The Department of Health and Human Services

CFS Advisory Committee Holds Timely Session

In the “Great Hall” of the Department of Health and Human Services building in Washington, D.C., the federal CFS Advisory Committee held its 16th semi-annual meeting on Oct. 29-30, 2009. Usually a quiet, sparsely attended session held in the 8th floor conference room, by contrast this meeting was illuminated by banks of bright lights, three hulking video cameras, about 100 observers, and a meaty agenda. Three weeks prior, researchers from the Whittemore-Peterson Institute (WPI) had broken new scientific ground with a high-profile paper linking CFS and XMRV, a retrovirus found in a subset of an aggressive form of prostate cancer. The WPI’s discovery set the stage for fascinating presentations, passionate public testimony, and spirited recommendations to the Secretary of Health over the two days. Designated federal official, Dr. Wanda Jones, and chairman Dr. James Oleske led the meeting, for which all 11 appointed members were present (for at least some portion).

Dr. Wanda Jones

Agency Reports
Representatives from the four of the five federal health agencies, Social Security Administration (SSA), National Institutes of Health (NIH), Food and Drug Administration (FDA), and Centers for Disease Control & Prevention (CDC), gave brief updates. SSA’s Mike O’Connor informed the Committee that they will be updating Social Security Ruling 99-2p that recognizes CFS as a potentially disabling condition to reflect medical and research advances made since 1999 when the ruling was published. He also stated that responses to 13 questions about Social Security disability received from the CFSAC were being researched and developed.

Dr. Eleanor Hanna from NIH reported on the meeting of funded investigators held at Banbury Center with the CFIDS Association of America, and plans to launch a formal network with assistance from NIH’s Biomedical Informatics Research Network. She stated that an NIH State of the Knowledge conference and Request for Applications funding announcement were being planned for 2010.

Dr. Marc Cavaille-Coll of the FDA could make no report on the status of Ampligen, an antiviral therapy awaiting marketing approval for CFS; however he did confirm that it had been granted orphan drug status several years ago, providing certain tax and exclusivity benefits to the manufacturer.

Although Dr. Michael Miller of CDC stated that the final version of the agency’s five-year plan for CFS research had been posted to its website, he did not distribute copies to the Committee or public observers. He referenced the 1,200 comments received from organizations and individuals about earlier drafts, commented that a broad restructuring under way might affect placement of the CFS program, and clarified that tests for XMRV would be performed by the retrovirus group using samples from the CDC’s studies of Wichita and Georgia, as well as from WPI. Dr. Miller’s report generated the most discussion by Committee members, who questioned CDC’s continued reliance on the empiric definition (and consequences for the XMRV study based on different populations studied). They also challenged the bias reflected in Dr. William Reeves’ statements to the New York Times in which he expressed doubt that CDC would be able to replicate the WPI research. Committee member Dr. Nancy Klimas stated emphatically her concern about using samples from the Georgia cohort, and the “tremendous damage” CDC would do to the field if these studies are not done properly. Dr. Miller defended the research plan, but declined to accept responsibility for Dr. Reeves’ predictions, saying only that Dr. Reeves would not be doing the laboratory work. Dr. Klimas reiterated earlier requests from the IACFS/ME and the CFIDS Association for CDC to include post-HIN1 CFS in its flu surveillance, in light of the first published case report made days earlier. She urged that CDC not spend its resources studying cognitive behavioral therapy and childhood stress in CFS and instead should accommodate the immediate need for post-flu follow-up.

Dr. Daniel Peterson

Dr. Daniel Peterson, Whittemore-Peterson Institute
Dr. Daniel Peterson began his talk by referring to the XMRV paper as a “scientific stimulus package” for CFS. He reviewed the methods used to achieve the results reported in the Science article and addressed the follow-up studies conducted on additional samples from patients with diagnoses including: CFS, Neimann’s Pick C (childhood Alzheimer’s), atypical MS, autism, and Gulf War illness. He classified these conditions as “XMRV-Associated Neuroimmune Disease potential candidates.” Dr. Peterson provided data on 20 CFS patients with subsequent cancer diagnoses, noting that 17 of 17 tested were positive for XMRV. He then fielded questions from the Committee, who applauded his willingness to share this information and collaborate with other research groups.

Annette Whittemore

Annette Whittemore, Whittemore-Peterson Institute
When asked about Dr. Miller’s statement that CDC would test samples from WPI, Dr. Peterson called upon WPI founder and president Annette Whittemore to answer. She could not confirm that WPI had sent samples to CDC. She then asked the Committee for time to present testimony since she had been wait-listed for the public session. Dr. Oleske resisted enforcement of the procedural rules and invited her statement. Mrs. Whittemore spoke passionately about her daughter Andrea’s 20-year battle with CFS and the hope for a healthier future that XMRV represented for the world. She requested a congressional hearing to examine roadblocks that have existed and demanded serious funding for XMRV research. She closed by dedicating her testimony to those who could not hang on to see this day.

Dr. John Coffin

Dr. John Coffin, Tufts University and National Cancer Institute
Dr. Jones introduced Dr. John Coffin as an internationally recognized expert on retroviruses and thanked him for agreeing to speak with less than 24 hours notice of the request. He reviewed his area of scientific interest for the past 40 years in retroviruses and the co-evolution of retroviruses and their hosts, focusing on drug-resistant HIV in recent years. He called the finding of XMRV in CFS “remarkable” and oriented the audience to his attempt to explain the origins of XMRV and to define what still needs to be understood about it and its role in CFS. XMRV is closely related to a mouse virus, murine leukemia virus and before 2005 had not been known to infect humans. Unlike HIV, it has a relatively slow replication cycle; good news for the potential to develop a vaccine, but bad news for the possibility of using antivirals/antiretrovirals that depend on rapid replication of the virus to be effective. Dr. Coffin also pointed out that while 99 percent of those infected with HIV will develop AIDS (if not treated), only a very small percentage of those infected with HTLV will develop disease. Both of these are retroviruses, and it underscored the point that not all retroviruses affect us the same way. While he noted that the WPI’s discovery was still in “very early days,” he was enthusiastic about the scientific interest it had already generated among colleagues studying retroviruses. “Everyone wants a piece of the action,” he said. His final comment before the Q&A session related to his “horror” that there was already at least one lab offering “undefined, unverified, unstandardized” lab tests for XMRV. While he refrained from stating what he “really thought,” he advised that it would be “a very bad idea” for patients to order tests before appropriate standardization and regulation processes had been completed. He later estimated that might take six months.

Q&A Session: Drs. Peterson and Coffin
There were many questions from CFSAC members, to which both Dr. Peterson and Dr. Coffin responded. The first questions centered on the possible role of other viruses commonly found in CFS patients (Epstein-Barr virus, HHV-6, enteroviruses, etc.). There was speculation that XMRV “kicked up” other viruses. Dr. Peterson stated that there were almost certainly cofactors involved in the causation of CFS, but this had yet to be determined. Dr. Coffin reported on a meeting hosted by NIH in July 2009 to gather those working on XMRV (including WPI) in prostate cancer and CFS. He affirmed that collaboration was under way to standardize assays, tests and reagents, and to address issues like the risk to the blood supply and other precautions. (Note: this topic was covered in more detail on the second day of the meeting.) The issue of CDC’s attempt to replicate the XMRV finding using a less restrictive case definition was raised; both Dr. Peterson and Dr. Coffin reinforced the importance of the clinical population and know who was being tested. They commented on the different repositories of patient samples that could be accessed to advance this research, and the large-scale financial resources required to ensure it was pursued vigorously.

Robert Miller

Public Testimony
In the first of three one-hour sessions devoted to hearing moving and passionate testimony from the public, each of the following individuals spoke for five minutes: Marly Silverman (PANDORA), Robert Miller, Courtney Alexander, Dr. Dharam Ablashi(HHV-6 Foundation), Joan Grobstein, Janice Bell, and Ruth Bell. (Note: Many of the statements delivered can be found in PDF format. There are also links to PDFs of statements submitted by individuals and organizations for the official record.)

Committee Discussion
Following a short lunch break, each of three subcommittees of the CFSAC brought forward issues explored in telephone conferences held since the most recent public meeting in May. The status of 38 (cumulative) recommendations made at past meetings was explored, with Committee members agreeing that the lack of implementation of the repeated request to establish CFS centers of excellence was most frustrating, especially given the clear need to link research, clinical care, and education of health care professionals. Continuing on discussion of the CDC research plan, several members expressed concern that the CDC’s plan was too broad and vague to inspire confidence that it would be implemented or lead to progress. Patients’ difficulties accessing knowledgeable health care professionals and disability benefits were also discussed.

Dr. David Bell

Dr. David Bell, Lyndonville, N.Y.
The May 2009 meeting had featured a half-day session focused on the special issues children and adolescents with CFS face. Dr. David Bell, a pediatrician and expert CFS clinician, was unable to attend that meeting, so his presentation on Factitious Disorder and CFS in Adolescents was postponed until the October meeting. He described cases in which school and social services officials had alleged neglect, Munchausen’s by Proxy, Factitious Disorder (by Proxy), and/or Pediatric Condition Falsification (PCF) in children actually suffering with CFS. He defined each of these conditions and illustrated how a diagnosis of CFS actually excludes these other diagnoses (unless there is proof of abuse). He urged action by various agencies to educate the medical and educational communities about CFS, and to provide adequate support services. Dr. Bell responded to questions from the Committee. He estimated that, in his experience, cases in which parents are accused of PCF can last from one year to 10 years. He noted that the trivialization of CFS results in certain traumas independent of the symptoms of the condition itself.

Public Testimony
The afternoon session concluded with a second hour of five-minute statements from members of the public. Kim McCleary (CFIDS Association of America), Sara Council Turner, Staci Stevens (IACFS/ME), Dr. Fred Friedberg (IACFS/ME), Cort Johnson on behalf of Dr. Charles Lapp (IACFS/ME), Marilou Regan, Nancy McGrory Richardson (Hemispherx Biopharma) and Dr. Janet Smith delivered remarks. Dr. Jones informed the Committee that the second day’s agenda would be adjusted to hear from Dr. Jerry Holmberg of the DHHS Office of Public Health and Safety on blood safety issues, and that more than 400 people had participated in the meeting via the live videocast.

Day Two
A brief agency report from Dr. Debra Willis-Fillinger of the Health Resources and Services Administration (accommodated due to her absence from the previous morning’s session) generated discussion about the need for clinical guidelines for CFS to improve health service delivery and care to CFS patients. The final hour of public testimony followed, with statements made by Mike Dessin, Laurel Bertrand (by video), Dr. Laura Black (Hunter-Hopkins Clinic), Dr. Ken Friedman (IACFS/ME), Debra Waroff, Dr. Lee Meisel (IACFS/ME and Epiphany Biosciences), Susan Magowitz, Meghan Morgan-Shannon, Harnor Sighn, Eileen Holderman (NJ CFS Association), and Albert Donnay (MCS Resources and Referral).

Dr. Jerry Holmberg: DHHS Office of Public Health and Safety
The Committee continued its discussion of past recommendations from the afternoon prior, and broke its dialogue to hear from Dr. Jerry Holmberg about issues related to the safety of the blood supply that have arisen the wake of the XMRV report. Dr. Holmberg identified his position in the Department of Health and Human Services as a coordinating body across all the DHHS agencies (NIH, CDC, FDA, etc.) He referred to a written statement and reiterated “lessons learned” from the HIV crisis and the effort to prevent that history from repeating itself. He explained the different testing methods used to screen the blood supply, nucleic acid testing being the most sensitive, and the need for FDA to approve any diagnostic test for XMRV. He cited the example of West Nile virus and development of a highly specific nucleic acid test within nine months. Dr. Holmberg commented on the need to regularly reevaluate the quality of health questions asked of blood donors and confirmed that his office was engaged with blood supply officials in other countries through the World Health Organization.

The CFS Advisory Committee

Before the next speaker arrived, the Committee returned to a discussion of the CDC’s research plan that had begun the day before. Dr. Miller was asked to comment on the limitations on the plan imposed by the allocation of resources, approximately $5 million per year. He replied that they assembled the plan with every intention of executing it fully, but that priorities might shift over time. He noted that XMRV studies had already risen in importance. He resisted the Committee’s suggestions that the priorities should be reflected in the plan itself, stating that “CDC was never asked to prioritize.” The Committee quickly reviewed its past recommendations to the CDC and agreed to return to the discussion after the final speaker and a lunch break.

Dr. Cheryl Kitt, NIH Center for Scientific Review
Dr. Cheryl Kitt provided an extended update on the review of research proposals – in general and specifically related to CFS – for the Committee’s benefit, the latest in a series of discussions about the peer review system used by the NIH to evaluate applications. CFS applications generally are referred to a special emphasis panel (SEP) that is constituted to review applications on CFS, fibromyalgia, temporomandibular joint disorder, and other painful conditions. There has been conflicting opinion offered to and within the Committee about whether this SEP is an advantage or disadvantage to researchers interested in conducting NIH-sponsored research on CFS.

Dr. Kitt reported that already in 2009, NIH had received a total of 115,000 applications, compared with 77,000 received in 2008. This was largely due to funding opportunities announced as part of the American Reinvestment and Recovery Act (ARRA). Dr. Kitt also explained the changes in the peer-review system implemented over the past year to streamline the application and scoring processes. She provided a historical look at the creation of the SEP and discussed the wide range of expertise required to review CFS grants that span many disciplines and fields. Dr. Kitt noted that the number of applications assigned to the SEP has not changed in the last three years. She encouraged submission of more applications, especially by new investigators and early stage investigators who receive certain advantages in the current review process.

Committee member Dr. Leonard Jason conveyed fellow member Dr. Ron Glaser’s analysis of the SEP composition, indicating that the more recent panels have reflected stronger CFS expertise than earlier ones. He also reported that the IACFS/ME had shared its view that the SEP should be maintained. Dr. Kitt reiterated her past advice that applicants should be in early and regular communication with NIH as they assemble their proposals, and that they should identify appropriate areas of expertise needed for review in the cover letter.

Committee Recommendations

In the last session of the day, Committee members put forward, debated, and revised several formal recommendations to the Secretary of Health. These four passed by unanimous votes. (Note: The "official" record of the recommendations can be found on the CFS Advisory Committe website.)

Recommendation 1:
The CFSAC renews its recommendation to the Secretary to establish Centers of Excellence for CFS that would effectively utilize state of the art knowledge concerning the diagnosis, clinical management, treatment and clinical research.

Recommendation 2:
The CFSAC renews its recommendation to the Secretary, as submitted 6 months ago, to establish progressive leadership at the CDC. It is disappointed that no response has been made to the earlier recommendation and it is interested in getting feedback, especially in light of the comments made to the New York Times by Dr. Reeves that reflect an inappropriate bias and undermine others’ CFS research.

Recommendation 3:
The CFSAC objects to CDC’s continued use of the inadequate and inappropriate 2005 “empiric” research definition for CFS. It recommends that CDC abandon the empiric case definition and the fundamentally incorrect conceptualization of chronic unwellness as being equivalent to CFS incorrect.

Recommendation 4:
The CFSAC has significant concerns about the CDC’s five-year plan. In particular, the priorities articulated in its recommendation of May 2009 have not been adequately captured in the latest draft. The CFSAC renews its recommendation that CDC prioritize: identification of biomarkers and (viral) etiology of CFS; partnership with organizations representing CFS scientific expertise to create guidelines for adult and pediatric management; provide web based guidelines for CFS management given our current state of knowledge and expert opinion; and provide comprehensive information about CFS in partnership with CFS experts to the scientific community, medical and mental health providers, educational institutions and the public for both adult and pediatric CFS through DHHS resources.  

Dr. Miller of CDC was asked to comment on the recommendations and said only that he would take the points of discussion and outcomes back to the program and the center leadership.

Before adjourning, each of the five Committee members whose terms end in January 2010 (Dr. Oleske, Rebecca Artman, Dr. Cindy Bateman, Dr. Morris Papernik and Kristine Healy) spoke eloquently about his or her experience on the Committee and the opportunity to serve the CFS community. Dr. Jones reported that the review process of the 25 nominations made to fill these appointments was under way and that she expected new Committee members to be named early in the new year. She also anticipated that the spring meeting date would be announced in March. Finally, she offered the Department’s thanks and appreciate to the members of the Committee, members of the public still in attendance, people viewing by videocast (which numbered 888 for the first day), and the ex-officio agency representatives.

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