IOM Panelists: The Unknowns
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.
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.
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.
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.
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.
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.
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.