BHC prepared the following response the NIH Request For Information (RFI) regarding the future of ME/CFS research
Sixteen different centers within the NIH sought input concerning new research strategies for ME/CFS. They asked patients and advocates to tell the Trans-NIH Working Group on ME/CFS what kind of opportunities they see for studying the illness, what technologies and tests might be utilized in studying it, and the challenges ME/CFS research faces today.
The Bateman Horne Center prepared the following submission.
Formerly the Fatigue Consultation Clinic (FCC) and the Organization for Fatigue & Fibromyalgia Education & Research (OFFER), the Bateman Horne Center of Excellence (BHC), was formed in 2015 as a 501(c)3 nonprofit organization.
The following perspectives as they relate to the Working Group’s planning efforts on the below issues are being submitted by BHC leadership, Lucinda Bateman, MD, Founder and Chief Medical Officer and Suzanne D. Vernon, PhD, BHC Research Liaison. Dr. Bateman served on the IOM Committee that created the evidence-based clinical diagnostic criteria for MECFS and feels strongly that the report should serve as a foundation for our approach to both clinical and basic research. The needs in this field are many and are clearly outlined in the IOM Report. These needs translate to rich research opportunities.
Emerging needs and opportunities that should be considered as new ME/CFS research strategies are developed
- Determine how to objectively measure the diagnostic criteria recommended by the IOM, since they represent the core underlying physiology. Get these methods and measures into the hands of primary care physicians. Use these objectively defined diagnostic criteria as outcome measures to interest pharma in pursuing clinical trials for ME/CFS.
Challenges or barriers to progress in research on ME/CFS
- Catch 22 – not enough funding dollars and therefore not enough scientists. Without enough funding for scientists, the chance of discovering biomarkers decreases.
- ME/CFS biomarkers may be evasive because scientists aren’t studying the “same” ME/CFS; some are looking for biomarkers in sudden onset, others in post-infection ME/CFS, others in severe ME/CFS and others cast a broad net and study all ME/CFS patients at once. Biomarker research has been hampered because we have not consistently studied gold standard patients – that is, patients that have been rigorously evaluated and followed by clinical experts.
- There are not enough clinical collaborators to make the clinically evaluated, “gold standard” patients available to research. There must be parallel efforts to fund research investigators and to increase expertise in clinical diagnosis.
Gaps and opportunities across the research continuum from basic through clinical studies
- In her 2012 presentation to DHHS and the CFS Advisory Committee Dr. Sandra Kweder said, “For progress to be made in ME/CFS we must define the core signs, symptoms and decrements in specific functioning”. The core signs, symptoms and decrements in specific functioning have been defined in the 2015 Redefining ME/CFS IOM report and are summarized here:
- Reduced functional capabilities on a global scale– -physical, cognitive, etc. This alone should be easily approachable with what is already known– -orthostatic intolerance, possible mitochondrial or cellular dysfunction, altered immunity and possible chronic viral reactivation, etc. Every study should be taking this into account.
- Post exertional consequences that parallel illness severity and the degree of effort/activity. Every study should involve measurements before, during and after an activity/exertion stressor, and should track at least to resolution of symptoms in all participants.
- Sleep is very abnormal, but variable across the population, resulting in unrefreshing sleep. Current methods of sleep assessment have been inadequate because light disturbed sleep is considered “sleep artifact” on polysomnography. New innovative ways of assessing sleep disturbance over longer period of time and in the home should be implemented.
- Orthostatic intolerance is an often overlooked aspect of illness that can be easily measured by a bedside 10 min stand/lean test of blood pressure, pulse and symptoms. This alone could easily subset groups of patients to target for research and clinical trials.
- Dysautonomia, POTS, orthostatic hypotension, etc, already have a significant base of research and a growing group of clinical specialists and we should learn from their experiences and leverage this knowledge to ME/CFS
- Cognitive impairment. While it is often difficult to measure cognitive impairment, there is an ample evidence base to investigate altered cerebral perfusion from chronic dysautonomia and neuroimmune illness altering brain tissue directly. Innovative cognitive testing should be implemented in research such as that used in TBI. For example, a 5-minute cognitive testing module can be implemented before and after a 10 minute lean test.
- Other important areas of exploration:
- Centrally mediated pain amplification, hyperalgesia, central sensitivity. There is a rich literature in fibromyalgia that should be considered in all ME/CFS patients who meet FM criteria, which are symptom based and easy to apply to this population.
- Neuroendocrine function. There are very few high quality studies that directly assess hypothalamic and pituitary function, yet the presentation of illness and the known science clearly suggests “downstream” endocrine issues– -low normal cortisol, a high rate of thyroid disease, significantly altered gynecologic health, low testosterone in male subjects, etc.
- Immune dysfunction. Clear evidence but needs larger sample sizes and more robust assays to validate as diagnostic and treatment biomarkers.
- Autoimmunity. There is growing evidence of autoimmunity involving the central and peripheral nervous system, high prevalence of thyroid disease, high rate of celiac disease, B12 deficiency, etc.
Research in ME/CFS has been lean and under-funded for several reasons, including the shortage of accurately diagnosed patients available for research studies. The Bateman Horne Center – a clinic specializing in ME/CFS, with a large number of patients who have been carefully and accurately diagnosed and continue to be treated effectively- is committed to bringing ME/CFS into the mainstream of clinical and medical science. Identifying biomarkers is a critical first step. BHC is a unique example of an independent non-profit integrative health center where medical care informs research, and research informs medical care. Efforts should be made to encourage the development of additional centers of excellence for ME/CFS in order to create collaborations between well-qualified patients and research partners. NIH grantees should be required to include clinical collaborators as a part of their grant submission.