque and difficult for
patients. It is inherently
difficult for patients to attend meetings, and it behooves the staff to make it
as easy as possible. The meeting
this time is one month later than usual, and there was very late notification
of how and when to submit testimony.
There was inconsistency and confusion about the date for testimony
submission. The agenda was not
posted by the promised date of June 4, 2012, making it difficult for patients
to make plans. When I notified the
staff that I intend to attend the meeting I received no acknowledgement,
despite information that seating would be limited. I also received the following instruction about the meeting:
Any object carried by the visitor that is deemed
inappropriate will be confiscated and disposed of by the security staff (italics mine). I asked for advice about what objects would be considered
“inappropriate” and have received no reply. This appears to violate my constitutional right to
protection from unreasonable search and seizure. This is hardly a friendly atmosphere for an exchange of
ideas between a government and its citizens about a serious disease.
I
started this testimony with the idea that this is a time for hope. However, it is not surprising that
patients and their families feel quite discouraged at this point. It seems as though we are still dealing
with many persistent problems:
despite the State of the Knowledge meeting, which occurred more than a
year ago, total NIH funding for ME/CFS continues to be much lower than diseases
with a similar impact on quality of life.
The number of studies funded is also low. There is no plan for progress, no consensus on what are the
most promising avenues for study.
While patients with the means to get to a doctor who offers effective
therapies are quite likely to
improve now, many patients still struggle to even get a diagnosis and cannot
find a knowledgeable doctor or cannot get to one or cannot pay for one.
Why
is this? We don’t have the information we need to develop an approach to ME/CFS
that can be taught to large number of doctors. There is no support for clinical research. The doctors who are beginning to know
how to treat this disease have no funding for data collection. They are inundated with patients. They have waiting lists that are years
long. They have no time to publish
their findings, and no financial support to do so. Where is our government? Where are our scientific and medical leaders?
Progress
in the diagnosis and treatment of ME/CFS is within our grasp. We have the tools, foremost among them
diagnostic criteria, diagnostic tests and effective therapeutic agents. It is time to move forward. Thank you for your dedication to the
effort to improve the lives of people with ME/CFS.
Disclaimer:
"I am posting this testimony, because there has been little
information available about the upcoming CFSAC meeting. In the
testimony I say that the CFSAC hasn't announced the new members and
Chairman or the agenda. That was true when I wrote it--there was
nothing on the website until shortly after the deadline for submitting
written testimony. All of the information is there now. CFSAC did
not adhere to its own stated deadline to post the agenda by June 4.
This failure made it impossible for people to respond to the specific
issues on the agenda in their written testimony. Also, we have no
information about what expertise the new members bring to CFSAC, so we
don't know how much we have to educate them to bring them up to speed.
My testimony, as always, does not address all the important issues.
There is not enough room in five pages of written testimony, or in
five minutes of oral testimony, to address all the issues. By posting
this testimony early on the internet, it is my hope that other people
who may be providing testimony in person at the meeting will be able
to elaborate on these thoughts and/or address other extremely
important areas of concern. Because the definition issue is an agenda
item on the afternoon of the second day, I think it is important that
everyone who provides testimony in any form include at least a simple
statement that both the empiric and Fukuda definitions are not
acceptable definitions, and that patients support the Canadian and
International Consensus definitions."