Protocol for Disaster?

disasterThe study protocol for the systematic review of ME/CFS was posted by the Agency for Healthcare and Research Quality yesterday. It’s a recipe for disaster on its own, and within the broader context of the NIH P2P Workshop it’s even worse. Let me show you some of the reasons why.

Remind Me What This Is

The systematic evidence review is the cornerstone of the P2P process. The P2P meeting on ME/CFS will feature a panel of non-ME/CFS experts who will produce a set of recommendations on diagnosis, treatment, and research.

Because the P2P Panel members are not ME/CFS experts, they need background information to do their job. This systematic evidence review done by the Oregon Health & Science University under contract to AHRQ will be that background information. The systematic evidence report will be presented to the Panel in advance of the public P2P meeting, and will be used to establish the structure of the meeting as well.

The systematic review is the foundation. If done correctly, it would be a strong basis for a meaningful workshop. If done poorly, then everything that follows – the workshop and the resulting recommendations – will crumble. Based on the protocol published yesterday, I think “crumble” is putting it mildly.

The Key Questions

You can’t get the right answer if you don’t ask the right questions. (Dr. Beth Collins-Sharp, CFSAC Minutes, May 23, 2013, p. 12)

As I wrote in January, the original draft questions for the evidence review included whether CFS and ME were separate diseases. That question is GONE, my friends. Now the review is only looking at two things:

  • What methods are available to clinicians to diagnose ME/CFS and how do the use of these methods vary by patient subgroups?
  • What are the benefits and harms of therapeutic interventions for patients with ME/CFS and how do they vary by patient subgroups?

These questions are based upon a single and critical assumption: ME and CFS are the same disease. Differences among patient groups represent subtypes, not separate diseases. The first and most important question is whether the ME and CFS case definitions all describe one disease. But they’re not asking that question; they have already decided the answer is yes.

The study protocol and other communications from HHS (including today’s CFSAC listserv message) state that the P2P Working Group refined these study questions. The implication is that since ME/CFS experts and one patient served on the Working Group, we should be satisfied that these questions were appropriately refined. But what I’m piecing together from various sources indicates that the Working Group did not sign off on these questions as stated in the protocol.

Regardless of who drafted these questions, they cannot lead to the right answers because they are not the right questions. And when you examine the protocol of how the evidence review will be conducted, these questions get even worse.

Protocol Problems

The real danger signals come from the description of how this evidence review will be done. The issue is what research will be included and assessed in the review. For example, when asking about diagnostic methods, what definitions will be considered?

This evidence review will include studies using “Fukada [sic], Canadian, International, and others“, and the Oxford definition is listed in the table of definitions on page 2 of the protocol. That’s right, the Oxford definition. Oxford requires only one thing for a CFS diagnosis: six months of fatigue. So studies done on people with long-lasting fatigue are potentially eligible for inclusion in this review.

The description of the population to be covered in the review makes that abundantly clear. For the key question on diagnostic methods, the study population will be: “Symptomatic adults (aged 18 years or older) with fatigue.” There’s not even a time limit there. Three months fatigue? Four? Six? Presence of other symptoms? Nope, fatigue is enough.

There is a specific exclusion: “Patients with other underlying diagnosis,” but which conditions are exclusionary is not specified. So will they exclude studies of patients with depression? Because the Oxford definition does not exclude people with depression and anxiety. We’ve seen this language about excluding people with other underlying diagnosis before – and it results in lumping everyone with medically “unexplained” fatigue into one group. This protocol is set up to result in exactly that. It erases the lines between people with idiopathic chronic fatigue and people with ME, and it puts us all in the same bucket for analysis.

And what about the key question on treatment? What studies will be included there? All of them. CBT, GET, complementary/alternative medicine, and symptom-based medication management. It’s not even restricted to placebo trials; trials with no treatment, usual care, and head-to-head trials are all included.

Let’s do the math. Anyone with unexplained fatigue, diagnosed using Oxford or any other definition, and any form of treatment. This adds up to the PACE trial, and studies like that.

But it’s even worse. The review will look at studies published since January 1988 because that was the year “the first set of clinical criteria defining CFS were published.” (page 6) Again, let’s do the math: everything published on ME prior to 1988 will be excluded.

Finally, notice the stated focus of the review: “This report focuses on the clinical outcomes surrounding the attributes of fatigue, especially post-exertional malaise and persistent fatigue, and its impact on overall function and quality of life because these are unifying features of ME/CFS that impact patients.” (page 2) In other words, PEM = fatigue. And fatigue is a unifying concept in ME/CFS. Did anyone involved in drafting this protocol actually listen to anything we said at last year’s FDA meeting?

Bad Science

Credit: ElodieUnderGlass

Maybe you’re thinking it’s better for this review to cast a broad net. Capture as much science as possible and then examine it to answer the key questions. But that’s not going to help us in this case.

This review will include Oxford studies. It will take studies that only require patients to have fatigue and consider them as equivalent to studies that require PEM (or even just fatigue plus other symptoms). In other words, the review will include studies like PACE, and compare them to studies like the rituximab and antiviral trials, as if both patient cohorts were the same.

That assumption – that patients with fatigue are the same as patients with PEM and cognitive dysfunction – is where this whole thing falls apart. That assumption contaminates the entire evidence base of the study.

In fact, this review protocol makes an assumption about how the Institute of Medicine study will answer the same question. It is possible (though not assured) that IOM will design diagnostic criteria for the disease characterized by PEM and cognitive dysfunction. But this evidence review is based on an entirely different patient population that includes people with just fatigue. The conclusions of this evidence review may or may not apply to the population defined by the IOM. It’s ridiculous!

But it’s the end use that really scares me. Remember that this systematic evidence review report will be provided to that P2P Panel of non-ME/CFS experts. The Panel will not be familiar with the ME/CFS literature before they get this review. And the review will conflate all these definitions and patient populations together as if they are equivalent. I think it’s obvious what conclusion the P2P Panel is likely to draw from this report.

I would love to be wrong about this. I would love for someone to show me how this protocol will result in GOOD science, and how it will give the P2P Panel the right background and foundation for the recommendations they will draft. Please, scientists and policy makers who read this blog – can you show me how this protocol will produce good science? Because I am just not seeing it.

What Do We Do?

This protocol is bad news but it is by no means the last word. Plans are already in motion for how the advocacy community can respond. I will keep you posted as those plans are finalized.

Make no mistake, this evidence review and P2P process are worse than the IOM study. We must respond. We must insist on good science. We must insist that our disease be appropriately defined and studied.


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44 Responses to Protocol for Disaster?

  1. Mary Dimmock says:

    Thank you for this rapid analysis, Jennie. You are correct. This is a disaster.

    This approach and the questions listed reminds me of the evidence based review that supported the creation of the NICE Guidelines.

    That review was also a fatigue focused review that lumped all definitions together and determined that there was no evidence of efficacy for drugs like Fluorinef and that the best treatments were CBT and GET.

    We must respond. We must insist that ME be defined, studied and treated separately from the wastebin of CFS.

  2. John says:

    Thanks Jennie. I got the impression too that this protocol was one big steaming pile of horse****. I saw Oxford mentioned and was like ‘oh no’. That’s also a very good point about excluding studies on ME prior to 1988 as well. Please keep us informed, this one is looks like it’s worth putting up a stink about.

  3. Sandra says:

    My heart sank as soon as I read the following:

    “The term ME was first used in the 1930s after an outbreak of neuromyesthenia and CFS was first coined in the 1980s, with both conditions having overlapping features.”

    Their use of the word “neuromyesthenia” told me right then and there where they are coming from. This term has historical connotations of emotional/psychological causation. Very troubling!

    • Jennie Spotila says:

      Yes! I noticed that as well. There is no way to catalog everything wrong with this protocol.

  4. Terry says:

    This does look very bad. Who was involved in reviewing the protocol? Are the mechanisms to allow patients to comment, and for changes to be made?

    Thanks for the analysis.

    • Jennie Spotila says:

      The protocol was drafted by the EPC, the people at the Oregon Health & Science University. There is a Technical Expert Panel, supposedly comprised of subject matter experts. There is supposed to be a patient on the TEP as well. However, the protocol document states that the TEP names are not released until after the study is completed. Jeannette Burmeister reported on her blog that her FOIA for the names was denied.

      There are no mechanisms for public comment on the protocol, and the review is underway. However, we will have an opportunity to comment on the draft report, most likely in the fall. But I don’t think we should wait until then, which is why I’m participating in other advocacy options. Details still being worked out, but I expect to have an update on that soon.

  5. Kati D says:

    Arrrrrgh. So scary. Why??? Why???

    • Jennie Spotila says:

      THAT is the ultimate question. We may never know. It certainly strains credulity to think that no one at HHS saw this was a bad approach.

  6. Jocelyn says:

    Thanks a million, Jennie; I was hoping you’d do this. I tried to fight my way through that thing three times, and my cognitive limitations are so bad anymore that I utterly failed.

    • Jennie Spotila says:

      I had to reread it so many times too! I could hardly believe what I was reading.

  7. Anne says:

    Its a Cochrane style systematic review with “Wessely school” all over it. Very very bad!!!

  8. Gina says:

    Am I upset? No I am livid. This is worse than the IOM!! No mention of real pain relief. Keep the suicides coming _7#;34’s!! Cymbalta should require a waiver, everytime prescribed! Getting off that antidepressant (btw with side effect of depression), is HORRIBLE! I was told never to take an antidepressant unless you are depressed by Dr Oz realizing he was making a serios statement, saying he will be upsetting…. My point opioid medicine works, not even listed under PICOTS population, interventions,etc.

  9. Anne says:

    That is so bad, it needs an injunction/restraining order to stop it!

  10. Tiki says:

    We’re looking back at 25+ years of ‘contaminated’ literature. Newbies read the science wrong all the time, because they’re not familiar with the historic

  11. Tiki says:

    evolution of the CFS definition. In this situation, without any awareness of the underlying issues, systematic reviews will get even the basic facts wrong.

  12. Carrie says:

    Thanks for this report, Jennie. Please do keep us informed as to how we can respond. We must keep standing up for what is right, but, geez, it gets old.

  13. Lindy says:

    Thank you, Jennie. I couldn’t possibly read the thing, myself. I’m speechless and, at the same time, infuriated.

  14. kathy d. says:

    Auuuugh! How horrible! I agree with you and everyone’s comments. It’s more than ridiculous; it’s outrageous.

    I think the government just does not want to recognize ME/CFS as a physically based disease, as officials do not want to pay more for research or do serious research, and pay for disability and medical care. Nor do private insurers.

    This reminds me of the ridiculous panel on “preventive” health care that determined women don’t need mammograms before 50. This to avoid Medicare and Medicaid (and private insurers) having to pay for them. Thankfully there was a firestorm of protest, so Medicare didn’t change its coverage rules.

    Well, the only thing is to keep on fighting with all the tools we have, now social media.

    You do us a great service, Jennie, by reading and analyzing these studies, something which some of me, myself included, just are not able to do. (I am cleaning my apartment; 45 minutes today, and my legs/knees started shaking, and I got dizzy, so that was that, but it impacts
    on my cognition). Your work is appreciated, and so is your organizing of responses.

  15. Chris Heppner says:

    Thanks for this depressing update, Jennie. May I add some paragraphs I wrote a while back, in the hope that they may still be sadly relevant here? I don’t know what else to do with them….

    Thoughts on Definitions and Consequences

    I fear that some have not read the Oxford definition with the care that it needs. Peter White was one of the team, and it was very carefully crafted, including a substantial “Glossary” which one needs to read carefully to realize just what the definition actually says.

    The Oxford document continually uses the word “symptom,” with the intent of distinguishing it from physiology, as the “Glossary” makes clear. It defines the term “Fatigue,” which is the “principal symptom” of the disease as defined here, in these words: “When used to describe a symptom, this is a subjective sensation and has a number of synonyms including tiredness and weariness.” Further, “Fatigue as a symptom should be distinguished from low mood and from lack of interest. The symptom of fatigue should not be confused with impairment of performance as measured by physiological or psychological testing. The physiological definition of fatigue is of a failure to sustain muscle force or power output.”

    Thus in the Oxford definition, the fatigue that is our “principal symptom,” is, by definition and from the start, a “subjective sensation,” not a physical reality. The unwritten but very clear corollory is that if this “principal symptom”, “fatigue,” were found to be a physiological reality, “ a failure to sustain …power output” (which is precisely what happens to people with ME/CFS in 2 day VO2max testing by Stevens and others), it would no longer qualify as a “symptom,” and patients suffering such “failure” should be excluded from the definition of CFS by the Oxford criteria! The large, expensive and much challenged and questioned PACE trial used the Oxford definition.

    In addition, the “impairment of performance”–particularly in mult-tasking– noted in several psychological tests, and the impaired blood flow in areas of the brain measured in other testsi after moderate exercise, including cognitive exercise, should remove such patients from inclusion in any trial purporting to deal with CFS. I shall repeat from the Oxford definition: “The symptom of fatigue should not be confused with impairment of performance as measured by physiological or psychological testing.”

    This means that if PEM/PENE is acknowledged as a necessary symptom for ME (both the CCC and the ICC demand it–correctly, in my opinion– for ME/CFS), then anyone who qualifies for either of those definitions cannot qualify for the Oxford definition–the two are mutually exclusive; PEM/PENE is literally an exclusionary condition (I deliberately do not use the word “symptom,” since that is reserved in the Oxford definition for a “subjective sensation” which has no physiological foundation).

    If PEM/PENE is accepted as a necessary part of the definition of ME/CFS (as I personally believe it should be), then any study using the Oxford definition should be excluded from any EBM consideration. The same may be less rigorously true of the CDC Fukuda definition, which does not insist on PEM/PENE, though it does not specifically exclude it as does the Oxford definition.

    I have noted this rather special use of the word “symptom” in many trials conducted under the Oxford definition; Dr. Alegria uses the word in this sense in the papers that refer to CFS, and Dr. A. Wearden uses it in that sense in her papers on CFS. It seems a usage widespread in England, and it is literally prejudiced and prejudicial–it includes an unproven assumption, prejudice in the literal sense, that a “symptom” is subjective sensation unsupported by physiology. It is of course quite possible that some reported symptoms are indeed “symptoms” in this specific sense, but to assume it without adequate testing is irresponsible.

    One of the trials using the Oxford definition and GET is that by K.Y. Fulcher and P.D. White, “Randomized controlled trial of graded exercise in patients with the chronic fatigue syndrome” BMJ, 1997, June 7; 314 (7095), 1647-52, PMID: 2126868. Dr. Mulrow, in her 2001 EBM review, acknowledges that the GET studies had a high drop-out rate, but since no serious adverse symptoms were reported, makes little of the fact. The setting for the study is a “chronic fatigue clinic in a general hospital department of psychiatry.” Subjects are defined as “66 patients with the chronic fatigue syndrome who had neither a psychiatric disorder nor appreciable sleep disturbance”–lucky them! BUT: “all patients with the CFS who also had a psychiatric disorder or insomnia were offered treatment for their comorbid disorder. If treatment was successful but the patients still met criteria for the CFS they were recruited into the trial.” In the “Results” section we learn further that 20 patients “were taking full dose antidepressants; 10 were taking low dose tricyclic antidepressants as hypnotics.. All patients were told to continue their medication unchanged.” This opens the possibility that a good number (nearly 30%) of these patients were actually depressed, but that taking antidepressants had not fully cured their possibly or probably depression-caused fatigue.

    This reflects another important fact about the Oxford definition. Among the exclusionary conditions, it gives “”Patients with a current diagnosis of schizophrenia, manic depressive illness, substance abuse, eating disorder or proven organic brain disease. [BUT]Other psychiatric disorders (including depressive illness, anxiety disorders, and hyperventilation syndrome) are not necessarily reasons for exclusion.” So the Oxford definition explicitly allows the entry of patients whose primary problem may be depression, and less explicitly, though by very clear implication, excludes those who demonstrate an inability to “sustain…power output,” which is one way of defining PEM, though not by any means an adequate one.

    Obviously this total cross-exclusiveness of the Oxford and CCC definitions is not achieved in practice; I am sure that a fair number of patients with ME have been included in trials conducted with the Oxford definition, and some with depression have doubtless been included in trials conducted under the CCC defintion. When Dr. Mulrow assisted in producing an EBM style review of treatments for ME/CFS in 2001, she wrote that the definition used seemed to make no difference to the outcome. That of course was before the CCC was published, and I have no doubt that the statement was then correct. I think today the choice of definition would certainly make a substantial difference, and is of course an element in the ongoing critique of the PACE trial results.

    (Quotations from “A report-chronic fatigue syndrome: guidelines for research,” published in Journal of the Royal Society of Medicine, Vol. 84, February 1991 [i.e. the “Oxford” definition.])

    And a Few Thoughts on EBM.

    Found a wonderful statement from early in the evolution of EBM–a letter published, I think, in the BMJ, from Dr. Nigel T. James, Sheffield: “Paradoxically, evidence based medicine seems to avoid all contact with the first hand evidence by replacing original findings with subjectively selected, arbitrarily summarised, laundered, and biased conclusions of indeterminate validity or completeness. It has been carried out by people of unknown ability, experience, and skills using methods whose opacity prevents assessment of the original data.”
    “At best, evidence based medicine is a heuristic method for a lower level partial abstracting service.”

    OK, I basically agree–my look at that Mulrow paper left me deeply unimpressed and disturbed–but of course there is now a huge literature on the whole thing that I have only just begun to look at. But one thing strikes me: it came into being (in bits and pieces until a few like Sackett began to articulate it ca 1995) as a defence against the imposition of lab, in vitro, results directly into clinical practice, where there were some disasters like the VIOXX affair. So it began focused strongly on making sure that medical interventions were not entered into with a blind faith in lab science to produce good results–we need to know how things work out in the real world of interventional medicine. Clearly here it has a strong role to play, if done well–which is difficult.

    But the P2P is proposing something very different–an EBM group of non-specialists is being asked to read and sort through a mass of clinical research, and draw conclusions and direction from it. I don’t think that the methodology (and there is an explicit, always being revised methodology) was designed for this kind of job. There is an interesting essay by Nicholas P. Negroponte from which I will quote some lines: “we cannot isolate thoughts about channel mode and capacity–flat estimates of how much information can travel how fast–from the computational resources at the ends of the network.” He gives an example–a wink from a friend across the table at a dinner party could be described in the language of information theory as representing one bit. Yet that one bit could in fact carry an enormous freight of information; if asked, you might need more than 100,000 bits to explain the contents of the message to a stranger. Behind such a wink lies a huge body of shared information and experience, which enters into both the initial coding and the subsequent decoding of that one-bit wink. (“Products and Services for Computer Networks,” Scientific American 265:3 (September 1991, p.106); Negroponte is co-founder and director of the MIT Media Lab, and a pioneer in computer-assisted design.

    EBM is a way of trying to access and distribute information in a specifically coded manner (there are now quite rigid rules for how to organize a RCT, for instance), but a great deal still gets lost in the transmission process. An experienced clinician and researcher brings quite another set of decoding skillls to a research paper on ME/CFS than does a reader with no substantive knowledge of the condition, and much will get lost in the processing of such information without such skills. It is then proposed to feed this resumed and quantified information back into the P2P process in some not fully defined way, but if the P2P Working Group does contain a significant number of members with substantial knowledge and experience of ME, I can see no real utility in this whole cumbersome-and expensive–process. Maybe someone can explain it to us….. How will the EBM group interpret the Mella and Fluge Rituximab trial, for instance? Will it be sidelined with the kind of comment the Mulrow paper uses, “insufficient evidence” and dismissed as she dismisses magnesium? Or will they be able to recognize the key importance of the statement that ALL symptoms improved across the board, showing that in 2/3rds of an admittedly small number of patients the intervention had obviously hit a central, key player in the disease? I have grave doubts….

    I fear the worst, and always did. Sorry. As a Canadian I feel a bit distant from all this–I cannot appeal to my senators or representatives–though I know full well that what happens here will have heavy impact here too. I did write to IOM and Sebelius, but of course received no replies.


    • Jennie Spotila says:

      Chris, outstanding comments as always. I especially like your analysis of Oxford. On the one hand, I’m glad to be excluded based on my VO2max testing. On the other, it makes this study protocol even worse for failing to recognize that.

  16. says:

    Thanks for looking into all this. I did not read all the protocol, but the assumption of equivalence between definitions is concerning. I hope they did not drop the ME vs CFS question because of that recent systematic review on the issue? There is also a lack of objective physical outcome measures, although there is something about work/school attendance. Any systematic review must be clear on what CBT and GET can do to important objective outcomes (which according to the evidence I have seen is that they basically do nothing of any clinical significance). This is important to prevent misleading assumptions and expectations.

    Even if the systematic review did focus on studies which included PEM, this could backfire as well. The description of post-exertional symptoms in the CCC and ICC is superior than that found in the CDC definition. The PACE trial seemed to show that CBT and GET can actually reduce the chances of reporting PEM. Of course, this may be due to reporting bias, but it may also reflect problems with how the presence of PEM was vaguely defined in the trial: “feeling ill after exertion […] more often than not” over the last week.

    IIRC, the work of Jason et al has shown that the prevalence of PEM depends greatly on how it is defined, and healthy people tend to experience or interpret PEM as emotional while those with ME/CFS tend to experience physical PEM.

  17. Chris Heppner says:

    Jennie, you deserve all our thanks-and admiration– for actually having submitted to that test, and living (barely) to tell the tale. But your experience does show up one of our many difficulties–it is all very well to try to insist on the necessity of repeated VO2Max tests, but since they may very nearly kill us, we really need more accessible ones. Let’s hope that Unger rejected the 2 day test for humane reasons, and helps find a more moderate but equally definitive test involving merely the donation of a little blood or something like that! In any case, I hope you never have to repeat the experience! Chris

  18. Pam A. says:

    Thank you for this very thoughtful analysis, Jennie! As I continue to read about the despairing government prejudice against ME/CFS, I continue to ask, “What are we doing wrong that others representing diseases like MS, and even Fibromyalgia, have done right?”. It seems that the critical piece we are missing is an aggressive scientific lobby (since the CAA seems ineffective). HHS hasn’t ever listened to us and might never listen to us. For whatever reason, patients are invisible and illegitimate in the eyes of the government. I’m not saying we should stop fighting the fight, but how do we activate and organize our experts worldwide in a way that’s relatively simple and easy for them and their busy lives? What can we learn from AIDS, MS, and even Fibro activists? Who can lead this charge? Something has to shift because the status quo of the past 30+ years is obviously not working.

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  20. Alex Young aka alex3619 says:

    I don’t think you are wrong about this in general. The specifics will elude us until we can see it in 20-20 hindsight though.

    One huge issue is that evidence based medicine and review is not science. Its an attempt to translate science into clinical practice using managerial processes. Its rubber stamping and bean counting. So when a review is formed its based on technical requirements, and typically on an assumption that the underlying science is sound … it passed review didn’t it? Its often an RCT, which is the highest standard of evidence, is it no?

    Yet we know RCTs can be very wrong, and further that meta-studies can suffer from GIGO, garbage in, garbage out. If the scientific methodology is not being examined, and evidence based reviews simply don’t do this as a rule, then its all accepted at face value.

    Any time you see a committee its translational medicine, or translational science, not really science. It thus has other criteria than scientific ones which direct the outcome.

    Psychogenic medicine, including the PACE trial, has so many flaws I cannot credit it as being science. So what is an RCT for nonscience? Does it have the same credibility as a quality scientific study? I don’t think so.

    Rather than go into the huge range of flaws in psychogenic medicine including PACE, about which I am writing a book, I just want to focus on one single thing here: subjective versus objective evidence. The arguments from psychogenic medicine usually come down to subjective evidence, evidence that is inherently less reliable and more subject to bias than objective evidence.

    Every time they have engaged in obtaining objective evidence it has run counter to their hypotheses. They usually avoid it like the plague, though it is likely this is just an entrenched flaw in methodology in this area. Yet this evidence, and the tiny and the tiny effect sizes that may be entirely due to bias, are judged alongside highly objective studies that have hard evidence to back them.

    It gets worse. Lets take, for example, Lerner’s work on antivirals. Its a case series, not an RCT. So the quality is low, right, it should be ranked lower than RCTs? Yet mechanisms exist within EBM to allow for upgrading of evidence under certain conditions, including large effect sizes. So a case series could easily be ranked as high as an RCT. Yet that is not all.

    RCTs that are of lower reliability can be downgraded. I would automatically downgrade any RCT based on psychogenic hypotheses by one or two rankings, simply due to methodological issues, and then examine them for reasons to downgrade further.

    In cursory bureaucratic reviews, nobody is going to look too hard at subjective versus objective, or methodological flaws, or upgrading or downgrading evidence rankings, especially on a tight budget. So the evidence base will be rubber stamp evidence, based on technical criteria, unless highly developed mechanisms are in place to prevent this. Somehow I doubt this is the case.

  21. Billie Moore says:

    Just what is so important/serious/involving of national security that an FOIA cannot be fulfilled? This is an issue for the Congresspeople – one that they could “get” far sooner than they could understand our many issues about unnecessary multiple studies or definitions. Just how much power does the AHRQ have, and WHY?


  22. TY Jennie. Glad to support the effort. Well put as always. If there is a way we can follow up as individuals, can you provide a link? I am sharing your post with this heading. Disaster Next Exit – The study protocol for the systematic review of ME/CFS was posted by the Agency for Healthcare and Research Quality by Jennie Spotila. Oxford Criteria? REAlly!

  23. Ess says:

    @Billie Moore
    BINGO!! WHY? So much behind the scenes that is hidden. WHY?

    All this ‘busy work’ –over 30 years — is just meant to keep the ME/CFS community ‘occupied’ as the whole distorted process regarding meaningful biomedical treatment for the millions and counting with ME/CFS continues round and round in never-ending circles–doggy chasing tail–never attaining goal.

    And the HHS, CDC, NIH process is ‘set’ to keep us stuck there.

  24. cort says:

    There are definitely lots of problems with the PCORI guidelines but this – whether CFS and ME are separate diseases – is definitely not one of them. A look at the research on ME/CFS indicates there is no way to answer that question at this point. This is because only a very few studies out of the 1,000’s done have tried to differentiate ‘ME/CFS’ from ‘CFS’.

    Even those studies have had mixed results. ME/CFS (CCC) appears to have more immune dysfunction but it was mostly a matter of degree – the same basic NK cell problems were found in both. Another study found similar exercise in problems in people who met the Fukuda critieria and those who did not.

    Since they didn’t have any solid data to answer the ME vs CFS question – why ask it?

  25. cort says:

    One part of the protocol explicitly asks that the different diagnostic methods be compared. That means that the different diagnostic methods will not be lumped together but be assessed.

    “What is the accuracy and concordance of diagnostic methods?”

    That part is actually a substantial step forward in my opinion. Isn’t a comparison of the different diagnostic methods a step forward?

    These types of reviews would never not include a major diagnostic protocol no matter how flawed. If they’re going to do a thorough and objective analysis they have to include everything. If its been used a lot it’s included.

  26. cort says:

    @Mary Dimmock

    I have a different interpretation. If they do what they said they will do I think they’ll distinguish differences between the definition. They are tasking themselves with assessing the accuracy and overlap between the different definitions. They also clearly highlighted definition controversy in the first part of the document. Are they going to ignore that after stating what an issue it is? I would be surprised if they did. This question

    What is the accuracy and concordance of diagnostic methods?

    Should open up the differences between the different definitions and this question

    “What harms are associated with diagnosing ME/CFS?” could mean they’ll be looking at harms caused by the use of poor definitions.

  27. cort says:

    A redo of my last comment – please use this one 🙂

    Asking an group like this to exclude the Oxford definition or any other definition that is currently in use before their analysis begins is to fundamentally misunderstand how these types of projects work.

    They don’t assume anything. They come at the research from a fresh and objective perspective and they take account of everything. To exclude something from your analysis before you even start it would be to irremediably taint the objectivity of that kind of process. Basically they HAVE to include it Note how much the Oxford definition contrasts with the other ones, though.

    For me I think there is enough evidence that the Oxford definition is baloney that that’s what is going to come out in this review. How can you justify a definition that is not only so different from the others but is basically bucking the trend, as the overview pointed out, towards highlighting post-exertional malaise. I think the Oxford definition will be exposed for the mistake it is and that could be the end of the Oxford definition. That’s my hope.

  28. Billie Moore says:

    @ Cort.

    The issue here is two-fold: why has this study been funded and implemented when there are two other studies underway (also unnecessary, many would argue) with all three are under different govt. agencies with no connection among them whatsoever? And why would you ever ask a group of non-experts to define anything, and certainly not a very complicated, controversial medical conditions? This study should not be being done. Period. And yes, Mary, we need to respond. Unfortunately our opposition is likely to be as effective as our opposition to the IOM – not. Responding to the HHS is an exercise in futility.


  29. Anne says:

    Non medical lay people are part of this. They have no idea what Oxford is, what Fukuda is, what Carruthers is, who Dowsett is etc…
    Why is Dowsett is in there and Ramsay isn’t?
    The bottom of that document is made so cognitive impaired people can not read it,
    but if anyone can, you can clearly see it all points to CBT and GET.
    The whole document points to that, and all of the other quack psych agenda that goes on in the UK.
    It doesn’t matter who the reviewers are to be quite frank, they have to review what is presented to them and look at whats presented to them.
    Its not science, its a crap shoot!

  30. floydguy says:


    That really is the question isn’t it? Objectivity? There is scant evidence of any objectivity in the universe of “ME/CFS”. Most of the “evidence” base consists of questionnaires and opinions (er statistical nonsense) of researchers/government bureaucrats and the mind/body industry. Sure there are some interesting tidbits here and there but little has been verified. It’s hard to see how this group of will make make any revolutionary changes in definition at this point in time. Furthermore, it’s almost certain that they will agree with the current CDC mantra of the only “approved” treatments are CBT, GET and anti-depressants. The process is designed so other outcomes are highly unlikely and the Feds can kick the can down the road another 5-10 years.

  31. Christine Williams says:


    It was good to see you this week. I hope your recovery won’t be too bad. I so appreciate your analysis of all of these moving parts. It continues to be an uphill battle for all of us who are ill.

    Take care of yourself.


  32. Anne Ö says:

    Thank you Jennie for keeping us informed of the developments. All very worrying!

  33. Mary Dimmock says:

    Sorry to be so long responding to your comment to me but I see that others have responded.

    I’d just add that the P2P study actually does make assumptions. First, P2P assumes that the concept of a clinical entity that is organized around only two factors – the ubiquitous, ill-defined symptom of subjective fatigue and the current state of medical knowledge – is a scientifically valid clinical entity. And second, based on that assumption, P2P then assumes that differences in the disparate definitions reflect subgroups of that clinical entity.

    But the first assumption, upon which everything rests, is invalid. Where is the scientific proof that all the disparate conditions and definitions that have been given the CFS label are biologically related and that studying them as a group will lead to real treatments. There isn’t any proof and the only sanctioned “CFS” treatments are based on yet another assumption that if science cant explain it, it must be psychological.

    The P2P could ask whether science has advanced enough to stop lumping the disease characterized by the CCC and the ME-ICC under “medically unexplained chronic fatigue”. The P2P could ask whether the clinical entity based on “medically unexplained chronic fatigue” is a valid research construct to begin with especially given that the most relevant research about fatigue is coming from medically known diseases like cancer

    But P2P didn’t because P2P is making assumptions.

  34. cort says:

    @Billie Moore

    Because that’s how the P2P workshops are done. If you look at the Opioid Workshop Panel you can find 4 or 5 people out of 15 or so that appear to be directly involved in pain judging from the descriptions and yes, non medical people are a part of that panel as well.

    Other disorders appear to fare OK during the P2P process.

    • Jennie Spotila says:

      Only one disorder has been through the P2P process start to finish: polycystic ovary syndrome. I’ve read the report, and it includes recommendations on name, case definition, education and research. I do not know how the PCOS community feels about the report.

      The Opioid P2P workshop will be held in September. The actual Panel has not been announced. The Working Group is posted, and yes, a few of those people are involved in pain management. The key is who will be on the Panel, since that is the body that will issue recommendations.

      I have not had the capacity to dig into either process and see if those subjects fared OK or not. The Opioid workshop is still in early stages, with no evidence review posted and no speakers listed on the agenda for that meeting.

  35. cort says:


    Why would a panel that populated mostly with pathophysiological researchers ignore the evidence of immune and other dysfunctions and decide that ME/CFS is a psychological disorder? Why? This panel is not set up to do that all. I think there’s plenty of research for the panelists to chew on.

    • Jennie Spotila says:

      I’m not sure if you are referring to IOM – which is made up of mostly clinicians and biomedical researchers – or P2P. Just to clarify, the P2P panel has not been announced, so we have no idea how many psychologists or biomedical researchers will be on that panel.

  36. cort says:

    @Mary Dimmock
    I think it’s incorrect to say the P2P assumes ME/CFS is one clinical entity. They refer to it as a syndrome, which by definition is not a disorder – and they are looking for subsets.

    I agree that this is not a great step forward for ME/CFS. I think it’s a missed opportunity. Too little research on treatments has been done to make this a powerful effort in my opinion. They should have book looking for gaps in research – that would have provided some impetus for an RFA. They’re also duplicating the IOM to some extent.

    I hope it will be helpful in delineating the differences between the definitions, but then again, as I pointed out earlier almost all research has involved Fukuda – which makes it difficult to assess the other definitions.

    Definitely a missed opportunity..

    • Jennie Spotila says:

      Actually, a “syndrome” is defined as a collection of signs and symptoms that are characteristic of a single condition. AIDS is acquired immune deficiency syndrome, because it is a collection of multiple things that in combination equal a single condition, in that case caused by a single pathogen (HIV).

      In our case, we know that Fukuda and Oxford capture broader populations than CCC or ICC. It is a fundamental question: is ME a distinct enough condition to be separated from the broader CFS population? That is one of the questions facing the IOM, but it is also a question facing the multisite study and P2P. But the design of the P2P study protocol does not ask this question.

      It is a question that should be asked!

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