Comments for NIH Research Program on ME/CFS

1.  It is critical that we find a way to diagnose the 850,000 Americans with ME/CFS who have no diagnosis today.

In 1988, after a series of cluster outbreaks across the nation, US experts attended a meeting put together by NIH and CDC to give a name to the disease that had been called CEBV.  They chose “chronic fatigue syndrome,” or CFS.  

That was nearly 30 years ago.  In the intervening time, CDC has so misjudged the prevelence, severity, and urgency of the need to get a handle on this disease, that today, with a national prevalence of at least 1 million adult Americans, CDC admits that only 15% of patients even have a diagnosis.  

That tells me that the decision to focus on “fatigue” was a disaster.  And I wonder where the other 850,000 Americans are.  Since this is an equal opportunity disease - but that’s not true of those who are diagnosed - the population of undiagnosed patients with this disease is going to be skewed towards people of color, and I also suspect people of lower income.  They are suffering alone.  

2.  We need to go back and investigate the phenomenon of cluster outbreaks.

Once EBV was dismissed as a possible cause of this disease (prematurely, as it turns out), all interest in the possibility of cluster outbreaks disappeared.  Yet many patients experienced this disease in what appears to have been a cluster outbreak.  CDC and NIH responded to the experience of patients by saying (to me, personally), these were not outbreaks of disease - they were outbreaks of diagnosis.  It was the belief of Drs. Straus and Reeves that since this was obviously not a disease that was in any way contageous (decided in Washington, not after looking at statistics), then the evidence of outbreaks must be cases where patients found a friendly doctor willing to confirm their belief they had a “real" illness.  

That goes against the evidence.

More important, where we are today, I believe there has been a new set of cluster outbreaks.  Why?  Because I have been contacted by patients for twenty years, and starting around 2010 I began to be contacted by young people in their 20s and 30s and the parents of teenagers.  They had become sick SINCE 2010.  If there is indeed a new set of cluster outbreaks, let me suggest that we start to get a handle on it by looking at cases of EBV and asking for evidence of the long-run health of patients.  

3.  We need biomarkers now.

Both Items 1 and 2 are direct consequences of the absence of biomarkers.  It is hard to find out how many people have this disease when you are reduced to questionnaires.  It is hard to find out whether there are cluster outbreaks (or outbreaks of diagnosis) without biomarkers.  

I have had specialists who have been using biomarkers for two decades.  I see no reason to have to start from scratch.  We will at least catch a significant subset of patients.  NIH needs to look at natural killer cell function as both a marker showing THAT you have The Disease, and also a marker of the SEVERITY of The Disease.  

The 37kDA Rnase-L was a useful biomarker for some specialists until we lost the ability to send blood to Belgium.  A new lab was started in the US, but the group it was connected to had problems and it closed.  The patent was owned by Temple University, but they have said they do not care if they are reimbursed - anyone may use it.  

Dr. Robert Suhadolnik, now deceased, did a study in the 1990s of 100 patients from the Incline Village cluster outbreak, 100 patients with fibromyalgia but no symptoms of CFS (Fukuda 1994), 100 patients with major melancholic depression (at the urging of Dr. Straus), and 100 controls.  98 of the 100 patients from Incline Village had the defective protein.  Only 2-3% in each of the other three groups did.  That is profound, but it was ignored.  

In the meantime, Drs. Catherine Bisbal and Luc Montaigner tested patients with PVFS in France and Belgium, and had similar results.  This is even more fascinating given that Dr. Suhadolnik was using an electron microscope, but Drs. Bisbal and Montaigner weighed the protein (hence the name 37kDA Rnase-L).  

So two different sets of researchers, on two different continents, using two different methods, found the same thing.  The researchers switched blinded samples and got them all right.  So I think the 37kDa RNase-l biomarker is also another important characteristic of at least a subset of patients.

So many different specialists have worked with cytokine profiles that I can’t even list them all here.  But that is also an area for biomarkers.

As I write, biomarkers are being proposed by researchers from Griffith University in Australia to Stanford and Columbia universities, to the Simmaron Foundation, the NOVA clinic in David, FL - we need a systematic way to look at the existing evidence and start using biomarkers to find at least a subset of patients.

4.  We need treatments now,

Ampligen is already available and it has been shown to lead to dramatic improvements in 30-40% of patients.  I am one of them.  We ask that NIH help us get this drug provisionally approved.  The company does not have the money to do another large double-blind study.  I would contribute my own money towards such an effort.  In the meantime, the drug needs to be made more available because of the severe geographic restrictions it puts on those patients (such as myself) who would be vegetables without it.  

Rituxmab needs to be researched.  It has shown promise in Norway.

Patients have improved on gamma globulin and on antivirals, specifically Valcyte and Vistide.

We need to find other drugs to repurpose.  I believe there also needs to be a push to develop more antivirals, period, and more pharmaceuticals targeted to the immune system.

5.  We need to pay more attention to viruses.

From the first diagnosis of atypical polio (which became Myalgic Encephalomyelitis in the British commonwealth nations and Epidemic Neuromyesthenia in the US in the 1950s, CEBV in the 1980s, and then CFS in 1988), the evidence has strongly suggested that the disease is connected to a virus.  Which virus?  If you don’t test people, how do you know?  Now that there are better methods for finding viruses, we need an all-out push to find the viruses behind cases of ME/CFS in the United States.  [In my own case, both HHV-6A and CMV were in my spinal fluid in 2009, during a 2-year period when I could not get Ampligen.]

The earliest viruses suggested were those in the polio family, now called enteroviruses.  Coxsackie B was considered a prime candidate for the culprit in the UK (before the psychiatrists got involved), and it has also been found in patients in the US.  I also know patients whose illness began with an episode of adenovirus infection.

However, in the US, the viruses most commonly found are EBV (particularly at the start) [HHV-4], CMV [HHV-5}, HHV-6A, HHV-6B, and HHV-7.  

6.  Pay attention to 12 years of CFSAC recommendations.

Every year, CFSAC creates a list of recommendations for the Secretary of HHS.  I know that they go to a lot of trouble to do this.  Most of these are very good recommendations.  Please go back and compile them and take them into consideration. 

7.  Don’t start from scratch.  Use existing research.

Let me suggest the numerous websites that i referenced in my May 12 blog, “ME is not a mysterious disease.”  It would take too much space to write it all down here now!

http://slightlyalive.blogspot.com/2016/05/for-may-12-2016-me-is-not-mysterious.html

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This spring I lost 3 good friends whom I had known for 20 years as fellow patients with this disease.  One had been sick for 32 years; another died at 40 from breast cancer because her ME-battered body could not take the necessary chemotherapy regimen; one died in the hospital of pneumonia, again because his body was so weakened.  I look at a new generation of patients who got this disease as teenagers and wonder - will they still have it in their 40s, as is true for many patients I know?  Are they doomed?  Please stop this rolling epidemic now, because more and more people have it every time there are a series of outbreaks.  

I thank you for the opportunity to comment, and I am hopeful that with the will to do so, NIH can stop this unending tragedy.  

Mary M. Schweitzer, Ph.D.

Open Letter to Dr. Sanjay Gupta on In-House NIH Study of ME/CFS

The following is a response to Dr. Sanjay Gupta's blog on the upcoming in-house NIH study on ME/CFS, which can be found at this site:  Medpage Today

Thank you for highlighting the first in-house study on patients with ME/CFS in two decades.

Over one million American adults suffer from ME/CFS.  A quarter of a century (28 years) after CDC adopted the dismissive name "chronic fatigue syndrome," 85% of these - that's 850,000 people - have no diagnosis.  CDC has long advocated treatments recommended by British psychiatrists of the so-called "biopsychosocial school."  The British psychiatrists argue that the patients perhaps once had a disease, but they became afraid of acting normal.  They are left with deconditioned bodies, which makes them look sick and contributes to what are called "false illness beliefs."  Thus they recommend Cognitive Behavior Therapy (CBT) not as it would normally be used - to help the patient adjust to having a chronic illness - but instead to address "false illness beliefs" and teach the patient she does not need to stay inactive; that goes hand-in-hand with a reconditioning program called Graded Exercise Therapy to return the patient to normal.  The combination is generally called CBT/GET.

It is important to note that these psychiatrists are quick to say that just because they call the disease "neurasthenia," they do not mean to say it is wholly psychiatric.  They say our criticism of their insistence that ME/CFS is a somatoform disease is due to prejudice against psychiatry, and a false adherence to "Cartesian mind-body dualism."  That is actually not true.  The criticism of their theory rests on their assumption that the patient suffers from MUS's (Medically Unexplained Symptoms); the criticism of CBT/GET is even simpler - it is due to evidence that neither helps patients, and graded exercise actually makes them worse.

For years, however, these psychiatrists have successfully deflected criticism of their work by instead criticizing their doubters.  In 2007 they were awarded a £6 million ($8 million) grant to prove, once and for all, whether the diagnosis and treatment they and NHS has been using for 2 decades is the best available.  The study was published in Lancet in 2011.  There were numerous problems with the study (for example, objective markers were dropped halfway through the study, and the goals for patients were actually changed mid-study).  Advocates have asked to see the anonymized raw data, but the principle investigators have refused, labeling these requests "vexatious." 

Recently Berkeley journalism and public health professor David Tuller published a series of articles on the problems in the PACE trials, on the highly-regarded blog site of Columbia University virologist Vince Racaniello.  Tuller and a group of scientists have asked to see the anonymized data.  This time they weren't told their request was vexatious (Dr. James Coyne, an open-data advocate from outside the ME/CFS community, was).  Instead, they were told they could not access the data because it would not be fair to the patients.  That's an odd response - they've already shared the data with the Cochrane Review (although the Cochrane Review study authors included one of the PACE study PI's), so one would think it has already been anonymized.  At any rate, one would think they know how to anonymize data sets - or no study involving clinical trials could ever be published!  Requests are making their way through the appeals process.  The Coyne request is more complicated - it is not a FOIA request; rather, Dr. Coyne is on the editorial board of PLOSOne, a series of e-journals that require authors to share data.  It is in that context that Dr. Coyne has asked for anonymized data from the study - and in that context he was told his request was vexatious.  Stay tuned - the PACE controversy is far from over.

The Tuller articles can be accessed online beginning here:  PACE: Trial by Error - Coyne's blog critiquing the PACE study can be found here: Uninterpretable: Fatal flaws in PACE .

It is odd that NIH would not be aware of the controversies surrounding the PACE study, particularly given that both CDC and NIH have frequently taken the advice of psychiatrists involved in the study, such as Peter White, Michael Sharpe, and Simon Wessely (the latter is not an author but was a participant).    for example, psychiatrist Peter White, who has been Chief Medical Officer of Scottish Provident Insurance Company and continues to advise Swiss RE, a multinational re-insurance company, led the 2009 evaluation of CDC's program on CFS. 

This position - that the disease is really a form of somatoform disorder - has haunted patients with our disease for 3 decades.  The authors do not recognize the large body of literature on physical abnormalities in patients.  Many of the studies on biomedical markers and evidence are small sample because it is next to impossible to get funding from NIH for this disease - at most, NIH has allocated $6 million/year for one million patients, roughly one percent of what they give to Multiple Sclerosis, itself hardly an overfunded disease.  So it becomes a tautology - no funding because there is no large-sample evidence of biomedical abnormalities; no large samples because there is no funding.

The choice of name - "chronic fatigue syndrome" - coupled with publicity about the disease being cured by "cognitive behavior therapy" and "graded exercise" and statements to the press that it is actually a somatoform disorder (what the public calls psychosomatic) - has led to mistreatment and  lack of any treatment at all even for the minority of patients who have a diagnosis.  Patients have also found themselves the butt of jokes because of the name - recently the cartoon strip Blondie took a pot-shot at patients for the latest name for the disease, SEID (Systemic Exertion Intolerance Disease)

I have gone through this rather lengthy detour because I wanted to be sure that you understood the patients' concerns about Dr. Walitt, who has been designated Lead Associate Investigator on this study.  This is the quote from the article cited on your blog that concerns us:  

"The discordance between the severity of subjective experience and that of objective impairment is the hallmark of somatoform illnesses, such as fibromyalgia and chronic fatigue syndrome."  

That article was published last year.

We know that the British psychiatrists who promote "CFS/ME" as a somatoform disorder will say exactly what Dr. Walitt said - that the only reason we are disturbed by the diagnosis is that we believe in the false Cartesian dichotomy of mind and body.  Walitt's defense for having so casually labelled CFS a "somatoform" illness was an oblique remark about the head being connected to the body.  Please forgive us if that sets off alarm bells.  And no, claiming to have found a biological cause for somatoform disorders does not alleviate our concerns. 

For three decades patients with this disease have endured the stigma of the name - chronic fatigue syndrome (chronic as in chronic complainer, fatigue as in "Yeah, I feel tired lately myself," and syndrome as in syndrome of the month), and the presumption of the disease being  - in the vernacular - psychosomatic.  We are not prejudiced against psychiatry.  But we are no happier being told our disease is psychiatric in nature than you would be if told your hot appendix was due to faulty thinking.  The entire thesis of these psychiatrists rest on the belief that patients' symptoms fall in the category of MUS's (Medically Unexplained Symptoms), and therefore when patients insist their disease is biomedical in nature, they are exhibiting false illness beliefs.  These psychiatrists have published articles claiming the disease is somatoform in nature without bothering to respond to the actual biomedical literature on this disease - indeed, if all you read was the psychiatric literature on this disease, you would not know that there is peer-reviewed published research on biomedical factors behind the symptoms.  Let me suggest this recent article from DePaul psychologist Leonard Jason summing up the current state of the literature on various symptoms of the disease:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761639/

Indeed, the Institute of Medicine of the National Academy of the Sciences stated firmly that the evidence on biomedical abnormalities in this disease is so strong that no one should look at it as psychiatric any more.  You can find their report (and less lengthy material) here:  http://nationalacademies.org/hmd/Reports/2015/ME-CFS.aspx

We are encouraged by Dr. Collins' interest in the disease, and the plans Dr. Nath has for the study are exciting.  However, given they are only going to look at 40 patients, we are very concerned about the possibility of bias in patient selection.  Early on we were told (apparently by accident) that the Reeves definition (2003) was going to be used.  This definition - actually a set of questionnaires - is wholly unacceptable.  It is modeled on the questionnaires used by the British psychiatrists, and a study has already shown that a cohort chosen using these questionnaires brings in patients with anxiety and depression instead of ME or CFS at the same time it fails to identify the most severely afflicted ME/CFS patients.  It is very telling that independent researchers have ignored the Reeves definition completely.  In that context, we find it concerning that CDC has just published an article on the Georgia cohort (diagnosed using the Reeves criteria) where they discuss the questionnaires without once mentioning Reeves' name - that is, without informing the reader that these questionnaires are precisely the ones created by the late Bill Reeves at CDC that have been called the "Reeves definition."  The unexpected sleight of hand has us concerned that the Reeves definition will be used by simply not calling it the Reeves definition.  It will help for them to then diagnose the patients using the Canadian Consensus Criteria, but having used the old Reeves definition as a filter risks deeply biasing the selection process.  With only 40 patients in the study, we are baffled that they would even take a chance on inserting these biases (Reeves questionnaires and Walitt's belief that the disease is somatoform in nature) into the project.

Over the past 30 years there have been numerous breaches of faith with patients.  CDC was even chastised by Congress in 1999 for diverting the paltry funds allocated to study CFS to a different disease entirely.  In the meantime, more patients come down with the disease every year, and very few fully recover. 

Despite the name, CFS is not characterized by "fatigue."  (You might want to fix the headline to your article, which referred only to "chronic fatigue.")  The identifying features of ME/CFS are post-exertional worsening of symptoms (as measured in two consecutive days of CPET studies), and significant cognitive dysfunction.

Many patients have already been shown to have significant immune defects - abnormally low natural killer cell function, abnormal cytokine patterns, and the abnormal 37kDa Rnase-L defect.  Many patients have been shown to be battling chronic viral infections, particularly the beta herpesviruses (CMV, HHV-6A, and HHV-7) and EBV (mono).  Others have Coxsackie B (an enterovirus) and/or adenoviruses.  To drag the medical community back to square one, when the disease was labeled a somatoform disorder, is extremely distressing.  Dr. Walitt may believe that somatoform diseases have a physical explanation (abnormal cytokines in the brain) - but he is still saying they are somatoform diseases.  

This is the first NIH study in 20 years on a disease that impacts one million adult Americans.  The first study on a disease that leaves 500,000 Americans completely unable to earn a living.  The first study on a disease that can attack teenagers and leave them disabled in their 40s.  There are patients who were never able to go to college, never able to date or marry, never able to have children, never able to have a career, and they live in fear of losing their parents as they age because they need a caregiver.  The first study on a disease that has killed patients from specific causes such as myocarditis (when the viruses get into the heart muscle), cancer, and general system failure.  The first study of a disease that has led to far too many suicides, because no one in the medical profession has been there for the patient, and the government has offered no hope of a better future.

Given that NIH is only using 40 patients because, they say, that is all they have the funds for, given the severity and prevalence of the disease, and given everything patients have been put through, I do not think it is too much to ask to dispense with the services of Dr. Walitt - someone who only last year breezily declared CFS a somatoform illness.  I do not think it is too much to ask of CDC that they not rebrand the Reeves questionnaires to sneak the Reeves definition back into the study. 

I do not think it is asking too much to have just one community-recognized ME/CFS specialist (perhaps Dr. Jason) on the ME/CFS expert committee. 

And I do not think patients are asking too much to be involved in the decision-making process. 

Thank you for your time and interest, Dr. Gupta.  I hope that you take our concerns seriously.  See also my open letter to Drs. Collins and Nath:  An Open Letter to Dr. Collins and Dr. Nath 

An Open Letter to Dr. Collins and Dr. Nath on the NIH internal ME/CFS study

Note: As of Sunday, March 6, NIH has dropped the somatoform comparison group.  Thank heavens!  But they are still looking for "the underlying physiology of fatigue."  So I still wish they would spend as much time learning about M.E. as they have spent deciding on the [admittedly admirable] lineup of tests.

Dear Dr. Collins and Dr. Nath:

I echo the sentiments of many ME/CFS patients in expressing concerns about the way the in-house NIH study on ME/CFS is proceeding.

The stated hypothesis of this new study is that: “post-infectious ME/CFS is triggered by a viral illness that results in immune-mediated brain dysfunction."  Is that really all there is to the hypothesis?  Dr. Wallit's participation raises troubling questions as to whether that is so.  The comparison groups chosen for this study also suggest there is more to the hypothesis than we have been told.  

I beg you, Drs. Collins and Nath, please rethink the hypothesis - and Dr. Walitt's role in this study. I also ask you to rethink the comparison groups. This disease has been a serious problem in the US for 30 years, and for 30 years both NIH and CDC have obstructed the creation of a strong biomedical research community – nevertheless, it has existed. 

What has happened here?  A hypothesis created by people who know next to nothing about this disease is being plonked on top of us. If I may say so, yet again.  Why?

Make no mistake about it, fellow patients: Dr. Walitt is playing with somatoform diseases here – he just thinks there’s a biological cause for them. 

He seems insulted that we might be unhappy about his inclusion.  All I can say is that anybody who uses the words "chronic fatigue syndrome," "fibromyalgia," and "somatoform illnesses" in the same sentence is unacceptable in a preliminary study of my disease sponsored by NIH.  

Last March Dr. Walitt published an article containing the following sentence:  "The discordance between the severity of subjective experience and that of objective impairment is the hallmark of somatoform illnesses, such as fibromyalgia and chronic fatigue syndrome. " (Chemobrain: a critical review and causal hypothesis )

I really do not care if Dr. Wallit is looking for a physiological cause for what are called "somatoform" illnesses.  The problem is that he thinks ME/CFS is a somatoform illness.

Then there are the comparison groups.  Where did these come from?  Two comparison groups:  post-symptomatic Lyme Disease patients, and patients with physical somatic disorders.  The choices of comparison groups themselves suggest that the research hypothesis for this project has not been fully revealed to patients.

With only enough money to put 40 ME/CFS patients in the study, may I ask why we are bothering with comparison groups at all?  Does it not make more sense to do this first study with ME/CFS patients v. controls - and then use more ME/CFS patients?  

Since 1998 I have known that i had the defective 37kDa Rnase-L and a severe case of HHV-6A. Later testing showed natural killer cell dysfunction (in my case, a natural killer cell function of 2-3%) and abnormal cytokine patterns. In 2009, Dr. Dan Peterson found active HHV-6A and CMV in my spinal fluid. Do you think that my serious encephalitic and neurological symptoms could have had something to do with that evidence? The immune defects and viruses go away on Ampligen and come back 7-12 months off it. I am a sample of 1, but there are more like me. Many more. We have patients improving on the antiviral Vistide at Dr. Peterson's (I cannot take Vistide; my liver markers shoot up).  The late Martin Lerner had patients on both Vistide and another antiviral, Valcyte;  Dr. Jose Montoya at Stanford has had success with Valcyte as well.  

Please pay attention to this evidence.  Talk to clinician/researchers.  

If not – then please run that hypothesis past some non-psychiatric specialists in our field before running with it in the first NIH internal study on our disease since Straus discovered (to his dismay) that we have abnormally LOW levels of adrenaline (patients with major mood disorders tend to have abnormally HIGH levels of adrenaline) 20 years ago.  Dr. Straus had planned to be able to say we really had depression; hence his disappointment. (Psychiatists in the UK - and CDC's CFS group - finally found a use for Straus's adrenaline study in the unsupported hypothesis that patients had too many stressors earlier in life and had, in effect, run out of mechanisms to cope with them.  If that were true, wouldn't one expect to find this disease much more common in Kosovo, parts of Africa, and in the embattled mid-east?  Why hasn't it popped up in refugee communities internationally?)

Perhaps you could put this off until you can hold a workshop with recognized ME/CFS experts. I am confident we could pull one together quickly.

The well-respected British organization, Invest in ME , is holding a research conference May 3 in London.  I am certain they would include you if asked.  Another international research organization for this disease, IACFS/ME (International Association for CFS/ME) is meeting in Miami in October. Put this on a workshop there, or let them help you set up an earlier one. Or ask the public members of CFSAC to help you create a workshop. Ask any of us to help you create a workshop. You need to discuss the hypothesis and comparison groups with the longstanding biomedical ME/CFS community before committing to them. 

In the beginning of 2000, ignoring the existence of CFSCC, the late Stephen Straus of NIAID and CAM at NIH ran a "state of the science" meeting about "CFS" with the usual suspects (if you forgive my saying so) – the psychiatrists from the UK who have had an inordinate amount of influence on perceptions of this disease both abroad and within HHS. After pressure from Congress he relented to having ONE public member from CFSCC attend (Nancy Klimas). But Congress continued to ask for a more objective  conference. Donna Dean had just been placed as head of CFSCC, and she ran a conference the next fall that was fantastic – full of science and discussions with researchers who had previously known nothing about the disease. Unfortunately, there was a presidential shift in 2001 and CFSCC was shut down (to emerge, weakened, as CFSAC almost three years later). Dr. Dean left, and nothing happened again until 2011, when Dennis Mangan ran another excellent State of the Knowledge conference at NIH, which then came to naught. 

When researchers do not know the very long history of this disease (technically going back to atypical polio in 1934, but practically speaking, back 60 years to the Royal College outbreak and creation of the terms myalgic encephalomyelitis in the UK and epidemic neuromyesthenia in the US), they make blunders. They can be perfectly well-meaning, but this topic is a mine field and requires someone who knows the history to navigate it. I am discouraged that once again NIH is going off on its own, as if we were never here at all.

One last way to salvage this study.  Simply ditch the hypothesis and comparison groups and run it as a study of potential biomarkers in ME/CFS, without prejudging their meaning.

This is a very raw hypothesis. I love the scientific evidence you want to bring to bear, but I wish you were working on biomarkers for ME/CFS – not the physiological basis for "somatoform" illnesses.

Mary M. Schweitzer, Ph.D.

The PACE trials: a £6 million failure

There is nothing complicated about the PACE trials – or at least, there should not have been. Patients were selected to participate in a trial of cognitive behaviour therapy targeted to their “inappropriate illness beliefs” and a course of “graded exercise therapy” to get them back in shape – together this is called CBT/GET and has been proclaimed as the “best” treatment for ME and CFS by the governments of the UK, the US, among others, for two decades now.  [For an excellent critique of the PACE trial, see  David Tuller's "Trial by Error" .]

These treatments are controversial, to say the least. The main reason is that the entire programme of “CBT/GET” with regards to ME and CFS is based on the assertion that the patients’ physical symptoms have no medical explanation – in insurance (and now medical) parlance, these patients all have “MUS”s (Medically Unexplained Symptoms).

But there are numerous studies that DO offer a medical, or physiological, explanation for the symptoms. Most specifically, research has shown that high-functioning patients who fit the Canadian Consensus Criteria for ME/CFS (2003) do perform roughly the same as deconditioned controls on Cardio-Pulmonary Exercise Testing (CPET)  – but on a  SECOND day of testing, while the deconditioned controls perform the same as they did the day before, the patients’ scores drop by as much as one-half. (See, for example, Discriminative Validity of Metabolic and Workload Measurements to Identify Individuals With Chronic Fatigue Syndrome, Christopher R. Snell, Staci R. Stevens, Todd E. Davenport, and J. Mark Van Ness, Physical Therapy (June 2013).

The CPET has long been used in cardiology – and athletics – and is highly regarded as objective. It can’t be gamed. The tester puts a mask over the patients nose and mouth (or over the mouth and clamps the nose shut) so that the air going into and out of the patients’ lungs is measured by a machine while the patient rides a stationary bicycle or walks on a treadmill that gets progressively more difficult. When the patient reaches maximal cardiac effort [a pulse of (200-age) x .8], the machine records the amount of oxygen intake and carbon dioxide release – that is, it measures how much oxygen the patient inputs and how much carbon dioxide has been produced.

CPET testing of patients with ME or CFS – which has now been replicated on three continents by numerous researchers (and is into second-order studies where the patients’ blood is tested for other characteristics before, during, and after testing) has effectively demonstrated that what patients have been saying for years – and what has been recognized by the non-psychiatric school of thought regarding the disease – is both profound and measurable – patients suffer from what is called in the literature “post-exertional malaise” or post-exertional worsening of symptoms.  

This symptom is considered so profound, and so important, that the recent Report on ME/CFS from the Institute of Medicine at the US National Academies of Sciences concluded it should be a requirement for the definition of the disease.

Now, imagine a patient for whom a defining symptom is the inability to maintain the same level of exercise two days in a row. Imagine a treatment where the patient is told to (1) increase exercise daily, and (2) ignore how it makes them feel. These patients end up operating in constant anaerobic metabolism, which is dangerous for trained athletes – certainly it is dangerous for patients.

That brings us to my own principle frustration with this literature. The psychiatric literature on the disease known as ME and/or CFS does not reference the great body of literature on physical abnormalities found in the disease. Those who know nothing of these diseases who read this psychiatric literature won’t know about post-exertional “malaise” (or worsening of symptoms); won’t know about significant cognitive dysfunction and sleep abnormalities; ataxia, gait abnormalities, muscle pain; and – above all – won’t know that one-fourth of patients are either bedridden or housebound.

Here, then, is the major source of the division between QMUL/KCL and the rest of the ME/CFS community.  It has nothing to do with how patients feel about psychiatrists or psychiatric diagnosis.  Rather, the QMUL/KCL world admits to no evidence of physical abnormalities in patients with this disease – an assertion I do not believe they are entitled to make. Certainly readers should have the opportunity to choose for themselves; a full and objective bibliography should be provided by the authors, not just a bibliography of work that agrees with their thesis.

Under the circumstances, the authors of this £6 million study – which used taxpayers’ funds – are being suspiciously coy. Patients have insisted for years that the CBT/GET protocol is not just meaningless – it is directly harmful. Indeed, if CBT/GET were a pharmaceutical drug instead of a protocol, it would have been denied a long time ago on the basis of the number of adverse events.

But both the UK and the US governments continue to recommend this treatment – and they base that recommendation on the PACE trials plus the body of literature written by the schools of psychiatry at QMUL and KCL.

It is not just an academic discussion. Policy choices rest on the conclusion. Treatment choices rest on the conclusions.

It is imperative that we get this right. If the authors are wrong, then this is actually harming patients, even as I write this sentence. They would probably consider that sentence harassment. But how else am I to say it? There is evidence that the adverse events from this treatment protocol are being swept under the rug.

One million American adults suffer from this disease. 250,000 patients in the UK are also victims. This is too important not to make absolutely certain we are doing the right thing.

What I do not understand is why the psychiatrists at QMUL and KCL don’t agree with that.

A postmodernist theory of medicine: "CFS/ME" and the PACE trials

What happens when a concept developed to analyze the arts, including literary criticism, migrates to medical science?  The concept is postmodernism, and it is a very strange philosophy for a science having to do with keeping human beings healthy.  Postmodernism is defined a bit differently depending on whether you are discussing postmodernism in architecture, the visual arts, or literary criticism.  However, there are a few basic elements:

• Rejection of a metanarrative
• Rejection of the modernist concept of progressivism - that knowledge improves over time
• Emphasis upon perception over “reality” - to some extent, a rejection of reality itself in the belief that we can only know perception

I am sure there are other ways to characterize postmodernism, but I think these three precepts run through most theories based upon postmodernism.

In this essay, I am going to suggest that there is a school of British psychiatry called “biopsychosocial” which is effectively postmodernist - a most peculiar theory upon which to base the diagnosis and treatment of real human beings in real time.  The patients who have born the brunt of this school of thought are those afflicted with the condition Myalgic Encephalomyelitis (ME), which (by way of a detour through “chronic Epstein-Barr virus”) became known as “chronic fatigue syndrome” in 1988.  It’s not a minor or rare illness - millions of patients worldwide have the disease; over one million in the US and 250,000 in the UK. 

ME, the disease, is based upon a set of symptoms having to do with muscle failure, cognitive dysfunction, “unrefreshing” sleep, and pain.  Perhaps the most unique symptom of ME is a delayed response to exertion, what patients call a “crash,” which can last days or weeks or even become permanent.  The most seriously ill patients with this disease are confined to wheelchairs, bedridden, even on feeding tubes.  It would hardly seem the best choice for a medical theory of postmodernism.

In contrast, “chronic fatigue syndrome,” or CFS, fits the bill for postmodernism perfectly, because it is almost entirely based upon perception - the perception of fatigue.  

ME was first diagnosed in the 1950s to characterize three large outbreaks of disease in the UK, the most famous occurring at the Royal Free Hospital in London as a new term for a condition that had been observed since 1934, “atypical polio.”  With polio supposedly conquered by vaccine (which only contains the 3 strains of polio considered most severe), medical researcher and clinician Melvin Ramsay, along with several colleagues, sought to define a condition that appeared to occur in cluster outbreaks, like polio, but had somewhat different characteristics.  ME was adopted by the World Health Organization in 1969, coded within the chapter on neurological conditions in WHO’s International Classification of Diseases (ICD).  It remains there in ICD-10, the current version.

In 1970 and 1971, psychiatrists McAvedy and Beard published two articles claiming that ME was actually mass hysteria (interesting time - just as psychiatry lost the diagnosis of hysterical paralysis for Multiple Sclerosis, they found a substitute in ME).  Psychiatrists jumped on the name change to CFS in 1988 - in particular, a group of British psychiatrists who declared themselves to be practitioners of something called “biopsychosocial” medicine:  most notably Simon Wessely, Michael Sharpe, and Peter White.  

The “biopsychosocial” school consisted mainly of the claim that its adherents practiced a holistic vision of medicine combining biological, psychological, and social factors - but in practice, very little was ever said about biology.  When the biopsychosocial psychiatrists were asked about the absence of references to biomedical research in their work, they tended to snap back with the non sequitur that the suggestion showed an adherence to “Cartesian mind-body dualism,” and prejudice against psychiatry in general.  

According to these psychiatrists, “CFS” and “CFS/ME” (their terms) was caused by “inappropriate illness beliefs.”  The patient had actually had an illness such as a bad flu in the beginning, but instead of going back to their normal lives after the virus was over, they became afraid to do too much in fear that the symptoms would return.  The result of their inactivity, deconditioning, became the evidence that they were still sick.  The cure could thus be found in a specific form of psychiatric therapy, cognitive behavior therapy (CBT) - to teach the patient that she wasn’t really sick as she thought - and graded exercise therapy (GET) - to get the patient’s body reconditioned.  The combination of positive thoughts about improvement and actual improvement caused by the exercise would therefore “cure” the patient.

The biopsychosocial school, in practice, is postmodernism as medicine:

• Rejection of a metanarrative - in this case, the authors claim to be rejecting outdated beliefs in “Cartesian dualism” that would differentiate between “biomedical” research and “psychiatric” research.
• Rejection of modern concepts of progressivism - the authors reached back to the nineteenth century diagnosis “neurasthenia,” citing books written in the mid-1800s about “nervous disorders.”  Their research, they insisted, was not driven by pure theory but “evidence-based.”  “Evidence-based” obviously sounds like a good idea, except that in this case it was based upon “evidence” from clinics where patients had already been diagnosed using their theories - it was, in effect, a tautology.  But they could then insist they did not have to reference research driven by path-dependent theories linked by time, or answer to critiques of neurasthenia over the past 150 years.  They were only studying the present.  
• Emphasis of perception over reality - the patient only THINKS he or she cannot behave like healthy adults.  It is the perception, these “inappropriate illness beliefs,” that need to be changed.  The cure, then, is to be found in treatments that change that perception both literally, through CBT, and changing the experience itself, through GET.  

It is in this context that I think we can best understand the £5,000,000 study commissioned by the UK government called the “PACE trials.”  The PACE trials were supposed to prove once and for all whether the prescription of CBT/GET could cure the disease the authors called “CFS/ME.”  Since the authors made their living - to a large extent - on the basis of this thesis, one would think the results would be evaluated using a fine tooth comb.  But no sooner had they been published than critiques arose from the community of patients afflicted with the disease, and those who either treated or studied it.  

Patients with backgrounds in medicine, science, and/or research were unable to break through to the public with their critiques.  Many of them asked to see the data behind the study to understand how the conclusions reached could possibly have arisen from the study.  Their requests did not exactly fall on deaf ears - to the contrary, the researchers complained both privately and publicly (in the press) that they were being harassed, the requests for data “vexatious.”  No data was released.  

Four years passed.

This fall, (2015), David Tuller, a Berkley journalism professor who had followed the disease for the New York Times and other outlets, wrote a detailed critique of the study, which was published on the blog site of noted Columbia virologist Vince Racaniello.  There it drew the attention of James Coyne, a clinical health psychologist who has spent several years focusing on deception in research.

In fast succession, a new request for data was filed - and refused. Queen Mary’s University London (QMUL) and King’s College London (KCL) both insisted that the request was without basis, that it was intended only to harass the authors - that is, that it was “vexatious” - and they refused to comply.

For an excellent rundown of where we were in the story as I wrote this essay (12 December 2015), see:

PACE Trials - Forbidden Fruit

Elsewhere on this blog, Slightly Alive, you will find testimony to CFSAC and FDA on my condition, testing, and the experimental immune medicine which enables me to be able to write this essay. 

Here, however, I wanted to add something new to the debate.   What happens when theories inspired by postmodernism encounter a discipline that requires the belief that there is a there, there - there is a real patient, the real patient has a real body, and real things go wrong with that very real body.  The result sounds like scholarship.  It sounds erudite.  But in the end, you cannot separate perception from reality in this manner.  You cannot simply assume that the only problem with a patient is his or her perception of their health, on the basis that (in insurance industry language), the patients’ problem boils down to “medically unexplained symptoms” (which has even earned an acronym, MUS).  

Aside from the costs to the patients who actually have the disease in question, ME, these theories are very dangerous to the larger discipline of medicine.  Just because symptoms have no “medical explanation” does not mean they are based solely upon perception.  No physician can possibly explain every medical symptom - and there are conditions that have yet to be explained.  The absence of an explanation is not proof of the absence of a medical condition.

But in the world of “biopsychosocial” medicine, the absence of an explanation is precisely that:  proof of the absence of a medical condition - of a purely medical condition, they would probably say.

Medical science needs to understand that this theory does not just apply to ME/CFS, and does not just apply to “MUS” conditions.  Simon Wessely, for example, has already applied it to Gulf War Syndrome. 

This is an enormously useful political concept in the current atmosphere of austerity.  Applying CBT and GET is a lot less expensive than testing for immune defects and pathogens, looking at SPECT scans and CPETs, treating with immune modulators and antivirals.  

The British government, which has much to gain from this theory that “CFS/ME” is perception rather than reality, and these researchers, who directly profit from that theory, were hardly disinterested parties to join together in conducting the PACE trials.  The same goes for the institutions SMUL and KCL.

As such, they are not really in a position to reject mounting requests for an independent review of the study.  They should not be permitted the final say.  

The ramifications of their intransigence are great.  There are many conditions to which this new postmodernist view of medicine could be applied, greatly cutting costs without benefitting people in need of care.  The risk is greatest with chronic illness.  It is hardly a secret that both insurance companies and penurious governments are concerned about the mounting costs of chronic illness.  What a convenient theory for such an austere time.  

The authors of the PACE trials (and those who funded the study) must not be permitted to slip away without a thorough examination, because too much is at stake.  Postmodernism and medicine are not a happy coupling.  The effort to join them must undergo even more scrutiny than usual, because what is being tried here is most unusual.  

It is highly unlikely that the authors of the study willingly would allow that data to see the light of day, because so far the evidence suggests the data cannot support the conclusions - and too much is riding on those conclusions.  

If the most basic rules of scholarship are permitted to be broken here, where then will they be enforced?  CFS/ME is merely perception.  Global warming is just biased statistics.  “Fracking” has no effect on the environment.  That may be your “view”, but my “view” is just as important. 

After all, it’s only perception.