Solve ME/CFS Initiative 2014 Webinar Series

July 8, 2014

Workplace-WebinarBeginning in July and continuing through year-end, the Solve ME/CFS Initiative (SMCI) will be bringing you a free, monthly webinar series. Anyone that is interested can RSVP to participate live. Each webinar will be recorded and posted to our website and YouTube channel within a week of the live date, so if you miss it, don’t worry! You can still have access to the great content at your convenience.

Read more about the series and RSVP today!

 

Suzanne

Research Institute Without Walls – Progress and Promise

HELD on Thursday, July 31, 2014
Video Link

Suzanne D. Vernon, Ph.D., scientific director of the Solve ME/CFS Initiative will provide an update on the work being conducted through our Research Institute Without Walls. Participants can also expect to learn more about how the SolveCFS Biobank works and is attracting some of the brightest investigators from the best institutions to ME/CFS research.  You will leave with an understanding of what makes the SolveCFS BioBank unique, how to get enrolled and what to expect when you participate.  Vernon will also provide a sneak peek at some of the types of research being conducted on samples using the SolveCFS BioBank.

 

McGowan

Investigator Report: Epigenetics of ME/CFS

Thursday, August 21, 2014
2-3:00pm Eastern (1pm Central/Noon Mountain/11am Pacific)

Space is limited –  RSVP to Reserve Your Slot – Click HERE

Patrick O. McGowan, Ph.D., is one of the Solve ME/CFS Initiative 2011 funded investigators.  McGowan is an assistant professor in the Department of Biological Sciences, University of Toronto at Scarborough.  He will talk about his latest results from our grant funding.  McGowan used blood samples from the SolveCFS BioBank to identify the chemical modifications (e.g., methylation) to the DNA that is different in ME/CFS patients compared to healthy people.  This type of research will help explain the immune dysfunction of ME/CFS.

 

Dane-Cook

Investigator Report: Deciphering Post-Exertional Malaise

Thursday, September 18, 2014
2-3:00pm Eastern (1pm Central/Noon Mountain/11am Pacific)

Space is limited –  RSVP to Reserve Your Slot – Click HERE

Dane B. Cook, Ph.D. is assistant professor of Kinesiology at the University of Wisconsin, Madison.  Cook is one of the Solve ME/CFS Initiative’s 2011 funded investigators.  Cook will describe the system biology approach his team is taking to provide a clear picture as to what causes post-exertional malaise.  This is critically important research for ME/CFS because as Cook notes, “You can’t begin to fix a problem like post-exertional malaise until you can understand its underlying cause.”

 

unutmaz

Investigator Report: Decoding the Human Immune Response

Wednesday, October 1, 2014
2-3:00pm Eastern (1pm Central/Noon Mountain/11am Pacific)

Space is limited –  RSVP to Reserve Your Slot – Click HERE

Derya Unutmaz, MD, is Professor of Microbiology, Pathology and Medicine at NYU Langone Medical Center.  Unutmaz is using samples from the SolveCFS BioBank to understand the “Good, Bad and Ugly” aspects of the immune response in ME/CFS.  Unutmaz hypothesizes that a disproportionate immune response leads to damage in ME/CFS.   He will describe what the immune signature of ME/CFS looks like compared to a healthy immune response.

 

PeterRoweInvestigator Report: Neuromuscular Strain in ME/CFS

Thursday, October 23, 2014
2-3:00pm Eastern (1pm Central/Noon Mountain/11am Pacific)

Space is limited –  RSVP to Reserve Your Slot - Click HERE

Peter Rowe, MD, who directs the Chronic Fatigue Clinic at Johns Hopkins Children’s Center, will describe some novel observations about restrictions in range of motion in the limbs and spine in those with ME/CFS. Many affected individuals have restricted movements and increased mechanical tension in nerves. Applying a further mechanical strain to the nervous system can provoke increased symptoms in some patients. These concepts are starting to help explain the pathogenesis of some symptoms and neurological abnormalities in the illness—not only how they might arise but also how we might treat them more effectively.

 

 

November and December webinars to be announced at a later date.

 

 

Same Mission | New Name

May 30, 2014

Solve ME/CFS Initiative

We’re delighted to announce that The Solve ME/CFS Initiative has a new name – the Solve ME/CFS Initiative.   While our name has changed, our mission steadfastly remains the same:  We will make ME/CFS understood, diagnosable and treatable.

Why the change?  We recognize the many changes in our organization and our illness space since the organization was first named so long ago in 1987.  While the name of our illness continues to be controversial, “ME/CFS” better reflects today’s understanding. And we believe that the word “initiative” (defined as ‘leading action’), expresses our strong commitment to funding ground-breaking research.

Since our organization was founded and named in 1987, we have been the leading organization focused on this illness.  Over the years, we’re proud of our remarkable advances regarding this controversial and misunderstood disease.

  • Under the 22-year leadership of Kim McCleary, the organization’s first CEO, the Association played an integral part in developing a policy ruling for the Social Security Administration that recognized CFS as a disabling condition.
  • We are the leading private funder of ME/CFS research, directly funding $5.5 million in ground breaking research which has been leveraged into more than $12 million in additional ME/CFS research.
  • The organization fought to create and continues to advocate to sustain a dedicated federal advisory committee on ME/CFS research and education (CFSAC).
  • We helped expose the misappropriation of $12.9 million in CDC spending, restoring these funds to ME/CFS research.
  • We led the first-ever public awareness campaign for ME/CFS, led lobbying events, organized Congressional briefings and regularly deliver testimony at numerous federal hearings and meetings.

Four years ago, guided by a desire to move into a new era of scientific progress on ME/CFS, the Association made a strategic decision to heighten its focus on research.  Our thinking was simple – the best way to use our precious dollars is toward solving this despicable illness.

Today, led by President and CEO, Carol Head, the organization continues to drive its mission forward – to fund research that will make ME/CFS understood, diagnosable and treatable.  How do we do that? By providing more funding for high-quality ME/CFS studies, fostering increased collaboration among ME/CFS researchers and pushing the federal government to make ME/CFS research a higher priority.  We are working to leverage our experience, relationships and collective knowledge to propel the ME/CFS research field forward. We are a catalyst for scientific advances that translate into better care for ME/CFS patients. We are accelerating ME/CFS research.

As we continue our efforts to make ME/CFS widely understood, diagnosable, and treatable, it is fitting that we have a name that more accurately reflects who we are: The Solve ME/CFS Initiative. We trust that you will continue this journey with us as we work towards a day when ME/CFS is no more.

 

Deciphering Post-Exertional Malaise

November 21, 2014

Guest Blog by Dane B. Cook, PhD

On September 18, 2014, Dane B. Cook, Ph.D., Associate Professor of Kinesiology at the University of Wisconsin, Madison and a Solve ME/CFS Initiative 2011 funded investigator, presented a webinar on the system biology approach his team is taking to provide a clear picture as to what causes post-exertional malaise. You can access the full recording of the webinar HERE.

In this guest post for our blog, Dr. Cook reviews the material presented and tackles the many questions we received from webinar participants.

__________

Post-exertional malaise (PEM) has been called “the illness within the illness” (Anthony Komaroff, 2011). It is the defining and cardinal symptom of myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and yet the term used to describe it is a horrible one that does not do justice to the suffering that patients experience. Deciphering PEM is a critically important area of research for ME/CFS; you can’t begin to fix a problem like post-exertional malaise until you can understand its underlying cause. The goal of our research is to help our understanding of PEM so that we are able to mitigate its effects.

In the webinar I discussed both the clinical and laboratory characteristics of Post-Exertion Malaise (PEM) emphasizing that the patient experience and the laboratory study of PEM do not always coincide well with one another.

Clinical Perspective
There are several ‘descriptions’ or case definitions currently in circulation for ME/CFS. The international consensus criteria (Carruthers et al., 2011) offers a detailed clinical description of PEM and has potential utility for physicians. This case definition refers to PEM as Post-exertional neuroimmune exhaustion (PENE) and notes that it is a required symptom for the disease. It describes PEM or PENE as:

  1. Marked, rapid physical and ⁄ or cognitive fatigability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.
  2. Post-exertional symptom exacerbation: e.g. acute flu-like symptoms, pain and worsening of other symptoms.
  3. Post-exertional exhaustion may occur immediately after activity or be delayed by hours or days.
  4. Recovery period is prolonged, usually taking 24 h or longer. A relapse can last days, weeks or longer.
  5. Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.

The current clinical description of PEM makes note of the large variability in time-course, severity and symptom make-up of this phenomenon among patients. This highlights the very real need for more research on these topics.

Research Perspective
Current clinical descriptions and case definition criteria of PEM are not currently quantified well-enough to be used in the laboratory setting. As a result, most studies have had to operationally define PEM. This has led to PEM being described and defined in a host of different ways including:

  • Increased symptoms of pain & fatigue
  • Reduced physical activity levels
  • Abnormal exercise responses
  • Changes in cognitive function
  • Circadian rhythm/period changes
  • Sleep disruption
  • Impaired pain regulation (central nervous system sensitivity)
  • Various biological markers (e.g. complement C4a, cytokines, natural killer cells, NF-кB, oxidative stress, gene expression, etc.)

Too many studies that have defined PEM based on biological outcomes have failed to measure symptoms. This is problematic because unless you demonstrate that biology is related to illness severity, you cannot attribute any changes in biology to the phenomenon of interest (in this case PEM).

The Solve ME/CFS Initiative funded a study led by my Master’s student Jacob Meyer.  This study, published in 2013 in the journal Fatigue: Biomedicine, Health & Behavior, is an example of how we study PEM in the lab.

  • This study examined gene expression for metabolite, immune and sensory receptors and symptoms pre and post exercise in ME/CFS patients and healthy controls who were matched on age and fitness. The study was an extension and replication of the work of Light and colleagues (2009; 2011) at the University of Utah.
  • Results showed that maximal exercise resulted in sustained up-regulation of the glucocorticoid (NR3C1) and alpha 2A adrenergic receptors for up to 72 hours in ME/CFS patients compared to controls.  Importantly, these changes in gene expression were significantly related to symptoms of pain, fatigue and confusion. These results demonstrate that ME/CFS patients have a different physiological response to exercise, one that appears to be consistent with exercise inducing an inflammatory state in ME/CFS patients and that clearly has negative consequences.

Our most recent study, “Post-exertion malaise in CFS/ME: Brain, inflammation and behavioral interactions”, also funded by SMCI, is a collaborative effort with Alan and Kathy Light at the University of Utah and Dr. Gordon Broderick at Nova Southeastern University in Florida. The project is a direct extension of our previous work (Meyer et al., 2013) and adds two critical components. The first is assessment of brain responses to cognitive tasks during a state of PEM. The second is the use of a “systems biology” approach to data analysis.

  • The overall goal of this study is to determine the dynamic relationships between brain structure and function, gene expression for sensory, adrenergic and immune receptors and self-reported symptoms in CFS/ME using a model of PEM
  • The key concept is that determining the interaction between several physiological systems (i.e. central and peripheral systems) will better predict PEM than determining the influence of any single system independently

The study protocol:

  • On Day one, we screen all participants for either ME/CFS or as healthy
  • Day two consists of detailed symptom measurement and functional brain imaging of both fatiguing and non-fatiguing tasks. Blood is collected both prior to and following brain imaging.
  • One week later participants return for exercise testing. A blood sample is taken and symptoms are measured. Participants exercise at 70% of peak heart rate for 30 minutes. Metabolic, heart rate and lactate responses to exercise are measured. Blood and symptoms are measured during the first 15 minutes post exercise.
  • Participants return 24-hours later for their second functional brain imaging session (i.e. they repeat day two of testing)

Cook_StudyProtocol

Though this study is not yet completed, this is what our preliminary data is showing:

  • Variability in symptoms from pre- to 24 hours post-exercise. These data demonstrate an incredible amount of variability in the magnitude, number and types of symptoms reported by patients. The variability is likely the result of a number of reasons such the severity of symptoms at baseline (i.e. ceiling effects), the individual time course of PEM (i.e. it may not have peaked for certain individuals) and how sick the patient was at study entry.

Cook_VariableSymptoms

  • Cognitive performance and brain responses for the fatiguing cognitive task. Patients tended to perform worse as they became more fatigued and performed more poorly post- compared to pre-exercise. The opposite was observed for controls. They tended to show improved performance during the first day and continued to improve 24 hours post-exercise.
  • Brain responses during the cognitive task reflected the cognitive performance results. ME/CFs patients showed greater brain activity than controls at baseline in brain regions involved in executive control (i.e. anterior cingulate and inferior frontal cortices) and memory (bilateral hippocampus).

Cook_BrainResponse1

Cook_BrainResponse2

Importantly, ME/CFS patients showed a different change in brain responses 24-hours post-exercise than controls and these changes in brain responses were significantly related to changes in symptoms. These data show that acute exercise has neural consequences for patients, suggesting that central nervous system outcomes are predictive of PEM.

Cook_BrainActivity1Cook_BrainActivity2

My take home messages:

  • Post-exertion malaise affects both the immune system and the brain.
  • No single outcome or biochemical is likely to explain the complexity of PEM
  • Determining physiological systems interaction will be critical towards understanding the mechanisms of PEM and perhaps how ME/CFS symptoms are maintained and/or exacerbated
  • There is still a large gap in our knowledge of what PEM is in terms of time course, variability, severity and primary symptoms.

- # -

 __________

This was our highest attended webinar of the year and there were far more questions submitted than we were able to cover during the webinar. Dr. Cook graciously took the time to answer a majority of the individual questions submitted and those responses are below.

Webinar Q & A

Q: Are there ME/CFS exercise studies with brain imaging before, during & after exertion?

A: To our knowledge only the study by Rayhan et al., (2013)in Gulf War Veterans with ME/CFS has looked at brain responses pre and post exertion.

 

Q: Why do you say “subjective” response & not “objective” to maximal exercise?

A: The subjective response I was referring to was the symptoms that the patients experience post exercise. We also focus on the objective responses to the exercise such as oxygen consumption.

 

Q: Are you taking in to consideration the age of your patients and the length of time ill when you look at your results?

A: We will look at this preliminarily, but with a sample size of 15 it may be tough to demonstrate a statistical effect. This is something we are certainly interested in and hope to be able to investigate in a larger study.

 

Q: Do you have a list of examples that you can offer about PEM to help physicians and others better understand that this is a disease within a disease?
A: Some personal examples:

  • Need to stop grocery shopping mid-shop, stow shopping cart, lay-down in car for ½ hour and then return to finish shopping
  • Completely unable to perform activities of daily living
  • A debilitating crash following minimal exertion that can take weeks to recover from

A: Here is the 2011 case definition PEM list:

  • International Consensus Criteria (Carruthers et al., 2011)

A. Post-exertional neuroimmune exhaustion (PENE): Compulsory

1. Marked, rapid physical and ⁄ or cognitive fatigability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.

2. Postexertional symptom exacerbation: e.g. acute flu-like symptoms, pain and worsening of other symptoms.

3. Postexertional exhaustion may occur immediately after activity or be delayed by hours or days.

4. Recovery period is prolonged, usually taking 24 h or longer. A relapse can last days, weeks or longer.

5. Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.

Q: Have they found any muscle shut-down and/or myclonis with PEM?

A: Not to my knowledge

 

Q: Are you using functional MRI’s versus regular ones?

A: we are using both MRI (to look at brain structure) and fMRI (to look at brain function.

 

Q: Are you working with anyone in the Northwest (Portland)?

A: We are not currently working with Northwest US researchers.

 

Q: Can you tell us more about the effects seen with the HPA axis, particularly (eventually) effecting hormones: neuro, reproductive, thyroid?

A: It is too early to tell the cause or consequence of our glucocorticoid findings. Although the HPA-axis is an attractive hypothesis, the receptor response we are seeing could also be in response to inflammation. Some of the downstream consequences, if are results are confirmed, could mean that the neuroendocrine system is being affected in ME/CFS. This system regulates a host of hormones, the immune system, mood, storage and spending of energy. This system also interacts with numerous brain structures that interact with these systems.

 

Q: Can the different results of the symptoms be because there are not enough patients in the study?

A: This could certainly be a factor for average changes in symptoms for the group, however the individual variability we are seeing is not due to small samples. It’s showing us that PEM is highly variable and that we need large samples to study this variability in depth.

 

Q: Is IL2 refering to Interleukin 2?

A: Yes

 

Q: Is the PASAT the same version as for diagnosing MS?

A: I’m not sure if it is the same as used in MS research, but if not, it is very similar.

 

Q: Did this study include ME/CFS with fms??

A: We did not exclude for FM and yes some of our participants have both. We will look closely at this during our final analyses.

 

Q: Do repetitive episodes of PEM decrease a patients chance to recover from CFS/me?

A: I do not know the answer to this question, but it is a good one.

 

Q: Do these PEM abnormality show equally to M.E. AND Fibromyalgia patients?

A: This question is unknown (no data that I’m aware of) and it’s also a very good question.

 

Q: Do you think changes in brain scan images are a sign that there is brain damage or just a side effect of the illness?

A: The scans I presented do not tell us whether there is overt brain damage or not. They inform us if the structure of the brain is different in size and whether brain function differs during a particular task between patients and controls and in our case pre and post exercise.

 

Q: Is their lactic acid build up in muscles with exercise?

A: Yes, particularly for exercise that is of higher intensity.

 

Q: Does the up-regulation in in NR3C1 mean that cortisol level are extremely low or non-existent in the morning when cortisol levels are supposed to be the highest?  And non-existent levels throughout the day known as adrenal fatigue?

A: The up-regulation we see could be in response to low levels initially or it could be in response to regular levels that don’t necessarily function optimally. Our data suggest that baseline levels of expression are not different between patients and controls, but this does not mean that the actual receptor numbers do not differ. That requires a different blood analysis.

 

Q: Were levels tested before exercise?

A: Yes, we tested levels at baseline. For our first study blood level for gene expression did not differ between patients and controls. I will add though that brain responses to cognitive tasks have differed at baseline.

 

Q: Have they studied Chronic Pain Patients in these same ways?

A: There are post-exertion malaise studies in chronic pain patients, but these tend to not have blood or brain outcomes. They tend to measure pain responses to pain stimuli.

 

Q: Is it possible to do research on patients that cannot function at a level to exercise for 30 minutes or do a 2 hour mental task? That IS the reality for so many of us. Even if you live in the area, just getting to the hospital for the research is a daunting outing.

A: At this point, I am not aware of studies that can accommodate the most severely affected patients. This is a sad and recognized limitation of this research. Once we learn more, perhaps we can investigate how little it takes to trigger PEM?

 

Q: Is it possible to do some of this testing in other places? What would be required? Equipment, training etc

A: Yes, we could design multi-site studies. It would require a significant funding level of course, but they could be done.

 

Q: Is there a difference in these tests if the person is new to the disease or someone who has had the disease a long time?

A: A great question and one we (and others) are interested in. At this point, we do not know.

 

Q: Is there any hope of a study to make sure that men show the same problems as women (i.e., that diagnosis and treatment should be the same for both)?

A: Mary Ann Fletcher just received an RO1 to look at sex differences in ME/CFS.

 

Q: Talk about the difference between post-exertional malaise and post-exertional relapse.

A: At this point, we don’t know the laboratory differences. Perhaps expert physicians would know the clinical differences?

 

Q: This is fabulous–the best webinar for me to share with family and friends to make them familiar with the condition. It would make it even better if it could be stated and printed in the PowerPoint that exercise tests are made to approximate the activities of daily living that cause PEM. I have had people respond with “just don’t exercise that hard.”

A: Thank you. I’m glad it was useful. My response to people who say “don’t exercise that hard” would be that research has shown that even light activity can result in a worsening of symptoms and to be honest we don’t know how much is too much.

 

Q: Were people in study suffering from ME/CFS only or have other medical conditions that may contribute to PEM? I am very healthy other than suffering from ME/CFS and PEM is one of the most severe symptoms, mentally and physiologically, I experience!

A: All patients had ME/CFS and no other medical explanation for their symptoms or intolerance for exercise.

 

Q: Does PEM typically have detrimental effects on the immune system?

A: The research to date suggests that PEM does affect the immune system. Some data suggest that these responses are detrimental, but there is much more we need to learn about the consequences of the changes that we are seeing.

 

Q: You mentioned brain inflammation, is there any way you have to measure that?

A: There are some neuroimaging techniques that get at brain inflammation. For example, MR Spectroscopy can be used to look at certain molecules in the brain that are indicative of brain cell health that might be related to brain inflammation.

 

Q: Do you find a delay in the response, at least in symptoms after the exercise?

A: There is research to suggest that symptom worsening can be delayed for many days. There is other research that shows symptoms get worse the day of exertion and stay bad for several days. We need more research to understand this variability better.

 

 

Two Important Federal Meetings Just 4 Days Apart

November 20, 2014

With only 4 days in between them, December offers two very important meetings to the ME/CFS community. On December 3-4, the CFS Advisory committee (CFSAC) will hold its third and final meeting of 2014. Then on December 9-10, after nearly 10 months of discussion, debate and anxiety among the ME/CFS community, the Pathway to Prevention Workshop for Advancing Treatment in ME/CFS will occur. Both in DC and both available via webcast.

Details on both of the meetings, including links to registration information is offered below.

With already overburdened December schedules taxing any ME/CFS patient’s energy envelope and health, the unfortunate scheduling of these two meetings so close together will lead many patients to have to choose one over the other. While the choice is completely an individual one, SMCI would like to encourage stakeholders that are able, whether live or via webcast, to participate in the P2P Workshop.

Despite many flaws in the process and concerns about potential outcome from many, the P2P process could be what is needed to break through the negative cycle of ME/CFS research to move us to a day when ME/CFS is appropriately funded. With significant stakeholder participation, the P2P has increased potential to further the recognition of the clinically devastating nature of ME/CFS and recognition of the disease as an urgent area of future study.

Your voice matters and your involvement in the process is important. Please consider registering for and participating in one or both meetings.

 

P2P Information & Links to Register

Registration is open for the Pathways to Prevention workshop for Advancing the Research on ME/CFS. Interested individuals may register to attend live or participate via webcast. It is our hope that many stakeholders will participate in this process in order to ensure the patients have a strong presence and a voice.

Our understanding is that stakeholders/patients will have the opportunity to participate in the discussion both in person and online by asking questions or making comments whether attending live or online.  There is a total of 3.5 hours of “Discussion” time noted on the agenda, where public input will be addressed.

To register to attend live click HERE 

To register for the webcast click HERE

If you plan on participating either live or via webcast, and want to learn more, our earlier posts on the subject should help inform your participation:

P2P Draft Evidence Review – Can a Process that is Inappropriate for ME/CFS Inform the Research Path Forward

P2P Releases Systematic Evidence Review

SMCI Position on the P2P

Pathway to Prevention for ME/CFS

 

CFSAC Information & Links to Register

The agenda for the December 3rd and 4th meeting of the Chronic Fatigue Syndrome Advisory Committee was published this week.While the date has been publicized for some time, the meeting details were just shared on Tuesday, November 18th. You can read the full agenda HERE.

In addition to the standard agency updates, the agenda includes:

  • A request for testimony on the topics of Centers of Excellence and patient registries
  • Dr Sue Levine will offer comments on the P2P report on opioid use in chronic pain and speak briefly on the “IOM Report Rollout”
  • Bob Miller will speak briefly about the ME/CFS P2P meeting
  • There will be two hours of committee discussion.

If you want to offer public comment by telephone, you must register by Monday, November 24th at 5pm. If you want to submit written comments to the Committee, those comments are also due November 24th at 5pm. Registration and instructions for scheduling public comments and submitting public testimony are available at www.blsmeetings.net/cfsac.

If you would like to receive notification of CFSAC activity directly via email, you can sign up for the CFSAC listserv at  http://www.hhs.gov/advcomcfs/cfsac_email_list.html

 

 

SMCI – Just The Facts

November 20, 2014

Who we are

  • Founded in 1987, the Solve ME/CFS Initiative (SMCI) is one of the longest standing organizations serving myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients and advancing rigorous research.checkbox
  • A national organization with international reach, led by a volunteer board of directors composed almost entirely of patients and their families.
  • Our mission: Make ME/CFS understood, diagnosable and treatable.
  • Our core asset: Research Institute without Walls program and the SolveCFS BioBank™.

 

Why we do what we do

  • Despite the fundamental complexity of this illness, we believe that ME/CFS can and will be solved in our lifetimes.

 

Does SMCI Receive any Federal Funding?

  • The Solve ME/CFS Initiative relies on the generous donations of patients and their loved ones – we have not received any government funding since 2010.

 

As an organization primarily focused on research, why is SMCI involved in activities on the federal level, like the CFS Advisory Committee, participating in P2P and IOM meetings?

  • SMCI is involved in advocacy efforts aimed at improving the research landscape for the early detection, objective diagnosis and effective treatment of ME/CFS.  As part of this effort, we work to validate the burden of illness imposed by ME/CFS in agencies where national policy is made and executed.  While there is still much work to be done, we are encouraged that ME/CFS is now receiving much attention on a federal level – our involvement is aimed at helping maintain this positive momentum.

 

Why is SMCI best positioned to improve the lives of ME/CFS patients?

  • We have a deep and longstanding commitment to this disease. Despite our modest budgets, we were the first to fund research into epidemiology, viral causes, Immunology, neuroimaging, exercise physiology and the autonomic nervous system.
  • Our Research Institute without Walls program allows us to fund the brightest researchers from the best institutions, without the cost of a bricks and mortar institute, while breaking down the barriers that typically exist between and among researchers. We have fostered and facilitate an innovative and collaborative environment that will only grow in the years to come.
  • Our SolveCFS BioBank™ provides the means for patients to participate in multiple research projects without leaving their homes, broadening the base of patients studied. Read more about the BioBank in this recent post.
  • We have earned a broad base of support. In 2013, nearly 2,000 individuals “voted with their dollars” and funded our organization. Several businesses offered in-kind goods and services to stretch those dollars, including more than $100,000 in pro-bono legal fees. Among other things, this legal support ensured the effective re-branding and re-naming of our organization met all legal standards without taking valuable funds from research coffers.

 

As we approach year end, many are considering giving to a charity that is close to their heart. big-donate-modifiedYou have the power to ensure the good work of our organization continues to propel us all closer to a day when the world is free from ME/CFS. Any and every gift makes a very real difference in this fight to make ME/CFS understood, diagnosable and treatable. Please  consider a gift that is meaningful to you and accept our heartfelt gratitude for your faith in our work.

Together we will solve ME/CFS.

 

The Importance of a Representative Patient Population for Research

November 18, 2014

Over the past 4 years, the SolveCFS BioBank™ has become a sought after resource for ME/CFS research. Ten of the brightest investigators from the best medical institutions have used the samples and information from the SolveCFS BioBank™ to conduct research in the following areas:PatientCentered

  •  case definition
  • patient-reported outcomes
  • autoimmunity
  • viral pathogens
  • epigenetics
  • immune function
  • biomarker validation

Importantly, 8 of these 10 researchers are new to ME/CFS research, most of them recruited to the field by our organization.  And ours is an illness which NEEDS more researchers…and much more research.

 

Why did we create the SolveCFS BioBank™?

The Solve ME/CFS Initiative recognized that in order to recruit the best and brightest into ME/CFS research, the researchers would need access to ME/CFS patients and controls. If we could offer researchers access to the right type of biological specimens for their experiment – access to ME/CFS patients with demographic and clinical characteristics that represent the full range of people affected with ME/CFS – it would remove one of the hurdles all researchers face. By creating a biobank, we realized that we could make ME/CFS research more appealing and/or accessible.

 

What is the ideal representation of patients and controls in any biobank?

An ideal biobank contains patients that reflect the population of all those affected by a disease.  We know that certain diseases can occur more frequently in women, children, or a specific race. There are some diseases in which what is truly a representative patient population is not known, either because population-based epidemiology studies have not been done or because many groups are historically underrepresented in medical research (e.g., because of race/ethnicity, access to care, socioeconomic status, gender, severity of illness).

Fortunately, this is not the case with ME/CFS. There have been several epidemiology studies that have clearly demonstrated that ME/CFS does not discriminate. Community-based research has shown that ME/CFS can strike anyone.  For example, Dr. Leonard Jason of DePaul University found that in Chicago, ME/CFS occurred at higher rates in women, Latinos, middle-aged individuals and people of middle to lower socioeconomic status.[1] Centers for Disease Control and Prevention (CDC) found that even in their epidemiology study with 86% Caucasian participants, rates of ME/CFS were higher in the non-white study participants.[2] The CDC also found the rate of ME/CFS in men and women varied depending on whether one lived in a major metropolitan area or a rural area.[3] There are many more epidemiology studies on ME/CFS. While none are without flaws, these studies clearly indicate that ME/CFS affects individuals of all ages, genders and race.

representative_crowdLooking forward to our goal – a treatment approved by the FDA – it is important that studies are done using a representative patient population. Therefore, it is important that researchers have access to representative patient populations so that their results can be generalized to the affected population as a whole.  For example, if research is only done on women, then these results may not be relevant to men.  This is not to say that research cannot ask specific questions about ME/CFS in women, for example, but the limitations of studying only women must be made clear.  And access to a representative patient population provides researchers the opportunity to conduct very specific research on sub-groups AND research that can be generalized to the population as a whole.

 

As a national organization, reaching patients online rather than in a clinic in a specific location, we have the unique and important ability to reach a broad, diverse population of patients.  Over the past year our SolveCFS BioBank™ has grown to 1,000 strong.  Patients, family members and friends have signed up to participate in research that will help us Solve ME/CFS.

BioBank participants have recently begun receiving survey requests that will help us begin to determine how representative our SolveCFS BioBank™ is at this time.  If we find that some patient groups are underrepresented, we will reach out to these groups to increase their enrollment. Earlier this year, SMCI was fortunate to have received from Google access to $10,000 per month in in-kind online advertising support through a program called AdWords. With this tool, we look forward to reaching even more patients and controls to further strengthening our BioBank… and in turn, strengthening our offering to the research community to further progress.

 

Read more about the future of the Solve CFS BioBank™ in this prior post: SolveCFS BioBank™: Then, Now & the Next Evolution

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big-donate-modifiedThe Solve ME/CFS Initiative is targeting our work in order to one day understand ME/CFS at an unprecedented molecular level and be able to guide research and development of new diagnostic tests and better treatments. Your support and participation has gotten us this far and it is critical to the path forward. Please consider a gift that is meaningful to you – any and every donation helps fuel the path forward.

SolveCFS BioBank: Then, Now & the Next Evolution

November 14, 2014

The SolveCFS BioBank™ was approved by the Genetic Alliance for operation in April 2010, launching with a partnership with GlaxoSmithKline (GSK) and several of the top ME/CFS expert clinicians in the U.S. This initial study was very specific – to determine if XMRV could be found.  We enrolled 240 cases and 87 healthy controls, collected information about symptoms and collected from each participant four tubes of blood.  By August of 2011, it was clear that XMRV was not associated with ME/CFS so this study ended.  (Results of the study have just been published in the open access journal BMC Research Notes.)  It is noteworthy that GSK, one of the largest pharmaceutical companies in the world, chose to partner with our organization – a testament to the quality of the SolveCFS BioBank™ as a unique and robust resource for ME/CFS research.

This study seeded the SolveCFS BioBank™ with an inventory of blood samples from ME/CFS patients being cared for by expert ME/CFS doctors, as well as healthy controls.  This inventory of blood samples, combined with the health information we collected and the expert manner that these samples were collected, quickly attracted other researchers to ME/CFS research and gave us a resource of great value to attract new investigators into the field of ME/CFS research.  Over the past 2 years, the SolveCFS BioBank has provided health information and these existing blood samples to 10 researchers – 8 of them new to ME/CFS research, most of them specifically recruited into this field of study by Dr. Suzanne D. Vernon, SMCI Scientific Director.

Current research being conducted on the SolveCFS BioBank™ asks specific questions like,

  • Are there autoantibody differences in ME/CFS patients compared to healthy controls?
  • Are there immune profile differences in ME/CFS patients compared to healthy controls?
  • Are there antibodies to viruses in ME/CFS patients that are different than health controls?
  • Are there blood biomarkers that distinguish ME/CFS patients compared to healthy controls?
  • Are there epigenetic differences in ME/CFS patients compared to controls?

Between now and the end of 2014, the Solve ME/CFS Initiative will post several blogs that will describe the exciting research coming from the SolveCFS BioBank™.  You can also hear more about this research in our investigator reports given in this year’s webinar series.

Typically, researchers work in a silo – each study done in its own lab, results held close and rarely shared with other investigators. Because of the unique and forward thinking design of our Research Institute without Walls and Solve CFS BioBank™, we will be able to “connect the dots” on these separate studies. We are not aware of any other ME/CFS organization doing this. This information/results sharing will also help inform the types of research that should be pursued.  This open-collaboration with research results is groundbreaking and a critical ingredient to accelerating progress.

In addition to attracting the brightest investigators from the best institutions to ME/CFS research, the SolveCFS BioBank™ must include patients that are representative of those affected by ME/CFS.  That is why in 2012 we encouraged anyone diagnosed with ME/CFS by their provider and anyone with ME/CFS symptoms to enroll in the SolveCFS BioBank™. (We will talk more about a representative population in our next blog post.)

Now, nearly 1,000 people strong, the SolveCFS BioBank™ is evolving into an excellent platform to study the natural history of ME/CFS.  Natural history means providing information about your disease over time – what makes symptoms better, what makes symptoms worse.  This information is essential to understanding the most meaningful clinical outcomes in ME/CFS, to understand the factors that are key to recovery.

In addition to natural history, the SolveCFS BioBank™ is growing to be a resource for genetic studies, which will need family members to serve as controls.  Additionally, for some ME/CFS studies, your healthy friends will make great controls because friends are often similar in education and socioeconomic status. In the future we will roll out resources you can use to get your family and friends interested in enrolling in the SolveCFS BioBank™ as controls.

Our intention is to evolve the SolveCFS BioBank™ into the most sought after resource for ME/CFS research in existence. In order to achieve this, we must grow in a rigorous and strategic manner.  If you are already signed up, you are our research-ready momentum leaders. Your registration already makes you part of the solution. If you haven’t yet signed up, please contact Gloria Smith at BioBank@SolveCFS.org or by phone at 704-362-2343 to learn more.

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big-donate-modifiedThe Solve ME/CFS Initiative is targeting our work in order to one day understand ME/CFS at an unprecedented molecular level and be able to guide research and development of new diagnostic tests and better treatments. Your support and participation has gotten us this far and it is critical to the path forward. Please consider a gift that is meaningful to you – any and every donation help fuel the path forward.

 

SMCI Survey Data Analyzed for Publication

November 7, 2014

The Institute of Medicine (IOM) study, commissioned by the Dept of Health and Human Services to develop and distribute diagnostic criteria for ME/CFS and possibly suggest the need for a new name, will come to fruition in spring 2015. In April 2014, the Solve ME/CFS Initiative created and circulated a survey to patients in advance of the May 5, IOM Committee meeting, in order to facilitate make it easier for patients to offer their thoughts and insights on the committees specific questions:

  1. In your opinion, what are the most important issues that healthcare providers should be educated about when it comes to diagnosis of ME/CFS?
  2. What are your thoughts on the current terminology used to describe this disease: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? If you could suggest new terminology, what would you suggest and why?

We compiled all of the answers into a report and submitted them in full, unedited, prior to the meeting, urging the committee to take the time to read all the responses, noting that, “For many, just the effort required to provide their response comes at a great cost in terms of energy spend. They ‘spent’ their energy reserve on this because of the magnitude of its importance to them personally and to the overall ME/CFS community.”

Being alerted to the data from this survey by a patient advocate, Leonard A. Jason asked for access to the full data set in order to more thoroughly analyze the it and present the findings for publication. We gladly gave Jason access to the full data set and the resultant paper is now being written up for publication. Given the timeliness of the findings, with the P2P Worshop just around the corner and the IOM committee results due out in the coming months, we wanted to share the summary findings that will be presented in the paper upon completion.

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ME/CFS Patient Perspectives on Name Change & Priorities for Healthcare Provider Education

By Leonard A. Jason, Laura Nicholson, Diana Ohanian, Kelly O’Connor, & Abigail Brown, DePaul University

A survey that was distributed by the Solve ME/CFS Initiative this past April was filled out by 143 patients. The survey was intended to provide feedback to the IOM Committee on patient perspectives on what healthcare providers should be educated about and terminology to describe the illness. Our research group at DePaul University has now analyzed the public data from this survey, and we are in the process of writing up this report for publication. However, given the timeliness of these findings, we thought it was important to provide the patient and scientific community the main results of this survey.

The first of  two open ended questions was: “In your opinion, what are the most important issues that healthcare providers should be educated about when it comes to diagnosis of ME/CFS? This first question brought a wealth of responses and suggestions on what healthcare providers should be educated about when it comes to diagnosis. Notably, a large portion (37%) of patients mentioned they wanted healthcare providers to know that it is a real and serious illness, 35% emphasized wanting healthcare providers to recognize the  severity and/or complexity of their symptoms, 26% highlighted the need for new and better treatment/diagnostic testing options, 25% stated healthcare providers should not blame their symptoms on psychiatric issues (i.e. depression), and 25% emphasized that there needs to be increased knowledge/awareness of post-exertional malaise (PEM) as it is considered a cardinal feature of the illness. These top five concerns indicate that substantial improvements need to be made in the realm of patient care.

The second question asked respondents: “What are your thoughts on the current terminology used to describe this disease: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? If you could suggest new terminology, what would you suggest and why?”  Our sample suggested 50 different names for this illness. The overwhelming majority of respondents chose the name Myalgic Encephalomyelitis . Specifically, 56% of respondents’ first preference for the name of the illness was Myalgic Encephalomyelitis , with the next most endorsed name choice of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome  receiving  votes from only 13% of respondents. Over 95% of participants who gave an opinion on the name Chronic Fatigue Syndrome either disliked or strongly disliked that name. We hope that the IOM panel members are able to consider the views of this sample from the patient community.

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We will let you know when the full paper is accepted for publication.

Research Digest – October 2014: The Search for Diagnostic Certainty

October 24, 2014

On Sept. 22nd the Agency for Healthcare Research and Quality (AHRQ) and their Evidence-Based Practice Centers published the draft systematic evidence review on the Diagnosis and Treatment of ME/CFS for comment. This report will be used for the Pathway to Prevention Workshop for ME/CFS to be held on December 9 & 10, 2014. (Read our full response to this draft report HERE.) One of the recommendations of the review is the need to test ME/CFS diagnostic criteria in other populations with diseases similar to ME/CFS where diagnostic uncertainty exists.  This is necessary because ME/CFS is defined by symptoms that are common in many other medical and psychiatric diseases.  Comparing ME/CFS to similar disorders helps determine effective diagnostic criteria to more specifically identify those who have ME/CFS.

Once ME/CFS is diagnosed there are many differences among patients; this is called heterogeneity and is common in most chronic diseases.  Objective biological measures – known as biomarkers – can be helpful for delineating this heterogeneity and identifying ME/CFS subtypes.  Importantly, biomarkers intended to be diagnostic for ME/CFS should be compared to diseases similar to ME/CFS to ensure the accuracy of the biomarker.

While there is more work to be done, in this month’s Research Digest we review three different studies that look at diseases that are common among patients labeled as ME/CFS and to identify more specific biomarkers for ME/CFS.

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 There have been studies published over the years that have looked at whether ME/CFS patients defined by the 1994 Fukuda criteria have other medical and psychiatric diseases that more accurately explain their symptoms.  A study published in the 2013 Journal of Psychosomatic Medicine found that undiagnosed and comorbid disorders were common in people with a presumed diagnosis of ME/CFS.(1) The investigators set up an integrated diagnostic pathway designed to detect known medical and psychiatric diseases that may otherwise go undiagnosed.  There were 377 patients with a presumed ME/CFS diagnosed referred to the study. Of these 279 were eligible for the study.  An unequivocal ME/CFS diagnosis was given to 65 patients.  Another 59 patients had ME/CFS together with a comorbid disorder that did not exclude the ME/CFS diagnosis.  The remaining patients had sleep disorders, medical diseases or psychiatric diagnoses that excluded an ME/CFS diagnosis.  This study highlights the importance of and need for diagnostic criteria that accurately detects ME/CFS and distinguishes it from other disorders.  This will help target treatments appropriately and avoid diagnostic labels that are potentially harmful.

http://www.ncbi.nlm.nih.gov/pubmed/24182640

 

Several studies have used blood gene expression in an attempt to identify biomarkers that delineate ME/CFS subtypes.  Jonathan Kerr has spearheaded many of these studies and in September published a paper in the Journal of Clinical Pathology titled, “Use of single-nucleotide polymorphisms (SNPs) to distinguish gene expression subtypes of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)”.(2) Kerr had previously identified 8 ME/CFS subtypes with different gene expression profiles (measuring the message RNA produced from genes.)  In this study, he used the DNA sequence information of these genes to determine if it could be used to identify the same 8 ME/CFS subtypes and distinguish from people with depression and healthy controls.  Kerr wanted to use the DNA genetic sequence rather than the message RNA because message RNA deteriorates quickly, making it challenging to use as a diagnostic biomarker.  Kerr found that only some of the 8 ME/CFS subtypes were identified using the DNA genetic sequence data but that this method was insufficient to reproducibly differentiate subtypes.  There are several reasons why this method did not delineate ME/CFS subtypes including small sample size and sample heterogeneity.  Nonetheless, these results help inform future studies using genomic technologies to develop objective biomarkers for ME/CFS.

http://www.ncbi.nlm.nih.gov/pubmed/25240059

 

Ekua Brenu and a team from Australia published an interesting paper about the potential for a particular type of biomarker  in PLOS ONE this September titled, “High-throughput sequencing of plasma microRNA in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis”.(3)  What makes this study interesting is the use of plasma – the clear liquid component of blood that is relatively easy and noninvasive to collect to detect microRNA.  Unlike message RNA (discussed in the above study) microRNA are a more readily measured because they are short and can evade destruction, making it intriguing for use as a biomarker.  MicroRNAs use their short sequence structure to regulate gene expression (they do not code for proteins as message RNAs do.)  Brenu and team identified 19 microRNAs that were differentially expressed in the plasma of ME/CFS patients compared to controls.  They confirmed significant up-regulation (increased expression) of three of these microRNAs. More ME/CFS patient samples need to be tested – as do diseases with similar symptoms – to determine the diagnostic utility of these plasma biomarkers for ME/CFS.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0102783

 

 

(1) Mariman A, Delesie L, Tobback E, Hanoulle I, Sermijn E, Vermeir P, Pevernagie D, Vogelaers D. Undiagnosed and comorbid disorders in patients with presumed chronic fatigue syndrome. J Psychosom Res. 2013 Nov;75(5):491-6.

(2) Shimosako N, Kerr JR. Use of single-nucleotide polymorphisms (SNPs) to distinguish gene expression subtypes of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). J Clin Pathol. 2014 Sep 19.

(3) Brenu EW, Ashton KJ, Batovska J, Staines DR, Marshall-Gradisnik SM. High-Throughput Sequencing of Plasma MicroRNA in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. PLoS One. 2014 Sep 19;9(9):e102783.

Article in APA Monitor Reaches 130,000 Professionals in the Field of Psychology, Seeks to Dispel Myths about CFS

October 23, 2014

APA_StoryThe Monitor on Psychology is a well-respected publication of the American Psychological Association (APA) – the largest scientific and professional organization representing psychology in the United States. According to its website, “APA is the world’s largest association of psychologists, with nearly 130,000 researchers, educators, clinicians, consultants and students as members.”

http://www.apa.org/about/index.aspx

In May of this year a freelance reporter, Kirsten Weir, contacted the Solve ME/CFS Initiative (SMCI) concerning an article she was writing about Chronic Fatigue Syndrome for the Monitor. She was hoping we could get her in touch with a patient that could answer a few short questions about living with the disease.

Understanding that far too many ME/CF patients have been adversely affected by the painful practice of dismissing ME/CFS as a psychological disorder vs treating it as the debilitating physiological disease that it is, we asked her to tell us more about the goal of her article. In her reply she told us, “The goal of the article is to update readers on the latest thinking behind ME/CFS — to underscore that it has biological roots and is not a psychological condition. To look at what the science says about possible causes and best approaches to managing the disease. I’ve spoken to several researchers who noted that patients are really frustrated by the myths and misunderstandings associated with the disease, and I’m aiming to find some patients who can speak to that issue.”

With that understanding, we reached out to several patients to inquire as to their willingness and availability to talk to Ms. Weir for her article. Anna Zapp and Carollynn Bartosh both agreed to be interviewed via email, thrilled that the interview pointed to the American Psychological Association acknowledging bio-organic roots of ME/CFS. Bartosh remarked, “It’s been a very long time in coming, and I am honored to be asked for an interview as a patient under the circumstances.”

She went on to tell Weir, “I think my fellow patients would want to be sure that practicing psychologists are aware of the fight that happened over the American Psychiatric Association including CFS as a somatoform disorder in the DSM-V. In 2010 all of the leading clinician-researchers and advocacy organizations from around the world, not just the US, as well as many patients such as me wrote letters pointing out the more than 2,000 studies published by that date into the bio-organic roots of the illness. Including CFS as they did seemed to ignore the science while offering no improvement in care for patients so diagnosed. I’m certain that many patients have been, are, and will be quite hurt by that inclusion, even by well-meaning psychologists.”

Earlier this month the October issue of the APA Monitor was released and Weir’s article appears on page 67-71. You can read the full text here: http://www.apamonitor-digital.org/apamonitor/201410#pg70 

This is a story that is long overdue. As the largest association of psychologists, the APA can and should play a role in dispelling disbelief that ME/CFS is a serious, debilitating illness. SMCI is happy to have helped this article come to fruition, but there is still work to be done. Old habits and attitudes can take time to be torn down, as evidenced by the quote pulled out at the top of page 69, which seems completely out of context with the rest of the article.APA_CallOut
Upon seeing the article, Bartosh, who is quoted in the piece, shared with us her preferred ‘call-out quote’ as the take-away from this article:

“…the take-home is simple: It’s time to give up the idea that CFS is a psychosomatic disease.”
-Marcie Zinn, PhD, neuropsychologist and research consultant at Stanford University

And we agree. Treating ME/CFS as a psychosomatic disorder is a practice that simply must end. It is our hope that this article in the hands of more than 130,000 professionals that are in a position to incite that change will begin to move us all forward.

 

P2P Draft Evidence Review

October 20, 2014

Can a Process that is Inappropriate for ME/CFS Inform the Research Path Forward?P2P_title

Summary Overview

As a research focused organization, the Solve ME/CFS Initiative (SMCI) understands the impact a program like the Pathway to Prevention workshop (P2P) can have on the research landscape.  Because of its importance, we have utilized the collective brainpower of our Research Advisory Council, led by our scientific director, Suzanne D Vernon, PhD, to perform a careful review and response to the Evidence-Based Practice Centers’ draft evidence-based review for ME/CFS. (Read our official submission HERE)  We have concluded that:

  • It confirms what we and others have suspected: the Pathway to Prevention (P2P) process is not appropriate for ME/CFS.  Among other reasons, it uses comparative effectiveness methodology to review the evidence to inform healthcare; in the case of ME/CFS the evidence base is much too slim for this method to be effective.
  • The P2P systematic review of the ME/CFS evidence base illustrates the lack of rigor in crucial research design elements and the absence of high quality clinical trial data. The review shines a bright light on the need for well-designed, adequately powered studies to identify diagnostic gold standards and safe and effective treatments.

Furthermore, it is important to note that the vast majority of ME/CFS research studies were omitted from this evidence review due to their inability to meet the rigorous standards required for inclusion. Of all of ME/CFS research studies funded by the NIH since 1991 ($191.5 million spent), less than 1% of those studies were included. So, not only has the NIH egregiously underfunded this illness (based on prevalence), but the research NIH has funded has not contributed to an evidence base that has moved the science forward.

This review substantiates the negative cycle currently in play with ME/CFS research – Because there is little funding, there is little research. And because there is little research, there is little evidence to prompt additional funding. But the P2P process may be what is needed to break through that negative cycle and move us to a day when ME/CFS is appropriately funded. It’s existence demonstrates that there is increasing recognition of the clinically devastating nature of ME/CFS and recognition of the disease as an urgent area of future study.

 

Background – How did we get here?
To review what has led up to this NIH P2P workshop for ME/CFS:

  • The 2011 NIH State of the Knowledge Workshop for ME/CFS concluded that there were problems with definitions, gaps in study design, and a lack of studies on co-morbid conditions, biomarkers, or genetics.
  • A year later, at the CFS Advisory Committee meeting, Dr. Sandra Kweder, FDA Deputy Director of the Office of New Drugs tells us there are so few applications to the FDA because there is no accepted ME/CFS definition, no accepted method for measuring how patients feel or function and no accepted biomarker to provide a simple, quantitative measure of disease presence or activity.
  • In 2013, ME/CFS is the first “patient-focused drug development” workshop held by the FDA. The outcome of that meeting, as expressed in the Voice of the Patient report, is that ME/CFS is a serious disease with significant unmet medical need that requires comparative effectiveness research to generate the evidence to assess the effectiveness, benefits, and harms of different treatment options.
  • In 2014, Dr. Susan Maier, Deputy Director of the Office of Research on Women’s Health at the NIH, who oversees ME/CFS research at NIH, successfully garnered a Pathways to Prevention workshop titled, “Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome”.

For much of this year, the Solve ME/CFS Initiative (SMCI), as well as many other individual advocates and patient groups, has been talking about the National Institutes of Health (NIH) Pathways to Prevention (P2P) for ME/CFS workshop. In April, we first reported on the possibility of the P2P workshop, then in the approval process. Once it was approved, the NIH worked with the Agency for Healthcare Research and Quality (AHRQ) and their Evidence-Based Practice Centers to conduct this evidence-based review.

In June, SMCI expressed concerns that the search criteria used for the evidence-based literature review would bias the review toward studies on CBT and GET. On Sept. 22nd AHRQ published the draft systematic evidence review on the Diagnosis and Treatment of ME/CFS for comment.  Several members of our Research Advisory Council together with Suzanne D. Vernon, PhD reviewed the draft and have provided peer review comment directly to AHRQ. SMCI and our research advisors believe that this systematic review has identified important and significant gaps in research that have contributed to the dearth of evidence needed to diagnosis and treat ME/CFS. Indeed, it is almost all “gap” and almost no substance.

 

Dearth of Evidence
From 1991 to 2014, NIH Research Portfolio Online Reporting Tools (RePORT) indicates a total of $191.5 million has been awarded to investigators to directly study ME/CFS or conduct research relevant to ME/CFS.  Spending for other medically unexplained disorders that often occur with ME/CFS, like Fibromyalgia and irritable bowel syndrome (IBS), is about $400 million for each in the same time frame. This is in contrast to multiple sclerosis (MS) – a condition with objective diagnostic biomarkers and treatments – where NIH spending in the same period exceeds $4 billion.

Further, a search of PubMed.gov for anything published on ME/CFS finds 5,450 peer reviewed scientific articles; there are 8,000 articles for Fibromyalgia and 9,000 for IBS.  This is in contrast to the 55,500 articles found in PubMed that make up the MS evidence-base.  There is a direct correlation between funding levels and the breadth of the published evidence-base.

 

The One Percentexamine
Now, the NIH P2P draft systematic review is out. All told there were 5,901 papers considered by the Evidence-Based Practice Center in the comparative effectiveness systematic review. In the end, less than 1% of these 5,901 paper met criteria for inclusion in the systematic review process. Why? 

  • Because comparative effectiveness systematic reviews are based on evidence-based facts. The P2P uses a rigorous process to empirically identify methodological and scientific weaknesses in each published paper.
  • The investigators conducting these evidence-based reviews are experts in this review process and come to the task at hand without any bias or preconceived notion about the topic they are reviewing.
  • The procedures for these reviews are possible because there are standard methods and procedures in place for conducting research; especially human research intended to impact clinical care. They systematically reviewed the ME/CFS papers using specific research design criteria known as PICOTS – Populations, Interventions, Comparators, Outcomes, Timing, and Setting.

While the draft comparative effectiveness review on the Diagnosis and Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) may be a hard pill to swallow for patients and for the many ME/CFS scientists whose research studies were excluded from this review, it identifies vast research gaps and provides important information needed to chart the way forward.

The rationale for evidence-based reports makes sense:

  • “Systematic reviews are the building blocks underlying evidence-based practice; they focus attention on the strength and limits of evidence from research studies about the effectiveness and safety of a clinical intervention. In the context of developing recommendations for practice, systematic reviews can help clarify whether assertions about the value of the intervention are based on strong evidence from clinical studies.”

And …

  • “This review is not intended to address the question of etiology nor underlying factors that lead to the onset or perpetuation of ME/CFS but rather to focus on the diagnosis and treatment of this syndrome.”

With this is mind, the review identified only 64 studies that met evidence-based criteria to address the key questions; 1) ME/CFS diagnosis and 2) ME/CFS treatment. For a diagnosis study to be included it had to discriminate ME/CFS patients from healthy controls and (ideally) from other diseases with similar symptoms and if the study used biochemical marker it had to be in the context of treatment versus etiology. Twenty-eight studies addressed various aspects of diagnosis. Most of the studies pertaining to diagnosis were rated as fair quality (on a scale of “good”, “fair”, “poor”). These diagnosis studies showed that certain measures that assess function are able to distinguish between ME/CFS and healthy people reasonably well. The studies were rated “fair” because they were small and diseases similar to ME/CFS were seldom included. The lack of a gold standard for diagnosis of ME/CFS limits how broadly the limited evidence base can be generalized to the ME/CFS community as a whole. The review notes that clinical experts identify post-exertional malaise (PEM) as a cardinal feature of ME/CFS yet current methods of testing, comparing, and monitoring PEM are lacking.

 

So what few studies WERE included and do they shed light?
There were 36 randomized clinical trial studies for ME/CFS treatment; 9 for medications, 14 for counseling or behavioral therapies, 7 for complementary and alternative medicine, 6 for exercise, and 5 comparing therapies:

  • Seven were rated as “good-quality” trials: 5 counseling and behavioral therapies, 2 complementary and alternative medicine therapies
  • 24 were rated “fair-quality”
  • 5 were “poor-quality”
  • The phase III Ampligen trial was rated “fair to good-quality” and it was the only medication trial to get this rating; all other medication trials were fair and poor-quality.
  • The PACE trial was rated as “good-quality” for both counseling and behavioral and for exercise intervention but the strength of the evidence was moderate to low for cognitive behavioral therapy (CBT) and graded exercise therapy (GET).
  • The other 5 studies that used an exercise intervention were “fair-quality” and overall, exercise intervention trials showed moderate strength effect in function and well being and low-strength effect on fatigue. Importantly, the high rate of refusal in one study may indicate that patients are concerned the possible adverse effects of repeat exercise testing (e.g., the first exercise test may have caused PEM prohibiting the ability to do the second test). This deserves further study and consideration as a possible outcome.

All of the clinical trials were compromised because of small and heterogeneous patient populations, differences in inclusion criteria – including use of different case definitions, and measuring different outcomes (e.g., fatigue, function, etc). This is exactly what Dr. Peter Rowe reported at the 2013 FDA workshop on Development of Safe and Effective Drug Therapies for CFS and ME (http://www.tvworldwide.com/events/fda/130425/). Measuring the effect of an intervention was likely diminished by the above factors. Ways to better detect the effect of an intervention are to measure certain clinical features present before treatment starts compared to after treatment, such as severity and frequency of specific symptoms like brain fog or PEM. This is called subgroup analysis; not one of the intervention studies did a subgroup analysis.

 

Is there a Silver Lining?
Despite the lack of an evidence-base, this systematic review shines a light on important areas that must be pursued to build the ME/CFS comparative effectiveness research evidence base:

1.  Determine diagnostic criteria that can be used as the gold standard for ME/CFS diagnosis.

  • We note that the work of determining ME/CFS diagnostic criteria is currently underway at the Institute of Medicine (IOM)

2. Test gold standard diagnostic criteria in other populations with diseases similar to ME/CFS where diagnostic uncertainty exists so that the treatment is specific to ME/CFS vs another similar condition.

  • Determine the outcomes that are clinically meaningful and ensure standardized assessment so that the effect of interventions can be measured
  • Post-exertional malaise is a cardinal feature of ME/CFS and potentially one of the most important outcome measures; research should be conducted to determine what it is and how to measure it

3. The biomarker research and clinical trials conducted to date provide clues to the possible causes of ME/CFS and can serve as “disease models” for further study of ME/CFS pathophysiology

  • All basic and intervention research should use methodological standards to  ensure that it meaningfully contributes to the ME/CFS evidence-base

This analysis illustrates the lack of coherence in the field and the absence of high quality clinical trial data.  NIH, through the P2P workshop, set out to identify gaps in the research, and they found more gaps than substance. Yet the existence of this effort shows increased recognition that ME/CFS is an urgent area of future study and clearly implies that more resources need to be focused on well designed, adequately powered studies. We believe that it is NIH’s responsibility to address their own finding.

 

What Happens Now?
The P2P panel will review this evidence-based report, including the comments and feedback now being submitted, in advance of the meeting that will take place on December 9 & 10, 2014. At that two-day workshop in Washington DC, the P2P panel will hear from the expert speakers and be able to ask clarifying questions in a town-hall-like Q&A that will take place after each session.

Experts in ME/CFS are being invited to address each agenda item. They will speak to their personal experience and expertise as a patient, caregiver, researcher, etc. The slate of speakers has not yet been released.

The day after the P2P meeting, the P2P Panel will write a draft report which will be published and the public will have time for comment on the final report, just as we are now commenting on the draft evidence review. The comment period is 30 days; the deadline should be around January 12th, 2015. Once the comment period closes, the report will be finalized and NIH will organize a plan to disseminate it widely.

The goal, as we understand it, is a report that contains a set of recommendations based on the totality of the evidence, in the hopes of having said recommendations carried out by Federal partners in 2015. These recommendations are aimed at improving the nature of the research being conducted in ME/CFS. The Solve ME/CFS Initiative will pass along additional information as it is received and when the opportunity for public comment is scheduled, we will report that and share the means by which you can participate.

For far too long, ME/CFS has been underfunded, misunderstood, and even disbelieved. Our community has been pushing a very heavy fly-wheel aimed at increasing understanding, acceptance and progress toward treatments and cure. Now there is federal activity, all aimed at moving the needle for ME/CFS – FDA Voice of the Patient, IOM activity on creating clean diagnostic tools and other much-needed tasks, and this P2P. What this evidence based report shows is that the status quo must change. We hope P2P will illuminate the clear need for more funding, increased research activity and faster progress.

 

What Can You Do?
Registration is now open for the Pathways to Prevention workshop for Advancing the Research on ME/CFS taking place on December 9 & 10. You can register to attend live or participate via webcast. It is our hope that many stakeholders will participate in this process in order to ensure the patients have a strong presence and a voice.

To register to attend live click HERE 

To register for the webcast click HERE

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Many other patients and advocates are also weighing in on the P2P and the draft evidence review. Read what just a few others are saying:

Medscape Medical News – a log in is required to view the article, but it is free and anyone can create an account.

Jenny Spotila, Mary Dimmock & others via Occupy  CFS

Cort Johnson via HealthRising

 

P2P Releases Systematic Evidence Review

October 1, 2014

P2POn Sept. 22nd, the Association for Health Research and Quality (AHRQ) released the draft systematic evidence review on the Diagnosis and Treatment of ME/CFS NIH requested the literature review for the purposes of the Pathways to Prevention (P2P) Workshop, and the Agency for Healthcare Research and Quality contracted with the Oregon Health & Sciences University to perform it. 

We first wrote about the P2P workshop program in April (http://solvecfs.org/pathways-to-prevention-for-mecfs/) and have been working with the advocacy community since then to stay abreast of the P2P process and assess its impact on ME/CFS. The NIH Office of Disease Prevention Pathway to Prevention (P2P) program approved the ME/CFS workshop earlier this summer and in June SMCI expressed its concerns about the protocol for the evidence-based literature review. (http://solvecfs.org/solve-mecfs-initiative-smci-position-on-p2p/)  

The draft report is an extensive review on ME/CFS literature covering diagnosis and treatment and is but one element of the NIH Pathways to Prevention (P2P) process. On December 9 & 10, the Pathways to Prevention workshop for Advancing the Research on ME/CFS will take place in Washington, D.C. and the panel will hear expert testimony at that time. Also, during the workshop stakeholders/patients will have the opportunity to participate in the discussion both in person and online by asking questions or making comments via microphones or computer; webcast viewers can type in comments and questions in a comment box on the webpage. There is a total of 3.5 hours of “Discussion” time noted on the draft agenda, where public input will be addressed. Interested individuals may register to attend live or participate via webcast.  It is our hope that many stakeholders will participate in this process in order to ensure the patients have a strong presence and a voice.

Learn more about how to register for the December 9 & 10 P2P Workshop in this earlier post: http://solvecfs.org/p2p-workshop-registration-now-open/

Comments on the draft systematic evidence review can be made until October 20 – Learn more about that process HERE.

scrutinizeThe Solve ME/CFS Initiative is in the process of reviewing the draft report more thoroughly with members of its Research Advisory Council in order to provide the most informed comments prior to the deadline of October 20, 2014.

We will keep you informed and share our thorough review once completed.