P2P: Eating Your Cake

OxfordIn a surprising move at the P2P Workshop yesterday, Dr. Beth Smith from the Evidence Practice Center (authors of the systematic evidence review) suggested: “Consider retiring the Oxford case definition.”

Why was this remarkable? Because the systematic evidence review had included Oxford studies, despite acknowledging that the definition may include people who do not have ME/CFS. Perhaps the Evidence Practice Center heard the well-supported criticisms from myself and others, because in revising their report they said: “Treatment trials . . . should refrain from using the Oxford case definition because it is less specific for ME/CFS than the other definitions are.”

But when I asked a question about the suggestion to abandon Oxford . . . well, here is what I said:

I would like to go back to Dr. Smith’s suggestion that the Oxford definition should be retired. The evidence review rated at least one Oxford study, the PACE trial, as good quality. And Dr. Snell quoted from the PACE trial manual about the assumptions behind CBT and GET treatments and the inappropriate patient selection in those types of studies.

So as a former attorney, I hope you will forgive my leading question: If the Oxford definition should be retired – and it should – doesn’t that lead to the obvious conclusion that Oxford studies should also be retired, at least as applicable to the ME/CFS population?

Dr. Smith’s answer was not quite logical. After reminding me that a “good” rating refers to methodology and not the possibility that a study was biased, she said that it was still good to cast a broad net in designing studies.

The Evidence Practice Center (and perhaps AHRQ and NIH?) cannot have its cake and eat it too. If Oxford captures people without this disease, then you CANNOT use Oxford studies to draw conclusions about people with this disease. It makes no sense to say the definition is flawed, and that it should not be used in future treatment trials, and then try to grip the Oxford studies in your sticky fingers by saying it’s good to cast a broad net.

The first step in designing a treatment trial or other study is to Define. Your. Study. Subjects. Define them clearly and accurately. It goes without saying that if you want to study a disease treatment, then you should study people with the disease.

Science moves on. That’s its purpose. Science is iterative, and as data are accumulated and advances are made, methods and approaches change, too. If the Oxford definition should be retired because the data show that it is inaccurate and flawed in describing people with ME/CFS, then all the data derived from using that flawed definition are suspect.

Chris Heppner was quite prescient in urging us to declare independence from the Oxford definition. Perhaps the P2P Panel will have the logic and common sense to do so, too.

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48 Responses to P2P: Eating Your Cake

  1. Grail says:

    They sure were excited to have the XMRV papers recalled. Oh, yeah, PACE fits the insurance corporations’ policy preferences.

    • Jennie Spotila says:

      Dr. Fletcher and Dr. Snell did a nice job pointing out that CBT/GET is cheap.

    • GKGK says:

      Has there ever been a peer reviewed publication claiming to have found errors in PACE? That’s a serious question. I know that Dr. Sheppard wrote a very long and detailed critique, but did it ever get published in a peer reviewed, indexed journal? I’ve read several letters-to-the-editor, but those aren’t peer reviewed, either. Having thousands of messages posted on line describing mistakes in PACE is one thing, but having a couple of publications in scientific journals is quite another.

      If you want scientists to disregard a paper published in a reputable journal, you are going to need evidence also published in a reputable journal, and I don’t remember that there is any.

      Later in this thread, people argue that if the Oxford criteria is phased-out, then shouldn’t PACE be similarly decommissioned? But the PACE researchers reviewed their findings, using just the subset of patients who met another standard (Fukada? CCC? I don’t remember which one.) and found no statistically significant difference. So even if Oxford was no longer used, you would have to also decommission that other standard also.


  2. Polly Gilreath says:

    Thanks, Jennie, for sharply phrased and pointed questions (I could hear the lawyer in you.). Beth Smith was flummoxed and never did answer your questions!

  3. floydguy says:

    The definition problem is certainly a core issue. It’s remarkable that people with PhDs can state that the population of a study isn’t that important – all that matters is process. Clearly they have spent too much time in the world of NIH and other bureaucracies.

    And you haven’t even brought up the issue that the ICC doesn’t require “fatigue” as a defining “symptom”. Yet every statement still defines “CFS” as “extreme fatigue” with possibly some other whiny complaints.

  4. Cheshire (France) says:

    Your question was clear, articulated and necessary.
    Their answer was just the opposite: blurred, illogical.

    Thanks a lot.
    I hope you’re not paying the price of being there to hard.

  5. N A Wright says:

    I actually think that Smith’s reply to you is logical. As I’ve tried to outline in a reply to Chris Heppner’s post, one shouldn’t confuse the failings of 1990 with the failings of PACE in 2007. PACE (at least its conclusions) fails on far more grounds than just patient selction. As you say science is iterative, but that implies acceptance of work that has preceded, even though the failings of that work are understood. In that context Smith’s reply is sound because science doesn’t just discard all that has gone before, by and large it seeks to build upon it. In the case of errors, that involves taking on the errors and adjusting accordingly. As I understand it there will be an opportunity to respond to the P2P report, I would urge responders not to get lost in the historic problematics of what the Oxford Definition does or does not encompass, but to identify it as no longer fit for purpose in future research, and quite separately to address the failings of PACE as a either a bridging point for future research, or as definitional of useful interventions.

    • Chris says:

      A response to N.A. Wright’s two responses to my recent blog and to Jennie’s current blog.

      I strongly support Jennie’s wonderfully sharp questions and her seconding of the notion that not only should the Oxford definition be retired, but that studies based on it should also be retired: as she states,” if you want to study a disease treatment, then you should study people with the disease.” Sounds definitive to me. Sensitivity and specificity are the two main criteria by which diagnoses are judged, and the two NIH projects running this year propose the examination of diagnostic criteria as a main objective, while rejecting the CCD for unspecified reasons. One does not accumulate inappropriate and failed diagnoses, one replaces them with better ones. The CCD was developed into the ICC, but was written as a replacement. Leonard Jason has pointed out some possible problems with it, and we await a fully reworked and improved replacement from some source, I hope.

      I don’t think we are being in the least “fetishistic” in focusing on the Oxford definition–it lies behind the many studies using CBT and GET that are based on the specific sense given to that key “symptom”, that “subjective sensation,” that has opened wide the door that leads towards “medically unexplained symptoms” and then forwards into the land of somatization, etc etc. It enabled those many studies that explicitly allow entry to those with depression but possibly not CFS/ME that found funding, and now weigh so heavily among the relatively few interventional studies. It is not of course the only problem, but it has played a key role. It sounds as if you are still resisting that key component of the Oxford definition–that the only required “symptom” is a “subjective sensation” unsupported by any physiological processes. I hope to write more on what has flowed from that belief–and that is exactly what it is, a belief–a concept unsupported by any physiological evidence.

      I am glad to see that you agree that there are many other problems with the PACE study, but those failings are not I think so much “confused” with the failings of the Oxford definition as supported by them. I am also going to disagree a little with both Jennie and you about science being an “iterative process, in which denigrating past efforts isn’t necessary, it is only required that an improved position is demonstrated”– and quite honestly I don’t know what your phrase “taking on the errors and adjusting accordingly” means. I really don’t. Sorry, but it ain’t always so–reread Kuhn, “The Structure of Scientific Revolutions.” Sometimes science progresses in a cumulative manner, but sometimes it makes a major paradigm leap. Either the world goes round the sun, or the sun goes around the world; yes, gravity works in both directions, but still… Either “refrigerator mothers” cause autism, or they don’t. Either masturbation causes schizophrenia or it doesn’t. And in our own time, first read Mukherjee’s “The Emperor of All Diseases,” with its focus on surgery, viruses, and then genetics, and then read Thomas Seyfried’s “Cancer as a Metabolic Disease”; we may be witnessing another major revolution. As Kuhn argues, it is often not enough to demonstrate “an improved position” for real change to occur. Stomach ulcers had to wait 18 years and 3 self injections with a bacterial agent for change in treatment to begin. Or as Kuhn says, one may have to wait until a whole generation of scientists die before a new generation can implement change. We would like it to occur a little faster than that. I absolutely fail to see the logic in your defence of Smith’s reply to Jennie.

      Back to the request that the Oxford definition should be retired, and that in addition studies based on it should also be withdrawn from consideration when talking about ME. I recall one such study that acknowledged that 20% of the study population was on “full-dose” anti-depressants. If that helped those patients, well and good–but should they have been included in a study of CFS/ME patients? Or, if there really is a substantial CFS/ME population for whom depression is genuinely a co-morbidity, and not just a result of years of fighting a losing battle against both the disease and the treatments or lack of treatments available, then let that population be described properly as a sub-group, and their results not simply be blended into the whole.

      On the specific critique of my singling out Wessely and Wright and ignoring Clare, you have a point about Wright, but I am less sure that you are right about Wessely. Clare’s record does show some earlier interest, but nothing like the cluster of essays published by Wessely (not always the sole or first author) between 1988 and 1991. He had already had a significant career in such areas as military psychiatry, and I would suspect may have been a very active participant, though that is only a guess, and I have no transcript or other evidence to back that up. I did ignore the others, I confess, and looking up Behan and Chaudhuri produced some interesting papers post 1991–but note that the Oxford definition makes a very clear distinction between CFS and PVFS–one or the other, choose. Their later papers sound interesting, and in large part because they are totally incompatible with the Oxford definition–they are tracing gene expression and stuff like that–in other words, those excluded physiological events–not “subjective sensations.” In any case, I am much more interested in what effects the Oxford definition has had than in how the signatories arrived at that position. That is their affair–the effects they have had on us are ours.

      Finally, a quick note on your reference to “art pedants”; I chose Poussin because I suspect there are 10 who have heard of him for 1 who has heard of Guercino. I chose this reference just to round out the little encapsulating autobiographical reminiscence with which I began–self-indulgent, maybe, and if some found it offensive or pedantic I apologize. I spent most of my working life in academia, much of it on the interface between literature and art (see “Reading Blake’s Designs,” Cambridge, 1995), and as they say you can take the cook out of the kitchen, but it is hard to take the kitchen out of the cook. Perhaps it is relevant that the book proposed a new paradigm for how to read Blake’s pictures, one that was by no means accepted by all–but oddly enough, nearly all accepted the final detailed reading of Blake’s most complex painting as representing a major step forwards–even though it depended throughout on my application of my new paradigm. Go figure.

  6. Catherine says:

    Thank you from my heart for your advocacy. Just watching the proceedings online yesterday from my recliner flattened me today – I hope your payback time is short. Thank you for holding them accountable, and cutting through to the questions that matter.

  7. Catherine says:

    I appreciated Dr. Kogelnik’s presentation yesterday. However, there was a huge hole in his presentation, namely, that follow-up studies on Rituximab would not have happened but for advocacy and patient crowd-funding.

  8. The PACE trial was rated “good”? And she referenced Snell et al saying they were REFUTING the PACE trial as evidence to stick with it?

    Why don’t they just stick us in NIMH (Natl Institute for Mental Health)? Rhetorical question – I imagine the professionals over at NIMH don’t believe the Wessely-White claptrap.

    Hopeless. Sigh.

  9. Oopsv- that was you who referenced Snell.

    SOoooo, we should take a broad approach to scholarship. Well then, I expect to hear more about XMRV.

    • As I was reading the responses to Jennie’s fabulous blog, I was thinking exactly the same thing Mary. Selective retraction seems-well-flawed, just as flawed as many studies for not having the right patient population, just like using one’s own database to prove a hypotheses as we have seen with Wolfe and Hauser with FM-supposed-research.

      The wheels of justice turn very slowly. Baby steps in the right direction are far better than a giant leap backwards, which has happened with the 2011 ACR Wolfe diagnostics for FM.

      Kuddo’s to Jennie. Onward and upward.

  10. Russell Fleming says:

    Has Oxford been used in any recent research? How might I find out? I am thinking in research since PACE perhaps. I seem to recall a couple of studies – details escape me now of course – but they also used other criteria as well.
    I don’t think science works as you might like, it does tend to build and seeks improvement, but of course the fear remains that if Oxford is considered usable by some it will be used and the results jumped upon.
    However, we do I think have to trust and advocate that – as Lenny Jason was so eloquently indicating – Oxford is defunct. Actually I felt – though I have only been able to listed to the P2P at the opening – Lenny Jason’s presentation was very strong and should be carefully noted by all concerned including what he said about the ICC-ME.
    Nice also to see him mention the London criteria which rarely if ever gets a mention but I think resulted in his work in the tightest definition of ME.
    Of course whether or not these ‘tight’ definitions are actually revealing the ‘true’ face of ME remains in my view to be seen.
    I do think Lenny is right, we need better: and I will be taking a closer look at what he had to say.
    Thanks Jennie as always.

    • GKGK says:

      I thought of this also. I don’t remember many recent studies using Oxford. I hope some one else does a more comprehensive review, but I looked at about 15 studies at clinicaltrials.gov, which were aimed at “CFS” had been entered into the system this year, and were still recruiting patients.

      Of those studies, none said they used the Oxford criteria for admission. One talked about fatigue for 6 months (so might have been using Oxford). Two or three talked about people diagnosed with CFS or ME without listed the exact criteria. But the most common criteria was Fukada, and the second was CCC. Several studies required both.

      So I think it’s far to say that most studies done now use Fukada or CCC or both, and very few (less than 10%) use Oxford or anything like it.


  11. Tina says:

    I may have misunderstood. I’m not well at the moment. But I understood her to say it’s best to cast a broad net in her analysis of the research, not that individual studies should cast a wide net.

    Although I do think it’s good for them to consider Oxford studies, if for no other reason than to say they aren’t good. And their report does point out the flaw in measuring recovery. Up ’til now, not been a lot of scientists give attention to that issue. I’m sure Tom Kindlon did and some patients did in that cute video. But now we have this scientific panel pointing out flaws.

    But, I thought Smith’s response that it’s good to not discard Oxford studies because some good can be found in them should be challenged. What good? If the people in it don’t have our disease, who does it do any good in understanding our disease?

    Well, the net result is good. Unger agrees Oxford should be retired. We have a swell building. And for that we can thank this P2P process. I think the end report will have some good, but not be perfect. I think the speakers and questioners did a great job. By the way, I submitted 7 comments today. Three were repeats of what I submitted yesterday. They said they didn’t receive but four so resubmit.

  12. Michael Allen, Ph.D. says:

    Thanks Jenny for your astute comments. There’s an old expression I learned in grad school regarding research that applies to the PACE Trials, “Garbage-in, Garbage-out”. If the subjects as defined by Oxford include people who do not have ME and are likely to suffer from depression than it the study itself and its results are pure garbage. From the perspective of the history of science I’d say PACE is very useful: as an example of bad science, not to be repeated or invoked.

  13. Cecelia says:

    I appreciated what you said and how you said it. Then the illogic of the response, focussing only on the methods employed in that PACE study WITH THE EXCEPTION OF A VALID CASE DEFINITION, made me feel confused and discouraged. How can the methods in a study be approved of if the case definition is not specific to the population supposedly being studied?

    30 years ago, when getting a Master’s in Counseling, I learned that studies of treatment modalities for depressed patients showed only two forms of treatments which were successful with that population. These were CBT and exercise. (This was before the days when anti-depressants took off as the main treatment.) Broad, non-specific definitions for CFS include a lot of depressed people, possibly more than those with genuine ME/CFS since depression is much more common. That is why those treatments must have been chosen and why they have failed our patient population. But until we have a case definition which distinguishes us from those with primary depression, our treatment will go no where. And that is depressing!

  14. rivka says:

    thanks for writing, and for being there and asking key questions.

  15. John says:

    I don’t know if excluding Oxford will have any effect since those idiots just came up with the even more inclusive definition in NICE. It’s like goddamn never ending whack-a-mole with these numbskulls. You have to recommend what you want, not what you don’t want.

    • Emma says:

      “You have to recommend what you want, not what you don’t want.”

      Very good point!

      Thanks to Jennie for your hard work. I hope you get through the crash it will surely cause.

    • Jennie Spotila says:

      Agreed. We tried to emphasize that NIH should study the disease we actually have, one that is characterized by PEM.

      • John says:

        In the CDC multi-site study, I think Dr. Unger has stated that not everyone reported having PED (post-exertional debility) so she doesn’t think PED should be mandatory. Dr. Jason has been quoted as saying that the amount of people who report PED varies according to how the question is asked. Any info on how the PED question was asked in the multi-site study?

        Also, even if some patients don’t have PED, PED seems as good a point as any to cleave patients into different groups. You have debilitating PED after even trivial exertion? You go in this group. You don’t experience such a distinctive and abnormal reaction after exertion? You go in that group. Capeesh?

        • Jennie Spotila says:

          Actually, Dr. Unger data show that 98% of subjects had PEM assessed by at least one questionnaire (as opposed to 84% based on chart review). The Multisite study used multiple questionnaires including the DePaul Symptom Questionnaire. In a document submitted to IOM, Unger said that she wasn’t confident that DSQ items like “heavy feeling after physical exertion” related to PEM.

          The key point is that 98% of multisite patients have PEM according to at least one measure. The multisite was designed for the seven clinicians to identify reference cases, people who definitely have ME/CFS. So why doesn’t she trust her own data?

          I would argue, along with many others, that people who do not “experience such a distinctive and abnormal reaction after exertion” do not have ME, as that is the defining hallmark. If you don’t have that symptom then you have idiopathic chronic fatigue or another undiagnosed disease. I await data that prove me wrong.

          • John says:

            That’s very interesting and also pretty incensing. What the hell is she talking about then that PED shouldn’t be a mandatory requirement? PED, sleep dysfunction and cognitive dysfunction = should be good to go, right? No need to complicate things by requiring 28 of 64 other symptoms from 17 of 24 different categories that no one is going to even bother to read about.

            I also appreciate Luis Nacul’s reported comments that specificity is better than sensitivity, ie it’s better to have less numbers of definite cases than more numbers of possible cases. Duh, right? Why the hell does it take decades for such obvious things to start coming to the mainstream?

          • jim says:

            Even though it seems to be a simple “yes I have PEM” or “no I don’t”, the reality is, of course, much more complicated. What about folks who control their energy envelope so well that they manage to avoid PEM? What about folks who are always beyond their envelope, so they are always in PEM, so have no non-PEM days to compare with? And then there are the people who have overall mild symptoms, are only recently ill, perhaps they are actually experiencing PEM but the symptoms are mild enough that they don’t stand out from the other constantly fluctuating symptoms.

            There is a fairly simple way to deal with all this by describing ME as requiring PEM, and describing ‘atypical ME’ for patients without PEM. Obviously we want research to concentrate on patients with PEM.

            But none of this will happen via NIH/CDC. Their agenda is to bury the disease, and kick the can down the road until Our Dear Leaders can wangle a nice position in the private sector.

  16. Mary Dimmock says:

    Great points, Jennie and I agree that Dr. Smith’s response was not logical – or medically ethical. You can not recommend treatments for one group of patients based on studies in another group of patients.

    Also, her continued defense of a GOOD rating for PACE was illogical since patient selection methods are foundational to the entire study. Even if everything else is perfect, you have no idea who it applies to.

    The problems with Oxford also apply to a lesser extent with Fukuda. Dr. Jason said that studies done with Fukuda have stated that between 25% and 100% of patients have PEM. That means that as few as 1/4 of those patients would meet Canadian and would instead have some other condition. Dr. Nacul has shown that only about 50% of Fukuda patients also meet Canadian. Dr. Nacul also stated that there are over 160 different combinations of Fukuda criteria and most of them do not require PEM.

    So depending on the investigator and the instruments that they use, a substantial number of patients in Fukuda studies may not have ME.

    To the point that you, John and Emma made, we need to be clear on what is needed – a definition like the CCC or the ME-ICC that describes ME with its hallmark PEM and cognitive dysfunction,

  17. Jerrold Spinhirne says:

    The Fukuda CFS criteria should also be retired. They have produced 20 years of unreliable, difficult to apply research. Their optional criterion of PEM is never described clearly enough for doctors or researchers to recognize it.

    This is the complete description of PEM from the CDC CFS Toolkit: “Extreme, prolonged exhaustion and sickness following physical or mental activity.” CDC PEM could simply be the result of deconditioning or a personality tendency to overdo things like play too much golf on a hot day. Who knows?

    This is the description of required symptom of PEM from the CCC:

    “Post-Exertional Malaise and/or Fatigue: There is an inappropriate loss of physical and mental stamina, rapid muscular and cognitive fatigability, post exertional malaise and/or fatigue and/or pain and a tendency for other associated symptoms within the patient’s cluster of symptoms to worsen. There is a pathologically slow recovery period–usually 24 hours or longer.”

    Unfortunately, the CCC still uses CDC fatigue terminology to describe this characteristic feature of ME. PEM could also be called post-exertional fatigue according to the CCC. What fatigue isn’t post-exertional? That would be unexplained fatigue. The CCC also requires 6 months of unexplained fatigue that isn’t the result of exertion. Despite their advances over Fukuda, the CCC are still a fatigue-based case definition.

    This is the description of PENE from the ICC:

    “Normal fatigue is proportional to the intensity and duration of activity, followed by a quick restoration of energy. PENE is characterized by a pathological low threshold of physical and mental fatigability, exhaustion, pain, and an abnormal exacerbation of symptoms in response to exertion.”

    It is followed by a prolonged recovery period. Fatigue and pain are part of the body’s global protection response and are indispensable bioalarms that alert patients to modify their activities in order to prevent further damage.

    “The underlying pathophysiology of PENE involves a profound dysfunction of the regulatory control network within and between the nervous systems [36, 37] This interacts with the immune and endocrine systems affecting virtually all body systems, cellular metabolism and ion transport. [38]”

    “The dysfunctional activity/rest control system and loss of homeostasis result in impaired aerobic energy production and an inability to produce sufficient energy on demand. A test-retest cardiopulmonary exercise study revealed a drop of 22% in peak VO2 and 27% in VO2 at AT on the second day evaluation. [39] Both submaximal and self-paced exercise resulted in PENE. [40] These impairments and the loss of invigorating effects distinguish ME from depression.”

    It’s easy to see why the authors of the AHRQ “ME/CFS” report were intent on misrepresenting the ICC as another fatigue-based case definition. PENE is not fatigue-based and is objectively measurable. HHS does not want the ICC ME definition to be used for research because it would lead to the unravelling of the CFS fatigue illness the CDC created ex nihilo – out of nothing.

  18. Alex Young aka alex3619 says:

    On PACE, my opinion is the studies are so seriously flawed, with such deeply entrenched flaws, that every PACE paper by the people who ran the study should be retracted.

    It is very much a case of selective retraction.

  19. Freda says:

    PEM was the first symptom I noticed- out of the blue walking and swimming made me feel ill. Not really bad but enough to cut back my exercise and then drop it. Now I try to keep my heart rate under (220-age)*.06= 100 and rest and if I do pretty much all the symptoms drop away. Yep I am left resting doing much feeling a box of birds…until I do too much i.e. I walk down the drive or buy groceries then it is a 5 day slow recovery.

    PEM is weird, distinctive and NEW for almost if not everyone with ME.

  20. kathy d. says:

    You all have a lot of patience. All I see is one step forward and one step back.

    Where are we in all this at this point? Will it make a difference in the
    committees’ recommendations to the government? And to the insurance
    companies which are aiming to avoid paying for this disease’s treatments,
    doctor visits, medications.

    And, yes, CBT and GET are cheap. GET is free. And CBT is counseling
    for 6 weeks? Much cheaper than years of doctors’ visits, tests, medications.

    We’re all getting older; some of us are getting sicker as we age, have less
    stamina, have more symptoms than ever.

    And I’d call the reality of PEM actually PEC, post-exertional collapse. Malaise
    is such a poor word, doesn’t convey anything particular about this disease. It flattens us if we do too much, and for us, that isn’t much at all.

  21. Kathy D. says:

    Or PER, post-exertional relapse.

  22. Heidi says:

    Yes, you can define ME as having PEM; and define PEM as flunking a two-day exercise test. (Nothing to do with questionnaires.) Very simple. Study the people who flunk the two-day exercise test, use that to come up with a less damaging test for clinical use.

    The only possible reason to argue about every step of that very simple line of thought, would be to prevent it from being implemented.

  23. Ecoclimber says:

    Scientific research papers must include all the data so that other scientists can reproduce or replicate the results. Whenever researchers refuse to release their data as in the Pace Trials even under the FOIA, then the data and the results must be suspect. Replication research is required as a standard in all medical science for the results to be accepted and verified by the scientific community as it was the case of XMRV. Therefore, the same standard and level of threshold must be applied to all ME/CFS research.

    Without this level of verification and replication, the Pace Trial results must be considered as invalid without further proof and the requirement for the release of all the data including data on the co-mingling of cohorts which include individuals who suffered major depressive disorders and not ME/CFS. Such suspicious behavior on the part of the authors of the Pace Trial for failure to disclose, gives rise that they are hiding or manipulating data.

    In addition, stating full patient recovery from ME/CFS using CBT/GET is committing fraud on the scientific community when their definition of full recovery is a 6 minute walking test.

    White PD, Goldsmith KA, Johnson AL, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet.
    2011;377(9768): 823-36. PMID: 21334061.

    Full recovery means the ability to accomplish the same level of activity as before the time patients were stricken with ME/CFS. There is no employment available for individuals who can walk for only 6 minutes. If the researchers believe that this is not the case, then they should list all job offerings for those that can only walk for 6 minutes in an 8 hour shift since patients are denied and/or no longer qualified for disability benefits once they are deemed recovered.

    It is ludicrous and disingenuous to perpetuate this kind of flawed research by particular psychological spinmeisters who believe they are immune from the requirement of adhering to the scientific method as required by those in medical research field. Especially since other prominent researchers in their field have conducted research stating that CBT/GET is not effective in treating patients.

    Because there is disagreement within their own field on the efficacious of this protocol, one can only speculate or surmise on whether or not such ridiculous research and conclusions are heavily influence by lobbyists from the health/disability insurance industry since they affect the medical policy of governmental agencies. Do they have the patient’s interest and recovery in mind or the profit margin of the insurance industry?

    As a patient recruiter on a ME/CFS patient research project for a world renowned research scientist, an excellent patient cohort would require that patients had no prior history of psychosomatic disorders, lived an active and healthy lifestyle with no major medical issues prior to ME/CFS and who were diagnose with ME/CFS by a competent clinician after a post viral infection, toxic or bacterial exposure, vaccine and who met the 6 month period of exhaustion requirement and furthermore met the additional CCC and ME-ICC criteria established by ME/CFS medical researchers and clinicians. Other prior medical conditions or treatment should also be established for exclusion such as MS, Lupus etc. The Oxford and Fuduka requirements fall well short of this standard.

    Fuduka and Oxford must be retired and all relevant research based on each of those criteria be discarded. This isn’t rocket science just plain use of common sense. It is not all that difficult to filter out patients that do not meet the above requirements. Or is the real purpose of the P2P to build-in a bureaucratic smokescreen to cover-up or cloud over their bias against the medical aspect of this illness?

    The astounding advancement of medical research and technology is constantly evolving and breaking new thresholds of discovery that will bring to light the etiology of many diseases.

  24. Chris says:

    Eccoclimber, while agreeing fully with most of your critique of the Oxford and much of the Fuduka, I will make two points. One is that we heard evidence from the P2P workshop that issues like the incidence of PEM in Fukuda studies could very greatly because of differences in how the diagnostic criteria were applied. There are a good many good and helpful studies done under the banner of Fukuda, and we might lose more than we would gain by retiring them, though it would be good if researchers stopped using it-and recall that many of the top researchers in the world did declare for the CCD.

    The other small point is that I believe the 6 minute walk test is not a test of whether or not a patient can walk 6 mins, but of how far they can walk within that time limit. The distances changed really very little in the PACE trial.

    • floydguy says:

      I agree with Eco. The Fukuda definition is only marginally better than Oxford. After 20+ years neither have proven to define a discrete patient population. I disagree with the notion there are any good studies that have come from Fukuda: there is no objective diagnosis improvement, no “officially” agreed upon treatments and certainly no respect for patients. It is still all about “fatigue” and other complaints that 99% of the medical establishment believe can be treated with an anti-depressant. I say start over. We’ve been going the wrong way for 20+ years. Let’s stop digging the hole deeper!

  25. Kathy D. says:

    Not totally on topic here because everyone is elucidating every point on this topic, I want to say here that I was very disappointed that writer Laura Hillenbrand did not mention ME/CFS when she was on NBC last week with Tom Brokaw and Angelina Jolie discussing the new movie that just came out based on her best-selling book “Unbroken.”

    I kept waiting and waiting for her to name her disability. It was said by Brokaw that she’d had many difficulties, had been exhausted and had terrible vertigo. Hillenbrand said that she had many days where she couldn’t walk outside.

    But at the exact time that we need validation because of funding issues and government inaction, this author who had a venue to raise this disease — even name it, did not do it. This was a huge disappointment to many of us.

    She had a terribly difficult time getting a medical doctor to validate her disease years ago. It took many doctors’ visits until she got a diagnosis. And when she was going through this, other ME/CFS sufferers sympathized with her and supported her. And
    we still do.

    She is the most well-known person with our disease. She had a podium. She should have used it. Her book has been on the New York Times’ bestseller list for more than three years. She’s successful enough that she would not have jeopardized her career.

    I wish she would publicly speak out. It would help us a lot, while two government committees are not promoting more research funds and are promoting GED and CBT instead of real medical treatments.

    • Jennie Spotila says:

      Laura has spoken out about her disease for years. If you have not read it, her article in The New Yorker, “A Sudden Illness” is amazing and won a national award. She has been open about ME/CFS in interviews ever since and supportive of research efforts. Laura has done a lot for us, and it’s not fair to judge based on one interview especially since we don’t know what got edited out of that interview.

  26. NA Wright says:

    @Chris. Retiring a set of criteria does not imply abandoning all that went before, merely that those critria it would not be used in future research. That is an entirely sensible way to progress. Few medical studies are perfect for all time, new science forces change on previous understanding and criteria have to change as part of that, but it doesn’t require denigration of the previous work. Not withstanding of course that the previous work may otherwise have been flawed.


    an excellent patient cohort would require that patients had no prior history of psychosomatic disorders, lived an active and healthy lifestyle with no major medical issues prior to ME/CFS and who were diagnose with ME/CFS by a competent clinician after a post viral infection, toxic or bacterial exposure, vaccine and who met the 6 month period of exhaustion requirement and furthermore met the additional CCC and ME-ICC criteria established by ME/CFS medical researchers and clinicians.

    This might be appropriate for an RCT, but at best it is geared to defining Illness X and fails to encompass the probability that ME/CFS (or whatever name) is neither a single disease entity, nor even a single disease process in those diagnosed with it. The whole criteria based approach is in itself a rather redundant approach, owing far more to 19thC nosology than modern medical science. In fact fetishising a single symptom such as PEM in the effort to achieve a cardinal sign looks more like a pre scientific notion of illness rather than anything to do with getting at underlying processes. More ‘bumps on the head’ than neurotransmitter function. Finding the one true ME whose patients never ever have had psychiatric issues is an attractive notion – but it’s got nothing to do with achieving help for the majority of the 17 million (or whatever figure) who are the mass of patients. Understanding variation across the global patient population is at least as important as narrow investigation of study groupings based on common and/or exclusionary symptomology.

  27. Chris says:

    A reminder that P2P promised a first draft of their report by Dec 18–very soon! Since they are inviting comments for, I believe, 30 days, we should maybe save some of our energy for then.

    But in the meantime a few comments and a hypothesis or two. I agree that the Fukuda should be past history, and I think soon will be. But soon we may have a new one–the IOM is scheduled, I think, to report in the spring. I agree with NA Wright that it is premature to get too involved with exact definitions while the outlines and basic pathways of this disease complex are still not fully understood, and I agree with him that there will probably not be a single, coherent typology–we may well end up looking more like Autistic Spectrum Disorder–I think I would prefer to be on a Spectrum than caught up in a Syndrome. This comparison is not random–you probably know that there are many parallels between the two groups–a read of Martha Herbert and Cindy Sage’s long paper on parallels between Autism symptoms and the kinds of damage caused by Radio Frequency (see BioInitiative 2012 on the web and now published as a two part essay) shows an astonishing number of close parallels in metabolic and other disturbances between Autism and ME (you have to add the parallels, they are not part of the paper). I would add RF to the short list given by Eccoclimber of triggers–viral or bacterial infection, vaccine, etc–doubtless there are others too. RF seems the likeliest stressor in my own case, and Martin Pall (remember his book, “Explaining Unexplained Diseases,” which had a large impact earlier this century on such as Paul Cheney) has recently proposed it is the major factor in both ME and the rise in heart failure.

    Back to Oxford and Fukuda for a moment. I supported retiring all studies done using Oxford because they had been used for many of the CBT and GET studies, and they, including PACE, weighed very heavily in sheer quantity of patients enrolled when looked at through the cloudy lens of an EBM review, and were doing us real damage. That seems to be fading in the current one, and maybe that will mark the end of its power–we hope so. Fukuda and its derivative were the main alternative until the Canadian appeared in 2003, and any attempt to retire all those studies-nearly a decade’s worth– would do real damage.

    If we look at the history through a long lens, it looks to me as if the Oxford (pace NA Wright) really was a conscious attempt to counter the growing impact of work by Ramsay and others which had made a useful beginning in outlining ME as we know it; there were papers like Arnold DL, “Excessive intracellular acidosis of skeletal muscle on exercise with a post-viral exhaustion/fatigue syndrome”, Lancet, 1984, for instance–sounds very up-to-date. As I see it, the Oxford and then Fukuda (remember that recently uncovered letter from Straus to Fukuda) a few years later were a deliberate attempt on both sides of the Atlantic to drown ME in a wider sea of neurasthenia updated, of depression, of somatoform disease, etc. I think that is true, whatever exactly ME turns out to be. And I do agree with NA W that there are almost certainly subgroups involved–there is already good evidence that some respond to antivirals or Rituxan and others do not, that there may be a group who are struck at a late age, like me–there is a short paper by Julia Newton’s group showing that their symptoms focus fatigue and OI–that’s me! And also a group of adolescents whose mono refuses to clear.

    But I don’t think there will be a subgroup without PEM in some form or other. I know that some object to making “fatigue” central to this disease, but I think that is unavoidable, if we understand it not as that “subjective sensation” described by Oxford, but as the partial registration within consciousness of complex physiological events throughout the body, including of course the brain. It seems clear now that there are dysfunctions within our energy producing systems–ATP production and recycling, ROS clearance, etc. Fatigue is a normal, indeed universal, process; put out too much energy for too long, and fatigue ensues. The heart of a marathoner shows damage after the event, but the damage clears and the heart is restored to better than before status after some time. The same kind of temporal pattern is visible in inflammation–basically a process triggered by damage, which then subsides as the damage is repaired and resolvins (relatively recently discovered particles) do what their name implies. Unfortunately those systems seem broken in us, and the result is that profoundly dysfunctional form of fatigue we call PEM, just as we seem to have some never fully resolved inflammatory activity. Activity, fatigue, restoration are complexly intertwined processes central to all life; ours are unfortunately broken.

    • floydguy says:

      I am guilty of the “fatigue” charge. I have yet to see “fatigue” defined as anything other than being tired. Is it even a “medical” term?

      I would agree this “condition” should have at the center of it a dysfunctional response to normal activity and exercise. Examples might be unusually low VO2 max, tachycardia, poor stamina, stiffness, extended period of recovery, poor cognition, etc. Why bring “fatigue” into it – which essentially means nothing and can capture millions of people with various and sundry conditions?

      I would like to hear you definition of fatigue vis a vis CFS and/or ME. And why it is an essential characteristic of the condition.

      • Chris says:

        Wow, floydguy, that is quite a challenge to a non-scientist! I may gather courage and take a shot at it after Xmas and P2P..no guarantees! Chris

  28. Kathy D. says:

    I have read two or three times Laura Hillenbrand’s 2003 article on ME/CFS, and another article a few years ago, too. I have read about her often.
    However, what I am saying is that the NBC program was a perfect moment to
    mention her disease, given what is going on with the governmental committees’
    and all of the shenanigans this blog and others have uncovered. And that they
    are voting on what HHS and NIH should do about this disease. It’s
    vital that everyone who can speak out!
    There are principles involved here.

    • Jennie Spotila says:

      I agree that the NBC program was a great opportunity, but Laura was not responsible for the final content. I also agree there are principles involved. One of them is not judging the situation without complete information. I’m trying to obtain more information about what happened with the interview, and will share if/when I am able. Please don’t blame or judge Laura for something you think she didn’t do, until you know for sure she didn’t try.

  29. Kathy D. says:

    Fair enough. I hope you find out something.

    I just found a short video interview with Laura from 2010 by Jamie Gengel on NBC’s Today show, where she did discuss having chronic fatigue syndrome by name.

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