Study evaluating NICE, Oxford, and Fukuda prevalence

In one way I would like to see what happened if the process were reversed. Rather than seek to give a name to each condition, knowing the tremendous variation within them, doctors instead focused on what treatments were appropriate to certain combinations of symptoms. Yes, I know that's a weird one, but what if we actually focused how to detect people who actually benefited from a certain treatment rather than give it to groups labelled in a particular way, knowing that only a proportion would benefit.

So I'd be happy if, rather than have a label of ME hung around my neck, so that most doctors could ignore my symptoms, the focus was on the symptoms and how to treat them.

 

I suspect costs, medical costs, would go down quite dramatically whilst best matches were arrived at.

At the same time I'd expect funerary costs to increase.

Which would help decrease medical costs, as it's rare for even really good physicians to try and treat the deceased for longer than a week or 2.

 

I think it is useful to be having this debate now because, as I understand it, the NICE committee will be dealing with diagnostic issues on Friday. Maybe one or two committee members will see this thread.

As Graham is suggesting, these guidelines are for the benefit of ill people, not illnesses. So the beneficiaries of this guideline are intended to be all those for whom a doctor may ask 'should I be considering this person to have ME/CFS and if so what does that imply for prognosis and care?'. For people with heart failure the fatigue can be linked to the heart failure so they don't need this guideline. For people with unexplained fatigue this is going to be the relevant guideline because it not only flags up ME/CFS but also talks about what tests should be done to exclude hidden causes of fatigue.

One could argue that the guideline should be for people with unexplained chronic fatigue as a whole or some other group defined by symptom pattern as Graham suggests but the reality is that medical information is catalogued by illness names and we are not going to change that overnight. It probably has to do with the way our brains work and we are not going to change that!

Yes, but the problem is actually much more serious the other way around - extrapolating from a narrow cohort to a wider one.

As far as I can see the scope of ME/CFS in the guideline is pretty close to what most of us are agreed on. It includes PEM. And for clinical care I don't understand why this needs to be picked over because we don't actually know whether the prognosis or appropriate management is different for any subgroup of people with chronic fatiguing illness.

I was trying to explain that there is a Catch22 that if you separate off CCC ME/CFS from Oxford CF then you create a group of non-CCC patients for whom it is harder to point out that CBT and GET are not justified. Particularly if the critique of PACE emphasises the Oxford entry criteria. It is much easier to point out that PACE tells us nothing and so separating people out for treatment recommendations is not appropriate. I see this as important because there is a lot of pressure on the committee to accepts that 'different people respond to different treatments'.

In reality we do not know if anyone responds to anything. If we accept that different people respond to different treatments it is hard not to allow recommendations for maybe some antivirals, maybe some supplements, maybe some CBT, maybe some GET and so on.

In the wider context of research I am sceptical of public pronouncements about needing tighter definitions. In my work on rheumatoid I never thought disease definitions were relevant to the reality of the biology - which as Graham says is always overlapping and multifactorial. Pulling out the elements that are relevant to a particular hypothesis is different every time.

But, as I hope I have made clear, this is not what the 2007 guidelines are doing and unlikely to be what the new ones will do. The guidelines recognise a syndrome with PEM, ME/CFS, but the intended beneficiaries of this guideline have to be all those people for whom the doctor asks 'is this ME/CFS'.

 

Right, but if we keep defining ME/CFS in terms of unexplained chronic fatigue (which has a prevalence that is much larger than that of ME/CFS) then doctors will be asking that questions on occasions when it is not appropriate. I thought the intent of the NICE guideline was to provide doctors with information when and where they should consider ME/CFS. So I think it's important it makes a clear distinction between ME/CFS and idiopathic chronic fatigue (ICF).

I recently wrote a short letter that summarized the reported differences between ME/CFS and patients with idiopathic chronic fatigue:

... The prevalence of idiopathic chronic fatigue is estimated to be several orders of magnitude larger than that of ME/CFS. [2] Consequently, only a small minority of patients with idiopathic chronic fatigue can be said to suffer from ME/CFS. [3] Patients with ME/CFS are generally more impaired than ICF patients. They have lower physical function [4,5] more bodily pain [4,6], more neurocognitive difficulties, [6,7] lower employment rates [8] and a worse prognosis [9] than ICF patients. Patients with ME/CFS are also more likely to attribute their illness to a physical cause [10,11] and more frequently report an acute infectious onset compared to patients with ICF. [5]

The lack of further differences between idiopathic chronic fatigue and ME/CFS could be seen as a critique of standard case-definitions of ME/CFS. [12, 13] These focus on fatigue and do not require the presence of other characteristic symptoms such as post-exertional malaise. Several studies have found post-exertional malaise to be a prime factor in discriminating ME/CFS from ICF. [14-16] Worsening of fatigue with physical exertion, and feeling worse for 24 hours or more after exercise are predictive of a poor prognosis. [17] In recent diagnostic criteria, post-exertional malaise has substituted fatigue as the hallmark symptom of ME/CFS. [18,19] Consequently, ME/CFS should no longer be seen as an extremity on the fatigue continuum.


[2] Steele L, Dobbins JG, Fukuda K, Reyes M, Randall B, Koppelman M, et al. The epidemiology of chronic fatigue in San Francisco. Am J Med. 1998 Sep 28;105(3A):83S-90S.

[3] Buchwald D, Umali P, Umali J, Kith P, Pearlman T, Komaroff AL. Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest health care system. Ann Intern Med. 1995 Jul 15;123(2):81-8.

[4] Buchwald D, Pearlman T, Umali J, Schmaling K, Katon W. Functional status in patients with chronic fatigue syndrome, other fatiguing illnesses, and healthy individuals. Am J Med. 1996 Oct;101(4):364-70.

[5] Evengård B, Jonzon E, Sandberg A, Theorell T, Lindh G. Differences between patients with chronic fatigue syndrome and with chronic fatigue at an infectious disease clinic in Stockholm, Sweden. Psychiatry Clin Neurosci. 2003 Aug;57(4):361-8.

[6] Hickie I, Davenport T, Vernon SD, Nisenbaum R, Reeves WC, Hadzi-Pavlovic D. Are chronic fatigue and chronic fatigue syndrome valid clinical entities across countries and health-care settings? Aust N Z J Psychiatry. 2009 Jan;43(1):25-35.

[7] Jason LA, Porter N, Hunnell J, Brown A, Rademaker A, Richman JA. A natural history study of chronic fatigue syndrome. Rehabil Psychol. 2011 Feb;56(1):32-42.

[8] L Darbishire, L Ridsdale, and P T Seed Distinguishing patients with chronic fatigue from those with chronic fatigue syndrome: a diagnostic study in UK primary care. Br J Gen Pract. 2003 Jun; 53(491): 441–445.

[9] Bombardier CH, Buchwald D. Outcome and prognosis of patients with chronic fatigue vs chronic fatigue syndrome. Arch Intern Med. 1995 Oct 23;155(19):2105-10.

[10] Lane TJ, Manu P, Matthews DA. Depression and somatization in the chronic fatigue syndrome. Am J Med. 1991 Oct;91(4):335-44.

[11] De Gucht V, Garcia FK, den Engelsman M, Maes S. Differences in Physical and Psychosocial Characteristics Between CFS and Fatigued Non-CFS Patients, a Case-Control Study. Int J Behav Med. 2016 Oct;23(5):589-94.​

 

I don't see anywhere where NICE 2007 defines ME/CFS in terms of unexplained chronic fatigue. It says the guideline is there to diagnose and manage CFS/ME (which is going to be ME/CFS this time I think) and it gives an account of how to recognise it, including PEM and various other symptoms.

If doctors are inexperienced enough not to know exactly when to think of ME/CFS the surely the need is for a guideline that tells them that. There is a risk of overdiagnosis and there is a risk of underdiagnosis but I am not aware that anybody knows where the best place to draw a line is. Whether or not ME/CFS is a single specific illness is not something to which there is likely to be a factual answer, just as there is no factual answer for whether there are two species of redpoll.

And I assume that if a doctor is faced with a seriously fatigued person who is not getting better they should at least think of ME/CFS even if there is no very clear history of PEM. A few members here say they do not have PEM as a recognisable symptom.

As I have tried to indicate, making a formal distinction between ME/CFS and NMECF (non-ME Chronic Fatigue) within ICF is not necessarily going to do anyone any good. If a were pedantic I could say that PWNMECF deserve as much space in the guideline as PWME, maybe five times as much. They appear to be a seriously discriminated against group with no advocacy voice at all and no guideline of their own. Maybe they should get five times as much research money so maybe studies with Oxford criteria are what should be funded. You see where all this goes?

As it is the guidelines say nothing at all about NMECF. Despite that seeming unfair I think it is for the best since all statements about NMECF look to be as long as a piece of string. The studies you have quoted for difference between ME/CFS and NMECF I suspect suffer from fairly circular arguments. If there are five times as many people with NMECF, even if their fatigue is on average less severe there might be a fifth of this group, as large as the ME group, with on average equally bad fatigue. Personally I think these sorts of arguments about average features are pretty unhelpful.

So if the guidelines distinguishes NMECF then it needs a management section. And according to the USA bodies who have made statements they should have CBT and GET because the problem with PACE is just that it covers NMECF. So we get a guideline with CBT and GET recommended. But of course CBT of this sort is based on the idea that there isn't really a separate ME/CFS category, it is just unhelpful thoughts on top of fatigue. So again, you can see where this might be going?

 

Bit confused and not sure what argument you're raising here.

With statements like these you seem to suggest that there is no need for a separate NICE guideline on ME/CFS and that it would be better to have one for all patients with chronic fatigue where no organic disease process can be found to explain the fatigue.

Why exactly do you want the ME/CFS guideline to apply for patients with idiopathic chronic fatigue as well? Why not make a separate guideline for those patients? In research, the two are usually separated.

So is this about frustration about the 2016 AHRQ decision to downgraded recommendations of GET and CBT for ME/CFS because of the Oxford criteria? I agree this was done for the wrong reasons and that there is no evidence for GET/CBT in patients with idiopathic chronic fatigue or in patients who satisfy the Oxford criteria.

Do not quite understand how this relates to the NICE guidelines where we want a description of ME/CFS that focuses less on fatigue.

 

If there were treatments that helped people with non-ME chronic fatigue but harmed people with ME, it would be important to distinguish between them. "Rehabilitative" CBT and GET are ineffective all round, so should be irrelevant. There shouldn't even be an option of "Well give it a go and see." The many reports that they, especially GET flavoured versions, have caused harm simply underlines that.

At the moment there are no treatments for any of those people. I am very uncomfortable about people's need to split ME and non-ME folk, given that none of us have any treatment available, and that different definitions separate different groups. What are you going to feel like if they come up with a test for "ME" in which you test negative?

It's different for research.

 

In Belgium there is a guideline for doctors that focuses on unexplained fatigue. It was written by the Finish company Duodecim that provides brochures of evidence-based medical information. Perhaps other countries use this information as well.

ME/CFS is shortly mentioned as a sub-category, a form of long-lasting fatigue, next to other examples such as burn-out. The information provided is trivializing. Nowhere is it explained to doctors how ME/CFS usually lead to severe disability. Doctors are reassured that for most patients with unexplained fatigue, the symptoms vanish over time.

Unexplained fatigue is such a broad category with enormous differences in severity of symptoms and prognosis (There is no good research on this but I deduce it from the larger prevalence), that I believe this is not a good basis to inform doctors on ME/CFS. I'm afraid this will inevitably lead GP's to underestimate the severity of ME/CFS which can lead to inadequate care. This is a problem when ME/CFS patients desperately want validation and a doctor who recognizes the symptom complex they have. This is one reason why I prefer a distinction between ME/CFS and unexplained fatigue.

Another one is that there is some evidence that GET and CBT do not work in patients with ME/CFS, while the evidence for that in idiopathic chronic fatigue is much lower. So a guideline on ME/CFS might inform doctors that there is some evidence that GET and CBT do not work and that patients frequently report harms by this intervention. For patients with idiopathic chronic fatigue, we don't really know much about these treatments and their reception by patients so such a statement might be inappropriate.

 

No, I think the guideline is quite good. I have been making arguments in response to people who seem to want to change it.

And I have said I think three times now that I do not think a guideline with a broader title of chronic fatigue is helpful.

But the guideline has to intended to be relevant to all people presenting with illnesses involving chronic fatigue because the doctor has to start with a problem and then decide what it might need to be categorised as. If the doctor looks at the guideline and concludes that the patient does not fit ME/CFS then the guideline has done one of its intended jobs!

Research has nothing to do with this. It is about a practical guidance resource for doctors meeting people with symptoms. I realise that for those who have not been in this situation it may seem that the decision making processes should work a different way but I cannot quite see how they can.

And if you have a separate guideline for non-ME CF then what are you going to put into it? Nobody seems to know much about it except perhaps that in quite a lot of cases depression may be a more useful category. Not that I think we have much idea what we mean by depression as a single category.

 

I agree with this actually. My letter ended as follows:

Flatt et al. [1] rightly highlight the debilitating nature of chronic fatigue, which has been overlooked by the clinical and scientific community. The confusion between ME/CFS and idiopathic chronic fatigue might have played a decisive role in this neglect. Most research on chronic fatigue has focused on ME/CFS, which might have provided a too narrow scope to this problem [20]. Conversely, the emphasis on fatigue in the study of ME/CFS has thus far been unproductive. [21] Greater differentiation between these two conditions could further research in both of them.
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I doubt this is the case. Most of the comparisons I cited where between ME/CFS and NMECF patients who visited a tertiary care clinic, usually specialized in ME/CFS. So one might think these NMECF patients represented the most severe group of the NMECF sample and those that are most similar to ME/CFS.

There are no good figures on idiopathic chronic fatigue (ICF) but based on the ME/CFS prevalence studies I suspect that the prevalence of ICF is almost 10 times as large. So that's 2% to 4% of the population. Most of these patients will not be nearly as ill as the average ME/CFS patients. If you weaken the severity and 6-month requirement of ICF as defined by the Fukuda-criteria, the prevalence of unexplained fatigue increases much more. So most of the patients with unexplained fatigue seen by GP's will have nothing to with ME/CFS. It would be good to highlight this in clinical guidelines.

I agree with that. If the symptom complex looks like ME/CFS but one element like PEM is missing I would advise doctors to still look at the ME/CFS guideline. It is very probable that our current case definitions are inaccurate and will need to be redefined in the future.

But suppose a patient with unexplained chronic fatigue without PEM or particular neurocognitive dysfunction. The symptoms which include joint pain and bloating are bad, but not as severe as is common in ME/CFS. The patient has no identifiable, immune-like trigger and although the exact cause remains uncertain the patient relates their symptoms to life events and psychosocial stress.

In such cases, I don't think doctors should look at the ME/CFS guideline to look for the most appropriate care. My problem with the current NICE guideline is that it doesn't make this distinction clear. It focuses too much on unexplained fatigue and too little characteristics of ME/CFS such as PEM and other symptoms.

 

I suspect lots of it is going to be similar to the ME/CFS guideline. It will probably provide information on conditions that doctors should consider and exclude as these might be a cause of long-lasting fatigue such as sleep apnea, atypical depression, anemia, EBV.

It might also provide information on more severe illnesses such as some types of cancer, multiple sclerosis that in the initial stages can cause fatigue without other easily recognizable signs. So the guideline might provide instructions to follow up on patients and consider these illnesses. ME/CFS might be mentioned here as well.

The estimated prevalence, prognosis and general description of non-ME CF will be different though than ME/CFS.

And as I said, in the ME/CFS guideline there could be a statement that GET/CBT have been shown not to work and that patients report harm by this approach, while for non-ME CF group such a statement might be inappropriate cause we don't know enough about it.

 

I am not sure that there is particular focus on unexplained fatigue rather than PEM, which is also a requirement. I understand that patients do not like the term fatigue but we have to be practical and use words that doctors can make some sense of. It is no use saying ME/CFS is an illness characterised by a persistent symptom that nobody except people with ME can understand and is not fatigue. How does a doctor ask a patient if they have that symptom! If someone feels too ill to do anything except crash out in bed, most people understand that as fatigue. It may be something else but what do we call it. Maybe it is really chronic dorzing syndrome, but a GP is not going to get anywhere asking people if they have had a lot of dorzing over the last few months.

 

So why bother to have two guidelines? I am afraid I don't get it. And I think it would generate exactly the problems people here want to avoid.

It seems me a bit like the business of objecting to ME being put under Women's Health and saying this leads to sexual discrimination when Women's Health probably sees its main job as offsetting such discrimination.

 

I'm not against the F-word but there are other ways to describe it: disability, exhaustion, flu-like feeling. It would be good if the NICE guideline provided a little more context here. For example how patients dislike the term fatigue to describe their symptom and how they experience something that is more profound, more aking to a flu that never leaves. I think that will help doctors to recognize ME/CFS.

As @Medfeb has argued the description of PEM in the 2007 guidelines is ambiguous and problematic. It is mentioned as one of the characteristics of fatigue, not as a defining symptom in its own right.

I would prefer the NICE guideline to provide more information, for example by what's on the CDC website, the IOM report or a simplified version of this definition by the NINDS/CDC Common Data Elements (CDE) working group on PEM.

"PEM is defined as an abnormal response to minimal amounts of physical or cognitive exertion that is characterized by:

- Exacerbation of some or all of an individual study participant's ME/CFS symptoms. Symptoms exacerbated can include physical fatigue, cognitive fatigue, problems thinking (e.g. slowed information processing speed, memory, concentration), unrefreshing sleep, muscle pain, joint pain, headaches, weakness/instability, light-headedness, flu-like symptoms, sore throat, nausea, and other symptoms. Study participants can experience new or non-typical symptoms as well as exacerbation of their more typical symptoms.
- Loss of stamina and/or functional capacity.
- An onset that can be immediate or delayed after the exertional stimulus by hours, days or even longer.
- A prolonged, unpredictable recovery period that may last days, weeks, or even months.
- Severity and duration of symptoms that is often out-of-proportion to the type, intensity, frequency, and/or duration of the exertion. For some study participants, even basic activities of daily living like toileting, bathing, dressing, communicating, and reading can trigger PEM."
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Simply saying the word post-exertional malaise isn't enough. There has to be some description of what it means because the term itself is a bit confusing.

I want the NICE guideline to inform doctors about ME/CFS so that they don't think ME/CFS patients are exaggerating or making things up when for example they say suffer a severe relapse with a delayed onset after exertion. Saying patients have post-exertional fatigue or malaise won't do.

 

While I am with you in spirit for your post I have today why would the advice be different? We don't have any reliable evidence about what to do in either situation.

 

I think the problem may be that you are wanting NICE guidelines to be a basic educational tool that tells doctors how to diagnose ME/CFS. But that has never been what NICE guidelines are used for. Their job is principally to indicate what management modalities are recommended and approved within the NHS. They include diagnostic section so that where there is reliable evidence for treatment efficacy it is clear what range of patients it applies to. But no doctor goes to NICE as a textbook of medicine. None of us learn diagnosis from a manual. We learn it from discussing real cases with senior colleagues. There are far too many complex contextual factors for a simple manual to convey how to make decisions of this sort.

What I think you are wanting should be somewhere else and, as I have mentioned before, I think it should be in the educational material for GPs from the RCGP that Steven Brine said was dealing with the misunderstandings!

 

I agree. I am not going to be making that decision but it would be reasonable, if CBT and GET are removed, to indicate explicitly why things have changed.

 

No, are they relevant to this discussion?