To: the United States Secretary of Health and Human Services (HHS) Kathleen Sebelius
Subject: Please, stop muddling with definition, start serious funding of biomedical research.
Date: 28 October 2013.
Dear Secretary Sebelius,
I was happy for some time ago (in 2010?) when I heard that the Chronic Fatigue Syndrome Advisory Committee (CFSAC) of U.S. Department of Health & Human Services (HHS) was going to adopt the Canadian Consensus Criteria (CCC) from 2003. Now I have heard that HHS have changed their mind and plan to create a new definition without involving the real experts in myalgic encephalomyelitis (ME), i.e. patients, clinicians and researchers.
I can not see how HHS would be able to come up with a better definition, especially if well established serious researchers or clinicians for ME would not the ones that are responsible for the work of creating the definition.
In any case, please do not add any more mess to terminology, by starting to change the meaning of established terms. Although CFS can be claimed to be unspecific, it has a definition made by CDC many years ago. It has been referred to in thousands of scientific articles and it is unwise to change the meaning of it. ME was first introduced as a term in the 1950's, so it has a long history and the name should be protected from having its meaning changed. If HHS come up with some new definition it should neither be called CFS nor ME, because it would hijack terms that have been used historically. If these terms would be hijacked, then it would be more difficult to understand what is referred to, and an unwanted mess is created. The scientific method is based upon categorizing and systematizing things, and staggering terminology will make the house of cards fall.
According to statements by CDC, patients with ME should not have a CFS diagnosis, because ME is accompanied with neurologic and muscular signs. Other typical symptoms in ME are postexertional relapse, circulatory impairment, ortostatic intolerance, cerebral dysfunction, intolerances to foods and drugs, sensory hypersensitivity, allodynia, 'feeling awful' (severe torturing malaise), and pain. I think that ME and CFS should have separate research budgets. I am a stakeholder for ME, because I have ME and I am head of an organisation for patients with ME in Sweden, and as such I ask for strong funding of biomedical research into ME. I have no firm opinions on the budget for CFS, because I am not directly a stakeholder for CFS (where ME is an exclusionary condition).
The International Consensus Criteria (ICC) from 2011 is very similar to the Canadian Consensus Criteria, and I think it is a small further improvement, but I think either will do a good job serving as a definition for ME, until we get clinical biomarkers for the disease, and likely also for subtypes.
I think resources should not be wasted on creating new definitions, instead they should be directed into biomedical research into ME. There are so many interesting research results that have to be confirmed by independent research teams. Also, there is research in many areas goes painfully slow due to the very limited budget for biomedical research into ME. The enigma of AIDS was broken after starting to heavily fund such research, there are now several drugs that give the patients a long and healthy life. The funding of ME is minuscule compared to AIDS and if the time between discoveries is inversely proportional to funding then we will indeed have to wait for a long time; 500 years according to my calculations, because ten years of AIDS/HIV research corresponds to 500 years of ME research, knowing that the funding of ME is 50 times lower.
Remember that ME is not only an extremely disabling condition. It is also accompanied by hard to treated pain, especially as the patients are intolerant to so many drugs. The patients do not only loose their lives because they can not participate or think; their lives are converted to prolonged severe suffering that can not be eased. Therefore, I think it should be a prioritized condition for biomedical research.
Recent research confirm that ME is associated with defects in for example mitochondria, muscle cell metabolism, brain function, immune system and cardiovascular system. The hallmark symptom "post exertional relapse" has a somatic basis as receptors, mRNA and cytokines (Alan R. Light) have pathogenic response. A repeat physical exercise separated by 24 hours result in abnormally decreased oxygen consumption the second day (Christopher R. Snell) also confirm that there is physical basis for "post exertional relapse". The CCC and ICC do have "post exertional relapse" as mandatory criterion which is very important.
There is an urgent need to study post mortem tissues because one need samples from for example brain, nervous system, cardiovascular system, immune system and intestines. It is unbelievable that the over 50 year old question, if there is inflammation of brain or spinal cord, has not yet been answered. In order to get an answer, one has to collect post mortem tissues. Also, researchers in the area of infection, need several tissues that are harvested post mortem.
I can really not see the motive behind changing the definition of ME. As far as I can see, neither researchers, clinicians, nor patients have expressed the need for coming up with a new definition. I think one has to have a well motivated reason for changing the definition. At the present time there is no clear direction in which the definition should be changed. In order to initiate a work in the definition of ME, I think there has too be many people that require the same thing. Such as for examples if researchers have found that the definition is too unspecific so too many patients are included, and therefore research is ineffective because cohorts are too heterogeneous. But for the time I think that there is a great consensus that the International and Canadian Consensus Criteria, are strict enough.
Actually, I think that the HHS initiative of changing the definition seems unworldly (detached from reality), knowing that we might be on the verge of a breakthrough in ME research. Research of Øystein Fluge and Olav Mella have shown that rituximab is an efficient treatment among 67% of the patients. Why does HHS not respond to this discovery and start up a clinical trial? How come it would be more interesting to muddle with the criteria, in a time where nobody has expressed a real need for it, and in a time where we are on the verge of biomarkers and effective treatments? Some studies have presented that there are subsets by biomedical measurements. It is probably very unlikely that muddling with the definition at this time will yield any further clarity at this time.
What would be more productive in increasing the understanding, is to use the different methods for distinguishing subsets on the same group of patients (cohort) and investigate how the subsets of the different methods relate to one another. Some examples of discovered subsets are in papers of Alan R. Light and Jonathan Kerr. Some examples of biomedical measurements are gene expression, mRNA, NK-cell function, cytokines, and pathogens. Jesús Castro-Marrero has shown that mitochondrial dysfunction may be a differential marker between ME and fibromyalgia. Consequently, my suggestion is that HHS fund a project where a cohort of manageable size of well defined ME-patients are studied by several methods, and that the results are saved in a database, enabling to search for relationships. This will enable a much deeper understanding than occasional fishing expeditions looking only on at at parameter a time. Pathways of pathogenic response could be found on an individual and subgroup level. The size of the cohort should not be too large because then it will be too expensive to make a deep and detailed investigation of each subject, and not too small because then it will not be able to distinguish subgroups or perform statistic analysis. Maybe around 200 patients would be appropriate to begin with in order to start up this kind of research. The same group can be used for longitudinal research.
I live in Sweden, but the USA is very important and influential when it come to medical research and influence, therefore what happens in the USA has influence over the whole planet. The USA has a large research budget and a culture of performing high quality medical research. I hope that the USA will pursue serious biomedical research into ME with the aim to understand the pathophysiology much better and to create effective treatments. The USA has historically been important in driving medical research forward while some of the European countries, have not been able to respond to challenges in an effective and coordinated manner. I hope the USA will pursue the challenge in the area of biomedical research into ME, because I and many other persons in Sweden are hoping for better lives, and we realize that we depend on the USA very much because here in Sweden the decision makers are passive.
This email is only very short because I have written before in this subject. Please, study my previous documents, especially the last in the list below directed to CFSAC in 2009.
Thank you for taking your time to take part of my opinions!
Sincerely, Kasper Ezelius, Örebro, Sweden, Europe
My previous documents in chronological order
Use the Canadian criteria 2003 for CFS in the USA.
Kasper Ezelius. June 22, 2008:
http://info.me-cfs.se/dok/080622-Use-Canada-criteria-in-USA.pdf
Resolution in order to make cohorts less heterogeneous.
Kasper Ezelius. 1st of September 2008.
http://info.me-cfs.se/dok/080901-mod-cfs.pdf
How to categorize ME and CFS.
Kasper Ezelius. 23 October 2008.
http://info.me-cfs.se/dok/081023-categorize.pdf
CFS is no longer CFS, and it was never ME.
Kasper Ezelius. 5 December 2008.
http://info.me-cfs.se/dok/081205-cfs-no-longer-cfs.pdf
CDC empiric definition for CFS from 2005.
Kasper Ezelius. September 28, 2009.
http://info.me-cfs.se/dok/090929-CDC-CFS-Reeves-2005.htm
Input to the CFSAC Meeting October 29-30, 2009
Kasper Ezelius. October 6, 2009.
http://info.me-cfs.se/dok/091006-CFSAC-USA.pdf