Thoughts about the IACFS/ME Conference, March 20-23, 2014

by Charmian Proskauer
President, Massachusetts CFIDS/ME & FM Association

In March, thanks to your support, I travelled to San Francisco to attend the scientific conference sponsored by the International Association for CFS/ME. It was an opportunity to learn about the latest in ME/CFS research and meet with researchers, clinicians, and patient/advocates. One activity which I enjoyed was meeting with representatives from other patient organizations to get to know one another better and begin discussions about how we can all collaborate more effectively. We hope to continue these conversations over the next several months.

Disclaimer: These are thoughts and observations from one lay attendee. Although I checked my statements with my notes, there are undoubtedly oversimplifications, misstatements and misunderstandings, and for these I apologize.

Scope. The conference was truly international in scope with 13 countries represented, and  a lot of information was packed into 3½ days, including 40 papers, over 75 posters, and a variety of workshops and breakout sessions. Topics covered included Virology, Immunology, Treatments and Clinical Practice, Case Definitions, Exercise (Provocation) Studies, Public Health, Pediatric ME/CFS, and Brain Research. Surprisingly, there was no session on mitochondrial abnormalities.

Old blood and new blood. Many of our long-time researchers, familiar names and faces all, presented new work. It is amazing and wonderful that so many have been committed to this work and to ME/CFS patients for so many years. A number of young investigators also presented papers, all from a pure research perspective. Although this was very heartening to see, with one exception there was a noticeable lack of young clinicians, either as presenters or attendees (although perhaps they were there and just did not identify themselves). We need both new researchers and new clinicians, and there is still an appalling lack of interest in teaching ME/CFS in the medical school curriculum, as discussed in a lunchtime breakout session.

Importance of private funding. What was most striking from this meeting was the importance of private funding and the general lack of funding by governments. Private funding from wealthy individuals with a personal interest in the illness is floating more than a few research initiatives and hospital-based programs, as well as providing seed money for new areas of research. A few new academic centers have been established in the last 2-3 years (Southeast Nova University, Griffith University in Australia, Stanford) and researchers there are producing encouraging research results. Most have long waiting lists (years) for new patients, however.

Biobanks and "Big Data." As noted by Dr. Komaroff in his conference summary (see link below), several large "biobanks" stored biological samples from well-characterized patients with associated patient data have been established in the last few years and are now starting to release preliminary results of analysis of the data. Complex statistical algorithms are applied to such "big data" and are providing the beginnings of "evidence-based" findings. For example, the Chronic Fatigue Initiative researchers have used their data (from 200 patients and 200 well-matched controls) to explore the frequency and type of other conditions associated with ME/CFS, as well as which ME/CFS symptoms tend to cluster together, what treatments patients find helpful, and more specific questions such as allergy-related immune signatures and how those relate to the duration of illness in CFS. Over time the questions will become more specific and even more interesting.

Were any of the first results coming out of these studies surprising? It was sobering to see unequivocal confirmation that ME/CFS patients suffer from so many symptoms and "co-morbid" conditions, the most common being fibromyalgia, anxiety/depression (higher in long-term patients), hypothyroidism and sleep disorders. The study also shows incidence of cancers four times the rate in the general population. It will also be interesting to see if the CDC's multi-site study confirms the symptom clusters found in the CFI analysis, and if these clusters represent true "sub-groups" that can be defined by unique patterns of bio-markers.

There is also the exciting opportunity to use the existing data to answer new questions in the future. One researcher was collecting questions from the audience after his presentation, saying, "That's an interesting question. We'll take a look at that!" These tools (biobank and data mining) have the potential to greatly accelerate the pace of research.

One disappointing aspect of the biobanks is the relative uniformity of the patient population which is represented. Since most of the patients for the biobanks were recruited from the big academic and clinical centers, they are a fairly homogeneous group – primarily white, middle-aged well-educated women who have had the illness for many years – the kind of motivated patients who will find their way to these tertiary care centers. This group does not represent the actual distribution of this illness within /economic and ethnic groups, and we see the illness in all groups around the world (for example, among Maori and Moriori in New Zealand). So we need to be cautious with regard to this skewing of demographics and aware of a possible skewing of results based on data collected on patients from a relatively homogeneous demographic group. Most especially we need to guard against the perception that ME/CFS is an illness found primarily in white, middle-aged, well educated, American (or British) women. Eventually we need to find ways to reach other demographic groups to confirm the initial results in diagnosis, treatment and research.

The "3 year" mark. Dr. Susan Levine presented work on allergy-related immune profiles that confirmed the importance of the "3 year" mark that was first noted by Dr. Lipkin in his talk for one of the CDC PCOCA calls. Certain allergy-related and inflammatory molecules have different profiles in patients with short duration of illness (less than 3 years) vs. those with longer illness duration. Although it is not a sudden shift at 3 years' illness duration, it seems to be significant. This suggests that certain treatments may be more effective in the early stages of the illness (one more reason why we need to greatly shorten the time needed to get an accurate diagnosis!) .

Case definitions. Dr. Lenny Jason noted that case definitions need to go beyond lists of symptoms and become more precise; for example, the frequency and severity of each symptom should be scored and cutoffs established for a diagnosis, rather than just noting the mere "presence" of the symptom. Otherwise it is too hard to compare apples to apples, at least for research. Using data mining techniques, he showed that a case definition requiring fewer "targeted and fundamental" symptoms resulted in better sensitivity, specific and accuracy in selecting cases, while case definitions requiring more symptoms tended to increase the number of patients with psychiatric conditions in the sample. He presented examples of the kind of scales that could be used. (Note: Dr. Jason is not on the Institute of Medicine Committee, but Drs. Klimas, Bateman, Chu, Keller, Lerner, and Rowe are, and were present. Dr. Jason will be presenting "Diagnostic and Criterion Issues for ME/CFS" to the IOM on May 5, 2014.)

Exercise studies. Oddly, there were no papers studying energy metabolism directly or mitochondrial involvement/research, only the by-now-well-known exercise physiology studies. There was an important paper by Betsy Keller which showed that a one-day test does not identify functional impairment in 20% of ME/CFS patients, whereas a 2 day test identifies functional impairment in 98%. Subjects had been diagnosed with ME/CFS by a "physician experienced in the diagnosis of ME/CFS." Furthermore, other studies showed that both submaximal workload prediction and standard validated VO2 prediction equations were also poor predictors of functional impairment in ME/CFS. These results clearly show the superiority of a two-day CPET exercise test over a one-day test or any other standard measure.

The revised Primer. The 2014 edition of ME/CFS: Primer for Clinical Practitioners was introduced (and available for purchase) at the conference. (Note: Our Association's past president Dr. Alan Gurwitt, now serving as chair of our Medical Advisory Committee, is one of the authors of the primer.) The primer contains more recent work on the pathophysiology of the illness, as well as an expanded section on the severely ill. One interesting discussion concerned the authors' statement "...ME/CFS itself is not known to be fatal." Dr. Lily Chu presented a persuasive case for questioning this statement, but also noted that more concrete evidence, such as recording ME/CFS as cause of death on death certificates, will be needed to back up the conviction of patients and families that ME/CFS can be at least a contributing cause of death (where "suicide" or "heart disease" or "cancer" might be listed as the official cause of death). This would be probably require an educational campaign to achieve, and certainly this idea deserves more attention. Note that Dr. Lenny Jason's mortality study (you can read more about it here) is another effort to address this question with harder evidence.

Another aspect which deserves more attention is how to most effectively distribute the revised Primer. The IACFS/ME seemed to take a passive "if you build it they will come" attitude the first time around, and even the link to the Primer on the IACFS/ME website is very hard to find. Certainly the original edition appears to have made only limited impact in general clinical practice, despite the efforts of individual patients to interest their doctors. We all, including the IACFS/ME, need to make a better effort to promote this valuable document. A spiral-bound printed copy of the 2014 edition is available for purchase ($20) and is also available for download (free, but donations are welcomed) from the IACFS/ME website (see links below). (Note: Our Association is offering the revised edition [download/print] free to our members and to Massachusetts health care providers, as we did for the original Primer. To request the link, please Contact Us.)

Convergence. Research from separate disciplines is converging onto common hypotheses (interactions of the brain and central nervous system, immune system, and the Hypothalamic-Pituitary-Adrenal axis). What's still missing is direct evidence of abnormalities in energy metabolism and mitochondria (indirect evidence for this comes from the exercise studies).

If you would like to read more details about the science that was presented, here are links to additional summaries/commentaries:

Links to the Revised Primer (2014 edition):