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March 8, 2016
NIH ME/CFS Advocacy Call
March 08, 2016
9:00 am CT
Coordinator: Welcome and thank you for standing by. At this time, all participants will be on a listen-only mode until the question and answer session of today’s conference.
At that time to ask a question over the phone lines, please press star 1 and record your name at the prompt. This call is being recorded. If you have any objections, please disconnect at this time.
I would now like to turn the call over to your host, Marian Emr. You may begin.
Marian Emr: Good morning. This is Marian Emr. On behalf of the NIH, I would like to welcome you to this morning’s teleconference and to thank you for your great interest in participating in this discussion with us today.
Here at the table this morning, we have Dr. Francis Collins, Dr. Walter Koroshetz who will introduce Dr. Vicky Whittemore, Dr. Avindra Nath and Dr. Brian Walitt.
Each will make very brief opening remarks and then we’ll open the phone call for your questions. Please be patient with us through this process. We will try to get to as many questions as we can in the time we have available to us this morning. Now Dr. Collins.
Dr. Francis Collins: Thanks and good morning everyone. I wanted personally to join this call to thank you for joining us for what I hope is an ongoing conversation about ME/CFS and how we can move the needle forward together on characterizing the cause of this perplexing disorder to help with better diagnosis and treatment.
I want to assure you that from the perspective of the NIH Director, that this institution is very committed to this area of research. Speaking for many of us, we want to move the research agenda forward here both in terms of intramural activities -- which you’ll be hearing about -- and extramural research programs as well.
I’m happy to tell you that with regard to the intramural effort, we have received IRB -- that’s Institutional Review Board -- approval and expect to be able to launch this study at the NIH Clinical Center and then begin to enroll individuals this summer.
I have great confidence in Avi Nath, who’s the principal investigator, who’s going to speak to you here shortly, who will lead this important study. And he can tell you more about it.
A Web site describing the intramural protocol actually went up this morning. If you haven’t seen it yet, this will give you a lot of the details about the design of this study and how it’s going to be conducted.
And I think this is a remarkable opportunity to try to bring the whole power of this really remarkably, interdisciplinary research hospital to bear on this set of serious questions about what are the causes of ME/CFS.
There’s a lot of heterogeneity of course in this condition. The choice here was to focus on individuals who had previously good health and then a clear-cut onset in the context of a flu-like illness, in order to limit the heterogeneity and provide us with a better opportunity for getting answers.
And we believe that this study in the world-class Clinical Center of NIH has the opportunity to provide some new insights that could be transformative for all of those who suffer from this condition.
So in addition, on the extramural side, a vigorous, reinvigorated Trans-NIH Working Group is working to define the strategic areas of research that would form the basis for a request for applications to the extramural community, both in the short-term and in the longer term.
And Dr. Koroshetz can tell you more about where we are about that particular set of discussions. We’re quite serious about looking for opportunities to expand our research in this area and to recruit new investigators into the field, bringing new eyes and new brains into the issue of trying to understand the puzzling aspects of this, that previously have eluded us.
So please take our commitment with great seriousness. Please also stay the course with us as we seek to identify the most compelling research questions and how we could address those.
I understand many of you have waited a long time, perhaps, to see this kind of attention. I hope you understand how much we are now looking at this in a very serious way and seeking to come up with some of those answers.
So if we can work together on that and not work apart, I think we have a much better chance of making real progress. We are your partners. We want to hear from you.
That’s why we’re having this call today. And we’re listening carefully to the comments and the suggestions you might have about how best to move this effort forward.
So that’s mostly what I wanted to say by way of introducing the call. I now want to turn this over to Dr. Walter Koroshetz who, as you know, is the director of the National Institute of Neurological Disorders and Stroke.
Walter is a neurologist -- a very experienced one -- and he has seen firsthand how devastating ME/CFS can be for patients. And he volunteered to chair this Trans-NIH Working Group and is working closely with other institute and center directors to promote research on ME/CFS.
And I want to say thank you to Walter for stepping into this space, and already with considerable vision, figuring out ways that we can make the kind of scientific contributions that this field very much needs. Walter, the floor is yours.
Dr. Walter Koroshetz: Thank you always Francis and again, I’d like to thank everyone for getting on. And I’d like to thank everyone for the expressions of interest and even the concerns that people have sent to us.
We are very interested in working together with the community to achieve our long-term common goal. And I think that common goal is shared unanimously, which is to find better treatments for people who are suffering with ME/CFS.
And I can just - like to start off by talking about the big picture - the intermural research protocol, I think, is one step but only one step in the trajectory that we need to get on to get answers that are going to be very helpful for patients.
And so this is, I think, a long-term quest. This is a difficult problem. I think if it was not difficult it would have been solved long ago. So I think we need to kind of get out there and bring in the best and the brightest from many different areas of science.
I don’t think we know where the solution is going to come from. So I think we need to cast a wide net, get involved a number of very experienced researchers and clinicians and work carefully with the doctors who are taking care of the patients.
As Francis said, I think the important thing is to stay the course and to look always to the long-term goal. At NIH, we have some bureaucracy which is not easy to understand.
But I would like to simplify it if I could that there is basically an extramural program, and the extramural program - you know, funds that go from the NIH out to universities, companies, other institutions to do research.
And there’s the intramural program where research is done at the Clinical Center in the Bethesda area. The Clinical Center is the world’s largest research hospital and really our only research hospital.
It has tremendous resources, but 90% of the funds from NIH go out to the extramural community. So in the long run, what we need to do is to engage both the extramural and the intramural community.
And you’ll hear about the intramural protocol which is starting up, but you also heard mentioned from Dr. Collins that we have a Trans-NIH Working Group. As I mentioned, we don’t know where the solution for this ME/CFS problem is going to come from.
So it’s very important to have the scientific input and the funding resources of multiple institutes at NIH to bring them to bear on this problem. The Trans-NIH Working Group has representatives from all the institutes and is working to develop plans that will move funds to very worthwhile, highly meritorious research proposals in the extramural community.
And we have the intramural program protocol which is going to be run by Dr. Nath. With that I’d like Vicky Whittemore to briefly describe the Trans-NIH Working Group and what it is about and thinking of doing in the short-term and the long-term. Vicky?
Dr. Vicky Whittemore: Good morning. This is Vicky Whittemore and I’m a program director at the National Institute of Neurological Disorders and Stroke. And I also would like to thank all of you for being on the call this morning.
I’ve been working with Dr. Koroshetz to coordinate the Trans-NIH Working Group and I have to say it’s really been a pleasure working with representatives from the staff of the 23 institutes and centers who make up the Working Group.
Everyone’s really dedicated and passionate about what we’re doing and what we’re working on. We are in the process of putting together as Walter said both a short-term plan, where we can try to activate some research on the shorter-term as well as initiative that would put in place better infrastructure as well as research funding for longer-term research projects.
And some of things we’ve been talking about -- clearly as the community has communicated to us as well -- the priorities of developing and identifying biomarkers for the disease, really understanding the underlying causes and mechanisms that lead to ME/CFS as well as getting a handle on and understanding what is causing what patients refer to as brain fog or the cognitive symptoms that many individuals with ME/CFS experience.
So our timeline is that we’re working very hard to put this plan in place and to present our initiative to the appropriate council for approval in the May timeframe and we will - to move forward with the initiative soon after that.
So we will be looking for input and feedback from the community. And I think several ways that we’re thinking about doing that is to put out specific requests to the community for feedback on ideas we have and things we’re thinking about, to have additional follow-up conference calls after this one in due time.
As well as to reach out to the research and clinical community to get feedback from them as well in terms of what we’re thinking and planning. So with that, I’ll turn it back over to Dr. Koroshetz.
Dr. Walter Koroshetz: So I just want to clarify one thing because I’m sure people are wondering out there why can’t we actually say what we’re thinking. And so it is important to understand that NIH has processes that ensure that research comes in and the most highly meritorious research is funded and that all groups have a fair hearing when they come in.
So what we can’t do is we can’t put information out before it’s ready to be made public to everyone. So that’s why we have to do a lot of work behind-the-scenes before we can make things public.
So it’s a kind of something that’s idiosyncratic, but it has its real purpose in presenting a fair and open process here at NIH. And that now I’d like to say also that as I mentioned before, I think it’s going to take an army of really good researchers to solve this problem.
I think that army has to work together. It can’t be individual groups working in isolation. So what we’d like to do is to form a consortium really of investigators who are working hand in step.
Not all doing the same thing, but a lot of innovation. And the first horse out of the gate is the intramural program. So I would like Dr. Nath, if he could, to try and briefly describe what the intramural protocol is all about. And I would add that Dr. Nath is calling in from Liberia where’s he doing fieldwork in Ebola.
And so we’re very gratified that Avi can get on the call and we hope that his line stays stable from Africa. Avi, would you like to describe the intramural protocol?
Dr. Avindra Nath: Oh thank you very much, Walter. This line should be fine because I’m using one at the U.S. Embassy.
Dr. Walter Koroshetz: Okay. Good.
Dr. Avindra Nath: So well thank you very much. So, you know, I’m delighted to be the principal investigator of the intramural study. And when Dr. Collins and Dr. Koroshetz asked me to consider this responsibility, I was actually very thrilled to be able to look at the syndrome and see if there is an immune or neuroimmune component here that may be driving the disease.
That is an area of my expertise. I have firsthand seen a lot of patients with the disease and know exactly how devastating it can be. And so, when I looked at the literature, it was very clear to me that there are very good reasons to believe that this is likely immune-mediated.
And so I designed a protocol that would address those kinds of issues. So the proposal I put together has three phases to it. The first phase is a cross-sectional study and that’s the protocol that’s on the Web and all the information that many of the groups have received.
However, and in in the plans is our second phase study. The second phase study would be a longitudinal study which will follow patients over a period of time with repeated testing but only with a small subset.
The first phase study has a lot of various kinds of investigations we will do. And then we’ll identify the ones from there that look most promising. And then in the second phase study, a much larger population, different types of population and then be able to study them over a longer period of time.
And then the third phase would be an intervention study. So based on the information that we gathered from the first and second phases that will guide us as to what kind of immune-modulatory therapy would have the best opportunity of making a difference in this patient population.
So that in summary is what we were thinking about as our goal towards developing a research protocol for a chronic fatigue syndrome…
Dr. Walter Koroshetz: Thanks very much Avi. Can you still hear us all right? Okay. So now I think I’d like to turn to Brian. Brian Walitt is a medical officer at the National Institute of Nursing Research.
He’s had considerable clinical and research experience in fibromyalgia and ME/CFS research. And he’ll serve as the lead associate investigator to help Dr. Nath coordinate the activity of a large number of investigators who will be involved in the study at the Clinical Center.
So Brian, do you want to tell us a little bit about what brought you to this really interesting protocol?
Dr. Brian Walitt: Yes, sure. Thank you Walter. Hi, I’m Brian Walitt. I am the lead associate investigator on the intramural protocol here at the NIH. My experience with all of this starts in my career in rheumatology where I had a lot of experience with hospital immune disorders and developed a specialization in fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
My interest in the disorders grew over time and led me to open a research clinic at Georgetown University where I saw patients on a regular basis. My patients taught me just how real these disorders are.
They are not just in one’s head. They do not reflect some unconscious choice and it is not possible to simply push through the symptoms. I tried my best to help my patients and learned just how limited the options really are and why there is an urgent need for a restorative treatment.
One that would give patients their lives back. I promised my patients I would do my best to find better answers for them. This passion is what led me to come work at the NIH.
Since I’ve been here at the NIH, I’ve been learning the ways that research is done here. I’ve learned a great deal about science from the world-class scientists that I get to rub elbows with.
I’m very lucky in that regard. I am very excited to help Avi Nath facilitate the protocol. I believe it’s going to provide some important answers to the big questions of ME/CFS: the role of infection, the role of immunity and the role of neurology and the generation and perpetuation of symptoms.
We’re also going to try to understand exactly what the biology of post-exertional malaise is. I believe these things will move the needle forward as Dr. Collins said. And I’m very excited to be part of this.
Dr. Walter Koroshetz: Thanks very much Brian. So I’d also just emphasize that the protocol at NIH has 26 associate investigators in addition to Brian and Avi, and they bring this really incredible expertise to the table in the study of the patients with ME/CFS in this protocol.
And this ranges from very high-level neuroimaging to high-level ability to look at cytokines, autoantibodies and we have people like Leo Saligan in the Nursing Institute as well who has been looking at chronic fatigue in patients with cancer and rheumatologic disorders.
So we have a really quite an amazing group and it’s different than what you might see in a hospital on the outside because everyone here is full-time devoted to research.
And so the community of researchers is quite extraordinary. And also the tools that we have in the Clinical Center are quite extraordinary. Very difficult to bring a patient in who’s very ill for research at a hospital any longer.
But here we have an in-patient unit where we can study patients over multiple days, even weeks. So we’re hoping that the resources of the Clinical Center will allow us to do some very unique things.
But I would also emphasize once again that this is a stepping stone. This is only one piece of the puzzle. I think it’s a very important piece but what our intention is, is to coordinate it with many of the other pieces that we’re going to start initiating across the country.
And with that, I’d like to open the phone to questions now and we’ll do our best to answer them. And once again, if we are not able to answer all of the questions, they can be directed to a Web site: firstname.lastname@example.org. So thank you very much and let’s open the lines. First question?
Coordinator: Thank you. We will now open the question and answer session. If you would like to ask a question over the phone lines, please press star 1 on your phone and record your name at the prompt.
To withdraw your question, press star 2. One moment please for incoming questions. And our first question comes from Robert Miller. Your line is open.
Robert Miller: Hi, good morning everyone. This is Robert Miller. I’m a long-time patient and advocate. And first I’d like to thank Dr. Collins, Dr. Koroshetz and team for taking this key first step in doing the Clinical Center study for ME/CFS.
I think it’s a long-time coming for this patient population. But I’d like to start off and address actually possible treatments and in particular the treatment Ampligen.
And I’d like to ask what homework has been done thus far regarding Ampligen and if there’s been any talk with the FDA, as this is the only treatment ever to be into Phase III trials for ME/CFS.
And that opening for this drug potentially could lead to this drug being our - or this patient population’s, AVT. You know, opening the door to pharma for much more research.
And most importantly it would give relief to many suffering patients. Thank you.
Dr. Walter Koroshetz: So thank you Mr. Miller. And, you know, indeed as I mentioned the goal that we’re all marching towards is to try to get a treatment. And clearly, to start off I think we are going to challenge our investigators to survey the area of therapeutics that have been tried in ME/CFS.
Others that might have been tried in other illnesses that might come into ME/CFS because those are more of the short-term wins should they be, effective.
Developing new therapies is basically a ten to longer process. So that is very important. And so we certainly at the NIH have open-door policy for people to come in and propose research.
And we have certainly met with many investigators and even the Hemispherx Company people and they presented the data that they have from their previous studies. And so that certainly is something that we are taking into serious consideration.
As I mentioned earlier, there is a process at NIH for the funds to go out. So the process is, again, a peer review process where investigators submit proposals, they get looked at by the leadership and then they go out to a peer review system and they kind of poke holes to make sure that the best proposals get the funding from the American taxpayers.
So that’s the system that would have to be engaged. It’s very different from an industry system where the industry makes the decision to put the funds down and they take all the risks.
Here we’re working with taxpayers’ dollars and so the process is very important to uphold. But certainly we are looking at that and we expect that we’ll be having discussions on the clinical trials as they come forward. So thanks very much for that question.
Robert Miller: Thank you.
Coordinator: Our next question comes from Donna Pearson. Your line is open.
Donna Pearson: Thanks very much. So there is substantial confusion between the diseases that you’re studying and other conditions involved in unspecified chronic fatigue. And that confusion impacts research, medical education, diagnosis, treatment and care at every level.
And I know that the name is not an issue that many people want to talk about in research. However, a name is the single most obvious way to distinguish a disease from another disease.
I mean I wouldn’t clearly agree that a name change is appropriate. I’d suggest the establishment of a new ICD code. So my question is, does the current study and the tests that you will be doing have the potential to determine if encephalomyelitis is in fact an appropriate name for the disease?
Dr. Walter Koroshetz: I’m not sure if Avi is still on the line.
Dr. Avindra Nath: Sorry, I’m here. I’m here. Yes.
Dr. Walter Koroshetz: Okay.
Dr. Avindra Nath: So, we are not looking at every single aspect of the disease. We are looking at a select population. And in that population, we can certainly tell you if there’s evidence of inflammation.
And if there’s evidence of inflammation then I think it’s fair to say that if present, an inflammatory process in the brain. Whether we use the word encephalomyelitis, the problem is that you have to demonstrate there’s an infiltration of cells.
Just activation of immune system in the brain alone is not sufficient to cause encephalomyelitis. You can get activation of the immune system in patients with Alzheimer’s disease or Parkinson’s disease. We don’t particularly call that encephalomyelitis.
But I think we will get closer to that answer because we will be able to look at a panel of cytokines and we may have some suggestion as to what kinds of cells are producing the cytokines.
And so, yes we will get closer to that definition. Whether we are able to establish it beyond an element of doubt or not, it won’t be from this study. We are planning some animal studies and I think that it’ll be a better chance for being able to answer that.
So the animal studies will take lymphocytes from the patients, inject them into the animals and try to reproduce the disease. If we can, then we can look at the brains of the animals and actually tell if their cells are infiltrating or not, if we produced the phenotype or not.
I think those kinds of studies have a much better chance of being able to answer the question that you addressed.
Dr. Walter Koroshetz: Let me just add a couple of points because I think they’re important to understand. And I’d say that the protocol at NIH is interested in trying to get at the biology, the biological basis of the illness.
Now eventually that might, the biologic basis of the illness in most of the illnesses is eventually what moves the definitions and allows break-up in the heterogeneity of a disorder.
It’s a particular biological entity. That process is a long process. And so, I would urge people to basically stay the course there. Clearly this protocol which is looking currently at 40 patients - what they find will then need to go into another stage to be validated in other groups of patients to make sure that it’s a real finding that can be generalized.
So generalizability is the next step that would come when a discovery is made. One reason we think it’s real important to organize ME/CFS researchers across the country is because many studies have discoveries but they’re never really validated to know if they’re generalizable.
And so, I think we have a lot clues in the literature but one thing we need to do is to make sure that they can be generalized across the population. And the expectation is, I think, that there are multiple, different types of ME/CFS.
And it may not, something we find here may not generalize. This protocol is for persons who develop the condition after a flu-like illness. There are other ME/CFS patients who develop the condition after other types of exposures.
Environmental exposures, allergic exposures, traumatic exposures. So we can’t solve the whole problem with this one protocol. This is, again, a piece of the puzzle. I urge people to think of it in that way. Okay. All right. Can we go to the next question?
Coordinator: Our next question comes from Cort Johnson. Your line is open.
Cort Johnson: Thanks. As I’m sure you’re aware that Ron Davis is taking on a similar exploratory study. And so what I was wondering was if it’s possible for Davis to follow-up on findings that you get and vice versa?
Can your team follow-up on findings that he gets? Is it possible to give him some funding to be able to do that? And my second question involves the exercise study.
Staci Stevens at Workwell has worked for years to develop standardized exercise protocols that work for ME/CFS patients. That exercise portion of the study is probably a critical part of the study. Is the team planning to contact her and work with her to be able to use a similar protocol in their study?
Dr. Walter Koroshetz: Okay. Brian, could you address the exercise protocol and then Avi, maybe if you could address the data sharing next?
Dr. Brian Walitt: So the exercise protocol for the study that we’re doing in the intramural program is designed to induce post-exertional malaise. Right? It’s a maximal effort exercise intervention.
It’s designed to provoke symptoms as opposed to being a treatment. The CDC, Beth Unger, has a lot of experience in doing this kind of work. And we’re going to be talking to them about designing proper ramps and so forth.
However, we are open to suggestions from all people with experience and we would be happy to reach out to others that may have useful things to add as we design the intervention.
Cort Johnson: Thanks.
Dr. Avindra Nath: –This is Avi. Let me just add to that. So,I did talk to Dr. Davis and we are absolutely delighted to collaborate with him. The kind of study he’s doing is not exactly the same that we are proposing to do.
So I discussed that with him in great detail. We actually exchanged a number of...
Dr. Walter Koroshetz: Oops. I think we dropped off Avi. But I think his point is that that yes he has been in contact with Dr. Davis and actually a number of other investigators around the country who are collecting samples and they will be sharing data.
Now I think also as we mentioned, what we’re hoping to do is to set up a series of investigators around the country who can work in concert with each other and share data.
As particularly with regard to looking at the second issue I mentioned before, which is generalizability. If you find something in one group and you check another group that you think is similar, do you see those same findings or not?
Unfortunately the history of these kind of biomarker studies is such that it’s a lot of things fall out and don’t replicate. So you really need to do this coordinated approach to make sure that what you’re putting your money on is a real thing. A real finding.
Okay. Can we go to the next question?
Coordinator: Our next question comes from Charmian Proskauer. Your line is open.
Charmian Proskauer: Hi. Thank you very much for this opportunity to have a discussion. I think this is great. You may have already answered this question in part through things that you’ve already said.
But I’m going to ask it anyway. Why only 40 ME/CFS patients? I realize that this is a very deep study but with 40 patients does that have the danger of falling into the category of just another pilot study with numbers too small to be really meaningful? That’s my question.
Dr. Avindra Nath: So let me address that. This is Avi.
Dr. Walter Koroshetz: ...question...
Dr. Avindra Nath: So there are two aspects to it. Number one is we’re going to be screening patients. It’s going to take us awhile. And then when we admit the patients, they’re going to be in for a week. So it’ll take us one patient per week.
So even if, you know, give or take 40 patients, it’s going to take a minimum of one year just to study 40 patients. Plus you’ve got the controls. So it’s going to take you a while to actually get through this population.
So if your entries are more and more, it’s going to take you longer to get to the answer. The other thing is that we’re selecting a very precise population. Within 40, there’s at least - calculated a lot sample sizes based on the information that we have.
If you don’t find a neuroimmune, you know, abnormality in 40, then it’s unlikely to be a major driver of the disease. And I’m pretty certain that this is a decent sample size for us to be able to find the kinds of immune abnormalities that we’re looking for.
So I think the sample size is pretty decent and it gives us an opportunity. And after that like I said, we’ll do a longitudinal study. So then you can enroll as many patients as you want from all over the country.
And other people can participate in the study and take those findings and look at multiple groups. So you have second phase of the study that allows you to do a more expansive study.
But you don’t want to do a huge expansive study the first time around. If it takes 1000 patients to find something, it probably isn’t worth chasing a result.
Dr. Walter Koroshetz: I think I’d also add that at NIH there’s a culture which is actually a try-and learn-as-much-as-you-can from every single patient. So there is, for instance, an undiagnosed disease clinic here where people come with diseases that could not be diagnosed on the outside. And they found causes for many of these patients.
They were all different though. So I think, you know, it’s also possible that with the kind of in-depth analysis that there may be very robust findings in even one or a small group of patients that will be very important. So it’s a little bit different - it’s definitely not an epidemiological study. The NIH is much more - it’s advantage is in deep study of small numbers.
But I think as the question you posed, the issue that to actually get the answer for all the patients who have ME/CFS, this is just one step and we have to see what we discover and how generalizable it is to the population.
And that’s going to require multiple steps and a larger group of investigators. Can we go to the next question?
Coordinator: Our next question comes from Joni Comstock. Your line is open.
Joni Comstock: Hi. I represent MEadvocacy, a grassroots, non-profit organization advocating for patients suffering from ME.
Dr. Walter Koroshetz: Hi.
Joni Comstock: Our focus is the severely affected patients, most of who are homebound and bedbound. Some are so sick they’re unable to care for themselves. We were dismayed to learn that the protocol and design for the intramural study has been well underway without any input from the ME/CFS expert clinicians, researchers, as well as from the patient and advocate community.
This became even more disturbing as so many flaws were revealed about the study. These deficits showed us that many of the ingrained agency misconceptions of the disease still exist and have not been clarified.
Therefore, we initiated and delivered a petition with 725 signatures to Dr. Collins, to stop the study and start it from scratch with stakeholders’ input from the get go.
Because of ingrained institutional misconceptions, whether deliberate or not, we expect the NIH to engage the expert community on any ME/CFS study from the moment of its inception.
They should have input throughout the entire process. This is includes the planning and implementation of the design, recruitment, trial, analysis, study outcome, peer review publications and the publicity.
Do you intend to respond directly to MEadvocacy about the petition and how do you plan to incorporate our concerns?
Dr. Walter Koroshetz: Well let me just start and I appreciate your concerns. And our intent is to reach out and get input from a wide variety of folks with expertise and with experience in this illness.
And we have been doing that right from the beginning at NIH through the Trans-NIH Working Group, through the CFS Advisory Committee. We’ve had multiple meetings with experts in the field and with advocacy groups. And I must say it has been a challenge for us because there are, well we may not have reached out to everybody.
And we apologize for that. But it’s been very difficult to know exactly who everybody is and that’s the reason we have these calls and this is not going to be the last of our calls.
But it’s only the beginning. And we will learn from patients. I think the history of medicine is that as you work with patients, the patients teach you lessons.
And so, I think that the major teachers at the NIH really have to be the patients who have made the sacrifice to join the protocol, to come into the Clinical Center and to work with the doctors.
I think that’s where a lot of the input is going to come. And the protocol itself, Brian can correct me if I’m wrong, but the protocol is always a work in progress. So a protocol gets put up. It has to get approved. Then it moves forward.
Then there are amendments that have to get approved again. Then it moves forward. And the protocol is something that’s going to have to be tested.
It’ll probably be bringing in control persons to see if they can manage the protocol as it stands before we bring in patients with ME/CFS and put them through the protocol as it stands.
So I think we are definitely interested in getting input. But in truth of the matter, the scientists at the NIH, they have to be the ones who are empowered to work with their patients to try and get at the bottom of what is the biologic nature of ME/CFS.
So we are very interested to move ahead and we can’t take all patients with ME/CFS or the very severe cases who are homebound, I think would certainly not be wise to start there. I don’t know - Brian, if you have any points on that.
Dr. Brian Walitt: You know, part of the protocol is to look at post-exertional malaise which requires pushing patients a bit and being able to exercise and being able to do things.
Taking a homebound population and stressing them more may lead to untoward consequences for the patients and we need to be concerned about those things. It’s definitely a very important population to study but that might be for the next phase.
Dr. Walter Koroshetz: Right. And I think, the Clinical Center does have the ability to bring people into the hospital who are in very poor condition because it is a hospital and has 24-hour nursing.
So it is something that we could potentially get to at some point. But I think it would be probably unwise to start there. So again, I apologize to the community for the perception that we’re not listening because we are very much listening.
And we will continue to listen and we will continue to communicate best we can. So thank you very much for that. Could I have the next question please?
Coordinator: Our next question comes from Lily Chu. Your line is open.
Lily Chu: Hi, good morning. This is Lily Chu. I was one of the co-authors of the IOM Report. I’m also the co-Vice President for the International Association for CFS/ME.
But my comments today are my own individual views. So I have two points. One is about the study itself and the second is about staff. One of things I found when I was reviewing the literature for post-exertional malaise is a lot of the literature only looked primarily at fatigue as a symptom.
And I’m trying to review the Web site you have up right now and again, it says that you’re going to have a diary of people recording their symptoms for at least a week once they’re back home.
And that’s good. But it says fatigue symptoms. So what I would suggest is, you know, PM is more than fatigue. And in our report we talk about things like people having problems thinking, people having problems sleeping, sore throats and enlarged lymph nodes, allover muscle pain.
So what I would suggest is that you ask for more symptoms than just fatigue and that you leave some open-ended areas where people can put in their symptoms.
The second thing is timing. So most studies, they just take a period like two days and that’s when they collect their blood tests or their other tests and their symptoms in patients.
And what I was finding from reading the literature, talking to patients and some data I have that I’m analyzing right now is that timing of PM can vary a lot.
So ideally, it would be nice if you could time the test to when people are saying this is the peak of my PM or even like have it after one day or two days.
Because sometimes people’s PM does not start until several days after whatever the triggering event is. In this case, it looks like you’re doing a treadmill to induce the PM.
So that’s my point about process. The points about staffing, I’m really glad that you have some experienced people on this project, including Dr. Lipkin. But one of my concerns is that you have both Dr. Walitt and Dr. Gill on this staff.
And I’m sure you’ve heard a lot to some degree already about Dr. Walitt. My concern about Dr. Gill is back in 2011, he did a talk for NIH and he had a lot of slides in there about pacing and about, not about pacing but about graded exercise therapy, cognitive behavioral therapy and about not ordering certain tests.
Like for example, tilt-table testing because they weren’t suggested by the CDC at the time. And so there are some concerns there -- I can send you links -- where a lot of the community had concerns about Dr. Gill and I even wrote Dr. Gill a letter before his talk.
I’m hoping his views have evolved and changed since then. So if he’s changed that’s great. But I have a little concern about that. Even if you have the right people for liking the patients, if the people interpreting the studies have certain biases - and we all have biases - but those need to be recognized when they go into and analyze or interpret the study.
So I’m wondering if the staff that’s on the study, are they going to be reading things like the IOM Report, the NIH Statement of Knowledge Conference Report from 2011 even and the ARC and NIH reports more recently? Thank you.
Dr. Walter Koroshetz: Thanks very much for that. I’m going to ask Brian to talk a little bit about the protocol with regard to the symptoms you mentioned, the trying to peak, and then the docs working on the protocol.
Dr. Brian Walitt: So that’s a very good point, that what exactly post-exertional malaise is has been poorly explored to-date. What we’re going to try here at the NIH is to induce it and describe it as it happens.
This will be done qualitatively by speaking with the patients and listening to what they have to say and hearing their descriptions of it. We may even do a qualitative study of the words that are used to describe it.
As well as biologic measurements that are taken sequentially starting before the exercise and following it over the course of their hospitalization. And the hope is that we’ll be doing all sorts of different biological measurements to try to capture different aspects of the biology of post-exertional malaise.
And so your comments about timing are very true and we are taking that into consideration.
Dr. Walter Koroshetz: Great and thanks for very much.
Dr. Avindra Nath: Dr. Koroshetz, this is Avi. So, throughout the protocol there will be continued seminar series, journal clubs, so on and so forth.
So that the team that is working on the protocol becomes well aware of the existing literature, the emerging literature, the pros and cons and the critiques of previous protocols and previous studies as well.
We’re going to have invited speakers come and talk to us so that we have a cutting-edge knowledge and state of art - the techniques that we are using in order to study the syndrome.
And that’s how we conduct all our other protocols. So that’s no different than we would do for my other protocols as I would do for this. The other thing is the way I’ve designed the study, there is no element of subjective bias because really what I’m looking for are immune abnormalities, where they’re going to be done in my laboratory, they’re going to be done in the Center for Neuroimmunology.
And although there are 26 investigators there, there are about, if we include the people in various laboratories and others that are doing the study, there are over 150 people.
So there is a huge number of people doing things in the study. I ultimately interpret all of these things. And then we will, you know, make the findings available to everybody.
And there’s an advisory group that looks over our study as well as our findings. So I’m not really concerned...
Dr. Walter Koroshetz: Right. So Avi dropped off again, but I think the point is that the NIH is a very unusual place in that the people here try and get at the bottom of problems.
And they have really the strictest scientific minds and I, rarely if ever, have seenwhat you might call a personal bias affect the study. So I think everybody here is really devoted to just getting to the bottom of the problem.
And I really do not see any chance that this is going to be corrupted at all. It’s a very unusual place where there’s very little incentive and actually it’s a career-breaker if that ever happens.
So I really do not feel that this is a concern that the community should worry about. But thanks very much.
Dr. Avindra Nath: And the design of the protocol is not going to allow any of that anyways.
Dr. Walter Koroshetz: Yes. Right. Okay. Great. Can we go to the next question?
Coordinator: Okay. Once again as a reminder to participants to ask a question over the phone lines please press star 1 on your phone and record your name at the prompt. Our next question comes from Jennifer Spotila. Your line is open.
Jennifer Spotila: Thank you and thank you -- excuse me -- to everyone on the panel, especially Dr. Collins. I appreciate your personal appearance here today. I have as you can imagine a million questions. I’m going to focus on three.
The first question for Dr. Koroshetz, can you make a commitment to this community today that a request for applications with set-aside funds is going to be part of the short- and long-term strategy coming out of the Trans-NIH Working Group?
My second question for Dr. Nath or Dr. Walitt is why the selection of Lyme disease as a comparison group? There’s a lot of overlap in the chronic Lyme community and the ME/CFS community.
People being diagnosed with one when they may have the other and also there’s a question about reliability of the testing. So if you were looking for a post-infectious group with no sequelae, I wonder why something like resolved influenza might not be a better comparison group.
And then the third question for Dr. Whittemore is how are you going systematically incorporate patient and subject matter expert input into this study and into the formulation of strategy?
I think these town hall meeting calls are a great tool for you to use but it shouldn’t be the only one. And I know I would really like to see some more systematic involvement of both patients and subject matter experts throughout the phase of the strategy. Thank you.
Dr. Walter Koroshetz: Thanks very much. Let me talk a little bit about the first question which was the commitment of funds and RFAs. So given the processes I mentioned at NIH, I can’t really say that.
I can tell you that that’s our goal. That’s what we’re working towards. And we’re hopeful. But I couldn’t say publicly what we’re going to be able to do until we have a plan that we can make public.
So I hope that’s helpful. In terms of the Lyme disease, Brian would you like to take that one?
Brian Walitt: Sure.
Dr. Avindra Nath: I can handle that. This is Avi.
Dr. Walter Koroshetz: Avi? Okay.
Dr. Avindra Nath: So the reason I asked for the Lyme disease group is because there’s two reasons for it. Number one is it’s a patient population of convenience for us because Adriana Marques, an infectious disease expert at NIH, has a patient population - she specializes in Lyme disease.
So she already has a well-characterized population of patients who we know that for certain had Lyme disease and they did get better or they did not get better. And so, we could very easily recruit from an existing cohort.
And so when we thought about working with these - we want a control population. This is not chronic Lyme disease. So that’s the other thing I want to make absolutely certain.
These are individuals who had an infection and that they did not develop any other chronic symptoms. They fully recovered. So in that sense that’s pretty close to a healthy normal, because normal individuals also develop infection at some point in time.
And most healthy individuals recover from it. But here, this is a specific infection, a sample size of individuals that already exists at NIH and we can easily recruit from them. They’ve already been studied at great lengths.
So we can actually use the information that already exists on them. So with all those things considering that’s why we chose this one. Not that the influenza population is not worthy of studying.
I think that would be fine too. But we picked this for the reasons that I mentioned.
Dr. Brian Walitt: If I can also add, the onset of Lyme disease has some very specific physical findings, in particular the rash of Lyme disease that helps us understand exactly when the infection started.
And so when we’re trying to look at people that are after the infection, it makes it easier to figure out actually when the infection started and pin down the time.
Dr. Walter Koroshetz: Great. And Vicky, do you want to talk a little bit about engagement of the community as we move towards extramural plans?
Dr. Vicky Whittemore: Sure. So for the involvement of the community with the Trans-NIH Working Group, we’re thinking about initiating a period of time with each of our working group meetings when we can open the lines and have input and/or potentially presentations from various members of the community.
Again, using our Web site to push information out and also to get feedback from the community would be really helpful. And I think we’re also always open to any thoughts that the community has.
We’re thinking about some workshop ideas where we would involve the patient and clinical and research community in the organization and putting that together and also then welcoming patients to attend that meeting.
I’ll let someone else address, maybe Avi, address involving patients in the intramural study.
Dr. Avindra Nath: Yes. Can you say that question again about involving patients as advisors or involving...
Dr. Brian Walitt: Yes, I think she was asking about the patient advisory group Avi. Yes.
Dr. Avindra Nath: Oh okay. All right. Okay. So we looked into some of the legalities about patient advisory groups and it’s a little bit complicated in the federal government.
But nonetheless, what we are absolutely committed to is getting input from patients throughout the study itself. So I think some input we’ve already received and we’re going to come up with a system whereby we can get continual input from patients and patient advocacy groups as our study moves forward.
As Dr. Koroshetz mentioned earlier, the protocol is a process and evolution. Just because you wrote up a protocol doesn’t mean that’s exactly the way it will be conducted.
There are a lot of changes that occur through the process. And so continual input is necessary throughout the life of the protocol. And so, we’re happy to receive that and we’re happy to work with the patients and the advocacy groups for that purpose.
Dr. Walter Koroshetz: I think that also the patients who are enrolled are going to have a lot of influence on the docs and how it moves forward. Okay. So thank you very much. Can we go to the next question?
Coordinator: Our next question comes from Wilhelmina Jenkins. Your line is open.
Wilhelmina Jenkins: Good morning. I’d like you to especially thank Dr. Walitt for being here. And I understand that Dr. Nath spoke specifically to the importance of keeping personal bias out of any research that goes on.
But I wonder if Dr. Walitt, just to allay the fears and concerns of the community, could speak directly to that himself. And I’m sure you understand the fears of the community based on many studies that have taken place, particularly the PACE studies in England.
That we are very concerned about that problem of bias within a study. That is has been shown to affect the results. I understand Dr. Walitt has worked with patients and I would just like to hear him speak again about how his own view of this illness will be incorporated within this study or will not affect this study.
Dr. Walter Koroshetz: Thanks very much. Brian?
Dr. Brian Walitt: First let me affirm by saying that Chronic Fatigue Syndrome, Myalgic Encephalomyelitis is a biological disorder. Research has shown that in every system of the body that has been investigated that there have been abnormalities when compared to healthy volunteers.
If Chronic Fatigue Syndrome, Myalgic Encephalomyelitis is all in your head, it’s only because your head is part of your body. In regards to my individual role in this study, I am certainly a facilitator of research hoping to coordinate all the scientists and all the medical professionals that we require to make this happen and to help provide care and to be a cheerleader for the patients as they come through the protocol.
I don’t have a bias and I don’t have the outcome that I hope to see except that we find an answer that makes people better.
Dr. Walter Koroshetz: Great. Thank you very much Brian.
Marian Emr: We have time for one last question.
Coordinator: Okay. It’ll just be one moment.
Marian Emr: Then let me just fill the gap by saying I know there are others of you waiting to ask questions of us. Please, thank you for your participation this morning. And send us those questions.
Please send your questions to email@example.com and we will make our best effort to respond to you in a timely manner. Thank you again for participation. One last question.
Coordinator: And our final question comes from (Deborah Waroff). Your line is open.
Coordinator: We’ll skip to the next question. The final question comes from Rivka Solomon. Your line is open. Rivka, you currently have an open line.
Rivka Solomon: Hi, sorry I was on mute. Sorry. Can you hear me now?
Dr. Walter Koroshetz: Yes, very well. Thank you.
Rivka Solomon: Okay. Thanks. Thank you very much for holding this meeting today. So I’ve been sick 26 years, much of that homebound and bedridden. And it’s obviously devastated my life and at least a million other patients are suffering with this illness in this country.
I think that we need equitable research funding at a level that’s commensurate with the degree of disability and with the population numbers. I know this is a first step you’re saying, but in my mind and in many patients’ minds we need probably something along the lines of $250 million a year to be able to address this illness properly.
And that doesn’t even count the 30 or so years that we’ve missed. So could somebody address that please?
Dr. Walter Koroshetz: Thanks Rivka. Yes, I think for this as unfortunately as well as many diseases, the amount of research funding does not match the burden of illness. In our institute, we have probably 300 different neurologic diseases.
And that’s the case for every single one of them. That being said, the process by which NIH deals with how to allocate these scarce resources is a tried and true process that’s been in place for 50 years where investigators submit grants, they get peer reviewed and they get scored.
And then the NIH starts to pay the ones that seem to be the most highly meritorious and go down the list until we run out of money. So the system is a peer review system and what we need in some diseases and I think in ME/CFS, we need funds to formalize the research, to get the research going.
To get really a large number of highly motivated and well trained investigators into the field, and that’s what we are planning to do in the fairly short time, is to try get that growth of investigators.
But the truth of the matter is to really get the funds towards ME/CFS to a higher level on par with many other like-diseases, we need those kinds of applications to come in and compete against -- and in a fair way -- with the other disorders.
And so I think as a short-term process that we definitely have to stimulate with funds that are particularly for ME/CFS and Dr. Collins is clearly behind that. But our hope is that this will actually spread.
That the community will come in and begin working with investigators at universities and clinics throughout the country.
And that groups will form that will submit applications that are clearly incredibly important and a high level of science that gets to the bottom of the problem.
So I think, again, we have to utilize the NIH resources as best we can for the long-term and I think we can do that. But we cannot do it alone. We need to do it with the patients and the advocacy groups together, working hand in hand as we try and fight this illness. So I want to thank everyone for coming on.
We’re out of time. We will certainly be looking at the questions that get submitted and we will, again, set up another call where we can continue the dialogue that we started today.
And I can’t say how much everyone around the table and Dr. Collins appreciates the interest and the concerns of the community. It’s really been fantastic. So thanks very much.
Marian Emr: Please send any of your unanswered questions to firstname.lastname@example.org. And for those of you who aren’t near a pencil and paper, you can go to the main NIH ME/CFS Web site and simply click on contact us to submit those questions. Thank you again for a very productive discussion this morning.
Coordinator: Thank you for your participation in today’s conference. You may now disconnect.
This page last reviewed on March 10, 2016