VIcky Whittemore and Dr. Koroshetz head the Trans NIH Working group  for ME/CFS which is leading the  charge to reinvigorate chronic fatigue syndrome (ME/CFS) research at the NIH. As the largest research funder in the world NIH funded research plays a major in the understanding in any disease. ME/CFS’s share of the NIH’s research pie, however, has always been  pitiful, and has even decreased over time. With the publication of the IOM and P2P reports, both of which took the agency to task for ignoring ME/CFS, the NIH’s stance towards ME/CFS changed. NIH officials, including Director Francis Collins and Vicky Whittemore, one of the group’s leaders, have publicly agreed that ME/CFS has been underfunded and Collins has personally pledged to change that.

It’s been nine months, though, since the NIH released a publich statement: NIH takes action to bolster research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

The NIH got the huge funding increase that we believed would fund this effort.  With that set, we expected the Trans-NIH Working group’s strategic plan to be signed, sealed and delivered a couple of months ago. With summer stretching on and no word on its fate, the question remains whether the NIH will do as it promised.  Will it increase funding enough to usher in a new era of ME/CFS research or will we get something more moderate? Will we get a single or will we get a home run?

 As Labor day approaches with no word  on the efforts fate, concerns have naturally mounted. Is the Trans-NIH Working Group having more difficulty than expected? Is the program being cut back? I asked Vicky Whittemore what was happening with the NIH and the plan.  She and Marian Emr provided a few answers.

NIH Interview

In your Invest in ME talk you noted that the Trans-NIH Working Group hadn’t done much working prior to this year; in fact, they had only met once in four years! That’s pretty shocking given that they were in charge of getting the NIH interested in this disease.  How many times have they meet since you’ve gotten involved?

The Trans-NIH ME/CFS Working Group has been meeting monthly since November 2015.  Additional focused meetings take place as needed.

It was reported that the Working Group was going to get new members with more clout; people who could more easily sign off on funding. Has that happened?

The Working Group has representation from 23 Institutes, Centers and Offices across the National Institutes of Health, and is chaired by the NINDS Director, Walter Koroshetz, MD.  The representatives are all very active participants in the Working Group and routinely report back to the leadership of their Institutes, Centers and Offices regarding the activities of the Working Group.

[Translation: a lot of people are working on ME/CFS, but aside from Dr. Koroshetz, the participants of the WG did not change]

We’re in middle of the summer. The intramural NIH study was reportedly going to begin in summer. Can you give us a progress report on that? Has the protocol been settled and have the patients started arriving?

The protocol and the informed consent forms are being finalized and healthy volunteers are being solicited to participate in the study with the goal of admitting the first set of health volunteers in September.  Once the techniques have been refined in studies of healthy volunteers, the protocol team will begin to bring individuals with ME/CFS to the NIH campus.

The idea of an RFA funding a consortium of centers that work together on large studies is very exciting. We thought, though, that we would hear about the fate of the extramural program before this. Can you tell us what’s happening with that?

The Working Group is preparing two RFAs which will support ME/CFS collaborative research centers across the United States and a Data Management Coordinating Center. We hope to finalize and release these funding opportunity announcements as soon once they complete the NIH approval process.

[A significant number of well-funded research centers that work collaboratively together would be a major step forward.  Determining the criteria for a research center ; i.e. who can apply for one, how they would collaborate together, and how much latitude each would have to explore projects will be important.

While research centers are a significant step forward it’s not clear how they will fulfill the glaring need of bringing new researchers into the field or how researchers outside the centers will get access to funds. There was talk of an RFA on “fatigue” –  which would have, if it required grantees to use an ME/CFS cohort,  fulfilled that need;  it doesn’t appear that that is going to happen, though.]

Would these consortium focus on research or would they include a treatment element as well?

The applicants will propose studies on ME/CFS that will be peer-reviewed in an NIH study section.  This consortium will not provide funding for clinical trials, but it will be important to document the current treatment(s) of any individuals with ME/CFS who take part in the studies.  NIH does not support clinical care, but clinical studies may be supported by NIH grant mechanisms.

[The NIH not just a research funding, it is actually one of the largest, if not the largest, single clinical study funders in the world. The consortium will not fund clinical trials but what about the rest of the NIH;  will it fund clinical trials for Ampligen and Rituximab?]

You’ve been involved with well-funded diseases  like epilepsy which have “made it”, and now  you’re deeply involved with a disease  ME/CFS which, with its poor funding, and many unanswered questions obviously hasn’t “made it” . Can you say the top three or four things you think the ME/CFS field needs to do to put itself in a position where research efforts can pay off and the research field can gain steam?

First, there needs to be more rigorous, hypothesis-driven research to determine the underlying mechanisms of disease that will then lead to improved care and treatments for individuals with ME/CFS. 

Second, many of the very “successful” disease research areas have significant support from private sector groups (e.g., Parkinson’s disease research is supported by the Michael J. Fox Foundation).  In the field of epilepsy, several nonprofit organizations (e.g., Citizens United for Research in Epilepsy, the Epilepsy Foundation and the American Epilepsy Society) have played a critical role in supporting young investigators and providing seed grants to investigators who are then able to successfully compete for NIH funding. 

And third, standardization of the tests and data elements collected during research studies involving individuals with ME/CFS would address the issue of many studies using small numbers of individuals with ME/CFS that are not replicated or statistically significant because of the size of the study population. 

[Hypothesis Driven Research – The NIH’s Blind Spot –  Ron and Mark Davis at Stanford won’t be happy with the emphasis on hypothesis driven research.  Hypothesis driven research is probably fine in diseases which have a substantial research base they can build hypotheses off of, but “hypothesis generating research” would probably be far more helpful in ME/CFS. given the state of the field.  We now have the capability to plow through immense amounts of molecular data in order to uncover findings that can provide excellent hypotheses.  Denying the funding needed to uncover the molecular roots of ME/CFS because a study is not based on a hypothesis just doesn’t make sense –  but it is the NIH way.

[Private Funding – The NIH always comes back to private sources of money  and usually ends up prodding the ME/CFS community to do more.

The revenue raised by the epilepsy foundations mentioned Citizen’s United for Research in Epilepsy, the Epilepsy Foundation, and the American Epilepsy Society last year was $5 million, $14 million and $5 million ($25 million total). Compare that to the $145 million dollars the NIH spent on epilepsy last year, and you’ll see a large gap between the funding that private foundations provide and the funding that the NIH does.

That NIH money helps promote the disease,  produce new findings that interest scientists, help to develop drugs, and provide opportunities for research; i.e. it provides the research backbone the non-profits need to do their business.

Now compare the $5 million dollars  or so in probable revenue for the biggest ME/CFS charities in the U.S. (OMF Foundation, Solve ME/CFS Initiative, Hitchen’s Foundation) this past year, to the $6 million the NIH spent on ME/CFS.  The fact that ME/CFS charities are generating revenue almost equal to that spent by the NIH suggests they may actually over-performing relative to their “resource base”.  It suggests that the NIH – a critical player for any disease – is not giving ME/CFS non-profits the support (the research findings, legitimization, the hope for the future) they need to be able to raise large amounts of funds.

It’s possible that the ME/CFS charities may be operating near maximum capacity given the infertile environment they’re  embedded in.  They can probably always do more,  find new and more clever ways to raise money, but until we get good science that energizes the public and the medical community the charities are going to be pushing against a headwind – a headwind that the NIH has lifted for many other diseases. It’s incumbent for the NIH to step forward and prime the pump. Good science will lift all boats.]

Coming from where it is ME/CFS may be in something of a unique position, but are you using any other diseases efforts as a template for what you want to accomplish?

The Working Group has been using the experience from across the NIH to determine the best ways to advance research on ME/CFS.  This has been a significant strength of the Working Group in that it draws from experience in many different disease areas and with many different stages of disease research.

How important is a tight research definition at this point? Is that an important thing to do right now or would larger, more expensive studies with looser definitions enable us to ferret out more potential subsets that way?

It is critical for the research community to begin using standardized testing and reporting of data elements so that data sharing and comparison across ME/CFS studies is possible.  It will be important for all studies to be transparent in defining the study participants who are included in their studies, as well as in reporting outcomes. 

Since ME/CFS is a heterogeneous disease, it is likely that there are subtypes that will need to be identified, defined and studied independently rather than in one ME/CFS category.  An example from the epilepsy field is that we now know there are many different causes for seizures that result in epilepsy.  The epilepsy research community has begun using the term “the epilepsies” and is modifying the design of pre-clinical and clinical studies as well as clinical trials to take this into account. 

Conclusion

The NIH has made several significant steps forward. The huge intramural study, the new leadership of the Working Group and it’s frequent meetings, the recent addendum to past funding, the effort to build research consortium, and, of course, Dr. Koroshetz’s and Dr. Collin’s public statements are all positive signs that something fundamental has indeed changed.

Chronic fatigue syndrome (ME/CFS) has many needs, however and a few signs of some pull-back have occurred. The makeup of the Working Group does  not appear to have changed substantially, and the RFA on fatigue that was anecdotally reported on, apparently isn’t going to happen. This communication didn’t indicate how young researchers – identified as a critical need by Vicky Whittemore – are going to be brought into the fold, or how researchers outside the probably quite limited number of research consortia will get access to new funding.

It should be noted that the NIH is a major clinical trial funder, but has never funded a clinical trial on ME/CFS. The fact that the AHRQ panel didn’t have enough data to analyse any other than CBT/GET studies indicated just how poorly supported ME/CFS clinical trials have been. An NIH funded clinical trial for Ampligen could be put together quickly and provide ME/CFS patients with their first FDA approved drug, and a trial for Rituximab is certainly warranted.

Keeping the Pressure On

With such uncertainty and with this process dragging on much longer than expected the one thing we can do is exert pressure.  Several congresspeople are doing just that; they’re passing around a letter for their colleagues to sign requesting that the NIH increase funding and report to Congress about their work with ME/CFS. Nothing get’s the NIH”s attention more than a congressperson with his/her finger on their purse strings. Please help out this effort.

• Spreadsheet containing estimated PWME and annual economic cost, by US Congressional district, is here:
• Feedback form so that we can track Congressional interaction is here:

URGENT ADVOCACY REQUEST/ CALL TO ACTION

U.S. Representatives Zoe Lofgren (CA-19) and Anna Eshoo (CA-18) have agreed to co-sponsor a U.S. House of Representatives letter to National Institutes of Health (NIH) Director Francis Collins. The letter solicits information about NIH’s current and future ME/CFS program and encourages the NIH to strengthen ME/CFS biomedical research. (Note: Both the letter and this message refer to the disease as ME/CFS, because that is the Representatives’ chosen language.) The language in the letter was drafted by the two Congresswomen’s offices and is NOT subject to change.

The letter is currently being circulated for additional signatures in the U.S. House of Representatives.

We need your help to add your representative’s signature to the letter. We are running on a deadline of representatives’ sign-on due by this Sept 7th, and need you to contact your representative ASAP.

Steps:

1. Identify your U.S. House of Representatives Member
2. Call your U.S. House of Representatives Member
3. Email your U.S. House of Representatives Member

Step 1: Find your House of Representatives Member:

To find your U.S. House of Representatives member, you may visit http://www.house.gov/representatives/find/

Please note that this action is for REPRESENTATIVES ONLY, NOT SENATORS. Please do NOT contact your senator about this letter. We hope to have another letter available for senators to sign at a later date.

Step 2: Call your House of Representatives Member:

NOTE: You may be asked for your exact address — including zip+4 – to determine whether or not you are a constituent. You can get your zip +4 at: https://tools.usps.com/go/ZipLookupAction_input)

Use this script:

My name is _________. I’m a constituent in    (city)   . I am calling with an urgent request for Representative ______ to sign on to a letter to the National Institutes of Health, sponsored by Representatives Lofgren and Eshoo of California. The letter supports the 1 to 2.5 million Americans like me [my sister/friend/etc] who are afflicted with the disabling, and costly disease Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome or ME/CFS. ME/CFS has no known cure or FDA-approved treatment, even though it can leave patients bedridden for decades.

May I be connected to your health legislative assistant?

Click here if they say YES

Click here if they say No

If no:

Leave a message with the intern or staff member.  FEEL FREE TO BRIEFLY DESCRIBE YOUR OWN STORY. REGARDLESS, YOU SHOULD ADD:

The deadline for signing on to Representatives Lofgren and Eshoo’s letter to the NIH is Sept 7th. I will email (or fax) your office the letter. You may contact Angela Ebiner, Legislative Assistant for Congresswoman Lofgren, at Angela.Ebiner@mail.house.gov or (202) 225-3072 to coordinate your participation.

It would mean the world to me, my family, and other ME/CFS patients in our district to have Representative ____’s support. May I call back tomorrow to find out if Representative ____ will sign this letter?

If yes:

If the legislative health aide picks up, read on or click here.

If you get the answering machine, click here.

Use the same script with the legislative health aide:

My name is _________. I’m a constituent in    (city)   . I am calling with an urgent request for Representative ______ to sign on to a letter to the National Institutes of Health, sponsored by Representatives Lofgren and Eshoo of California. The letter supports the 1 to 2.5 million Americans like me [my sister/friend/etc] who are afflicted with the disabling, and costly disease Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome or ME/CFS. ME/CFS has no known cure or FDA-approved treatment, even though it can leave patients bedridden for decades

The legislative aide does not pick up.

Leave a brief voicemail for the Health Legislative Assistant.

Use this script:

My name is _____, and I am constituent in    (city)   . (I /my loved one suffer(s)) from the debilitating disease Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome or ME/CFS, which has no known treatment, or cure. I would like Representative _____ to sign on to a letter addressing NIH Director Francis Collins, in support of ME/CFS patients and research. The letter is sponsored by Representatives Lofgren and Eshoo of California. The deadline for signing on to the letter is Sept 7. Please call me back at ___________.  I will also email your office a draft of the letter, and will call back tomorrow to confirm that you received it. Thank you, and have a wonderful day.

Step 3: Write your House of Representatives Member:

If you are provided with an email address, you may use the email draft below. If not, you can use the Representative’s website form to send the draft email.[1] Please note that #MEAction has made its Fact Sheet copied below available for use with this action.

Thank you for all your hard work – we can make a difference by fighting in small but significant ways for better treatment, better funding, and better medical education for ME/CFS patients.

EMAIL BLAST

Dear [Staffer’s Name],

I’m emailing with an urgent request regarding the disabling neuro-immune disease Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome or ME/CFS. Representatives Lofgren and Eshoo of California are sponsoring a letter to NIH Director Francis Collins in support of ME/CFS patients and research. ME/CFS costs the U.S. economy $17-24 billion annually; leaves its patients with lower quality of life scores than lung cancer, stroke, and rheumatoid arthritis; and has no known FDA-approved treatment or cure. Would you please support me and the 1 to 2.5 million Americans suffering from this disabling disease, by signing this letter? It would mean the world to me, my family, and other ME/CFS patients in our district to have your support.

I’ve copied final language for the letter to NIH Dir. Collins below. Please contact Angela Ebiner, Legislative Assistant for Rep. Zoe Lofgren (CA-19) at Angela.Ebiner@mail.house.gov or (202) 225-3072 to coordinate your participation. The letter’s deadline is 9/7.

Thank you so very much for your support on this critical action. I look forward to your reply on this request at your earliest convenience

Warmest Regards,

[Your Name] [Your Contact Info, Including address and +4 zip]

The Congressional Letter

Text of Letter to NIH Director Francis Collins

Francis Collins, Director
National Institutes of Health
1 Center Drive, Room B1-126
Bethesda, Maryland 20892-0001

Dear Dr. Collins:

We write to thank you for your attention to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and encourage you to continue to strengthen the National Institutes of Health’s (NIH) efforts in ME/CFS biomedical research.

As you know, ME/CFS is a complex, debilitating, and chronic disease afflicting 1 to 2.5 million Americans. It costs individuals, the U.S. health care system, and our economy an estimated $17-$24 billion annually. Yet, as the Institute of Medicine noted in its report, “Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness,” there has been “remarkably little research funding” to date to discover its cause or possible treatments.

A number of us sent you a letter in March of 2014 to express support for ME/CFS research and are heartened by your commitment to advance diagnosis, treatment, and a cure for ME/CFS through a reinvigorated Trans-NIH ME/CFS Working Group (Working Group) housed within the National Institute of Neurological Disorders and Stroke (NINDS), and new intramural and extramural research programs that will bring new investigators into the field.

We encourage the Working Group to consider in a timely manner the input received through its recent Request for Information (RFI) regarding emerging needs, opportunities, and strategies for ME/CFS research and research training. We also ask that you provide us with the current status of this planning effort and the specific intramural and extramural activities planned for the rest of FY 2016, 2017, and 2018.

Thank you for your attention to these critical issues. We look forward to your response.

Sincerely,

Zoe Lofgren                          Anna G. Eshoo
Member of Congress          Member of Congress