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IOM Panelists: The Unknowns

December 5th, 2013

In this post, we present profiles of the seven members of the Institute of Medicine ME/CFS definition panel who were unknown to the ME/CFS community. You can read about the team who put this together and the methods we used in this previous post.  In assessing conflict of interest in these profiles, we defined conflicts very narrowly. We looked for direct financial interests that could influence panel members in defining ME/CFS. For example, payments from disability insurance companies would be highly relevant and potential conflicts. The conflicts assessments presented in this post are limited to those direct interests. In a future post, we will share a summary of our discussion about whether to define conflicts more broadly and consider other types of financial issues.

 

Ellen Wright Clayton, Chair

Simply put, Dr. Ellen Clayton is a heavy hitter. She holds joint faculty appointments to the Vanderbilt University School of Law and Medical School. She received degrees from Duke University (BS), Stanford University (MS), Yale University (JD), and Harvard University (MD). For more than thirty years, she has focused on the crossroads of law, ethics and medicine in genetic testing. Dr. Clayton has established expertise in newborn and pediatric genetic screening issues, and co-founded Vanderbilt’s Center for Biomedical Ethics and Society. She directed that Center for twelve years, and has served on more than forty Vanderbilt University committees since her arrival there in 1988. More recently, Dr. Clayton has focused on genetic biobanks and big data projects, including the International HapMap Project and the Human Genome Organization. While some of these issues are relevant to ME/CFS research, particularly given the growing number of biobanks and big data, Dr. Clayton has no discernible subject matter expertise in ME/CFS or in creating case definitions.

However, Dr. Clayton has a remarkable amount of Institute of Medicine experience. She was elected to the IOM in 2006, but her IOM service dates back to 2002 when she began a five-year term on the Board on Health Sciences Policy. She has served on a total of ten committees since 2003, and chaired four of them. Specifically, Dr. Clayton chaired the Committee to Evaluate the HHS Program on Family Planning in 2009, and now chairs the Standing Committee on Family Planning. Dr. Clayton co-chaired the Committee on Commercial Sexual Exploitation and Sex Trafficking of Minors in the United States which just issued its report in September 2013. Her combination of legal and pediatric experience was particularly relevant here. Finally, Dr. Clayton chaired the Committee to Evaluate Vaccine Safety, which delivered its report in 2011. The Committee investigated the evidence for a number of adverse events connected to vaccines, including autism and chronic fatigue syndrome. While there was causal evidence for many adverse events, no connection was found with autism or CFS. Two other members of that committee are of interest: Dr. Anthony Komaroff, a well-known and highly regarded ME/CFS expert, and Dr. Betty Diamond, who has also been appointed to the IOM ME/CFS panel and who is profiled below.

In addition, Dr. Clayton has been a member of the IOM Advisory Council since 2010, and in 2012 she was appointed to a three-tear term as Chair of the Board on Population Health and Public Health Practice. In October this year, Dr. Clayton received the David Rall Medal for exemplary service to the IOM. The medal is awarded to a member of the IOM that has demonstrated “a commitment substantially above and beyond the usual expectations of a committee chair.”

Bottom line? Dr. Clayton knows IOM. She has already chaired four committees, including one investigating the controversial topic of vaccine safety. She has a distinguished academic career, demonstrable leadership capacity, and significant influence at the IOM itself. We found no evidence of financial conflict of interest or bias on ME/CFS. However, it should be noted that Dr. Clayton has no experience in creating case definitions, and little public knowledge of ME/CFS. She may have been selected as chairman for her IOM process experience, her ability to tackle big issues, and (perhaps) because this panel has already been so controversial.

Margarita Alegria

Dr. Margarita Alegria is a psychologist with a focus on mental health population research. She holds degrees from Georgetown University (BA), the University of Puerto Rico (MA), and Temple University (PhD). Her academic career has been spent at the University of Puerto Rico and at Harvard University, where Dr. Alegria has been Director of the Center for Multicultural Mental Health Research (CMMHR) since 2002. She has served as a consultant to multiple academic institutions and an expert presenter for Shire US, Inc., a pharmaceutical company. According to her CV, Dr. Alegria served on the Steering Committee for the DSM-V Developmental Workgroup in 2001, and has been a grant reviewer for NIH. Her work has been funded by NIH and most recently by PCORI. Dr. Alegria’s research has focused on mental health disparities and care delivery in multicultural populations, and this is also the mission of multiple research projects at the CMMHR.

Dr. Alegria was elected to the Institute of Medicine in 2011. She currently serves on the Board on Population Health and Public Health Practice (chaired by Dr. Ellen Clayton, profiled above).  Dr. Alegria served on the Committee on Standardized Collection of Race-Ethnicity Data for Healthcare Quality Improvement, which issued its report in August 2009. She also served on the Committee on The Mental Health Workforce for Geriatric Populations that delivered its report in July 2012. Finally, Dr. Alegria is a member of the Committee on Initial Assessment of Readjustment Needs of Military Personnel, Veterans, and Their Families which issued two reports in March 2010 and March 2013. While these reports do discuss fatigue and related syndromes like Gulf War Illness, they do not discuss ME/CFS in a substantive way.

The HHS announcement of the IOM contract stated that the committee would include expertise in behavioral health, and Dr. Alegria fits that category. We think it is safe to assume that ME/CFS advocates would prefer for psychologists/psychiatrists to be kept far away from this panel, although that was never likely given the large body of research in this area. Dr. Alegria has not done any research on ME/CFS, but she does have several publications that may give some advocates pause. Two papers examine the connection between physical symptoms and mental health services delivery. In 2010, Dr. Alegria co-authored a paper that concluded, “physical symptoms are an important component of common mental disorders such as depression and anxiety and predict service use in community populations.” A followup paper in 2012 found that the presence of physical symptoms was not a barrier to mental health service use by some minority populations. Finally, Dr. Alegria co-authored a paper finding comorbidity between neurasthenia and psychiatric disorders. The term neurasthenia has been controversially applied to ME/CFS, as recently as this year.

Despite these publications that relate to psychology and somatic symptoms, they represent a tiny fraction of Dr. Alegria’s body of work. We found no evidence that she believes ME/CFS is psychogenic in origin, or that she supports CBT as a treatment for the disease. In addition, we found no conflicts of interest or negative bias.

Charles Cleeland

Dr. Charles Cleeland is a psychologist by training, but has focused his work on pain and cancer studies. He is Chair of the Department of Symptom Research, Division of Internal Medicine, University of Texas MD Anderson Cancer Center and is also director of the Pain Research Group at that institution. Dr. Cleeland has authored more than 350 publications, many of which are focused on pain. He is a past president of the American Pain Society, and member of the International Association for the Study of Pain. This research is potentially relevant given the prominence of chronic pain for many ME/CFS patients. In addition, Dr. Cleeland is familiar with animal models of sickness behavior (such as Dr. Glaser’s work) and “hypothesizes that inflammation and its downstream toxic effects represent a significant biological basis for subjectively reported clusters of symptoms, cognitive impairment, and neuropathies.”

A closer look at Dr. Cleeland’s work also shows him to be interested in quality of life measures, outcome measures, symptom burden, cognitive impairment (usually as a result of cancer treatment), and cancer-related fatigue (CRF). Dr. Cleeland has helped develop three symptom inventory scales:  The Brief Pain Guide, a widely used self-assessment scale of pain and function (used by Dr. Fred Friedberg in a CFS study); the MD Anderson Symptom Inventory (MDASI), a multi-symptom patient-reported outcome (PRO) measure focused on core symptoms that have the highest frequency and/or severity in patients with various cancers and treatment types; and the Brief Fatigue Guide, an assessment of cancer-related fatigue and quality of life. Each of these scales are validated self-assessment measures of symptom severity, function, and symptom impact, at least in cancer if not other conditions.

In 2011, Dr. Cleeland edited Cancer Symptom Science: Measurement, Mechanisms, and Management, for which he was also co-author of the Introduction and three chapters. Keeping in mind that he was the editor of the book and not the sole author, it is interesting to note that chronic fatigue syndrome is mentioned in several places in the book. CFS is characterized as a physiological illness (with a viral connection implied), and in more than one place the book mentions that studying the brain mechanisms of CFS could “help us form hypotheses relevant to the cortical processing of cancer-related fatigue.”

Dr. Cleeland co-chairs an independent and multidisciplinary work group: Assessing Symptoms of Cancer Using Patient-Reported Outcomes, that is developing recommendations for symptom measurement in oncology clinical trials, with financial support from pharmaceutical companies. ASCUPRO has noted that the fatigue in CFS, multiple sclerosis, cancer and other diseases is pathological, may differ between disease states and may possibly require different fatigue measures. Dr. Cleeland has chaired NIH and NCI advisory groups in the area of pain and symptom research. He has also participated in clinical trials to improve cancer pain management, including in under served populations. Dr. Cleeland receives substantial NIH support for his work. He is neither a member of the IOM, nor has he served on any IOM committees.

We have not found evidence of conflict of interest or negative bias. We also did not find direct evidence that Dr. Cleeland is familiar with ME/CFS definition issues. However, as we have noted, Dr. Cleeland does seem to recognize that CFS (at least) is physiological, and is concerned about symptom burden and cognitive function. Dr. Cleeland’s expertise in the creation and application of patient-reported outcome measures is highly relevant to ME/CFS, as evidenced at the April FDA Drug Development Workshop. Understanding epidemiological data and measurement questions will also likely be part of the ME/CFS case definition effort. These factors and his expertise with pain both suggest Dr. Cleeland could play a positive and significant role in the ME/CFS case definition study.

Betty Diamond

Dr. Betty Diamond is a rheumatologist educated at Harvard University (BA, MD). She is chief of the Autoimmune Disease Center at North Shore-LIJ Health System, and head of the Center for Autoimmune and Musculoskeletal Diseases at The Feinstein Institute for Medical Research. The Feinstein Institute is an enormous research institution focused on disease-oriented research, and receiving $45 million per year from NIH.

Dr. Diamond’s laboratory studies the role of B cells in the systemic lupus, an autoimmune disease. Her team has also investigated whether autoantibodies might cause brain injury if they penetrate the blood-brain barrier. These antibodies may contribute to acquired changes in cognition or behavior in people with and without autoimmune disease, as well as autism or PTSD. Her discoveries have led to the development of possible treatments for lupus, and Merck funds lupus treatment research at Feinstein. She has conducted clinical trials in lupus and rheumatoid arthritis, and has published extensively in these fields.

When she joined the Feinstein Institute in 2007, Dr. Diamond was the third-largest recipient of NIH funds in the New York metropolitan area.  She is a past president of the American Association of Immunologists and in 2008 received the Lupus Foundation of America’s Evelyn V. Hess Research Award for lifetime achievement in lupus research. She has also won an NIH MERIT award, which is intended to “provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner.” Investigators do not apply for MERIT awards; they are selected by NIH Institute Councils for their excellence in research. Beyond bench and clinical trial research, Dr. Diamond’s group provides consultation services to lupus patients, and she has spoken about the racial and economic disparities that impact lupus and autoimmune disease research. Dr. Diamond was elected to the IOM in 2006, but has only served on one Committee, the Review of Adverse Events in Vaccines which was chaired by ME/CFS panel chair Dr. Ellen Wright Clayton (profiled above).

Not surprisingly, given her clinical trial research, Dr. Diamond has multiple connections to pharmaceutical companies. She received approximately $19,000 in 2010-2012 for consulting services to Pfizer, Merck, and EMD Serono. She previously served on the scientific advisory board of Anthera Pharmaceuticals and is a scientific advisor to Sequenta, Inc., a biotech company focused on clinical diagnostics based on immune system status.

Dr. Diamond’s experience as a rheumatologist and in autoimmune disease research is highly relevant to ME/CFS, especially given the research advances published in the last several years. She is passionate about her work and helping people with lupus, and has had a successful and distinguished career in her field of study. We found no indication that Dr. Diamond is familiar with ME/CFS definition issues, nor did we find any evidence that she has preconceived ideas about the disease that could create negative bias.

Theodore Ganiats

Dr. Theodore Ganiats is a Professor of Family and Preventive Medicine at the University of California San Diego (UCSD) School of Medicine, where he received his own medical degree. His research focuses on outcomes measures, quality of life assessments, and how outcomes research is translated into the clinical setting. He also maintains a clinical practice specializing in family medicine and primary care at the UCSD Health System and was Chief of the Division of Family Medicine from 1986 to 1997.

Dr. Ganiats is the Executive Director of the UCSD Health Services Research Center, a non-profit research organization focused on understanding how clinical and treatment services affect health outcomes.  Projects have included mental health prevention, mental health services, PTSD outcomes for veterans receiving cognitive processing therapy, as well as a variety of studies such as TB diagnostics and diabetes prevention programs. He has well over 100 publications, focused mainly on outcomes research. We found only one payment for consulting and travel from Pfizer in 2010.

Dr. Ganiats was elected to the IOM in 2006, and served on the Committee on Oral Health Access to Services, which delivered its report in 2011. Last month, he was nominated by the American Academy of Family Physicians to a vacancy on the Board of Governors for PCORI. Dr. Ganiats has represented the AAFP on a number of clinical guidelines committees, which seems like a natural fit with the IOM ME/CFS study. However, his ties to the AAFP may give some advocates pause, given some of their publications on ME/CFS. (I analyzed some of that material last year.)

We did not find any evidence that Dr. Ganiats has a bias about ME/CFS. However, one of his close colleagues appears to have one. Dr. William J. Sieber is the Research Director for the division of Family Medicine, and has co-authored papers with Dr. Ganiats. Dr. Sieber is also a part of Inner Solutions for Success, which provides consultation and coaching services to healthcare professionals. Dr. Sieber’s bio page includes a slide deck titled “Calming the Anxious Brain.” Some of the material on CFS in that presentation is accurate, but it also includes statements like this: “Metabolism of CFS patients is normal so symptoms are due to psychological factors, with mental fatigue considered a lack of motivation (brain is major consumer of resting cellular energy!)” (p. 21)

Dr. Ganiats brings expertise in family medicine (a stated interest of the IOM study) and outcomes measures (an important part of operationalizing a case definition). He also has broad experience in creating clinical practice guidelines and measuring how outcomes research translates to the clinical setting. All of this is highly relevant to the IOM ME/CFS study. We do not know what, if anything, Dr. Ganiats knows or thinks about the disease, but his connections with the AAFP and Dr. Sieber at least raise the possibility that Dr. Ganiats may believe the disease is something very different from what we all understand it to be.

Cynthia Mulrow

Dr. Cynthia Mulrow is an adjunct professor of medicine at the University of Texas Health Science Center at San Antonio. Dr. Mulrow received her MD from Baylor University, but has spent most of her professional career specializing in research methodology, systematic review, and evidence based medicine. She is a senior deputy editor for the Annals of Internal Medicine, and former director of both the San Antonio Cochrane Collaboration Center (now closed) and San Antonio Evidence-Based Practice Center.

Dr. Mulrow has been on the faculty at the Health Science Center since 1987, and also served as a member of the U.S. Preventive Services Task Force from 1998 to 2002. She has authored many publications on systematic reviews, and evidence based clinical guidelines.  Her focus is the methods “that aid comprehensive collation, unbiased and explicit evaluation, and systematic summarization of available research.” It is not at all surprising that the IOM sought to include this expertise on the panel.

Dr. Mulrow was elected to the IOM in 2007, and has served on two consensus panels. The first examined Cognitive Rehabilitation Therapy for Traumatic Brain Injury and delivered its report in 2011. The second panel examined Standards for Developing Trustworthy Clinical Practice Guidelines.  Its report, also issued in 2011, recommended eight standards for developing rigorous, trustworthy clinical practice guidelines. Dr. Mulrow has also participated in several IOM workshops, including a discussion of data standards for PCORI.

All of this experience makes Dr. Mulrow very qualified to tackle the massive systematic evidence review that will be part of the IOM ME/CFS study. However, this will not be the first time she has worked on an evidence review for chronic fatigue syndrome. In 2001, Dr. Mulrow led the contract at the San Antonio Evidence-Based Practice Center to do a systematic review on Defining and Managing Chronic Fatigue Syndrome. Obviously, the science was different in 2001, but one of the main conclusions of the review was

Definitions, developed primarily by expert knowledge and consensus, have evolved over time. A few comparative research studies support the concept of a condition, characterized by prolonged fatigue and impaired ability to function, which is captured by the case definitions. The superiority of one case definition over another is not well established. The validity of any definition is difficult to establish because there are no clear biologic markers for CFS, and no effective treatments specific only to CFS have been identified.

It’s important to note several things about this report. First, the technical experts and peer reviewers included: Dr. Leonard Jason, Dr. Nancy Klimas, Dr. Anthony Komaroff, and Dr. Peter Rowe, as well as others not so well-regarded by the ME/CFS community such as Dr. Simon Wessely and Dr. Peter White. Second, the Agency for Healthcare and Research Quality is embarking upon another systematic review as part of NIH’s Evidence-based Methodology Workshop, which will (hopefully) update and expand the 2001 analysis.

Also in 2001, Mulrow and colleagues published Interventions for the Treatment and Management of Chronic Fatigue Syndrome in the Journal of the American Medical Association. The review followed the same approach that the current IOM study appears to be using, in that “CFS was taken to mean all illnesses, including ME and PVFS with symptom complexes similar to CFS, unless otherwise stated.” (p. 1360) The analysis found that there was no significant association between the definition used and treatment study outcome (p. 1366). However, the paper also reports many weaknesses and limitations in the treatment studies, including the failure to characterize baseline functionality in a standardized way. CBT and GET were considered promising, but “All conclusions about effectiveness should be considered together with the methodological inadequacies of the studies.” (p. 1367)

The main issue regarding Dr. Mulrow is whether she can look at the ME/CFS world of 2013 with fresh eyes. There have been scientific advances since the 2001 review, but many challenges in the data remain. We found no evidence of any statements or publications by Dr. Mulrow about ME/CFS since those 2001 papers, so we do not know if she has a dogmatic and unchanged view. It is possible that she will be an asset to the panel, both for her methodological expertise and her previous examination of the data. That will depend on whether she is able to examine the evidence and listen to the panelists without undue bias.

Michael Shelanski

Dr. Michael Shelanski is Chairman of the Department of Pathology and Cell Biology at Columbia University.  He received an MD/PhD from the University of Chicago. Dr. Shelanski’s research has focused on cell and animal model approaches to study memory disruption and synaptic dysfunction in Alzheimer’s and other neurodegenerative diseases. Dr. Shelanski is on the faculty of the Taub Institute at Columbia, an NIH-funded Alzheimer’s disease research center. His extensive publications cover cell biology, neuropathology, gene expression, and impact on disease. Dr. Shelanski has received extensive funding from NIH for his work, and has served on multiple advisory committees and boards during his career, as well as the editorial boards of many scientific journals.

Dr. Shelanski was elected to the Institute of Medicine in 1999, but has only served on a single committee: the Review of the Appropriate use of AFIP’s Tissue Repository Following its Transfer to the Joint Pathology Center committee. The committee’s report, issued in October 2012, made recommendations regarding the preservation and use of the Army’s extensive repository during its transition. The repository is significant for, among other things, preserving the tissue that made the genomic sequencing of the 1918 influenza virus possible.

We found no evidence for conflicts of interest, nor did we find any connection or bias regarding ME/CFS. However, Dr. Shelanski’s participation in the panel is a bit of a puzzle. Certainly research into neurodegenerative conditions could be relevant to ME/CFS, and Dr. Shelanski is clearly a distinguished scientist. His work has focused on cell biology and animal models, more of a “bench” than “bedside” approach. Given that the IOM panel will be creating an evidenced-based clinical case definition, we do not understand Dr. Shelanski’s qualifications to create such a definition or a plan for disseminating the definition to health professionals.

Acknowledgements: This post was a group effort, and would not have been possible without the assistance and participation of Lori Chapo-Kroger, Claudia Goodell, Chris Heppner, Denise Lopez-Majano, Mike Munoz, Darlene Prestwich, Tamara Staples, WillowJ, and one advocate who wished to remain anonymous.

 

  1. Kati D
    December 5th, 2013 at 21:00 | #1

    This is slightly off-topic here, but I would like to make this observation abut the known ME experts: Bateman, Klimas and Chu are not known for using an aggressive pharmalogical approach with ME (to be honest I don’t know about Lily Chu)- and in my opinion there needs to e a balance of expert opinion on the treatment approach as well. Montoya, Kogelnik, Peterson all use anti-virals. Peterson is one to have the most experience with viruses as it relates to ME, including testing spinal fluid and using an array of treatments.

    This said thank you for this work and providing insight in these people.

    • Jennie Spotila
      December 5th, 2013 at 21:06 | #2

      It’s a good point, Kati. I think we’ll address it in the next post which will be profiles of the expert panelists. Thanks for raising it.

  2. Tina
    December 5th, 2013 at 21:31 | #3

    I’m glad to see Diamond. Lupus and RA face many of the same issues as ME/CFS. There is even name controversy on RA. They are hard to diagnose, particularly lupus, and have different presentations in each patient. The importance of getting an early and accurate diagnosis is surely something she understands, not to mention complexities on disease mechanisms. I bet she and Dr. Klimas end up in some very scientific conversations.

  3. Carrie
    December 5th, 2013 at 22:40 | #4

    Thanks to everyone who did the work to put this together so quickly for us!

  4. Julie Rehmeyer
    December 5th, 2013 at 22:52 | #5

    Thank you for this impressive, careful review of the work of the candidates. Really nicely done.

  5. Kati D
    December 6th, 2013 at 00:43 | #6

    And as a quick add on, Dr Bateman and Klimas are co-authors of the MEICC.

  6. Ess
    December 6th, 2013 at 01:38 | #7

    A lot of hard work has gone into researching all of that important info–thank you! A comment to make–concern that five of these doctors are/have been involved in the mental health field–Margarita Alegria, psychologist; Charles Cleeland, psychologist; Theodore Ganiats, mental health projects; Michael Shelanski, Alzheimer’s–mental health; Cynthia Mulrow, cognitive rehabilitation therapy and evidence-based medicine.

  7. DZ
    December 6th, 2013 at 02:48 | #8

    With regard to Dr Alegria, you stated that “We found no evidence that she believes ME/CFS is psychogenic in origin, or that she supports CBT as a treatment for the disease”.

    The 2010 paper co-authored by Alegria that you cited includes this argument:

    “This strongly supports the observation of many previous studies in the US and abroad that have shown that somatic symptoms represent a common expression of psychopathology and predict disability and service use [8, 11, 30, 31]”

    Citation 11 is a paper by Wessely et al which posits that CFS is one expression of an underlying functional somatic syndrome, and describes CBT as “superior to minimum care for most of the syndromes in which this approach has been assessed, such as chronic fatigue syndrome, premenstrual syndrome, irritable bowel syndrome, and nearly all the various pain syndromes”.

    While that is not direct evidence (we don’t know if she linked that paper to the argument or personally authored that line at all), it is not something that should be overlooked either.

    • Jennie Spotila
      December 6th, 2013 at 07:54 | #9

      I’m glad you raised this. There is an inherent difficulty in finding bias from small or isolated pieces of evidence, as opposed to someone’s entire body of work. The quote from the 2010 paper: “that somatic symptoms represent a common expression of psychopathology and predict disability and service use” is accurate from many points of view. For example, recall the advertising campaign for antidepressants that say “depression hurts,” meant to refer to the physical pain associated with depression. So that quote in Alegria’s paper is true about depression: depression is associated with somatic symptoms (like pain), and that such a presentation could logically lead to more service use because that depression would be more severe than depression that did not cause pain.

      The KEY question is whether she believes that is universally true. Are ALL somatic symptoms manifestations of psychopathology? Is all chronic pain caused by psychopathology? Or are somatic symptoms more likely to cause emotional difficulties like depression and anxiety?

      We have no evidence to suggest that she believes psychopathology to be the source or cause of all somatic symptoms like pain and fatigue. If she believes that CFS is a functional somatic syndrome that can be effectively treated with CBT, we have found no proof that she has ever said that.

  8. December 6th, 2013 at 10:36 | #10

    I wish we could interview these people and get a better sense of their starting beliefs.

  9. AJ
    December 6th, 2013 at 14:52 | #11

    I’m not sure having been on the Vaccine Safety Committee is a recommendation: http://www.ageofautism.com/2013/01/barbara-loe-fisher-on-iom-vaccine-report.html

  10. Anonymous
    December 6th, 2013 at 22:03 | #12

    @Kati D

    It depends on what you mean by “aggressive.” I am a patient of Klimas and I would say she is plenty aggressive about treating ME/CFS, including recommending prescription immunosuppresants to me that have been used in RA, lupus, and cancer. However, her suggestions depend on each patient’s symptoms, studies, and tolerance of risk. On the other side, I also see Dr. Montoya and he is not as familiar with those meds so doesn’t use them. I don’t know Peterson personally. Lerner on the panel has long experience with antivirals.

    There are also many docs who use unproven or even dangerous remedies out there that would be considered “aggressive” by their patients but foolish by mainstream scientists/ physicians.

  11. Justin Reilly
    December 6th, 2013 at 23:11 | #13

    We really need to look really closely at Mulrow and Alegria.

    Mulrow has written some pretty bad stuff in the past on ME, only recommending GET and CBT and the only GET studies she looked at were Oxford studies which she and her coauthors rated highly. They also said they came across a paper on CBT that was aimed at reducing activity in ME patients and they said they might not even consider that to be CBT because its aim was not to promote GET!! Jennie and co. say this paper makes her qualified, I strongly disagree.

    Alegria has written at least 3 study papers on Neurasthenia and supervised studies by at least 2 grad students on it. I want to see what they say but they are all behind pay walls I think. Does she equate Neurasthenia with ME?? She has also authored a paper on somatic symptom diasorders.

    I think even just knowing what we know now about these two, they are both completely unacceptable.

    I also wonder about Dr. Cleveland, a psychologist focused on symptoms (in cancer). In some respects he seems ok, but Id like to see deeper digging into this guy to see I f there are any skeletons.

    Neither ALegria’s work on NEurasthenia nor Mulrows on ME were disclosed in their bios. Such nondisclosure of biases and conflicts of interest is typical of IoM panels according to the Center for Science in the Public Interest Report.

    • Jennie Spotila
      December 6th, 2013 at 23:31 | #14

      I did not say that Mulrow’s 2001 JAMA paper made her qualified for the panel! In fact, Mulrow troubles me. We looked for, and could not find, evidence that Mulrow has written or spoken publicly about ME/CFS since 2001 to see if she persists in the conclusions in that paper and the AHRQ report. We couldn’t find anything, but if someone does I definitely want to see it.

      Perhaps my introduction was not clear enough. This post is descriptive of what we found in their backgrounds. Tomorrow’s post does the same for the “knowns.” We have not yet attempted to reach consensus on what we think about the panel overall, or who we might want to see removed/added.

  12. Justin Reilly
    December 7th, 2013 at 00:36 | #15

    Jennie, sorry, I got mixed up. But you did say the following paper, along with another and some workshops make her “very qualified” for the ME study.

    Graham R, Mancher M, Wolman DM, Greenfield S, Steinberg E, eds. Clinical Practice Guidelines We Can Trust. Washington, DC: National Academies Press; 2011.

    But, check out this damning critique of that paper:

    Are the Institute of Medicine’s Trustworthiness Guidelines Trustworthy?

    “The IOM standards for the development of Clinical Practice Guidelines do not meet their own criteria of trustworthiness. Further study is needed to determine the best methodology to evaluate CPGs.”

    http://www.rimed.org/rimedicaljournal/2013-08/2013-08-13-iom.pdf

  13. Justin Reilly
    December 7th, 2013 at 00:48 | #16

    Here are ALegria’s 3 papers on neurasthenia:

    Prevalence of neurasthenia, comorbidity, and association with impairment among a nationally representative sample of US adults

    “Less acculturated individuals were at a decreased risk for lifetime and past-year neurasthenia. Lifetime neurasthenia was associated with increased odds of meeting lifetime criteria for any depressive, any anxiety, and any substance use disorder…

    Conclusion
    Neurasthenia is a prevalent condition deserving further research attention given its comorbidity with other psychiatric disorders and its association with functional impairment.”

    http://link.springer.com/article/10.1007%2Fs00127-012-0489-6

    Read the paragraph with the highlighted words in the following book:

    http://books.google.com/books?id=LOU1L3v1DaQC&pg=PA50&lpg=PA50&dq=alegria neurasthenia&source=bl&ots=vgQ5yj7ccE&sig=s1qdsNjIss23QB7rsfvJjCA_9Sg&hl=en&sa=X&ei=pDegUofIHIbakQeVroDQCQ&ved=0CEAQ6AEwBDgK#v=onepage&q=alegria neurasthenia&f=false

  14. Justin Reilly
    December 7th, 2013 at 01:33 | #17

    @DZ
    can you Pls provide access to this paper and also Allegrias on Neurasthenia if possible? thanks for considering.

  15. Justin Reilly
    December 7th, 2013 at 02:11 | #18

    @AJ
    I have the same feeling.

    in this press release, Dr. Clayton seems to overstate the results of the report. Some of the press release- like the first paragraph, surprise, surprise- clearly overstates, and is contradicted by statements buried further in the press release.

    http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=13164

    I personally don’t know enough about the vaccines in this and other IoM reports but the Age of Autism people sure seem to be outraged about them.

    Since I know that the government has lied consistently about ME, Lyme, the Anthrax and Polio vaccines, it seems very plausible that Clayton and Diamond’s IoM vaccine report was intentionally misleading.

  16. Mary Dimmock
    December 7th, 2013 at 13:40 | #19

    Thank to to Jennie and all the others for doing this. Very helpful

    Regarding your comment on Alegria, you might want to review this article.
    “Whether medically unexplained or not, three or more concurrent somatic symptoms predict
    psychopathology and service use in community populations”
    Javier I Escobar, MD,1 Benjamin Cook, PhD,2 Chi-Nan Chen, PhD,2 Michael A Gara, PhD,1,3
    Margarita Alegría, PhD,2 Alejandro Interian, PhD,1 and Esperanza Diaz, M.D4 (2010)
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905311/

    I havent read the entire article but the title and abstract indicate a belief that sufficient somatic symptoms do indicate psychopathology.

  17. Amanda rankin
    December 7th, 2013 at 18:38 | #20

    Thank you for all your hard work and providing this information

  18. Ren
    December 8th, 2013 at 06:18 | #21

    @Mary Dimmock

    I mentioned this on PR – but will add it here as well. Escobar was on the committee for Gulf War and Health Treatment for Chronic Multisymptom Illness – which frequently cites his work, including the above-named paper with Alegria.

    Additionally, there is a VA webpage which names CFS as a chronic multisymptom illness. Does this mean VA applies everything stated about CMI to CFS? (To my understanding, the Gulf War and Health volumes and the VA describe CMI as another term for medically unexplained symptoms (MUS).) http://www.publichealth.va.gov/exposures/gulfwar/medically-unexplained-illness.asp

    And finally regarding Alegria, I’d like to know if she has any influence in what’s been termed medical kidnapping by Boston Children’s Hospital. (Originally shared by leela on PR.) http://westhartford.patch.com/groups/around-town/p/protest-planned-to-fight-hospitals-kidnapping-of-west-hartford-girl

  19. Els Van Hoof
    December 8th, 2013 at 09:59 | #22

    I wonder how one can see anything remotely positive in the appointment of dr. Allegria when all I can see are BIG question marks …

    No, there isn’t any “evidence” about her speaking about ME or CFS, probably because she never dealt with ME or CFS before.

    “She has served as a consultant to multiple academic institutions and an expert presenter for Shire US, Inc., a pharmaceutical company.” (!)

    “According to her CV, Dr. Alegria served on the Steering Committee for the DSM-V Developmental Workgroup in 2001″ (!)

    “and has been a grant reviewer for NIH.” (!)

    “Her work has been funded by NIH and most recently by PCORI.” (!)

    “Dr. Alegria’s research has focused on mental health disparities and care delivery in multicultural populations,” (!)

    The 2 papers mentioned in your blog aren’t very reassuring to me, to say the least! Neurasthenia seems to be her “specialty” and we all know what ME or CFS was and sometimes still is called, don’t we?

    “Despite these publications that relate to psychology and somatic symptoms, they represent a tiny fraction of Dr. Alegria’s body of work. We found no evidence that she believes ME/CFS is psychogenic in origin, or that she supports CBT as a treatment for the disease. In addition, we found no conflicts of interest or negative bias”

    Could it be that there is no evidence because she never (!) dealt with ME or CFS before?

    No bias or conflict of interest?
    She sat in the steering committee of DSMV; She has ties with the pharmaceutical industry; She worked for and has been funded by NIH; …

    I totally admire all your work on these biographies but I’m really wondering about some of the “reassuring” conclusions. They aren’t reassuring to me. Quite the opposite in fact.

    • Jennie Spotila
      December 8th, 2013 at 11:06 | #23

      The profile of Alegria is not the final word, and our team is actually troubled by what we’ve learned. We see the same red flags that you have listed. We’re currently working on additional analysis, so the subject is neither closed nor do we intend to “reassure” anyone.

  20. Ruthann Auten
    December 8th, 2013 at 11:25 | #24

    Thank you all so much for all the hard work!

  21. DZ
    December 8th, 2013 at 17:13 | #25

    @Jennie, my point was that the argument made in the quote I provided references Wessely’s paper that DOES clearly include CFS in the realm of psychosomatic disease, which suggests that, if Alegria approved that reference, she may be coming from a background not just of lack of knowledge about CFS, but of psychosomatic bias regarding it. I only submitted that as something that we may ‘know’ about one of the ‘Unknowns’.

    But consider this more direct statement from the paper she co-authored on Neurasthenia (Molina et al 2012):

    “Kawanishi [50] warns against making any firm conclusions
    about specific pathology being more prevalent in one culture
    than another, since prevalence of certain mental disorders
    may be dependent on the social group, cultural
    context, and diagnostic system used [4, 23, 38]. Likewise,
    as Lee [51] argued, the ‘‘disappearance’’ of culture-bound
    syndromes is related to changing sociocultural conditions,
    including economic and political factors and changes in
    managed care and pharmaceutical forces, to name a few.
    Indeed, chronic fatigue syndrome (CFS), also a controversial
    illness which has been argued to be a variant of
    neurasthenia [4, 21] has become increasingly diagnosed in
    the US [52, 53], whereas neurasthenia is virtually no longer
    diagnosed in the US context [51].”

    That sounds pretty clearly like support for the hypothesis that CFS is just a culturally sanctioned name for neurasthenia, a psychiatric disease. Note this paper is from last year.

    Neurasthenia is not a very popular diagnosis in the US, as Alegria and colleagues point out, but it is more common in outside the US, and cross-cultural psychiatric diagnoses and epidemiology are among Alegria’s interests. The international diagnostic criteria for neurasthenia are actually very close to case definitions for ME and CFS; in fact, it essentially includes both mental and physical PEM in a subjective sense of the term. There are, by the way, some psychiatrists who would like to see neurasthenia diagnosis receive more attention.

    • Jennie Spotila
      December 8th, 2013 at 19:15 | #26

      DZ, I don’t interpret those three sentences the same way you do. Indeed, these sentences seem to conflate prevalence of a disorder with how it is diagnosed, and how frequently. I disagree with the idea that prevalence changes based on cultural context. DIAGNOSIS will change based on context, but that doesn’t mean the incidence has changed. In any event, I have not been able to get full access to this paper. Do you have a copy? I would greatly appreciate it if you could provide it to me. A paper on neurasthenia is a red flag, but I really need to be able to read the full argument.

  22. Ren
    December 9th, 2013 at 07:54 | #27

    Regarding the “culture-bound syndrome” meme (perhaps also called “cultural expressions of distress”):

    For Alegria, researchgate.com lists David Takeuchi as Alegria’s second most-frequent co-author with 20 shared publications. Takeuchi’s U. of Washington bio page states,

    “Depression and neurasthenia represent compelling contrasts since the first is a prevalent mental health problem in the United States and the latter is a relative common health problem in China. Analyses show that stress is linked to neurasthenia symptoms but not depressive symptoms among recent immigrants. The opposite is true for more established Chinese immigrants; stress is associated with depressive symptoms but not neurasthenia. The results argue for the inclusion of multiple indicators of health and cultural expressions of distress…Analyses are underway to shed light on how geographic region is associated with different outcomes for a single ethnic group.”

    I have heard/read that neurasthenia has come to be seen as outdated in the West but is still a common diagnosis in the East. Sorry to be vague – but that thought came to mind when I read the above on Takeuchi. Additional thoughts: Does Takeuchi (does China) make a distinction between ME and neurasthenia? Or does Takeuchi view these as “cultural expressions” of the same entity?

    Alegria researchgate: http://www.researchgate.net/profile/Margarita_Alegria2/

    Takeuchi bio: http://csde.washington.edu/people/interests.php?id=46

    I understand it’s most important to have access to and analyze what Alegria herself has authored, but with limited access to that info – I thought perhaps we might better understand her point-of-view by understanding the work of those with whom she often publishes.

    Just as more general info, I also happened upon this little “gem” on medscape – “Rare and Unusual Psychiatric Syndromes Part 2: Culture-Bound Conditions – 11/19 Shenjing Shuairuo (Neurasthenia)… The description of shenjing shuairuo would also fit chronic fatigue syndrome, which remains poorly understood.”

    http://www.medscape.com/features/slideshow/culture-synd

    I didn’t look indepthly at the sources but did notice Takeuchi (as well as Canino – see below) as a repeated reference in source 2.

    Additional fyi, researchgate names Glorisa Canino as Alegria’s most-frequent co-author, if anyone recognizes her name (Canino) in relation to anything. Please forgive any info repeats. I haven’t been able to keep up with all the new posts/info on different sites.

    • Jennie Spotila
      December 9th, 2013 at 08:19 | #28

      Ren, this is very helpful!! Thank you! We’ll look into this (today, hopefully).

  23. Ren
    December 9th, 2013 at 08:52 | #29

    Post 27 note: The medscape link posted above asks for sign-in info. To avoid this, google “Shenjing shuairuo medscape” – should be the first link which appears. ;)

  24. DZ
    December 9th, 2013 at 18:05 | #30

    @Jennie Spotila

    Yes, I should have clarified that my interpretation of those lines was within the context of not only the whole study but of the evaluation of CFS within the field of somatoform disorder research and some of the key sources cited by the authors, which I do think is essential to consider. The authors do not argue that the diagnoses are technically the same, as clearly they are separate within the ICD-10 itself. Indeed, they suggest that neurasthenia may be getting ‘misdiagnosed’ as CFS, depression, or anxiety. What I find to be concerning subtexts are the tendency (as I interpreted it) to equivocate between diagnoses of ‘medically unexplained’ disease, and especially the unwillingness to consider that diagnostic constructs like neurasthenia lack empirical substance and therefore may not reflect any real psychopathology; indeed, they may lead to psychiatric overdiagnosis of physical disease. Note how close the ICD-10 criteria for neurasthenia are to various criteria for CFS. However, one construct (unscientifically) assumes psychiatric etiology, and one does not. The only way many clinicians would be able to exclude neurasthenia, given how vaguely it is defined, in a CFS case would be to assume a given patient’s illness is primarily physical.

    If you can send an email to the address I gave for this reply, I’d be happy to send you the full text of this paper.

    • Jennie Spotila
      December 9th, 2013 at 21:10 | #31

      Fantastic!! Emailing you now. Thanks!

  25. December 11th, 2013 at 01:46 | #32

    Having read Cynthia Mulrow et. al.’s paper on “Interventions for Chronic Fatigue Syndrome” (linked above), I felt that she and her co-authors appeared to approach the subject with remarkable objectivity and couldn’t see anything that suggested a dogmatic view of this illness. While acknowledging that GET and CBT “appear promising” due, in part, to the fact that those studies were well-constructed studies (since they get all the funding) whose positive results are, thus, going to be more generalizable (the writer in me cringes at this wannabe word), Mulrow et al also noted that CBT and GET studies had particularly high dropout rates which may limit how generalizable they really are. There was even concern that such a high drop out rate may “indicate a trial protocol that is too rigid to accommodate any but a very specific group of participants” or may even be due to “…adverse effects arising from the intervention.” The fact that they raised many of the same concerns about the behavioral studies that we patients have been raising over the years was very encouraging to me.

    Moreover, Mulrow et al noted that patients in all of the studies under review in the paper represented higher-functioning patients who could walk, get out of bed, and get to clinic “so it is not possible to assess whether the interventions investigated [including CBT & GET] would be effective, ineffective, or even hazardous for a more severely disabled group of people.”

    She and her colleagues were also critical of the vagueness of the end result of “improvement” in all of the studies and pointed out that “the person may feel better able to cope with daily activities because they have reduced their expectations of what they should achieve rather than because they have made any recovery as a result of the intervention.” Being able to go back to work or school (or, perhaps, increase activity on an actigraph?) should be the metric used for “improvement,” rather than merely saying they feel better on a questionnaire.

    And echoing a concern I’ve heard Christopher Snell and Stacy Stevens raise, Mulrow et. al. complained that because ME/CFS is a long-term condition — and a relapse/remit condition at that — patients should be followed up long-term to demonstrate that their improvement was not due simply to the “naturally occurring fluctuation in the course of the illness.”

    They recognized that multiple definitions were used and, in a great table (Table 2.), lay out which interventions used which definition, with the behavioral studies all using the broader Oxford criteria. They were not particularly thrilled with any of the studies, and as you point out above, Jennie, stated that all of the studies had “methodological inadequacies.” While they say CBT and GET showed promise, it wasn’t exactly a ringing endorsement. To be sure, for busy providers who are not going to bother carefully reading the study, even that can be potentially harmful for patients.

    But I actually was quite heartened reading this paper that she is going to give everybody — not just biomedical researchers — a skeptical read. Which is the way it should be. This is science, after all, not religion where “orthodox belief” is required. I have no problem with a scientist being skeptical of ME/CFS and, indeed, I have no problem with a panel that includes scientists who have to be persuaded about the seriousness of this disease. If it was simply a panel of ME/CFS experts — like CCC/ICC is — my guess is that the result would remain just as ghettoized as CCC/ICC has been.

    What I do I have a problem with is when the psychogenic school gets all the funding to construct well-designed studies while our biomedical people are having to cobble together studies with scraps of funding here and there and at the end of the day, those cobbled together studies simply don’t come up to scratch. But given that the panel is made up of 7 those biomedical researchers who can impress upon the rest just how unfair the deck has been stacked with next to no psychogenic researchers to argue otherwise (with the exception of Alegria?), I think someone like Mulrow could be made a powerful ally for biomedical research into this disease (she’s the editor of the Annals of Internal Medicine!), as well as just about anyone listed here. Not that I think everything is all hunky dory now. We should still be watching this committee like hawks. Which we’re much more able to do thanks to you and the all the wonderful people working with you — thanks!

    • Jennie Spotila
      December 11th, 2013 at 08:15 | #33

      Excellent comments, Michelle. Thank you!!! We’re having the same discussion in our team – does her work show that she’s capable of setting aside any bias, or does it demonstrate bias? It’s a bit like reading tea leaves.

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