NINDS director, Dr. Walter Koroshetz, sent the following response to #MEAction’s Oct. 21st letter calling on the NIH to take immediate actions to address the crisis of myalgic encephalomyelitis (ME). We analyze Dr. Koroshetz letter in blue text below to put his statements into context with the reality of what is happening with the ME crisis.
JOIN US in calling on Dr. Koroshetz to take urgent ACTION for ME. We are launching a video campaign to tell Dr. Koroshetz that his plan is failing people with ME. We need you to add YOUR voice to the video campaign to put pressure on Dr. Koroshetz and the NIH.
Don’t forget to sign and share the #NotEnough4ME petition to show your support for #MEAction’s demands to NIH to accelerate ME research.
November 4, 2019
The Myalgic Encephalomyelitis Action Network
3900 San Fernando Rd, Unit 1010
Glendale, California 91204
Thank you for your October 21 letter concerning the report from the National Advisory Neurological Disorders and Stroke (NANDS) Council Working Group for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Research. The report was a product of a Working Group that was composed of ME/CFS stakeholders, including individuals from #MEAction who actively participated in the group and subgroup discussions and in the writing of the report.
The Reality: As part of the working group, #MEAction urged the NIH to boldly and rapidly address the problems that were recognized in the report. Unfortunately, the final report only proposes weak strategies that do not get us where we need to be with any urgency. It also fails to address several of the critical barriers impeding progress.
The charge to the Working Group was to provide scientific guidance to the NANDS Council on how best to advance research on ME/CFS at the National Institutes of Health (NIH) and they delivered on that charge. As you are aware, the report was presented to the NANDS Council and was accepted by unanimous vote. The Council is advisory to the NINDS director and cannot create new programs or issue funding opportunity announcements. They are researchers, health care providers, and members of the public who do not have the ability or the legal authority to implement any of the strategies outlined in the report.
The Reality: While the Working Group did not have implementation authority, it did have the authority to make recommendations that would address critical barriers such as funding and the research case definition. While they did identify many critical problems, the recommended strategies are too weak to quickly and effectively address the problems described.
The Trans-NIH ME/CFS Working Group, composed of staff from 23 NIH Institutes, will prioritize and coordinate the implementation of the strategies that were outlined in the report as quickly as possible.
The Reality: The Trans-NIH ME/CFS Working Group is a closed-door working group that does not include ME researchers or clinicians, people with ME or other stakeholders. There is very little accountability or transparency other than the occasional updates on NIH calls. Further, as noted above, the strategies identified in the report and now being considered by the Trans-NIH ME/CFS Working group are not robust enough to address critical issues in a timely manner.
I appreciate the effort and thoughtfulness that every member of the NANDS working group contributed. Several strategies were outlined that NIH can now consider and implement, in partnership with other ME/CFS stakeholders, to advance research on the disease.
The Reality: This sounds really promising when Dr. Koroshetz talks about identifying several strategies that they can “now consider and implement” but the reality is that none of the problems identified in the report are new, and the strategies to address those problems are too weak to do so in a timely and effective manner. The plan’s implementation relies on mechanisms that have failed to address the funding shortfall for decades. We need a comprehensive, proactive and funded response that urgently addresses the barriers that are impeding ME research, and provides the set-aside funding necessary to rapidly grow the field.
We agree with the Working Group’s finding that addressing stigma will be critical to making real progress in this disease. We are currently, and have been, working to address this issue. Last Spring we hosted a large, multi-day conference focused on ME/CFS at NIH.
The Reality: Of course, hosting a multi-day conference on ME/CFS is wonderful, but the conference mostly included researchers already in the field who are already presenting at other conferences. So, it had much less of an impact than was expected or needed.
To further address stigma, we will continue to raise awareness about the disease with the general public as well as healthcare providers and researchers. We look forward to publicizing the results of NIH-funded research studies when they are published in peer-reviewed journals. We also speak regularly with the media about the biological nature of this disease and keep them apprised of progress in this field.
The Reality: It’s not evident that the NIH is regularly and proactively speaking to the media. In contrast, we continue to see articles, such as those in The Guardian, Psychology Today and Reuters in the past year, that challenge the biological basis of ME and depict the ME community as anti-science. A conference was recently held at Columbia University that presented ME/CFS as a psychogenic disorder. The NIH has not pushed back on these narratives in any way. Thus, the medical community continues to believe a false narrative about ME/CFS. The NIH must be much more proactive about destigmatizing ME/CFS wherever it occurs.
We also agree that there is a need to expand the ME/CFS research field. Most NIH-funded research grants are investigator-initiated, and not in response to disease-specific requests for applications (RFAs). Investigators who are interested in ME/CFS research can apply during each of the three grant cycles per year to standing (parent) grant announcements and do not need to wait for disease-specific funding opportunities. To increase funding in this field, there must be an increase in the number of investigators doing research on ME/CFS and the number of meritorious research applications submitted to NIH.
The Reality: For many years, NIH has been telling us that funding will not increase until more researchers enter the field. CFSAC and researchers have repeatedly told NIH that due to decades of stigma and underinvestment, experienced researchers have left the field and that new researchers are not entering the field because it is too difficult to get funding for ME/CFS research. Finally, researchers have noted that when NIH has issued funding opportunities with set-aside funding, once in 2006 and again in 2017, the number of applications increased substantially.
Recent trends in the numbers of researchers and the NIH budget for extramural research outside the CRCs reported by Ms. Spotila demonstrate that the NIH’s plan to grow the field by waiting for researchers to apply is not working.
The fastest and most effective way for the NIH to increase ME/CFS research funding to levels commensurate with similarly disabling diseases (in the hundreds of millions) is to set aside funds specifically for ME/CFS research. This will encourage established and new investigators to join the field, will ensure studies get funded, and will fund initiatives to overcome critical barriers.
We are committed to working with patients and advocacy organizations to increase the number of young investigators doing research on ME/CFS who will, in turn, provide a pipeline of investigators for the future.
The Reality: The NIH’s intent to attract young investigators is important but it is even more important that the NIH recruits established investigators from other fields. This requires multi-year funding opportunities with set-aside funding.
Program staff across NIH talk to and are working with investigators who are preparing grant applications for submission to NIH. The ME/CFS Collaborative Research Centers now will provide a strong foundation for ME/CFS research through the rigorous and collaborative projects underway.
The Reality: The ME/CFS Collaborative Research Centers is a good foundation but funding for the Centers at $7 million per year is a drop in the bucket for what is needed; the researchers involved have said it themselves. The NIH should have funded many more of the 11 applicants who applied to be involved in the CRCs from the beginning.
The timeframe for the CRCs to begin achieving real results is way out in the distant future. People with ME cannot wait several more decades to begin to see a change to this crisis. There are steps that can be taken now in parallel with the CRCs to begin making meaningful progress for people with ME.
The young investigators’ meeting, “Thinking the Future: A Workshop for Young Early Career ME/CFS Investigators,” was an important step towards reaching that goal. We met several investigators who are interested in doing research on ME/CFS and making it their career. Through them we hope to see more meritorious applications, which will mean more funding for ME/CFS.
The Reality: Young investigators are great, but what we really need is to pull large numbers of established, mid-career researchers into the field who can rapidly deliver major discoveries. There is no ME research lab infrastructure to absorb young investigators right now, and it could take a decade or more for a young investigator to get to the point of being able to submit successful applications. That is an unacceptable timeframe.
The NIH can and must do more to also bring in established mid-career investigators into the field of ME/CFS.
We have previously encouraged advocacy organizations to take a role in research by funding pilot, or seed, grants, which can serve as the basis of applications to NIH. This can be effective in ME/CFS, and we have already seen this happening. For example, Dr. Jarred Younger recently received an NIH grant based on research that was initially supported by the Solve ME/CFS Initiative.
The Reality: The ME community is fighting tooth and nail – sacrificing our health along the way – to try to fix this crisis. In spite of how disabled and impoverished the ME community is, we are raising research funds (likely outpacing NIH in 2020) and are also striving to overcome the stigma and neglect from the academic research community. NIH should be leading these efforts and providing substantially more funds than the community.
NIH will be issuing Program Announcements (PARs) for ME/CFS. We hope that these will emphasize our commitment to this field and encourage many researchers, both inside and outside of ME/CFS, to apply for funding. The PARs clearly state that ME/CFS-related applications will be sent to the ME/CFS Special Emphasis Panel, which includes experts in the disease and reviewers with expertise in the methods and technologies being proposed.
The Reality: Dr. Whittemore announced that Program Announcements would be issued but failed to state which problems these will tackle and which will remain unaddressed. Nor did she state when these will be issued and whether they will be sustained year-over-year.
More problematic is the lack of set-aside funding in these PARs. Without set-aside funding, these are unlikely to galvanize a field that has been starved and stigmatized for decades.
The ultimate goal is to get to clinical trials to test treatments for individuals with ME/CFS. We understand that many people with ME/CFS are interested in and ready to participate in clinical trials, but we need to ensure that the research is done in an ethical, rigorous manner to prevent harm to individuals and to help improve our understanding of the biological mechanisms underlying the disease. As we noted during the NINDS telebriefing on October 17, 2019, we do not know enough about the biological mechanisms underlying ME/CFS to design a new drug to treat this disease. It is likely that clinical trials in ME/CFS will first test one or more repurposed FDA-approved treatments, but strong preliminary data and scientific rationale are needed to move clinical trials forward. NIH funds clinical trials through specific grant funding mechanisms. NIH program staff are eager to discuss clinical trials with investigators who are planning trials with preliminary data and strong scientific rationale.
The Reality: While we may not understand the biological mechanisms well enough to pursue “rational drug design” of treatments against defined targets (where you have the target already identified and you design a drug to interact with that target), ME/CFS clinicians have substantial experience with repurposing approved drugs to treat symptoms and improve patients’ quality-of-life.
As we have seen with treatment trials in Norway, well-designed clinical trials of these therapies can help refine outcome measures and study design approaches, and clarify key disease subsets. Such studies could also reveal the underlying mechanisms of the disease.
We agree that identifying biomarkers will be critical to advancing the field and helping move toward clinical trials. NIH has issued several Funding Opportunity Announcements (FOAs) over the past few years for research related to biomarker development, identification, and validation. We promote these FOAs to ME/CFS researchers, encouraging them to apply. Biomarker development is critical to many diseases and it is possible that research in other areas may lead to clues about ME/CFS, and vice versa.
The Reality: Again, as stated above, issuing a funding opportunity without set-aside funding in a field that is stigmatized and starved of researchers is unlikely to attract the influx of researchers needed to ramp up the field and solve critical problems such as the lack of biomarkers.
If NIH is serious about addressing this most pivotal problem of a lack of biomarkers, then it will issue an RFA with set-aside funding targeting this specific issue.
Expecting us to wait for research on biomarkers in other diseases to deliver clues for ME/CFS biomarkers or issuing funding opportunities with no set-aside funding is not an acceptable solution. The lack of biomarkers impedes progress in nearly every other domain and must be addressed boldly and urgently.
We are aware that large amounts of data have been collected in this field and agree that combining the data from many studies could be powerful for making new discoveries. While we are first focusing on building a database that will help the investigators in the ME/CFS Collaborative Research Centers to combine and analyze the data from their studies, the database will also include datasets from peer reviewed publications and will eventually be open to outside investigators once they have completed their analyses. A concern in ME/CFS research is the heterogeneity and variability in the way that the data has been collected, the small numbers in some study cohorts, and the lack of transparency in reporting the clinical characteristics of the study participants. This concern is what led to NINDS and the CDC partnering with ME/CFS stakeholders to develop the Common Data Elements (CDEs) to help standardize data across research studies. An oversight committee has been organized to review and update the ME/CFS CDEs on an ongoing basis. NIH is eager to work with the community on the diagnostic criteria/case definition and CDEs that can be used across clinical studies so that datasets can be combined and/or compared.
The Reality: NIH’s 2011 State of Knowledge Report stated that lack of consensus on the case definition and selection methods was “threatening the entire scientific enterprise”. But the CDE effort did not address this lack of consensus on criteria and how the criteria are applied. The NANDS report acknowledged this problem but made no recommendations to address it either. This is a huge issue that continues to be unresolved.
Meetings of the Trans-NIH ME/CFS Working Group have been closed to the public because the discussions focus on internal NIH processes, grant review and the development of FOAs, which cannot be discussed openly with individuals outside of NIH due to confidentiality restrictions. Although the meetings are closed, the Trans-NIH ME/CFS Working Group strives to keep the community informed about the discussions. The Trans-NIH ME/CFS Working Group hosts telebriefings with the community three times a year to provide updates and listen to feedback. Updates are also provided at other venues, such as ME/CFS conferences, the NIH ME/CFS website, and through the listserv. The Interagency Collaborative Group, which was recommended by the NANDS Council report, will provide an avenue for open discussion and dialogue about ME/CFS research between representatives of NIH, other federal agencies, and patient advocacy groups that support research.
We recognize that many of the barriers to advancing research on ME/CFS have been discussed in other venues, such as CFSAC. This report provided strategies approved by the NANDS Council that serves in an advisory role to the Director. We at NIH will continue to work in partnership with all ME/CFS stakeholders and to address the identified research gaps within the mission of NIH, which is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.
I hope this information is helpful.
Walter J.Koroshetz, M.D Chair, Trans-NIH ME/CFS Research Working Group