The prestigious US scientific journal Annals of Internal Medicine has just published a position paper – Advancing the research on ME/CFS – which summarizes the conclusions of the ‘Pathways to Prevention’ Workshop organized and co-sponsored by the National Institutes of Health (NIH).
The workshop took place over two days in December 2014, and was informed by a systematic review (also published in Annals of Internal Medicine in the same issue) of the scientific evidence on ME/CFS conducted by the Agency for Healthcare Research and Quality. It included expert presentations and public comments, and was attended by a wide range of experts who had been invited to discuss and weigh the evidence. The final document was produced by an independent panel, with the aim of identifying research gaps and future research priorities.
In its introduction, the position paper makes clear that ME/CFS “is a chronic, complex, multifaceted condition characterized by extreme fatigue and other symptoms, including pain, impaired memory, sleep disturbance, and insomnia that are not improved by rest”. It points out that one million people are affected in the USA, mostly women; that the estimated economic burden is between $2 and $7 billion in the US alone; and that the condition has a tremendous effect at the individual, family, and societal level. Importantly, it states that “Both society and the medical profession have contributed to the disrespect and rejection experienced by patients with ME/CFS. They are often treated with skepticism, uncertainty, and apprehension and labeled as deconditioned or having a primary psychological disorder…Overall, the debilitating effects can cause financial instability due to the consequences of the illness (such as the loss of employment or a home).”
The report identifies many of the difficulties that have bedeviled research into ME/CFS in the past. These include the lack of a specific and sensitive diagnostic test, and disagreements over clearly defined ‘gold standard’ criteria for diagnosis that have “hampered research on pathogenesis, treatment, and conceptualization of ME/CFS as a distinct entity.” Partly as a consequence, the research base is weak compared with other chronic illnesses, and very few disease-specific clinical trials have been conducted – something ME Research UK has often pointed out (see ME/CFS Research: What do patients want? Why isn’t it happening?).
The authors’ assessment of the role of psychological therapies is particularly interesting. They point out that ME/CFS is not a primary psychological disease, although like other chronic illnesses it may have psychological repercussions, such as depression. Accordingly, existing interventions examining counseling and behaviour therapies or graded exercise therapy “are not a primary treatment strategy and should be used only as a component of multimodal therapy”.
The report goes on to discuss ways to encourage research and help the development of treatments. As several symptoms of ME/CFS substantially overlap with other pathological diseases (such as fibromyalgia and chronic pain or inflammatory conditions), it recommends that future studies should distinguish between ME/CFS alone, ME/CFS with comorbid conditions, and other diseases. Current research has neglected many of the biological factors underlying disease onset and progression, so research priorities should shift to include basic science and mechanistic work. In the authors’ view, questions that need to be answered include:
- What is the pathogenesis of ME/CFS?
- What are the roles of virologic mechanisms, especially herpes viruses?
- Does mononucleosis lead to ME/CFS in adolescents?
- What are the roles of other pathogenic agents?
- Is this a genetic disease? Is there a gene–environment interaction?
- Is it a spectrum disease?
- Are different pathways responsible for different symptoms?
Overall, the report recommends “bench-to-bedside research”, in which developing biomarkers and diagnostic tests should be a priority; the creation of opportunities for junior and new investigators; and the setting-up of an international research network to clarify the case definition in order that a consensus can be reached. In particular, given the relatively small number of researchers in the field and the finite resources available, it points up the need for partnerships across institutions to advance the research. As well as the seed-corn projects and investigator-initiated studies funded by organizations like ME Research UK (see our Overview of Biomedical Research), it is important to encourage larger national funding agencies to fund or co-fund research “to promote diversity in the pipeline”. In addition, the report considers the specific training and education of healthcare professionals to be vital; “We believe that [ME/CFS] is a distinct disease that requires a multidisciplinary care team (such as physicians, nurses, case managers, social workers, and psychologists)…Therefore, a properly trained workforce is critical”.
In their conclusion, the authors express the hope that their work has “dignified ME/CFS and affected persons while providing expert guidance to the NIH and the broader research community”. Certainly, as a concise summary of the current status of ME/CFS research and related issues, the report is a positive development, and its statement of intent is welcome. The proof of the pudding will come in the eating, of course, and we hope that the NIH Office of Disease Prevention will convene another expert panel in 5 years time, as recommended, to monitor the progress that has been made.
National Institutes of Health Pathways to Prevention workshop: advancing the research on myalgic encephalomyelitis/chronic fatigue syndrome. Position paper. Green CR, et al. Annals of Internal Medicine, 2015; 162: 860-865. Read more (full text).
Treatment of myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review for a National Institutes of Health Pathways to Prevention workshop. Beth Smith ME, et al. Annals of Internal Medicine, 2015; 162: 841-850. Read more (full text)