Reprinted with the kind permission of Cort Johnson and Health Rising.
By Cort Johnson | Nov 11, 2015
The lack of validated treatment options for chronic fatigue syndrome are 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.
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 treatments 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 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.
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 studies.
Sixty-nine percent of the citations referred to behavioral, exercise or pacing studies and thirty–one percent referred to non-behavioral studies.
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.
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.
The Federal Funding Imbalance
I wasn’t able to ascertain the source of the funding for the CBT/GET studies in the UK, the Netherlands and elsewhere but without a commercial product such as a drug being involved the funding presumably came from government sources.
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 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.
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.
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 lesser respect. Virtually all the behavioral studies, on the other hand, took place in countries with more respected research entities.
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, 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.
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.
Until federal funders in the US and elsewhere support ME/CFS clinical studies, federal funders in the UK and the Netherlands will largely be able to dictate the treatment regimens available in doctors offices. In consequence, 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.
About the Author: Cort Johnson has had ME/CFS for over 30 years. The founder of Phoenix Rising and Health Rising, Cort has contributed hundreds of blogs on chronic fatigue syndrome, fibromyalgia and their allied disorders over the past 10 years. Find more of Cort’s and other bloggers’ work at Health Rising.