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.