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CDC Study Must Include CPET, NK Cell and Viral Testing, Advocates Insist

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Mark Berry invites readers to join 11 organizations and 31 advocates and write to the CDC, asking them to include appropriate medical tests in their multi-site study.

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The historical approach of the US Centers for Disease Control and Prevention (CDC) to the study of ME/CFS has not been universally well-received - and that's an understatement. The majority opinion of the ME/CFS community seems to be that the CDC has had its head stuck in the sand, as far as ME/CFS is concerned, ever since CDC epidemiologists finally rolled into Lake Tahoe to investigate the outbreak there in 1984. But in recent years there have been some promising signs that the CDC may at last be starting to take the disease more seriously.

The CDC's multi-site, multi-phase clinical assessment study aims to “describe the differences and similarities among CFS patients,” “improve how we measure illness domains of CFS,” “address the CFS case definition,” and possibly allow patients “to be sub-grouped to improve therapy and allow the underlying biology to be discovered.”

Such a large study, led by a federal agency, represents a major opportunity for patients, both in the United States and around the world. There is at least a chance that it might bring some much-needed clarity to the questions and problems surrounding case definitions and subsets which have dogged ME/CFS research for decades.

So it's a very important study for ME/CFS patients, and it's important too for the credibility of the CDC, so badly damaged in the eyes of the patient community by the scandal over the diversion of funds allocated for ME/CFS research - not to mention more than 25 years of failure to make meaningful progress in the study of an illness that blights the lives of millions of patients. The CDC study is already collecting a mountain of data - but in research, what answers you can find depends on the questions you ask, and the data you collect...and there, it appears, we may have a problem...


Missing Information

Although the study has already collected a vast array of data on clinical history and demographics, and patients have filled in a long list of questionnaires, so far there's been a worrying lack of tests that could help confirm biological abnormalities in ME/CFS patients. More worrying still, at the last CFSAC meeting in May 2013, Dr Unger appeared to indicate resistance to the idea of conducting the very tests that many consider crucial to understanding the nature of the pathology in ME/CFS.

Repeat exercise testing is considered by many to be the fundamental test necessary to confirm post-exertional malaise - widely seen as the cardinal symptom of ME/CFS - but is the CDC prepared to conduct the tests necessary to demonstrate it, or will it deploy other tests that are known to miss this crucial phenomenon? Simon McGrath reported on Dr Chris Snell's recent study of CPET abnormalities earlier this week - both Keller and Vemeulen have also confirmed what many practitioners and patients know from long experience: repeat testing is necessary to demonstrate the distinctive effects of exercise on ME/CFS patients. This finding may be in tune with patients' subjective experiences, but it does need further confirmation in larger studies. What better opportunity than the CDC's large-scale study to explore this crucial question?

A wealth of research has also highlighted the significance of viral infections and immune dysfunction in ME/CFS, but will the CDC even measure NK Cell Function and test for viruses associated with ME/CFS?

It is far from clear that the CDC intends to ask any of these questions: the detail so far on the promised blood testing seems vague at best. And with the CDC having already admitted that their study has not yet found a way to study any of the most severely affected housebound and bedbound patients, there's a considerable risk that the CDC's study may fail to study ME at all - a frightening prospect if its conclusions are going to be interpreted and applied as if they had done so.

What hope is there for a useful outcome from this study if the CDC fails to assess the most promising candidates for biomarkers discovered in the last 20 years of ME/CFS research? What chance that the research will help to restore common understanding to a fractured field if it excludes the most promising tests indicated by the work of ME/CFS researchers? Do the study's findings, and any recommendations for case criteria which may result from it, have a realistic chance of being respected and accepted, rather than opposed by the patient and advocacy community, if the study fails to ask the very questions that many patients, advocates and researchers consider to be the most crucial?

The danger that this study may become yet another missed opportunity - or worse, bury the reality of a serious illness even deeper below a mountain of obfuscation - seems very real to many advocates, who are disturbed by the apparent intention of the CDC to exclude crucial evidence from the study.


Letter to the CDC

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With these concerns in mind, on July 22nd, 11 patient organizations (including Phoenix Rising) and 31 patient advocates wrote to Dr Unger, Secretary Sebelius, Dr Koh, Dr Frieden, the sites participating in the CDC study and their clinicians, and the members of CFSAC, urging them not to rely on self-reported measures but to include objective measurements in their study. Specifically, the letter calls for the inclusion of 2-day Cardiopulmonary Exercise Testing or CPET (using the Stevens Protocol) and laboratory tests to measure Natural Killer Cell function and viral load, including enteroviruses.

The letter includes an extract from the CFS Advisory Committee meeting of May 2013, reminding Dr Unger of the testimony of Fred Friedberg that post-exertional malaise is "uniquely important" in the essence of this illness, and of Steve Krafchick who said that he would "get down on his knees and plead" with Dr Unger for the integration of neuro-psych testing and CPET into the study because it represents "the most objective evidence that you could ever hope to get", adding: "patient report is nice, and it’s cheap, but if we’re trying to do what you said you were trying to do - don’t miss this opportunity please."

Also included with the letter are academic references in support of the call for the use of CPET, and the list of organizations and advocates who signed it. You can read the letter and supporting information here, and the letter sent to clinicians is available here.

The letter's conclusion sums up its message: "Objective, biological measurements are vital in order to describe the differences and similarities among patients, determine how we characterize and treat patients, address the case definition issues, educate our medical community, and further our understanding of the underlying biology of 'CFS'. For that reason, we urge you to consider incorporating these important tests as soon as possible".

"Please know that we are willing to do everything within our power to work with you and the clinicians involved in order to accomplish this crucial goal. Like you and your colleagues, we want this study to be a success."

So: A wide range of organizations and patient advocates have spoken. Over now to Dr Unger and the CDC: are they prepared to test ME/CFS patients for biological abnormalities, or are their heads still stuck firmly in the sand?


How to Add Your Voice

11 organizations and 31 patient advocates have spoken - now we urge the wider ME/CFS community, including non-US residents, to add their voice and add to the pressure on the CDC to include these objective measurements in their study.

Erica Verillo has produced the following template letter - a shorter version of the letter already sent to Dr Unger - which you can use to add your voice in support of this campaign. Please feel free to edit it and add your own comments...and to indicate your support for the letter on the discussion thread below this article...


Elizabeth Unger, PhD, MD, Chief of the Chronic Viral Diseases Branch

Centers for Disease Control and Prevention (CDC)

1600 Clifton Road

Atlanta, GA 30333


Dear Dr. Unger,

In 2012, the CDC initiated a multi-site, multi-phase clinical assessment study to describe the differences and similarities among ME/CFS patients, determine how we characterize and treat patients, implement an accurate case definition, educate our medical community, and further our understanding of the underlying biology of ME/CFS.

Because the CDC’s multi-site study represents a major opportunity to make a difference for patients – both in the United States and around the world – objective, biological measurements are vital. However, a clinical investigation that does not include proper methodology to obtain objective data will fail to achieve its goals and will result in lost time, lost investment, and worst of all, lost opportunity.

It is absolutely essential that the CDC study include two objective tests which have consistently revealed abnormalities in ME/CFS patients. These tests are:

1) The two-day Cardiopulmonary Exercise Test (CPET). The two-day CPET provides gas exchange and other objective and measurable results “which can’t be faked.” Numerous studies have shown that the 2-day CPET – as opposed to the 1-day CPET – is a reliable and consistent method for measuring post-exertional malaise (PEM), the hallmark symptom of ME/CFS. This test can be done employing technology which has been used in hospitals for decades.

2) Low Natural Killer Cell Function/Viral Load. Abnormally low NK Cell activity and high viral loads are consistent findings in patients with ME/CFS. These tests can be done in many labs around the country and will provide objective, measurable data for comparison purposes.

Measuring and understanding post-exertional malaise (PEM) is crucial to this study. PEM is not only the primary symptom that distinguishes ME/CFS from depression, deconditioning, and other fatiguing illnesses, it is the ME/CFS sufferer’s main obstacle to daily activities, gainful employment, and leading a normal life.

Please include the 2-day CPET and tests for NK-Cell function and viral load in the CDC’s multi-site study.

Thank you,

(Your name, City and State, or Country)




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Maybe some docs need to be in on the meeting. I think the most important point would be to get people that she respects at the table, specifically researchers that understand how to set up study designs.
Dr. Unger should know that using these tests to confirm ME is endorsed in the ME Primer by clinicians and researchers on the ME International Consensus Panel:

Carruthers, Bruce M, MD, CM, FRCPC; clinician: internal medicine with focus on ME
Independent, Vancouver, British Columbia, Canada

De Meirleir, Kenny L, MD, PhD; clinician and researcher: physiology & medicine
Professor: Physiology and Medicine, Vrije Universiteit Brussel, Belgium
Director: Himmunitas Foundation, Brussels, Belgium

Klimas, Nancy G, MD; clinician and researcher: microbiology, immunology,allergy
Professor of Medicine and Director: Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale-Davie, Florida
Director: GWI and CFS/ME Research Center, Miami Veterans Affairs Medical Center, Miami, Florida, USA

Broderick, Gordon, PhD; researcher: systems biology, mathematical immunology, computational genomics – ME, CFS, Gulf War Illness (GWI)
Associate Professor: Pulmonary Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada

Mitchell, Terry, MA, MD, FRCPath; clinician:internal medicine - pathophysiology and haematology
Retired clinical haematologist with 28 years of experience of ME and chronic fatigue syndrome, Suffolk, UK

Staines, Don, MBBS, MPH, FAFPHM, FAFOEM; public health medicine, occupational and environmental medicine, researcher
Public Health Physician: Gold Coast Public Health Unit, Robina, Queensland
Associate professor: Faculty of Health Sciences and Medicine, Bond University, Robina, Queensland
Faculty of Medicine, Griffith University, Southport, Queensland, Australia

Powles, A C Peter, MBBS, FRACP, FRCPC, ABSM; clinician: internal medicine: sleep medicine, respirology
Professor Emeritus: Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario
Sleep Disorders Consultant: St. Joseph's Healthcare Hamilton, Ontario, Canada
Diplomate: American Board of Sleep Medicine

Speight, Nigel, MA, MB, BChir, FRCP, FRCPCH, DCH; paediatrics
Retired clinical paediatrician with many years of experience of ME and chronic fatigue syndrome. Durham, United Kingdom

Vallings, Rosamund, MNZM, MB, BS, MRCS, LRCP; clinician: primary care with focus on ME
Howick, New Zealand

Bateman, Lucinda, MS, MD; clinician: internal medicine with focus on ME & FM
Fatigue Consultation Clinic, Salt Lake City
Utah hospital affiliation: Salt Lake Regional Medical Center
Adjunct Instructor: Departments of Anesthesiology and Family and Preventive Medicine, University of Utah, Salt Lake City, Utah, USA

Bell, David S, MD, FAAP; clinician and researcher: paediatrics
Retired clinical paediatrician with many years of experience of ME and CFS, Lyndonville, New York
Department of Pediatrics, State University of New York, (SUNY – Buffalo) New York, USA

Carlo-Stella, Nicoletta, MD, PhD; clinician and researcher: immunology, immunogenetics of ME
Azienda Ospedaliera della Provinca di Pavia, Pavia
Primary care private practice with focus on ME, Pavia, Italy

Chia John,MD; clinician and researcher:internal medicine - infectious diseases, immunopathogenesis
Clinical assistant professor: Harbor-UCLA Medical Center, University of California, Los Angeles, CA
Director: EV Med Research, Lomita, California, USA

Darragh, Austin, MA, MD, FFSEM (RCPI, RCSI), FRSH, FI Biol I (Hon); clinician and researcher: endocrinology
University of Limerick, Limerick, Ireland

Gerken, Anne, MB, BS, D ObstRCOG, FRCPath: clinical microbiologist
Retired consultant microbiologist with many years of experience working with ME, Suffolk, United Kingdom

Jo, Daehyun, MD, PhD; clinician and researcher: pain and anesthesiology
Director: Pain Clinic, Konyang University Hospital, Daejeon
Professor: Department of Anesthesiology and Pain Medicine, Konyang University, Daejeon, Korea

Lewis, Don, MD; clinician: primary care with focus on ME
Donvale Specialist Medical Centre, Donvale, Victoria, Australia

Light, Alan R, PhD; researcher: Physiology, neuroscience, medical neurobiology and neuroanatomy, mechanisms of pain & fatigue
Professor: Anesthesiology and Neurobiology and Anatomy; Molecular and Cellular Neuroscience, University of Utah School of Medicine, Salt Lake City, Utah, USA.

Light, Kathleen C, PhD; researcher: behavioral medicine – physiological dysregulation in chronic pain and fatigue disorders, behavioral factors in cardiovascular disease, health benefits of family support, minority and women’s health issues
Professor: Anesthesiology and Psychology, University of Utah School of Medicine, Salt Lake City, Utah, USA.

Marshall-Gradisnik, Sonya, PhD; researcher: immunology -natural killer cells, vasoactive neuropeptide dysfunction and receptor expression, T cell regulatory dysfunction
Professor: School of Medical Sciences, Griffith Health Institute, Griffith University, Southport, Australia

McLaren-Howard, John, DSc, FACN; clinical biochemistry, biochemistry of nutrition, biochemical features of ME, mitochondrial dysfunction, vascular disease & intestinal dysbiosis
Fellow: American College of Nutrition
Director: Acumen Medical Limited, Tiverton, Devon, United Kingdom

Mena, Ismael, MD; nuclear medicine
Director: Imagenologia Funcional Cerebral, Department of Medicina Nuclear, Clinica las Condes, Santiago, Chile
Professor Emeritus: Radiological Sciences, UCLA School of Medicine, California, USA
Doctor Honoris Causa: University, d'Auvergne, France

Miwa, Kunihisa, MD, PhD; clinician and researcher: internal medicine: cardiology, cardiovascular physiology
Director: Miwa Naika Clinic, Toyama, Japan

Murovska, Modra, MD, PhD; researcher: virology, medical microbiology, molecular biology
Director: A. Kirchenstein Institute of Microbiology and Virology, Riga Stradins University, Riga, Latvia
Associate Professor: Riga Stradins University, Riga, Latvia

Stevens, Staci, MA; exercise physiology
Director: Workwell Foundation, Ripon, California, USA

With Dr. Broderick's having relocated to Florida, eight of these authors are based in the US. Drs. Klimas and Bateman are also involved in Dr. Unger's multi-site study.
 
From the CDC website regarding the ME/CFS multi site study:

This will help us to describe the differences and similarities among CFS patients. The data collected using a standardized approach from expert clinical practices will be used to address the CFS case definition. Ultimately, this study aims to improve how we measure illness domains of CFS. This may allow patients to be sub-grouped to improve therapy and allow the underlying biology to be discovered.

How can they accurately sub group us if they don't take the relevant tests that are critical in the diagnosis of the disease?

What is their ultimate aim with this study? They are basically taking current patients from seven clinical sites. They are having them fill out a complete questionnaire. They are "studying" them, in a fashion that is not clear or disclosed to us.

I am afraid that the result of this study will show that there is very little to unify us. It will show that we are just a conglomerate of so many different issues resulting in "fatiguing" type of illnesses. It is not a real disease, they will say, it is just a syndrome of many symptoms which need to be treated symptomatically.

The reason why this is my fear is that if they were truly concerned in finding "the underlying biology', they would concentrate on the testing that have shown in past peer-reviewed studies, abnormalities in ME/CFS patients. They would also include severely affected patients as well as children.
 
The CDC are not great at keeping the community up to date with exactly what they are doing, but they have given out some information about their ongoing study.
The CDC don't seem to be engaging continuously with the wider ME community, but they are engaging with significant parts of the ME community, especially the experts and clinicians who are involving in their study.

It's a mistake to say that the CDC are only using questionnaires.
Their study is evolving and seems to be open-ended, and they have now gone beyond questionnaires, and physician reports, and are looking at some biomarkers.

Beth Unger seems to recognise that heterogeneity is the biggest problem. And she's looking for data to find well-defined subsets. Finding subsets seems to be her mission. I can't fault that mission.

She has said that, in the long term, none of the existing diagnostic criteria will be perfect, and she is looking towards defining subsets by looking at treatments, and finding out the differences between the patients who respond and those who don't respond. She gave Ampligen as an example of where some patients respond to treatment and others don't.
She says that finding out why some patients respond to treatments (what is different about them - are there any biomarkers?) will probably prove to be the best way forwards in terms of defining the disease. I think she's spot on.

Importantly, and very relevant to this thread, they are already taking the study to a new level, and looking at biomarkers. They are taking DNA/RNA samples, and testing for morning cortisol levels. And also doing cardiopulmonary testing during exercise tests, and cognitive testing post-exercise. (Although currently these are planned to be one-day and not two-day tests.)

So, to summarise, my understanding is that the CDC have already started carrying out further tests including:
  • DNA/RNA testing. (I'm not aware of the exact details.)
  • Morning cortisol levels.
  • Cardiopulmonary testing during exercise tests (one-day testing)
  • Cognitive testing post-exercise (one-day testing)
At the most recent CFSAC meeting, Beth Unger also expressed an apparent willingness to incorporate post-exertion resting heart-rate into the study, although she didn't make it a firm commitment.

This is my understanding of it anyway. I may have misinterpreted something, because I've gleaned the information mainly from the chatter in CFSAC meeting videos.

I think prompting the CDC to look at two-day exercise testing is helpful, but keep in mind that Dr Snell has had some mixed results from two-day exercise testing, and has only carried out relatively small studies, and he has suggested that his work has not been reliably replicated by others. So two-day exercise testing may or may not prove to be as helpful as we hope.

My own interpretation is that Beth Unger and her team are moving in exactly the right direction, but still have a very long way to go. I don't think we should assume that Beth Unger is like previous CDC employees. She seems to be wiping the slate clean, and starting from scratch and approaching ME/CFS with an open mind, and basing her work on the data outcomes. This is absolutely the best way to go about it. But it's something that should have been done 30 years ago, so the CDC is behind schedule. My own interpretation is that Unger is taking her job seriously, and treating this illness seriously. Of course, I might be wrong, and perhaps I have a tendency to be over-optimistic, but I'm trying to be fair minded, and base my opinions on my interpretation of the evidence. The evidence suggests to me that she is doing the right stuff, but has a long way to go, and the CDC is at least 30 years behind schedule. I'm sure that others might disagree with me.


I've previously posted about these issues in a jumble of posts, if anyone is interested in reading further (but I've copied the essential information into this post):
http://forums.phoenixrising.me/inde...ase-definitions-now.23217/page-12#post-367643
http://forums.phoenixrising.me/inde...-war-illness-and-cfs.23958/page-2#post-367368
http://forums.phoenixrising.me/inde...ase-definitions-now.23217/page-10#post-366821
 
Bob,

I guess we have different perspectives, looking at the same data.

So far, from my understanding the CDC first phase of the study has been accomplished.
This included 450 patients from 7 clinical sites.
It involved:

-physical exam (not clear if this was done by the clinicians or CDC reps)
-patient questionnaires - including measure of fatigue, sleep, pain and function
-data abstraction of medical records by clinic personnel

They have collected all (95%) of the data and analyzed it, comparing the different sites and comparing some of the data with different illnesses.

The second phase, we are told, involves:

From all clinical sites
-saliva morning cortisol collection (??? this will find subsets?)
-blood DNA & RNA (sounds important but, what is it?)

Additional studies at some clinics:

-comparing healthy controls
-cognition and exercise testing

From CFSAC:

"final dataset will allow comparison of instruments measuring domains of CFC illness"

I wish someone can explain to me what this means exactly.

I don't have anything personal against Dr. Unger. I don't think that she has the power to "wipe the slate clean". I think that she is just doing the job she is told to do.

Why is the CDC totally ignoring all the scientific studies that are already out there?
They give the impression that this is a legitimate and important study because they are involving patients who are part of major clinical practices. In what way, are they going to find a biomarker for ME/CFS with this study as it is?

I don't feel that heterogeneity is the biggest problem. I feel that finding a biomarker and diagnostic criteria are. Many other illness are heterogenic, that doesn't necessarily mean that it is not one disease. Any multi-system illness will be heterogeneous. Lupus, for example will appear totally different in each patient. Separating the patients into different illnesses, would have been a major mistake.

Why am I so disillusioned with the CDC? Because they are totally ignoring the fact that we have the CCC and the ICC. They are acting as if they don't exist. I don't have any medical or science background but, from my knowledge of the history of this disease, what they are doing now in this study, does not make sense to me.
 
According to Dr. Unger, the patients they are studying are the ones that each clinician has diagnosed with cfs, post viral infection, ME - it doesn't say by which criteria.

No particular criteria is necessary for the study. The clinicians just have to diagnose the patient in their own way, according to their expert knowledge. I expect that each patient will subsequently be diagnosed as per various criteria, for the purposes of gathering extra data.
 
No particular criteria is necessary for the study. The clinician just has to diagnose the patient in their own way. I expect that each patient will subsequently be diagnosed as per various criteria, for the purposes of gathering extra data.

This was to have been my next comment. I hope that the data gathered will be used in 'research' as we might better understand it; and those who are sub-grouped in this initial business are then studied under the microscope as it were. I may well be wrong of course.
 
I'm assessing Beth Unger's progress relatively from a standing start, and not from where we want the CDC to be. I'm not trying to pretend that everything at the CDC is wonderful, but there has been change, and I'm quite impressed with what I've seen recently, in terms of attitude. I imagine that many people will be shouting at their computers whenever I say anything positive about the CDC, and I totally understand that.

Of course there is a huge distance that they need to travel, but this is not Beth Unger's fault. So I'm assessing her progress from a standing start, and not from where the CDC should be. And I'm not suggesting that we shouldn't be critical of the CDC, and or that we shouldn't put pressure on them. We should be critical, and we should put pressure on them. I just think that it's helpful to observe what they are actually doing.

The CDC currently appears to be very resistant to suggestions from the ME patient community, but I think this is because they have a very bureaucratic and specific way of doing things, and their plans take a long time to implement. I think this can give the appearance that they are not listening and that they don't care. But I think we should be aware of their bureaucratic processes, and not assume that they are ignoring our community to spite us. I saw evidence of flexibility, engagement and receptiveness, from Beth Unger at the recent CFSAC meeting, although it wasn't obvious.

Before Beth Unger, I had no respect for the CDC at all. And it took me a long time to learn what Beth Unger's approach would be. Only recently have I really learned what her approach is, and I've only learned it by listening carefully to what her team have said at the CFSAC meetings.

Like I said earlier, I may well have misinterpreted, and I may be far too optimistic, but I am optimistic about their direction of travel. Of course, they yet have to prove themselves. I'm also aware that many will strongly disagree with my assessment.


I don't have anything personal against Dr. Unger. I don't think that she has the power to "wipe the slate clean". I think that she is just doing the job she is told to do.

Beth Unger seems to be approaching the subject without preconceived ideas, and she has stated that she is following the data. I think that's the best way for her to go about it. It really does seem to me that she's made a fresh start of ME/CFS at the CDC. I'm basing this on what she's said, and on the project that they are carrying out. She has a very long way to go, but that's not her fault. What she is doing now should have been done 30 years ago.


Why is the CDC totally ignoring all the scientific studies that are already out there?

My understanding is that it is because they require a certain standard of evidence. Yes, there is research out there, but is any of it conclusive? I'm not aware of any conclusive top-quality research in terms of objectively defining ME/CFS. Are you? There is some evidence re exercise testing, tilt-table tests, brain scans and immune activity, but none of it is of a high enough standard to be widely accepted, as far as I am aware. Unless I'm forgetting something.

The CDC needs data from studies with large numbers of participants. And any objective biomarkers need to be reliably reproducible in further research studies. The CDC have now started looking at large numbers, and have also started looking at potential biomarkers. But, yes, they've yet to demonstrate exactly what they are studying in terms of biomarkers.

Beth Unger has acknowledged that she's yet to get to grips with PEM, in terms of defining it for research purposes, and she's acknowledged that it could be a useful biomarker if she is able to define it to her satisfaction for research purposes. Sure, this sort of thing seems very basic to us, but she's got to define it in a way that is reliable and replicable in research studies. Should she use self-reported questionnaires, immune biomarkers, exercise testing, or something else? What reliable biomarkers are there for PEM? Is there any top quality research that defines reliable biomarkers for PEM or PENE? I'm not aware of any. Dr Snells recent research is very promising, but it's just one small study.


They give the impression that this is a legitimate and important study because they are involving patients who are part of major clinical practices. In what way, are they going to find a biomarker for ME/CFS with this study as it is?

I get the feeling that it's an open-ended, evolving, exploratory study. So far, there are some potentially decent biomarkers involved, although the details are sketchy. Exercise testing, post-exertional cognition testing, DNA/RNA analysis, and post-exertional resting heart rate testing seem like pretty good objective biomarkers to be starting with. Two-day exercise testing, immune signatures, viral testing and protemics are maybe the next step.

Likpin is doing an extensive viral and proteomic study, and it is something that the CDC should have been doing years ago. If we compare Lipkin's study with the CDC study, then the Lipkin study puts the CDC to shame. But I'm assessing Unger from a standing start. I hope that the CDC will be funding research similar to Lipkin's after they have done their current basic biomarker research.

Yes, the CDC is doing far too little, far too late. But I'm not assessing Unger on where I want her to be. I'm assessing her on where she is, based on a standing start. So I'm trying to assess her motivation, rather than her accomplishments.


I don't feel that heterogeneity is the biggest problem. I feel that finding a biomarker and diagnostic criteria are. Many other illness are heterogenic, that doesn't necessarily mean that it is not one disease. Any multi-system illness will be heterogeneous. Lupus, for example will appear totally different in each patient. Separating the patients into different illnesses, would have been a major mistake.

I think that many of us would accept that CFS may not be a single disease, and some of our community would like ME to be distinguished from CFS. Unger is attempting to identify subsets. She has said that she is open minded to defining ME separately, if her data leads her that way. Without getting to grips with heterogeneity, if there is any, and defining subsets, then biomarkers and objective diagnostic criteria would be impossible to define. Defining subsets is the best way to start, or biomarkers will be impossible to find.


Why am I so disillusioned with the CDC? Because they are totally ignoring the fact that we have the CCC and the ICC. They are acting as if they don't exist.

I think that the CDC has accepted that research should be carried out with Fukuda and CCC, haven't they? The reason that they are partially ignoring the CCC is that they don't believe that it is evidence based. Not to the standard that they require. So they have set about finding subsets for themselves, using their newly gathered data. Whether it's the right or wrong approach, the CDC requires a certain quality of empirical evidence.


I don't have any medical or science background but, from my knowledge of the history of this disease, what they are doing now in this study, does not make sense to me.

It makes sense to me. And I like what they are doing. It's just not enough, and not fast enough.
I like what I've heard Beth Unger say recently.
She does sometimes seem resistant to suggestions from the ME community, but I don't think she ignores us.


Anyway, it's just my own assessment, and I know that many won't agree, but I haven't seen any evidence of cynicism from Beth Unger.
 
Forgive me for butting in my 2 cents since over the years here at PR my comments have become extremely sporadic due to the Damn Disease (not that they would be worth more than the aforementioned 2 cents anyway ;-) ), but I cannot agree with Bob more. All CCC and ICC give us is a dim picture that some very good clinicians & researchers have been able to cobble together using a relatively tiny bit of money to do tiny studies that have not been adequately replicated for the purposes of helping other clinicians trying to provide some sort of support for patients with a disease that cannot yet be treated beyond palliative care. None of the diagnostic testing mentioned in CCC and ICC (or Fukuda, for that matter) has been clinically validated, i.e. they have been studied in thousands of patients and replicated so consistently that almost everybody agrees they will reliably diagnose (or assist in treatment of) this disease. There are simply all the authors of those criteria had/have at the present. But they do not have nearly enough data to be definitive because they have not had the funding nor the infrastructure to do the studies needed to produce enough data one way or the other (thanks NIH and CDC!). We simply do not know with anything close to certainty that CCC or ICC or Fukuda can definitely diagnose this/these illness(es).

However the CCC/ICC group do have years of clinical experience, which Dr Unger and the current CFS program at CDC appear to acknowledge and are trying to utilise with a far bigger cohort than any one of these clinician-researchers could muster on his or her own. Moreover each of these clinicians have their own approach to diagnosing this disease. By collecting data from their patients (who have already ostensibly been diagnosed using CCC/ICC since all the clinicians in this study were involved in creating those criteria) and comparing/contrasting this data, it will either show that CCC/ICC are good at distinguishing this disease from depression and other co-morbidities, or it will show that there are tests/symptoms that are more helpful than those listed in CCC/ICC. It may be that NK cell function testing or 2-day CPET only catches a subgroup and misses a huge swath of patients that has hitherto been missed because of the tiny cohorts used in testing thus far. It may be that vertigo or delayed gastric emptying or some other random symptoms end up being more definitive than NK cell function or CPET (I strongly doubt it but without a large enough data set, who knows?). But the data from this CDC study will be far more robust than anything CCC, ICC, or Fukuda can provide.

If we do not deal with the issue of heterogeneity, we will get no where (we HAVE gotten no where). Whether this is one disease with multiple presentations or multiple diseases with similar presentations, we must, must, must start subgrouping. It's what Fukuda called for nearly 20 years ago. It's what just about every one of the clinician-researchers we talk about (Peterson, Klimas, etc.) mention at every ME/CFS conference they speak at -- big or small. It has been THE problem impeding progress in figuring out biomarkers and establishing diagnostic criteria with which every researcher can agree and -- more importantly -- use for further research (as well as finally put a cork in the psychogenists!). And from what I've seen of Unger's CDC study, it appears to be finally -- FINALLY!! -- addressing this issue (30 years late but I'd prefer it now than in another 30 years).

I agree that there should absolutely be transparency in how CDC is carrying out the test and would think CFSAC should be seeing to that (note I say "should"; given the last meeting, god only knows what they're doing). While I'm cautiously hopeful about this big study, I haven't forgotten the last 30 years (half of which I've spent wasting away my 20s and 30s). That they have much to prove to us is an understatement. But, aside from some sort of an exercise and cognitive stressor, I'm rather agnostic on what tests CDC must use. I think they need to have the flexibility to go where what they find (i.e. data) tells them would be the best place to go so that we don't spend precious time and money chasing theories that look promising but just don't produce consistent findings.

Sorry. I'll return to radio silence. I get way too wordy when I comment (though it probably helps me get to sleep to write this down rather than spend hours talking to myself about what I would say if I was going to comment...yes, that IS sad...lol).
 
Michelle, I agree with nearly all of your post, but I wouldn't have quite used your wording with the following:
All CCC and ICC give us is a dim picture that some very good clinicians & researchers have been able to cobble together using a relatively tiny bit of money to do tiny studies that have not been adequately replicated for the purposes of helping other clinicians trying to provide some sort of support for patients with a disease that cannot yet be treated beyond palliative care.

I think you make a half-valid point here, and I agree that without biomarkers and treatment, that the CCC and ICC are of limited value. But they are based on expert observation of patients, and I think these criteria have an important purpose. The CCC is now widely being used for research, and it's an extra way to subset patients, which might prove to be very helpful. I also think it's helpful to define a disease, or a subset of patients, in a more precise way than the more inclusive CFS criteria, based on careful clinical observation. It hopefully will give the illness and patients more credibility, over time, and it better informs clinicians about the nature of the disease.

But yes, proper empirical data, based on objective observations of large number of patients, has the potential to transform the field.

But I acknowledge that I have a very optimistic view of the future of CDC. And I make the assumption that the CFS division of the CDC is no longer corrupt. It might be the case that the CDC produces absolutely nothing useful. Their study is not yet ambitious enough, and they appear as if they are dragging their feet. They have to prove themselves.