When I first developed myalgic encephalomyelitis in 1994, I had no idea that I would be just as sick 25 years later, or that there would still be limited scientific understanding of the disease and no effective treatments. Nor did I imagine that my career as a lawyer was over, and that I would instead become an advocate for myself and others with ME (sometimes misleadingly called chronic fatigue syndrome, and referred to as ME/CFS by U.S. federal agencies).

An estimated 1 million Americans with this condition have been living for decades in the crisis mode of disability and lack of treatment. We have repeatedly pressed the National Institutes of Health to address the problem by increasing research funding; one ME/CFS organization even met with NIH Director Francis Collins in December 2018 to make that point. The response from the NIH is always the same: Researchers should submit more high-quality grant applications.

On the surface, this sounds reasonable. From documents a colleague and I obtained through a Freedom of Information Act request, I calculated that between 2011 and 2016 the NIH funded 25 percent of ME/CFS grant applications, a higher acceptance rate than the average for all grants. It seems obvious, then, that more applications would yield more funding.

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But it’s not that simple: Despite growing interest in ME/CFS, NIH grant applications to study the disease have dwindled since 2015.

Why? The NIH has erected an obstacle course for those wanting to do research on this disease. I see at least five obstacles that scientists must navigate on the path to funding.

Obstacle 1. In order to have a grant even considered for funding, a researcher must demonstrate that the proposed research is significant, that she has the capability to carry it out, and that it is based on solid science. Good ideas and “what if” proposals are not enough, and the NIH generally doesn’t fund proposals that don’t include preliminary data, such as blood test or brain imaging results from pilot studies. Yet even well-established ME/CFS researchers have difficulty providing preliminary data because the field has been stunted for decades by stigma and the false narrative that the disease is caused by deconditioning and depression. ME/CFS researchers need funding to conduct exploratory studies and generate hypotheses for further research, but NIH won’t fund those kinds of projects.

Obstacle 2. NIH funding for ME/CFS research has traditionally been low. Between 2008 and 2016, its total investment in this area averaged $5.1 million per year. 2017 represented the high-water mark — in that year the NIH issued two Requests for Applications for three collaborative research centers and a data management center, in addition to regular grant funding. Unlike regular grant applications, Requests for Applications come with funding already set aside. Researchers responded eagerly: At least 10 groups submitted applications and the NIH distributed almost $14 million for ME/CFS research.

Funding in 2018, however, dropped 17 percent from the 2017 high, and the NIH has clearly indicated that it has no intention of issuing another Request for Applications for ME/CFS research any time soon.

The situation is made worse because the NIH has no current general invitation for ME/CFS research proposals, called Program Announcements, as it does for diseases like hepatitis B or Alzheimer’s disease. These invitations are important because they communicate to the scientific community that there is interest in these proposals, and therefore potential for funding, even though none is set aside. The NIH’s last Program Announcement for ME/CFS research was issued in 2012 and it expired in 2015.

Obstacle 3. The NIH is made up of 27 institutes that tend to take responsibility for specific diseases: heart disease and stroke by the National Heart, Lung and Blood Institute; Alzheimer’s disease by the National Institute on Aging; and the like. No single institute within the NIH is responsible for ME/CFS research. That opens very wide cracks for applications to fall through. None of the institutes include ME/CFS in their own strategic plans or make it a priority for funding. Researchers are left on their own to find NIH program officers among the different institutes with an interest in the disease.

Obstacle 4. The peer-review process presents unique hurdles for ME/CFS applications. The NIH convenes a new ME/CFS Special Emphasis Panel three times a year for which it must recruit reviewers based on the expertise needed for each meeting, determined by the topics of the applications. ME/CFS applications can encompass immunology, neurology, imaging, bioinformatics, epidemiology, and many other fields. The downside is that only some of the reviewers have expertise in ME/CFS. With data obtained through the Freedom of Information Act request, I examined the makeup of these panels since 2000. Between 2000 and 2010, only 15 percent of the panelists were ME/CFS experts. Although the situation improved between 2011 and 2017, with panels including an average of 63 percent ME/CFS experts, it dropped back to 37 percent in 2018.

Scientists from related fields can certainly apply their own areas of expertise to ME/CFS. Yet they lack knowledge that is essential for evaluating these grant applications. They’re unlikely to understand, for example, that multiple case definitions, involving different symptoms, have been used over the years. An independent panel even urged the NIH to abandon one of those case definitions, but that information has not circulated widely.

The expectations of non-ME/CFS experts regarding study design and data quality may be inappropriate given the state of the field. A cancer or heart disease researcher, for example, may be used to seeing grant applications with data from large multicenter studies, but those kinds of studies have not been possible in ME/CFS.

Even worse, some non-ME/CFS expert reviewers have demonstrated outright bias against the disease. ME/CFS researcher Ian Lipkin said that happened with one of his grant applications in 2014: “[O]ne of the people who critiqued my work said, in fact, that this is a psychosomatic illness.” Lipkin, who directs the Center for Infection and Immunity at the Columbia University Mailman School of Public Health, receives millions of dollars from the NIH for his non-ME/CFS research. If a prejudicial reviewer can tank one of his applications, what hope do other researchers have of fair reviews?

Obstacle 5. If an ME/CFS grant application manages to survive peer review, it must then compete against all the other applications submitted to the particular institute’s council for decision. These councils do not have ME/CFS experts on them, and ME/CFS is not a named priority for any institute. That means an infection-related ME/CFS study submitted to the National Institute of Allergy and Infectious Diseases might be fabulous compared to other ME/CFS applications scored by the Special Emphasis Panel, but it might come up short when compared to hepatitis or influenza proposals that have larger sample sizes or more preliminary data.

Given these hurdles, it’s hardly surprising that researchers hesitate to submit ME/CFS grant applications to the NIH, or perhaps even choose to move to entirely different fields. Those who do apply must navigate this unique set of hurdles, created in part by NIH’s past actions. Its pronouncements that the only solution is more grant applications is unrealistic and, given the immense suffering of patients over decades of their lives, cruel.

The NIH needs to clear these obstacles. While there is no single solution for its broken response to ME, there are many actions it can take that would lower these barriers and encourage more applications for funding ME/CFS research. Difficult problems require complicated solutions, not unrealistic pronouncements.

Jennifer Spotila is an independent advocate for ME/CFS. She writes about the disease at Occupy M.E., where a longer version of this article appeared. She once collaborated on a grant submitted to the NIH in response to one of the Requests for Applications mentioned in the article; the grant was not funded.

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  • Thank you to both the writer Ms. Spotila and to STAT for making this important essay available. I hope NIH leadership reads it and feels actual shame at the situation they have helped to create. They can change this situation, if they want.

  • On Tuesday, January 15, 2019, the MGH Institute of Health Professions hosts an event for over 600 healthcare professionals, researchers and graduate students, and the public, to learn about the highly disabling disease ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome). The program will be held at 341 Huntington Ave, Boston, MA, in Northeastern University’s Blackman Auditorium, at 5:30-7 pm (doors open 5 pm). Pre-registration not required.

    The larger New England healthcare, academic and disability communities, as well as the public, are also invited to attend this program titled Invisible Disability: Providing Compassionate Care for a Person with ME/CFS.

    The program moderator is Massachusetts General Hospital’s Ronald Tompkins, MD, ScD, a co-director of the ME/CFS Collaborative Research Activities at MGH and the Harvard Affiliated Hospitals.

    For more information about the Jan. 15th event:
    https://www.mghihp.edu/ann-w-caldwell-presidents-lecture-interprofessional-rounds

    • Thank you Rivka for the information. I’ll look forward to your thoughts on the event. Wouldn’t it be grand to have these events in hospitals across the country? I’ve come to believe that this has now become a Medical Civil Rights issue. Medical care is being denied, PwME are being told they are depressed and we should exercise and approximately 80% of the people with Myalgic Encephalomyelitis are women. If 80% of 1-2 million American men had this disease, we would have treatment by now. After having ME for over 2 decades and being 67 years old it is a challenge every minute of every day to have hope for any change in the future. I wish you well and send Blessings to you and your family for the advocacy you do for the Myalgic Encephalomyelitis community. With Peace, Love and Healing, Kathryn Mullins

  • It’s a no win situation, without the right data to get a grant for ME, we can’t get the grants for the research to find the answers, re: ME…
    It gets less respect then it’s related cousins, Fibromyalgia, irritable bowel syndrome.
    If NIH doesn’t fund studies, it leaves public thinking it’s not
    real,hysteria, insignificant…meanwhile doctors following example `set by Bush’s
    do not learn to take this disease serious enough. Or even how to treat it?

    We can stick our heads in the sand while millions suffer,
    Or we can look for the answers, and set the message, that we the USA as a great nation take ME seriously, we acknowledge that millions of you are ill, and even though we don’t have the the correct answers, and cure today….We are willing toncommit to we find them!
    Or we can fund studies about the history of smoking in Russia? Or 150.000 study on why filing taxes, stresses the average American out?
    So many outrageous, one may want to say retarded studies…that waste all the funds!
    That I have read about…is shameful..

    When research teams have to beg for grants to study M.E.?
    What has to happen for this disease to be taken serious enough..
    So many people have lost years upon years of quality of life..
    If we `Patients’ just gave up , like NIH is, and let’s face it we are living proof of the true horror of this disease, and it’s effects,
    Than we’d have no where for future inflicted generations to turn for answers..
    Because of ME..

  • @Michelle Heck. While researchers in other fields do face these barriers, they are extremely more difficult in ME/CFS research. This is best demonstrated by the fact that great, successful researchers, who have received many NIH grants in other fields, have great difficulty in this field. Ian Lipkin was already mentioned. There are more: Ron Davis, Prof of Biochem and Genetics and Director of the Stanford Genome Technology Center; Maureen Hanson, of Cornell, etc. These people know how to write grants and understand the system. Most of their ME/CFS grants are turned down. They know that these barriers are in the way of ME/CFS funding. They know that NIH needs to prioritize this and make their funding available to this field in a fair and urgent manner.

  • NIH does not even fund all the excellent ME/CFS grants it receives. It is wholly disingenuous to claim they would fund good grants if they received them. They haven’t funded many of the good grants they already have!

  • CFS/ME may simple. Our body controlled by brain signals. The CFS / ME is where the brain stops controlling our bodies. CFS / ME does not require research but requires treatment. Treatment can remove the causative agent and restore brain function.

  • In response to Michelle Heck’s comment (sorry, I couldn’t find a way to respond to your comment in the thread, Michelle), it is true that all NIH applicants face barriers like this to some extent. There is no special requirement that ME applications provide more preliminary data, for example, than other fields.

    The problem is that unlike virtually every other field, NIH’s own actions raised the barriers higher for ME applications and are maintaining them at the higher level. For example, between 2000 and 2010 only 15% of reviewers for ME proposals were disease experts. Is this true for another disease that has been recognized for decades? Can you imagine if only 15% of breast cancer grant reviewers were oncologists?

    There is a short and very direct line between the extremely low levels of funding over the past twenty years and the difficulty investigators have in gathering preliminary data. If there is no money in a field, then there is no way to gather those data. If there is no money in a field, there are no doctoral candidates and post docs to do some of that early work.

    The problems are perhaps most clear in the case of researchers who succeed in getting funding for work in other diseases, but when they submit applications for the same kind of studies in ME, they do not get funded. It is clearly not a matter of the quality of their applications alone.

    My argument is not that these obstacles do not exist for other scientists. My argument is that NIH contributed to the deterrent effect of these obstacles in ME research, and that NIH must take proactive steps to correct this.

  • I am relatively new to diagnosis, I really empathise with those who are enduring M.E on a long term basis already. The frustration I feel in my daily life like I am just existing- barely managing to ‘tread water’ in respects to completing even the most basics of tasks for survival- is only compounded by the disheartening lack of medical research. I do have one question – is there any way we can influence these medical bodies etc to change these ridiculous guidelines?

  • Thanks so much to Jennie Spotila and Julie Rehmeyer for the research and analysis required to produce this excellent article!

    Underlying the problems of ME/CFS is deep-rooted cultural contempt.

    We are all, in contemporary society, either ‘workers’ or ‘shirkers’.

    The person with ME/CFS, lacking visible explanation, becomes a ‘shirker’.

    (Ironically, the conscientious who fight to keep going become severely ill, while the less conscientious, who ‘give up’, have a much better chance of improvement. ME/CFS punishes virtue and rewards the sociopath.)

    Even more relevant is our culture’s contempt for women, which we learn about through #metoo, the publication of gender salary differentials, and from every doctor who tells us we are just depressed, and need to lose weight and exercise.

    Medical contempt for women has been documented by Maya Dusenbury in ‘Doing Harm’. A recent Facebook post mentioned a doctor who was terrified his colleagues would discover that he had been diagnosed with ME..’Doctors have even more contempt for patients with ME than they do for patients with depression.’. (Bit of a revelation!)

    I found it even embedded in my own language in describing gendered responses, writing ‘When men report their symptoms, …..but when women complain of their symptoms…..’. Is male report versus female complaint rooted in language or even in my own thinking?

    ‘Reports’ require addressing the issues reported. ‘Complaints’ require silencimg the complainant.

    How better to silence people with ME than to choke off research funding?

    Diverting allocated funding, as the CDC did, minimising funding, giving assurances with no intention of acting on them, setting up a long-drawn-out research program under the supervision of a man who believes the disease is psychosomatic….these are stark examples of institutional contempt….

    We need to find a way to address the psychosocial roots of our neglect…

    • Unfortunately, the majority of the limitations you describe here are also limiting for scientists in most, if not all fields. It is challenging for panel managers to recruit experts to serve repeatedly, and even more so if the field is small. Misinformed reviews tank grants all the time. This happens to all scientists at some point in their careers. Common misinformation about a particular disease, technique or study have to be addressed in grant writing with references so reviewers who are not experts in the field of study can better understand and contribute to the review process. The issues you raise in this article are not unique to studies of ME but rather are problematic in all areas of science, including funding rates, competition with higher profile diseases, panel composition, peer review, calls for proposals and so on. Historically, any high risk research proposal without preliminary data or evidence that the team can do what it is saying it can do will not be funded. This is also a universal because people can ask for money to do anything, but is it feasible? Finally, NIH limits how much funding an investigator can have at any one time. Universities will not allow their PIs to over commit their time above 100% effort, which makes sense. If the top ME labs are already well funded, they will be less competitive or maybe ineligible for funds in the next fiscal year. I am sorry you are dealing with this and many of the frustrating realities of our scientific processes. I can assure you that scientists across the board share these frustrations regardless of field of study.

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