The lack of validated treatment options for chronic fatigue syndrome is well-known. No drugs have been approved by the FDA in 30 years, and only one has made it through the FDA pipeline. None appears to be under development.
Chronic fatigue syndrome (ME/CFS) is a disease that affects at least a million people in the US. Studies indicate that it impacts functioning and quality of life at least as much if not more than major diseases such as multiple sclerosis.
Funding has an enormous impact on the types of treatments available at doctors offices
The IOM committee stressed that chronic fatigue syndrome is a “serious illness that requires timely diagnosis and appropriate care.”
Appropriate care can only take place, though, when the full range of treatment options are present and affordable (i.e. covered by insurance). Those two factors require that large, rigorous treatment studies take place.
Non ME/CFS experts stick to treatments that have been validated in clinical trials and passed down to them by treatment reviews. The options most people with ME/CFS are left with reflect the options that the “treatment marketplace” has opened for them.
The availability of those options are largely dependent on funding. Parties that are willing and able to fund large clinical trials can get their treatment out to practitioners. Small, unreplicated clinical trials, on the other hand, get almost no attention. Large funders, therefore, generally define the treatment options most doctors are aware of, and most patients get.
The few patients with the access and the money needed to see ME/CFS experts gain access to a wide range of treatments. These specialists use research findings and their experience to develop their own unique treatment protocols – which are rarely covered by insurance.
The vast majority of people with ME/CFS are, except for generic symptomatic treatments, restricted to treatment options that have been validated in treatment trials. Let’s see what the treatment marketplace has provided for them in the past three years.
Survey
In an attempt to assess what the “treatment marketplace” is providing for people with ME/CFS, I went through around 1,000 citations dating back to the beginning of 2013 and plucked out those that had to do with treatment.
I included every kind of treatment study, big or small, rigorous or not, or any analysis of a treatment study, or any description of a treatment study, as well as treatment reviews.
I broke the treatment citations up into behavioral/exercise and non-behavioral categories and determined the country of origin of each. I also examined the study size of some of the studies.
Results
Sixty-nine percent of the citations referred to behavioral, exercise or pacing studies and thirty–one percent referred to non-behavioral studies.
Behavioral Studies
More behavioral treatment citations came from the UK than any other country
CBT and CBT/GET studies dominated behavioral regimen with 71% of the citations referring to these studies (sometimes in combination with another treatment regimen such as the Lightning Process.)
Country of Origin – Over two-thirds of the behavioral studies originated in two countries — the United Kingdom (22) and the Netherlands (14). Other countries included the US — 5, Belgium – 4, Norway – 3, Australia – 2, Spain – 1, India — 1, Japan – 1.
Non-Behavioral Studies
About thirty percent of the treatment citations referred to non-behavioral studies. Most of these studies, even if successful, have little chance of making into the treatment lexicon for ME/CFS. This is because these studies lack replication (validation), are mostly small, and many come from countries with smaller research programs and thus are probably not respected.
In contrast to the behavioral studies, no types of studies and no countries dominated the non–behavioral citations. The wide spread of studies in this category (22) has implications – if studies are not replicated they won’t make it into treatment reviews for doctors.
With only one type of non-behavioral treatment, acupuncture, being assessed in more than one study, few of these treatment options have a chance of going mainstream. (CBT/GET studies showed up in 38 citations). The countries that dominated the behavioral studies (n=36) – the UK and the Netherlands – showed a distinct preference for the types of studies they wish to fund; they produced only three non-behavioral studies.
Critical Factors
The Federal Funding Imbalance
Magnitudes more funding for behavioral treatments means they dominate the treatment regimens for many
The implications of two governments focusing substantial funding on one treatment type is clear: a dramatic restriction of the possible treatment options recommended for doctors and ultimately for most patients. Few of the treatments ME/CFS experts use showed up in this survey and few of which are available to patients seeing non-experts.
When a slim portion of the possible treatment options for a disease gets outsized attention three things happen: that treatment gets an undue focus in the media, doctors and patients treatment options are limited, and patients miss possibilities for treatment.
The importance of federal funding in a disease like ME/CFS which is not being courted by pharmaceutical companies cannot be understated. Few funding sources for large, effective clinical trials exist other than federal funders.
The critical role federal funders play can be seen in Rituximab. The one large study underway (in Norway) is receiving significant federal support. No studies are underway in countries that are not providing federal support.
In the U.S., the National Institutes of Health frequently funds clinical trials including a Rituximab trial on myasthenia gravis. Despite clear indications that two drugs, Rituximab, and Ampligen, are helpful in ME/CFS no NIH-funded trials are underway. With Rituximab going generic and Hemispherx Biopharma unable to fund a large trial no trials are underway for either in the U.S..
So long as federal funders in the U.S. and elsewhere balk at supporting clinical trials for ME/CFS and the U.K. and the Netherlands are willing to pump large sums into their behavioral trials, it’s hard to see how those treatment options will not continue to predominate in ME/CFS.
Study Size
The difference in study size and country of origin in behavioral and non-behavioral treatments is dramatic. Study size tends to be high for behavioral studies and low for non behavioral studies. High study size means increased validation plus the ability to ferret out more moderate treatment effects.
Many well funded treatment trials have allowed behavioral therapies to put a chokehold on options for ME/CFS patients.
With nil or low participation from federal funders and drug companies many of the non-behavioral studies are small, lack rigor and are underpowered. Of the six drug trials over the past three years, for instance, only two had over 30 participants and two had less than five. Compare that with the number of participants in the most recent behavioral studies produced by two prominent behavioral practitioners, Bleijenberg (Netherlands) and Chalder (UK).
Number of Patients in Treatment Trials
- Bleijenberg – 244, 204, 142, 169, 112, 261, 120+,
- Chalder – 481, 641, 389, 1643, 9
Country of Origin
Whether a study originates in a country with a large, established and respected research establishment or another country matters. The eleven non-behavioral studies from Turkey, Serbia, Italy, Korea and China will be valued less than studies originating in the U.S., the U.K. or Australia. Almost half the non-behavioral studies originated in a country that commands less respect. Virtually all the behavioral studies, on the other hand, took place in countries with more respected research entities.
Conclusion
The treatment options available for most people with chronic fatigue syndrome are not a function of the treatment possibilities present. Instead, they are largely constrained by which party is willing to commit the money needed to produce large, well-replicated studies that make it out to their doctors.
Symptomatic treatments to help with sleep and pain are available to many people with ME/CFS but when it comes to targeted treatments for their disease, behavioral therapies often top a very short list of treatment options. The dominance of the behavioral therapy regimen in ME/CFS is the result of two factors.
Poor research funding left the door open for well-funded behavioral trials to seize the day in the treatment realm.
One is the unwillingness of federal funders such as the NIH to fund research that will reveal viable treatment targets for drug manufacturers. This poor research funding has left ME/CFS a biological mystery. This has opened the door, as has happened so many times to so many diseases over time, to a behavioral interpretation of it.
The willingness of federal funders in the UK and Europe to pump large amounts of money into the behavioral treatment trials has effectively exploited that opening. A significant portion of the medical profession either accepts a behavioral interpretation of ME/CFS or has little or no knowledge of other possible treatments.
The behavioral/non-behavioral treatment divide has been exacerbated by the dominance of large, replicated behavioral studies from more respected countries and smaller, unreplicated non-behavioral studies, many of which are from less respected countries.
The solution is having federal funders in the US and elsewhere fund ME/CFS research to identify biomarkers and ME/CFS clinical studies. Successful Rituximab and Ampligen studies would provide a significant counterweight to the ongoing (and seemingly never ending) drumbeat of behavioral trials emanating from across the Atlantic.
The upside of the attention given to CBT/GET is that the studies have drawn the attention of outside reviewers. Overviews have found them to have only moderate effects on fatigue and no effects on functioning. That suggests their influence could be eroded by well-designed trials that have more positive results.
Until those studies are done federal funders from the UK and the Netherlands will largely be able to dictate the treatment regimens available in doctors offices and few people will have access to the wide range of treatments that might help them.
Funding Rituximab and Ampligen trials in the U.S. would be a good first start for the NIH.
- Next up – a look at fibromyalgia treatments
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Thanks for your support. Cort
Treatment Survey
Behavioral = 53 citations
CBT alone or CBT/GET -38 citations Graduated exercise therapy – 6 Pacing — 3 Yoga — 2 Others – 8 • Multidisciplinary Study • Relaxation Therapy • Stress Management • Meditation – symptom management • Self-management • Guided Self Instruction • Symptom control • Emotional involvement significant others
Non-Behavioral = 25 citations
Drugs
• Rituximab (29 people) – Norway • Cytokine blocker (50 people) – Netherlands • Clonidine (176) – Norway • IVIG (1) – Italy – • Ondansetron (5)- Netherlands • Valganciclovir (30) – US • lisdexamfetamine dimesylate (26) – US
Supplements and Diet
• GcMAF – Japan – case studies – 3 people • B-12/Folic Acid – Sweden • Diet – Review article – US • COQ10 – Spain • Herbal China review – China • Vit D – UK • Herb – Italy – II – french oak wood extract • CoQ10 – Spain • Traditional Chinese Medicine – Review – China • Multivitamin – Serbia • Acetaminophen – Belgium
Other and Alternative Health
• Acupuncture – S Korea, China, S Korea • Hyperbaric Oxygen Therapy – Turkey • Mercury removal – 1 person case study – Korea
Other
• Multidisciplinary Treatments – Italy
Countries of Origin
US – 4 Italy – 3 Korea – 3 China – 3 Norway — 3 Netherlands – 2 Spain – 2 Belgium – 1 Turkey – 1 Serbia – 1 Sweden – 1 UK- 1
Kind of embarrassing to be British after that analysis!
The problem we’re finding in the UK is not just that the funding has gone down the drain of the behavioural approach but that one huge study that dominates the evidence because of its size – the massive PACE trial of CBT and GET – is a failure being spun as a success.
The blatant misrepresentation of null long-term follow-up effects in PACE to make the trial appear successful is what apparently disgusted Prof. James Coyne enough to launch his attack on PACE in his two recent blogs.
The petition to have misleading analyses in PACE retracted is so close to its 10,000 target now that we’re only hundreds of signatures away now, not thousands.
In only two weeks we’ve gather over 9,400 signatures. Only 586 left to go now.
Please, everyone, sign and pass the petition on:
http://my.meaction.net/petitions/pace-trial-needs-review-now
Thanks, Cort, for this article. Behavioural research such as PACE has been a monkey on all our backs.
A British monkey! I’m so sorry.
Kind of embarrassing to be British after that analysis! 🙂
The petition has over 10,000 signatures now (and it’s still going up!).
Thanks for your support, Cort!
Cool 🙂
If just a handful of high profile Americans, i.e. celebrities, CEO’s, politicians, etc. were to be diagnosed with cfs/me/fm, you betcha there would be a campaign for successful treatments. I wonder what color the ‘find the cure’ ribbon would be to slap on your car?
How can anyone still maintain that it’s not physical after the dramatic results from Rituximab? At the least, the temporary suppression of the immune system by that drug proves that the symptoms are the result of an immune system response. The continued emphasis on behavioral studies must be the result of ignorance and inertia. How discouraging.
Hi David – I think that what we’re missing in Rituximab are the results of a big trial. Once those come in – and they are positive – watch mouths drop and things change. Rituximab is a powerful, well-known drug – if the results of the big trial are positive it will be a game-changer – a dramatic game-changer; I don’t see how it could be otherwise.
A positive Ampligen trial result would be big as well – if an Ampligen trial can get supported by the NIH.
Until then or until we get a big result from a research study or a result from another treatment trial I think yes – there is a great deal of inertia built up from all the money going into CBT/GET trials. I think this year we’ve had something like eight studies.
Thanks, Cort. The Ampligen trials should have been done years ago. Meanwhile, money and energy is being wasted on these pseudo-scientific charades while there is not a single proven palliative on the shelf for patients.
The Norweignas are launching a large-scale trial of Rituximab, following the success of their small trials (source: a talk by Dr David Shepherd, recently). It will, of course, take several years. If it shows good results, the UK is likely to launch one too – which will again take several years.
I think you’re wrong about the way things are funding in the UK. To get funding for a big trial, one must first have conducted more than one small trial which shows promising results. Only sensible. Sadly, lots of promising treatments (such as B12 injections) are given only by local specialists, who haven’t done trials, but rely on their own experience.
The first step in large trials would be to persuade those doctors or other researchers to start the small trials that they are crying out for. But that takes funding.
The bottom line is that in the UK, under the current government, the ideal funding level for any research into anything is zero. They have implemented austerity policies, and are busy slashing services, not building them. My local CFS clinic is under threat: and is the only support offered to sufferers for about 20 miles. It might close in early 2016. Altogether.
Cort,
After having ME/CFS for over 22 years I finally was able to see an ME/CFS doctor for the first time earlier this year. Among other things she insisted my surgeon follow the protocol on hydration (extra saline) during a recent surgery. I had the response many have had- I came out of major surgery feeling better than on an average day. Since then I have studied Dr Bell’s experience with his patients on IV saline as successful in increasing quality of life. But this falls where many treatments have: understudied, unproven, anecdotal…However, there is a ten year study going on at Vanderbilt university due to be out in July 2016. https://clinicaltrials.gov/ct2/show/NCT00580619?term=%22chronic+fatigue+syndrome%22+AND+%22Saline%22&rank=1
From what I discern, there are 80 participants, is this considered sizable? And if it has positive outcomes would it be respected enough to affect average PCPs & insurance companies?
I am trying to begin a 2 week trial of daily saline IVs thru peripheral line as prescribed by my ME/CFS Dr but we are already running into insurance problems. How much harder will it be to get a chest port approved?
Thanks for all your hard work! This site is a lifeline.
The saline trial and the other drugs they are testing is a definite bright spot. Eighty participants is certainly enough for a rigorous trial. I imagine that one trial is not enough for insurance companies to cover IV saline but hopefully it will be enough to stimulate other trials. Another saline trial would be a great trial for the NIH or the FDA to support. Saline is obviously used a lot, the pluses and minuses of saline are well known, it’s not expensive and it really appears to make a difference – even if its temporary – in ME/CFS..
It points an arrow straight at blood volume and the blood vessels….I’m looking forward to the results! Thanks for the reminder that this trial is going on 🙂
Thank you for mentioning the anecdotal saline observations and study. I am glad it is finally being checked out.
I’ve had two surgeries in two months. I had no problem waking from the first while it took 7 hours and narcan (used to combat overdoses) to wake me after the second. I remember being full to bursting after the first but not peeing until late night after the second. It is quite possible that is notcoincidental, though I will need to examine the anesthesia records tomorrow to see what actually happened during the second surgery. Still, if something as simple as extra saline during surgery could prevent serious adverse anesthesia effects in ME and CFS patients, that alone would be worth a well-funded NIH study.
Several people have reported how helpful saline was during surgery. One person I know of had a horrific time recovering from a relatively mild surgery. Her issues mostly disappeared after she finally got some saline.
I agree with what you said. One thing to think about which I have experienced and I’ve heard of others too is a dramatic temporary improvement following surgery even without saline.
With me it was a feeling of well being and a sharp clear mind I hadn’t felt in a decade. I wasn’t running around but I felt like myself. The wired/toxic slow brain thing was gone for a day. I and others think it was the affect of the anesthesia. Like Cheney has said about people going into a coma feel better after coming out because the slight seizure brain was given a rest.
I’ve always had a problem with treatments that try to create more energy and do better with treatment that calm which really a challenge when the name of your disease is chronic fatigue syndrome. 🙂
Thanks Cort for an excellent analysis of the papers.
One problem with clinical trials in ME/CFS is there are still no good objective outcome measures, so the subjective ones rule (fatigue scores, SF-36 etc). Even the rituximab trial is using a subjective primary endpoint, though it’s quite a complex one that they have devised. This is something we could all put our heads together about – what could be used and wouldn’t do patients harm – which the 2 day CPET could!
Thanks. There appears to be some good news here – if I’m reading it right –
http://www.cortjohnson.org/forums/threads/fda-making-progress-on-critical-need-in-chronic-fatigue-syndrome.3328/#post-9150
Check this blog out:
A superb blog and portrayal of a person with ME/CFS, EDS and POTS visit to a federally funded UK clinic. The doctor was very nice and lots of blood tests were taken and, in fact, the blood tests indicated he/she had Epstein-Barr virus reactivation but none of that mattered – the UK apparently provides two types of treatment – you can guess what they were.
http://natashalipman.com/i-went-to-a-fatigue-clinic/
Yep, that’s the UK for you. 🙁
BTW, we’re a kingdom rather than a federation of states so we refer to our stuff as “government-funded” rather than federally funded.
Not sure what the term would be for stuff funded by the European Union – let’s hope that we’ll need that term one day! That would be big money.
Thanks for a good article. The phrase from my engineering classes floated into my brain, when the only tool you have is a hammer, all your problems look like nails. The hammer being shrinks doing studies on a non-shrink disease. My idle mind then thought we should send power screwdrivers, garden hoses, maybe a power saw or drill to the funding agencies, until they get the point, and use appropriate tools, putting that hammer down.
Sasha, it is not the UK,it is one cluster of shrinks who have no evident ability to see the world more than one way, their way. Let them take the responsibility for their own work, and their huge network of friends who publish their work. I suspect that any medico who advises insurance companies not to pay out for a large class of sick people and generates a ton of published papers to make their fee worth it, will have a lot of friends. Not a reflection of medical success, just the way we all let insurance companies run our lives.
PS Cort, those boxes with the outline of a person still cover up a chunk of the text of the posts, words that cannot be seen.
Hi Cort,
I guess I’m kind of wishing in a way that I didn’t come upon this article. I live in the US and my plan was to begin the Gupta Programme. I saw a Gupta coach in the US who recovered from the Fupta Programme and has reopened her therapy practice a year in a half ago. I have also thought about giving the Lightning Process a go. I feel like I’ve done so much and only 1 thing has helped which is always being threatened to be taken away from me. That’s Xyrem but I won’t get in to that. Are you saying that you do not believe in treatments such as the Gupta Programme and the LP?
Please be honest.
Thanks!
Hope
Not at all Hope. I’m sorry if I gave that impression. I actually very much support those programs and am engaged in my practice through Landmark Education of using mindfulness techniques for a better life. I simply believe that programs like CBT/GET are getting too much coverage – that they are dominating the treatment regimens too much. I’m not even against CBT – I think anyone with diseases like these can use assistance in managing them. I think that’s pretty much inevitable actually.
Toni Bernhard, by the way, has a new book out about living with chronic illnesses. I imagine there is a lot of good stuff in there. Also be on the lookout for a blog in this area that is going to knocks your socks off. 🙂
As ever, a really important article!
Can anyone help with the following three questions.
I am severely ill (bedridden, often unable to sit up at all and unable to speak) but prior to CFS was a (UK) journalist.
I’m trying to collate the most compelling information stemming from the massive amount of work relating to the PACE trial (Tuller etc)in order for it to be crunched down into a strong article for the mainstream press – help with the following would be great:-
1) Has the UK ever funded trials for a non-behavioural interventions. Have there been any UK studies for biomedical treatments in the past 10 years?
2.a) Re Cort’s statement that, when diseases are a biological mystery the behavioural interpretation is the go-to explanation that is left to plug the knowledge-vacuum. I’m looking to give some powerful examples of exactly which physiological diseases of the past used to be cast as illnesses of maladaptive behaviour or psychiatric in origin?
2.b) As an addendum – have there ever been, or are there any, psychiatric illnesses that present physical symptoms of equal potency and severity to CFS?
We know major depression can effect energy levels, appetite, digestion; panic attacks create powerful but relatively brief cariopulmonary symptoms but do psychiatric illnesses give the physical symptoms that massively impact physical function and quality of life, and/or symptoms that outside CFS we do not normally blame on mental-states eg sore throat, tender lymph nodes and low blood volume.
3) Does the scientific literature unequivocally confirm that CBT and GET do not improve functioning. If all meta-analysis, and other forms of overview research really do all reach this conclusion this is such a powerful point. I would love to see a reference and source that makes this point. And if this could conceivably contested to what extent do they claim to restore healthy/normal function?
just looking for something positive – or a bit of moral support today. I’ve been sick since I was pregnant in 1987 and running out of steam & hope lately! What a miserable way to live your life’s!!! In the last 6 hours, I got up once to use the bathroom and keep everything I need next to my chair. There isn’t anyone around to help me or even to talk to that can possibly understand what this feels like. Just laying on my heating pad day after day…..thinking about all that I should be doing. I’m so exhausted & lonely!!! Please put me in touch with someone in my area that believes ME/CFS does exist!
Cindy – please don’t torture yourself with thoughts about what you “should” be doing. Those thoughts are inevitable – we’re all probably beating the heck out of ourselves deep inside for not doing what we think we should be doing.
I imagine that you’ve tried as hard as you could to do those things. I imagine that you’ve probably injured your health to some extent trying to be who you were. The inevitable outcome -as strange as it sounds – is that by being in bed you are doing exactly as you should be doing. So maybe the thing to do is to be in bed the best way you can.
Good luck!
It can be so hard to get the medical profession to take this disease seriously and you can partly blame their education. I have been a registered nurse x 40 years, and up to the time I contracted this wretched disease almost two years ago I had no idea what it really was! Their is an attitude that it isn’t serious and people just need to get up and get moving. Until this condition is seen for what it really is the struggle will continue! My own fantastic and caring physician knew nothing about it and I am the one who made the diagnosis six months after the symptoms started. This was after a psychiatrist and a neurologist suggested I was malingering! My prayer is that a treatment will come soon while I can at least enjoy my grandchildren since my career has been destroyed. My lack of memory makes it impossible to use my education and experience now.
Well said Kaylyn – your caring and compassionate physician simply didn’t know…
Around 3-31/2 years ago I had a very stressful incident both physically and emotionally. It resulted in what I can only describe as Chronic Fatigue. I could hardly walk. I had trouble breathing. I could not drive the car. My Dr said Chronic fatigue from Epstein Barr, although the test for it was inconclusive.
My Dr recommended ALA IV’s. I took a few weeks of them with no positive results. I spent every day in bed and had to hire help for everything. This went on for about 2 months at least. I had to try somethingDifferent. I asked my helper to drive me into Truth or Consequences to take a thermal bath. I took a highly mineralized hot springs bath for about an hr. Then went home and slept. When I woke up in the morning I was shocked. I felt totally normal. I could do everything. The effect started to wear off in a few days so I took another bath. It took 3 baths a week to keep me healthy . After a few months I was able to maintain health w 2 baths. I was still taking 2 baths a week when the pandemic hit, many baths closed. But I stayed healthy without the baths and never became fatigued again.
Some personal observations:
I have discovered that, when I am very sick with the flu-like symptoms, if I take two Benedryl tablets during the day, I feel significantly better within 30 minutes. I have also had consistent improvement of the flu-like symptoms and the profound fatigue, following day, if I take Nyquil at night . I am guessing it is the dextromethorphan.
Also, I had constant pain from interstitial cystitis and diarrhea from gluten. I went on the KETO diet for six months and both of those symptoms went completely away. I have found that I can eat bread or desserts made with wheat flour if they are made with flour from Europe or, if the flour is organic. I have read that the reason for this is that European and Organic wheat is not treated with Round-Up and that is why so many Americans have developed gluten intolerance.
When I had the virus which precipitated the onset of the FM/CF, five years ago, I lost my senses of smell and taste and they have never come back. Another common symptom with Covid long-haulers’ disease.
How much would it cost to do a Rituximab study in Canada or the US? I would be willing to heavily back that financially.
Hi Valerie! It’s already been done and unfortunately after two really positive early study results – it failed pretty miserably. One researcher believes the trial was flawed. Just check out Rituximab on Health Rising and you’ll see a lot about it. If you’re interested Klaus Wirth and his partners have a drug they believe can help and there’s the Cortene trial which I think is about halfway funded.