On 10 November 2020, the National Institute for Health and Care Excellence (NICE) released the outline for its new guideline on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In a previous blog post, I wrote a summary of this document, highlighting some useful recommendations and notable changes compared to the previous NICE guideline.

NICE’s draft was welcomed by the ME/CFS community as a step in the right direction and a substantial improvement compared to the previous guideline. But there is always room for improvement. In this article, I will highlight some problematic sections and make suggestions on how the document can be further improved.

Overstating the evidence for pacing/energy management

First, I think that the draft overstates the evidence for pacing (which is called ‘energy management’ in the document). Although patients report in multiple surveys to favour this approach, convincing scientific evidence that pacing is an effective management strategy or has a beneficial impact on the long-term prognosis of ME/CFS, is currently lacking.

In my view, some of the recommendations in the draft are stated too strongly. Healthcare professionals are for example told that they should advise patients “not to use more energy than they perceive they have − they should plan their daily activity to stay within their energy envelope and not push through activity.” In another section on energy management, the report advises to “reduce activity as the first step” and to “incorporate the need for pre-emptive rest.” The committee also argues that “faster access to  diagnosis and appropriate care will lead to better symptom management and to substantially better outcomes for people with ME/CFS.”

Although many of these recommendations are sensible, I think they should be worded in a more careful manner, one that accurately reflects the current lack of evidence. Statements such as the ones above might give a false impression to healthcare providers that pacing is effective and that patients will improve (or that it will slow down deterioration) if they follow this advice. It might also suggest to long-term patients that if they had paced at the beginning of their illness, they would have never gotten this ill. This might be true, but we don’t know it. Believing this to be the case could lead to inappropriate remorse, guilt, or grudge against persons who do not deserve it. Whether pacing significantly affects the long-term progression of ME/CFS remains uncertain. Therefore I hope the final version will be worded more cautiously and highlight the current lack of scientific evidence for pacing.

Does ME/CFS often involve periods of remission and relapse?

Second, I think section 1.6.4 “Information about ME/CFS” needs a rewrite. It highlights that ME/CFS is a “fluctuating medical condition …, in  which symptoms and their severity can change a lot over a day, week or longer.” It also states that ME/CFS “often involves periods of remission and relapse.”

Given the paucity of other background information on ME/CFS in the report, these statements are unfortunate as they might give readers the impression that ME/CFS patients are fine one day and severely ill the next. In my view, this is not an accurate reflection of what it’s like to have ME/CFS. I suspect that most patients are ill all the time and I haven’t come across research that suggests otherwise.

Confusion might have arisen from studies (such as this one by the CDC), showing that patients sometimes fluctuate in meeting the ME/CFS case definition or not. Because case definitions require multiple symptoms (and often specify a required severity or duration), reporting one symptom less could result in no longer meeting the definition. This doesn’t mean that patients’ symptoms have suddenly remitted. It could just as well reflect a relatively minor change in the severity or number of symptoms reported while the patient remains very ill. This is one of the big issues with case definitions that do not rely on objective markers but on the presence and severity of symptoms.

Section 1.6.4 also has some other unfortunate word choices. It states that “many will need to adapt to living with ME/CFS” and that ME/CFS “can have a major impact on people’s lives.” Given how ME/CFS is defined, all patients will need to adapt to living with it and for all patients, mild, moderate or severe, it will have a major impact on their lives.

Diagnostic criteria: more info on required tests and exclusions

Third, I think the information on diagnostic criteria could be a little clearer. It only lists four vague and commonly reported symptoms – fatiguability, post-exertional symptom exacerbation, unrefreshing sleep, and cognitive difficulties – and says that the diagnosis can be made if patients have these symptoms for 3 months.

Research, however, has shown that it is not the type of symptoms reported but rather their severity, duration, and a lack of alternative medical explanations that define ME/CFS. These are the criteria that lead to most exclusions, for example in studies on the prevalence of ME/CFS (examples here and here). Therefore, I think it would be helpful to give more information on common medical conditions (mononucleosis, Addison’s disease, sleep disorders, etc.) that can result in a similar symptom pattern and that are preferably excluded before making a diagnosis of ME/CFS.

The previous NICE guideline also gave a list of tests that are useful to perform in a patient with suspected ME/CFS (urinalysis for protein, thyroid function, erythrocyte sedimentation rate, gluten sensitivity etc.)

In short, I think more information should be provided on what is required to make the diagnosis as this would help healthcare professionals to understand what ME/CFS is and what it is not. I’m concerned that the current information might lead to overdiagnosis of patients who will turn out to have another (medical) explanation for their symptoms when a thorough clinical examination is performed.

The guideline focuses too much on the GP

This brings me to my fourth point, namely that the draft focuses strongly on the general practitioner (GP) for the diagnosis and management of ME/CFS. I doubt that GPs have the required expertise to do so.

Research has shown that approximately 40% of patients in whom a diagnosis of ME/CFS is suspected, turn out to have another explanation for their symptoms (see here, here, here, here, and here). Making a diagnosis of ME/CFS is quite complicated because many alternative causes need to be excluded. It is not unusual that months of testing go by before doctors have some confidence in the diagnosis of ME/CFS. I would prefer if the NICE guideline recommended GP’s to refer patients with suspected ME/CFS to specialists that are better equipped to perform these tests and to search for alternative explanations for patients’ symptoms.

The same criticism applies to the management of ME/CFS. Although the draft suggests that, after diagnosis, patients should be referred to a specialist team experienced in managing ME/CFS, it also states that “care for most people with ME/CFS can be managed in primary care after their diagnosis is confirmed and they have a management plan agreed.”

I’m not so sure about that. ME/CFS is a complex condition. Some patients are severely debilitated and have multiple complications. It would be better if patients are followed up by someone with more expertise than their family physician. This is already the case for lupus erythematosus, multiple sclerosis, rheumatoid arthritis and many other conditions, so I think it should be possible for ME/CFS as well.

Access to internists, instead of CBT and activity management

This brings me to my fifth point. When I talk to ME/CFS patients in the UK, it often surprises me that some do not have access to a specialist in internal medicine. Local ME/CFS clinics frequently offer physiotherapy, cognitive behavior therapy (CBT) and all sorts of activity management programs but not access to a doctor who is well qualified to treat and manage a complex condition such as ME/CFS.

In some countries such as Belgium, patients can simply ask for an appointment with a specialist in a local hospital. In the UK this is much more difficult because patients have to be referred by their GP. If their GP doesn’t take ME/CFS seriously and think further tests or investigations are unnecessary, he or she may act as a bad gatekeeper and prevent patients from seeing the specialist they require. 

While the draft talks about offering physiotherapy, activity management programs and CBT, it says little about what seems to be the biggest problem for many ME/CFS patients in the UK: access to well-qualified specialists. A lot of the text is about activity management problems. Although the recommendations are more modest and sensible than in the previous NICE guideline, the focus on activity patterns still seems inappropriate. For all we know, there may be nothing wrong with ME/CFS patients’ activity patterns and changing them may have little influence on the progression of the illness. 

No warning against sleep restriction programs

The draft recommends against graded activity programs, something patient organizations requested multiple times because of reports of harm in their surveys. The committee has tried to word this carefully and cautions against, not only graded exercise therapy but many other programs that aim to treat ME/CFS by gradually increasing activity levels.

In my view, there is one important point missing from this caution, namely sleep hygiene interventions that aim to gradually reduce sleep time. ME/CFS patients, especially in the beginning of their illness, frequently report that they need to sleep 12 hours or more. Some doctors treat this by gradually reducing sleep time, based on the assumption that patients do not need that much sleep and that sleeping less would do them well.

As far as I’m aware there is no evidence to support this approach. Anecdotally I’ve heard patients say that these kind of sleep interventions make them worse, in the same way graded exercise therapy does. Sleeping less than the amount of sleeping hours a patient feels he or she needs, might lead to overexertion and post-exertional malaise. Therefore I think it would be helpful if the draft also makes clear that there is a lack of evidence for such sleep restriction programs and that these aren’t necessarily regarded as best practice by ME/CFS experts.

Two symptoms are worded rather confusingly

Finally, I think that the guideline errs in describing two important symptoms of ME/CFS, namely  orthostatic intolerance and unrefreshing sleep.

Orthostatic intolerance (OI) is defined as the “inability to regulate blood pressure and cerebral blood flow when upright, usually when standing, but it can also occur when sitting.” I think cause and effect are confused here. OI is a symptom, namely feeling bad in upright posture or an inability to maintain this position. There are many explanations for why ME/CFS patients experience this symptom so prominently. The most popular explanation has to do with blood pressure, cerebral blood flow, and postural orthostatic tachycardia syndrome (POTS) but there is also some data (examples here and here) that speak against this hypothesis. There could be other explanations so it is important not to mix up the symptom with the blood-flow hypothesis. Others have made this point before me, most notably Prof. Emeritus Jonathan Edwards on the Science for ME forum.

The issue with unrefreshing sleep is that I don’t think that the sleep of ME/CFS patients really is ‘unrefreshing’. Patients wake up with a dreadful feeling as if they haven’t slept at all; this is what the term usually refers to. But they will probably tell you that, if they slept less, they feel even worse. That’s likely the reason why many ME/CFS patients sleep normal hours or more: because it helps to feel a little less awful. Therefore the term ‘unrefreshing sleep’ might be somewhat confusing – it suggests a problem with sleep being too light or non-restorative, something we don’t really know is true or not.

I realize both issues arise in multiple documents and diagnostic criteria and are not unique problems of the NICE draft. But because the draft chose to rephrase some key terms of ME/CFS (for example pacing or post-exertional malaise), I thought it was appropriate to include this as feedback. It would be great if the NICE draft could bring more clarity in describing these terms and symptoms.