Specifically, HHS’ task order (aka charge) asked the IOM to:
- Conduct a study to identify the evidence for various diagnostic clinical criteria of ME/CFS using a process with stakeholder input, including practicing clinicians and patients;
- Develop evidence-based clinical diagnostic criteria for ME/CFS for use by clinicians, using a consensus-building methodology;
- Recommend whether new terminology for ME/CFS should be adopted;
- Develop an outreach strategy to disseminate the definition nationwide to health professionals. (IOM, 2015, p. 14)
However, this was not the only information the IOM committee received regarding its task. During the committee’s first public meeting, Deputy Assistant Secretary for Health, Dr. Nancy Lee (representing the study’s sponsors), briefed the committee in more detail. (Lee, Background and Charge to the Committee, IOM video, January 31, 2014.)
Specifically, she noted “for the purposes of this study, HHS uses “ME/CFS” to refer to conditions that include Myalgic Encephalomyelitis [ME], Chronic Fatigue Syndrome [CFS], Chronic Fatigue and Immune Dysfunction Syndrome, Neuro-Endocrine Immune Disorders, as well as other terminologies. These may be distinct disease entities, part of a spectrum, or a similar phenotypic response to a variety of external and internal assaults on the individual.” (Lee video, 1:52-2:23) (emphasis added).
According to Dr. Lee, “the Committee may well decide that different criteria are needed for different disease entities that fall under the broad umbrella of ME/CFS. This could help health care providers distinguish between these different conditions,” (5:40) adding that “[notably, there is a debate whether ME and CFS are distinct entities or different names for the same or similar syndromes.” (5:54).
In response to a question from one of the IOM panelists, Dr. Lee stated that the committee could recommend the use of existing definitions rather than come up with a new one. (14:00-15:05) This relates to the second stated task, “Develop evidence-based clinical diagnostic criteria for ME/CFS for use by clinicians, using a consensus-building methodology”. In other words, the committee was under no obligation to create new diagnostic criteria.
So why weren’t ME and CFS separated?
Despite this briefing, the committee abandoned ME and instead chose to focus on the chimera of ME/CFS with little rationale. Note there is no disease or syndrome associated with the nomenclature, ME/CFS. Whatever meaning is ascribed to ME/CFS is imposed on it by the reader and therefore varies tremendously.
The report gives short shrift to the history of ME and CFS (pp. 23-25). The importance of the Lake Tahoe, Nevada and Lyndonville, NY outbreaks in the mid-1980s and how they were greeted by the Centers of Disease Control (CDC) and the National Institutes of Health (NIH) are only touched on. The significance of the CDC’s cursory investigation of the Lake Tahoe outbreak (considered by experts an ME outbreak) and the subsequent critical disappearance of ME via the 1988 Holmes criteria for CFS is marginalized in the report.
There is a rather odd citation to a 1991 publication by Stephen Straus, lead investigator of CFS at the NIH at the time (p. 24; Straus, 1991). Straus, who essentially controlled CFS research at NIH, is on record stating “this syndrome...reflects an excessive risk for educated adult white women...[with] histories of unachievable ambition, poor coping skills, and somatic complaints” (Strauss, 1988) and “[t]hese patients are cerebral people who spend a lot of time considering their symptomatology.” (Hales, 1987). Once he dismissed EBV as a causal agent and his small treatment study using Acyclovir did not prove fruitful, Straus, while subsuming historic ME into CFS, increasingly spoke and wrote of CFS as a psychological disease, an attitude that remains highly prevalent at NIH to this day.
Surprisingly, despite this well-known history (which is not addressed in the report) there is a reference to “the relatively limited research efforts to study ME” (p. 24). It would have helped if the committee had mentioned the 1992 investigation of the Lake Tahoe cohort by non-governmental researchers in this part of the report. (Buchwald et al., 1992). As referenced on p. 132 in the section dealing with infections and ME/CFS, this Harvard-led research team found abnormal MRI brain scans, significant alterations in white blood cells counts and functioning, and signs of active infection with a recently discovered pathogen, HHV-6a. The illness was recognized as a chronic, immunologically mediated inflammatory process of the central nervous system. This contradicted the CDC’s studies on the same cohort.
The committee also failed to take into account how the NIH climate affected the research produced once CFS was coined and defined (and redefined via the 1994 Fukuda criteria). Funding opportunities were rare, small, and geared toward psycho-social research and the grant review panels tended to be made up of individuals biased against biomedical (especially immune or infection related) proposals. This resulted in the starvation of promising research and a rise in research on fatigue, co-morbid conditions, psychology, and general pain.
The committee apparently did not find sufficient evidence to support ME as a distinct diagnosis. But the panel’s methodology for review of the literature, no matter how robust and well-intentioned (pp. 17-20), is built on a skewed evidence base due to the above-referenced history. Of course there is little research on ME to be found. Most of it is dated and descriptive, and evidence of important symptoms, signs, and potential biomarkers is hidden in research labeled CFS or ME/CFS. Much literature on ME was missed, as the committee assumed reviewing papers published during the past 10 years would catch older research in the introduction and discussion sections. (p. 19, fn.). And, as the authors repeatedly note, use of various definitions and patient cohorts has lead to incomparable research. Clearly, an evidence-based review is simply not suitable for a disease as politicized (and, as a result, understudied) as historic ME, named and defined as far back 1956, with outbreaks going back to 1934, and updated by the 2011 International Consensus Criteria for ME (ME ICC; Carruthers et al., Criteria, 2011).
So how can any conclusions be drawn? Faced with a similar quandary for its Gulf War Veterans report, the IOM decided that evidence for a new case definition was lacking to date and recommended the use of two pre-existing criteria. (IOM, 2014). ME/CFS has several definitions, as noted by Dr. Lee and the panel. SEID appears to be an unwieldy melding of parts of Fukuda CFS and some CCC criteria. Why not leave CFS as defined by Fukuda and ME as defined by the most current criteria, the ME ICC?
The 2011 ME ICC and its accompanying primer (Carruthers et al, Primer, 2012) were reviewed according to the report’s references, but little mention of their dismissal as ME criteria can be found. When ME is mentioned, it is in the context of a proposed new name for ME/CFS (pp. 9, 14, 51). Of note, however, the committee recognized that “the diagnostic criteria for ME have required the presence of specific or different symptoms from those required by the diagnostic criteria for CFS; thus, a diagnosis of CFS is not equivalent to a diagnosis of ME.” (p. 51). This is exactly what Dr. Lee was driving at.
By proceeding with a literature search and input from clinicians familiar with and patients diagnosed with various forms of ME/CFS, the committee decided it had sufficient evidence to target symptoms and signs for a new definition. Refusing to acknowledge that the evidence base was flawed, it came up with Systemic Exertion Intolerance Disease, aka SEID. In constructing SEID, the panel ignored that they were dealing with a very real disease, ME, and a social construct, ME/CFS.
SEID is not ME. ME is much more complex than the SEID criteria (and includes exclusion criteria), and the ME IC Primer point to biomarkers, not subjective questionnaires, to help clinicians diagnose the disease. ME can never be the name for the IOM committee’s new creation, SEID, as ME already is linked to a disease. Comments that the name, Myalgic Encephalomyelitis, is not supported by evidence ignores that disease names do not have to be perfect to be useful. A disease like ME linked to substantive and historical diagnostic criteria for over half a century cannot be “disappeared”.
The consensus-based ME ICC deserves to be recognized as most up-to-date criteria for those who meet its definition. As the ME IC Primer states, “ Myalgic encephalomyelitis, a name that originated in the 1950s, is the most accurate and appropriate name because it reflects the underlying multi-system pathophysiology of the disease. Our panel strongly recommends that only the name ‘myalgic encephalomyelitis’ be used to identify patients meeting the ICC because a distinctive disease entity should have one name. Patients diagnosed using broader or other criteria for CFS or its hybrids (Oxford, Reeves, London, Fukuda, CCC, etc.) should be reassessed with the ICC. Those who fulfill the criteria have ME; those who do not would remain in the more encompassing CFS classification” (p. ii).
Distributing the ME iCC criteria to clinicians is not difficult. The ME IC Primer includes a three-page clinical assessment and diagnostic worksheet (pp. 10-11) which may be copied and used by practitioners. The Primer itself can be downloaded from a number of sites and purchased in pamphlet form from the UK group, Invest in ME. HHS and other non-governmental organizations have the resources to do develop a dissemination strategy, based on the IOM panel’s recommendations toward the end of its report. Even individual patients can bring the worksheet or Primer to their office visits.
It’s not that complex. The disease ME, however, is complex.
Buchwald, D., Cheney, P., Peterson, D., Henry, B., Wormsley, S., Geiger, A., Ablashi, D., Komaroff, D. et al. 1992. A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active Human Herpesvirus Type 6 Infection. Annals of Internal Medicine 1116: 103-13
Carruthers BM, van de Sande MI et al. Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med 2011; 270:327–38.
Carruthers BM, van de Sande MI et al. Myalgic Encephalomyelitis – Adult & Paediatric: International Consensus Primer for Medical Practitioners. Published online October 2012. (pamphlets for purchase available toward bottom of http://www.investinme.org/InfoCentre%20Education%20Homepage.htm)
Institute of Medicine. 2015. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: Redefining an illness. Washington, DC: The National Academies Press.
Institute of Medicine. 2014. Chronic Multisymptom Illness in Gulf War Veterans: Case Definitions Reexamined. Washington, DC: The National Academies Press.
Lee, Nancy, Background and Charge to the Committee, IOM video, January 31, 2014, https://www.youtube.com/watch?v=3eXOVyx1vkU
Hales, Diane. “The Epstein-barr Virus May Be In Vogue Among Yuppies, But Doctors Find It Hopelessly Vague”, American Health Magazine-Washington Post Writers Group. 13 May 1987.
Straus, S. E. 1988. Allergy and the Chronic Fatigue Syndrome. Journal of Allergy and Clinical Immunology. 81: 791-95.
Straus, S. E. 1991. History of chronic fatigue syndrome. Reviews of Infectious Diseases 13 (Suppl. 1): S2-S7.