"ME/CFS Funding Worsens As NIH Maintains Status Quo"

https://www.healthrising.org/blog/2019/12/20/me-cfs-funding-worsens-as-nih-maintains-status-quo/

 

Very disappointing to see:

 

I know some people are probably bored of me saying it and/or would prefer if I didn't say it but while the ME/CFS community is doing a lot better than it has been, I still think a lot more could be raised worldwide for research. In my country, it is largely a few dozen families who raise most of the money we raise either through monthly donations and/or the odd fundraising event. We raise proportionally more than a lot of other countries but so much more could be raised if more people focused on the issue.

I just think there needs to be more of a mindset that a lot of research money needs to be raised privately rather than simply blaming governments for a lack of funding.

 

What I wish is that we could get input from current researchers about why the field is steadily shrinking at a time when the barriers to receiving NIH funding have dropped. Clearly NIH should do whatever it can to change the current situation, but this strikes me as a difficult problem.

Just money is not enough. We want researchers who are challenged by this complex disease and bring fresh ideas to the table. I fear that the lack of applications reflects an indifference in the research community to jump into this work. And we need all of the good minds that we can get.

 

Could this partly be a sign of success? We've helped make it clear that CFS is a condition surrounded by poor quality research where poor quality research is no longer seen as acceptable. In the long--run, that's a good thing, but it's not something that is going to encourage an immediate glut of PhD students.

 

I do not think it is part of the ‘success’. For millions afflicted, there are only a few clinicians practicing knowledgeable enough to discuss clinical aspects of the disease without mentioning psycho-social factors. Half of these physicians will retire or are past retirement.

Universities do not have for the most part a program that teaches students, both science and medicine for ME, Stanford is working on theirs. Miami’s is not a mainstream university. Who knows what’s happening in Reno Nevada?

There are very little incentive for researchers to enter the field and it may well be a minefield for them to do so. There is a steep learning curve and tremendous gaps to overcome in order to be successful.

 

Yes, this is something I suggested to Lenny and also the CFSAC years back - we need to systematically study why scientists aren't choosing to enter the field and then try and fix those problems.

However I still believe that the low application rate at the NIH is a catch-22 - low applications because most researchers expect to be turned down, hence don't bother.

 

Would it be possible to see what those applications were (like the title and author) cause that seems like the only way in figuring out what's happening.

I sometimes wonder whether the following might have something to do with lower applications in recent years: the fact that ME/CFS is less seen as the fatigue condition par excellence. I think that in the past researchers who wanted to study fatigue used CFS patients to do that. If I remember correctly, that's how Alan and Kathleen Light got involved in CFS. There were also prevalence estimates saying that CFS affects up to 2,5% of the population. That suggested it would be rather easy to recruit a lot of patients.

Now that ME/CFS is increasingly seen as more than just unexplained chronic fatigue, but a complex condition with a range of symptoms and a lower prevalence rate, this might look less attractive for some researchers to enter the field.

If fatigue researchers are less interested in studying ME/CFS, it might be a solution to attract researchers with expertise in exercise intolerance, as this symptom has replaced much of the emphasis on fatigue in diagnostic criteria for ME/CFS.

 

Want to emphasise here that I’m playing devil’s advocate here and don’t hold these views but....why *would* you want to enter the field?

It’s a field that at present is:

- mired in controversy
- little direction
- no real foundation to build upon
- doesn’t have the ‘glamour’ of curing something like cancer
- doesn’t have any big name charity attached to it or celebrity awareness

I’m just trying to see it from the perspective of an early career researcher and someone trying to map out what their career might look like. In any field, most people want to take the path well trodden, perhaps with some level of innovation and unique contribution of their own. Very few people seem to want to be the first to stand up and say, yeah this thing hasn’t been explored but I think it’s important and here’s why and here’s how I’m going to do it. I’m saying that about all industries really.

So I guess it’s a challenge of how do you address those very valid qualms of someone who wants to research it.

 

Here's my attempt to convince the devil's advocate.

Because the research community in ME/CFS is so small, anyone stepping in will have a relatively larger influence than in other fields of medicine such as cancer or Alzheimer research. While in other fields a researcher will follow a well-trodden path, in ME/CFS they can help set the direction. The importance and influence of a researcher might be higher in ME/CFS than in many other conditions, especially for young researchers with little experience. In other fields there are enormous collaborations and multisite trials conducted by large and experienced teams that set the tone. As a young researcher stepping into the field you can only be a small part of that effort. It might be harder to pursue your own hypotheses and theories or force a small breakthrough on your own, compared to a less developed field such as ME/CFS.

ME/CFS is not rare and causes enormous disability yet it's currently overlooked by most of the medical profession. That alone could excite a researcher to enter the field. I think Ronald Davis once said that everything else will be either rare or insignificant, meaning that in other fields the illness will either have a much lower prevalence or cause less disability (for example because some effective treatments have become available). I would also think that the very severe ME/CFS who lie constantly in the dark or the empty shoes of millions missing displayed on 12 May each year provide powerful images that might convince some to join the effort because of the social injustice and lack of recognition of this illness. Researchers would get a lot of support and recognition from the ME/CFS community and would be regarded as heroes by the many patients who follow the research closely.

Finally, I think that the most popular model of ME/CFS within the medical profession, the fear-avoidance model, is clearly problematic. So there's a need for new models, new ideas, new hypotheses. Perhaps that might excite researchers to enter the field as well. We have some evidence that an infection like EBV-infection, increases the prevalence of ME/CFS. So some people get this common virus but don't recover. They remain terribly ill for decades and nobody knows why. I suspect that's an intriguing question for researchers, an interesting puzzle to solve. Post-exertional malaise is also intriguing: why do patients get worse if they try to do more and why does there seem to be a delay in the payback? What biological mechanism could explain this?

So I do think we have some strong cards to play and attract more researchers in ME/CFS, even though the figures reported recently are rather disappointing.

 

Just repeating what I’ve said before: one thing people can do to help the field that costs them nothing generally is circulate recruitment appeals. I’ve seen studies in different countries struggling to reach their targets while at the same time it seemed few patients were circulating appeals. I think the MRC-funded Nutt study on sleep may not have reached its recruitment target which may be why we have never seen any results.

 

The problem is we cannot see the applications that were never submitted.

The NIH claim that there is no bias because they fund applications at slightly higher levels than expected compared to other conditions. They point to low application rates as the primary problem. Yet they don't bother to ask why there are low application rates and whether their bias on what they do and don't approve has something do do with it.

The higher funding rates may instead show that there is a survival bias of applications - riskier research grants are simply not submitted for CFS due to low expectations of success, whereas they are submitted for other illnesses.

Besides a big market for treatments, I'm sure there might be various big prizes including the Nobel if there are major breakthroughs. Certain members of the Open Medicine Foundation can nominate and the patient community could show strong public support through a petition.

But you are right, science lacks job security as it is, let alone going into a field where there are limited footholds and funding difficulties.

 

I have lots of issues with NIH, but they are very much aware of the lack of grant applications. The big question is what they are willing to do about it. At the moment, they are willing to do very little. Their tried-and-true method for growing the field is the RFAs that created the Cooperative Research Centers. This approach was not sufficient in our case. They are still in a wait and see mode. Clearly this is not enough for us.

I find the low rates of approval to be an insufficient argument for the lack of applications since the even lower rates don’t stop researchers in other fields from flooding NIH with applications. I do think that @Michiel Tack ’s message above is a great argument for entering the field. Scientists want to make as big a contribution as possible. If that message could get out to more researchers, accompanied by another round of set-aside funding, we might get somewhere.

 

Ron Davis mentioned this in yesterday's Christmas address, that one of the reasons OMF and the Stanford center are having trouble is because they are not experts in the field they are making research proposals for. Which I guess means no one is since it's entirely new territory, building new technologies and relying on new areas of science. Without funding you can't train experts, and without experts you can't get funding. Goody.

So we are kind of back to the fact that the field of ME is still in observation and hypothesis-making phase, which is explicitly not funded by most medical institutions, they expect things to be further along before they do that. But in nearly every other disease, there are labs, research institutes and entire departments that are fully-funded to do this kind of work outside of specific grants. This has nothing to do with the NIH, this funding has to come from universities and medical departments, who refuse to spend a single dollar on what they perceive is a waste of time.

This isn't something we can do by ourselves, no amount of funds raised will lead to many leading medical schools take on the normal responsibilities they have been rejecting for decades. Neither can the NIH or CDC. The universities are waiting for the research to knock, fully-solved, at their doorstep before they begin, and meanwhile their choosing to ignore us entirely means the first steps cannot be done at the scale that is needed.

I have no idea how we resolve this catch-22. Davis, and Tompkins I think, has been spending a lot of effort talking at those institutions, but no matter how well-respected he may be, there are decades of inertia behind the dismissal of this disease so it's just not enough yet to push us over the threshold.

Medicine simply doesn't have a way to deal with a disease so maligned that nothing can get off the ground without fully solving the entire problem, doesn't know how to handle the reality of there being more people invested in sabotaging efforts than in solving the problem. There aren't supposed to be such a thing as "enemies" of an entire disease. And yet here we are.

 

Ron Davis, in a recent update, highlights that they are submitting good applications to NIH - they are not getting funded.

Ron also highlights that NIH basically requires you to have done the study before they will fund it - no funding for "fishing expeditions". Take Unutmaz's recent publication which showed that MAIT cells, in the mucus lining of the gut, where basically exhausted - possibly due to repeated stimulation. To me we already knew that since Unutmaz's pilot study data indicated that MAIT cells were exhausted.

Set-aside funding would be good i.e. at a level which reflects the disease burden (1.2 million people in the US? and disease impact) and which reflects the fact that so little is known about ME - cause is not known, no reliable biomarkers ---. So the assessment of grant applications needs to take the low level of scientific knowledge of ME into account.

I do some work in relation to this EU Petition for biomedical research for ME - Petition No 0204/2019 [https://petiport.secure.europarl.eu...petition/content/0204%2F2019/html/missinglink]
I'm interested in this discussion i.e. to assist with that petition - thank you for your contributions!

 

I think I recall Ron Davis retelling a conversation with Maureen Hanson (OMF Symposium - September?), regarding options for recently graduated Ph.D. students. Ron/Maureen agreed that you couldn't recommend going into ME research.

I think Universities are similar to consultancy firms; if you don't bring in funding, then you don't have a job. ME isn't an area which has "low hanging fruit" in research funding terms. I assume there are areas where commercial interests fund research i.e. areas where it easier to bring in funding and keep your job. That's why public funding i.e. from government (NIH, EU Commission ---) is so important.

Pascal Arimont [Member of the European Parliament - MEP] asked a Parliamentary question on funding for research into ME. The European Commission responded that it had funded research into "a probiotic designed to correct the gut microflora imbalance" [http://www.europarl.europa.eu/doceo/document/E-9-2019-002599-ASW_EN.html]. So, in the EU, we have a system which provides public funding for research into commercially viable products (probiotics) but not research into ME [http://www.europarl.europa.eu/doceo/document/E-8-2017-006901-ASW_EN.html]
So even the limited public funding available for research can end up directed to commercial interests - I think we may need to try to challenge funding priorities.

 

T

I f this is true, I am very unhappy about that message. If not now, when? Funding for ME/CFS will only grow if people submit proposals. If the researchers who have NIH funding are not encouraging young researchers to apply for NIH funding, how can we make progress?

While activists are pushing for more set-aside funding from the outside, we need the researchers to encourage more bright young minds to enter the field and let them know, first, that this is a field in which they can make a real difference, and, second, that there are ways to apply that will increase their likelihood of being funding.

I understand that people are angry with Dr. Collins for not doing more for our disease, but realistically, he won’t be head of NIH forever and he has done more that any other head. He is familiar with this disease. This may be the best time for a young researcher to apply. I can easily see a new head of NIH coming in who knows absolutely nothing about ME/CFS and cares even less. We need to take advantage of this moment - activists and researchers alike.