Centers for Disease Control and Prevention CFS Public Health Research Program 5-year Strategic Plan
(October 2009)

In November 2008, CDC convened an external peer review panel to examine its Chronic Fatigue Syndrome Research Program. One recommendation of this panel was to develop a strategic plan for research. CDC sought broad public input in the development of its plan, including comments during and following an April 2009 public meeting, discussions with collaborators, and input received at and following the May 2009 HHS CFS Advisory Committee meeting.

In response to CDC´s request for input to the strategic research plan, from April 27 through July 30, 2009, we received almost 1,200 items of correspondence from scientific societies, patient advocacy organizations, researchers, physicians, and many individuals with CFS and their family members. Comments specific to the draft could be categorized into the following topic areas:

• Pathophysiology of CFS
• Causes of CFS
• Diagnostics
• In-hospital and pharmacologic studies
• Treatment and management of illness
• Provider and public education
• CFS in children

The current strategic plan addresses all of these issues.

Many comments received also raised questions not directly related to the research plan and pointed out misconceptions about CFS and CDC´s activities. We are developing a revision to our website to address these questions and concerns and will also explore other mechanisms to improve our communications with patients and our partners regarding these important issues.

The CFS Public Health Research Program 5-year Strategic Plan published below reflects CDC´s goals and planned activities to address this important public health issue.

CFS Public Health Research Program Strategy

CFS is a complex illness representing alterations in multiple ecologically and biologically interrelated homeostatic systems. CFS is clinically heterogeneous and comprised of subtypes. CFS is not the result of a single mutation or simple environmental factor but likely arises from a combined action of many genes, environmental factors (including infection), and risk conferring behaviors. CDC´s CFS Public Health Research Program´s 5-year strategic plan takes into account recommendations of the November 2008 Peer Review Panel, comments solicited from stakeholders, and discussions with collaborators. As noted by the Peer Review Panel´s report and in alignment with CDC´s public health mission, program strategy has successfully focused on obtaining baseline information necessary to plan interventions and to qualitatively and quantitatively measure associated outcomes. These activities complement clinical research initiatives that focus on the causes, consequences, and treatment of CFS and related diseases, such as those sponsored by the National Institutes of Health (NIH) and other research organizations. CDC has ongoing collaborations with these organizations and plans to strengthen these collaborations further, as recommended by the Peer Review Panel.

Over the next five years, the CFS Public Health Research Program strategy will follow an interactive, biosystems model approach with increasing emphasis on translational research that involves the design, implementation, and evaluation of clinical, educational, and public health interventions. By conducting public health research that leads to control and prevention strategies, the overarching goal is to reduce the morbidity associated with CFS (and similar medically unexplained chronically fatiguing illnesses) and to improve the quality of life of persons with these illnesses.

CFS Public Health Research Program Goals - What CDC desires to accomplish

Refine understanding of the etiologic pathways involved in CFS in order to improve diagnosis and to identify therapeutic targets

• Identify risk factors related to constellations of clinical attributes (i.e., subsets of CFS)
• Identify psychosocial, clinical, and laboratory biomarkers associated with the clinical course of CFS and subsets of the illness
• Measure neuroendocrinologic, metabolic, immunologic, and infectious characteristics of CFS to identify potential diagnostic and therapeutic targets for various subsets of the illness
• Elucidate pathophysiologic mechanisms associated with symptoms and subsets of the illness
• Develop collaborative data-sharing networks to extend knowledge concerning CFS

Improve clinical management of CFS patients by developing and providing evidence-based educational materials that address evaluation and clinical management of CFS

• Develop international consensus regarding diagnosis of CFS in clinical and research settings (i.e., research, clinical, pediatric/adolescent case definitions)
• Develop international consensus regarding management of CFS and future research direction
• Provide current evidence-based information on diagnosis and management of CFS to health care providers, persons with CFS and their caregivers, and evaluate associated outcomes
• Evaluate effects of access, utilization, and quality of health care on clinical course of the illness

Improve diagnosis and management of CFS through basic research

• Collaborate to establish an international CFS research network
• Collaborate to conduct clinical intervention trials

Move CFS into the mainstream of public health concerns

• Develop collaborations with national, state, and local public health authorities
• Provide current evidence-based information concerning CFS to federal, state, and local public health authorities, related government agencies, and HMOs
• Evaluate outcomes associated with dissemination of public health information

CFS Public Health Research Program Activities - How CDC plans to meet its Goals

Population-based surveillance

First Follow-up Study of CFS and Chronic Unwellness in Georgia

Field work on the first follow-up study of CFS and chronic unwellness in Georgia was completed in August 2009. Approximately 80% of those who participated in the baseline survey also participated in the follow-up study. Analysis, interpretation, and presentation of findings will occur through early 2011. Focus of initial analyses will be on information that can be used to modify provider education activities.

• Determine knowledge, attitudes, and beliefs concerning CFS and the effect on clinical course of the illness
• Evaluate direct and indirect economic impact of CFS
• Evaluate association of barriers to healthcare utilization with illness course
• Evaluate association between medical history, exercise patterns, tobacco use, and CFS
• Refine analysis of allostatic load, cortisol, alpha amylase, inflammation index, and genetics of CFS
• Evaluate incidence of metabolic syndrome and diabetes

Second Follow-up Study of CFS and Chronic Unwellness in Georgia

Field work on the second follow-up study of CFS and chronic unwellness in Georgia will begin in mid-2010 and continue into 2011, with analysis of results occurring through 2012.

• Identify defined subsets of persons with CFS
• Modify provider education activities, evaluate effects of education activities, and plan intervention trials
• Explore associations between clinical parameters, laboratory biomarkers, psychosocial, and environmental factors and the risk of incident CFS, persistent or progressing CFS, and recovery from CFS
• Measure the contribution of electrophysiologically identified sleep disorders to CFS and to the clinical course of the illness

Mayo Clinic Rochester Epidemiology Project

Retrospective collaborative study will utilize medical records from the Rochester Epidemiology Project to study risk factors associated with the incidence of CFS and clinical course of the illness in the population of Olmstead County. Work will begin in late 2009 with analysis, interpretation, and publication of data occurring through 2011.

• Categorization of risk factors associated with CFS

Bibb County CFS Patient Registry - initial enrollment

The initial round of patient recruitment will be completed by December 2009. Analysis, interpretation, and presentation of findings will occur through mid-2010.

• Identify the most efficacious and efficient manner of identifying, screening, and enrolling patients in longitudinal registry
• Identify clinical differences between patients enrolled through the registry and persons with CFS identified in the population-based studies
• Identify provider education issues

Bibb County CFS Patient Registry - first follow-up study

First follow-up and modification of patient registry activities will occur though FY 2012. In 2013, a provider registry may be considered in another region of the country.

• Evaluate clinical course and outcomes of intervention protocols
• Identify well-characterized participants for clinical studies

Clinical and Laboratory Studies

In-Hospital Clinical Studies

Field work from a three-day, in-hospital study, in collaboration with Emory University, was completed in July 2009 and analyses will occur through early 2011. Study findings will be integrated into protocols for population cohort studies, provider education activities, and clinical intervention trials.

• Identify brain regions associated with cognitive deficits in CFS
• Identify neural circuits involved in CFS-associated interoception
• Evaluate HPA axis, autonomic nervous system, immune system, and neuroendocrine system function during stress
• Identify genetic and epigenetic covariables
• Identify pathophysiologic and clinical subsets presenting as the illness CFS

Laboratory Studies

The integration of laboratory studies with specific CFS research protocols helps to clarify associations of behavioral and environmental risk factors (including infection) with clinical and psychosocial attributes of CFS, to identify subsets of the illness CFS, and to identify potential therapeutic targets.

• Measure neuroendocrinologic, metabolic, immunologic, and infectious characteristics of CFS
• Evaluate genetics, epigenetics, and gene expression
• Identify potential diagnostic and therapeutic agents
• Evaluate the potential association of human herpes virus 6 (HHV-6) and xenotropic murine leukemia virus-related virus (XMRV) with CFS using specimens from well-characterized patients and matched controls
• Maintain a biorepository of clinical specimens collected during population and clinical studies for in-house and collaborative molecular analyses
• Develop a funding opportunity announcement to explore the application of novel pathogen discovery approaches to existing, well-characterized clinical specimens

Clinical Intervention Studies

Clinical behavioral intervention studies will be conducted in collaboration with Emory University School of Medicine, Bibb County Medical Society, Mercer School of Medicine, Mayo Clinic, and UK National Health Service. Anticipated protocol development will begin in late 2010-2011, with studies continuing through 2013.

• Evaluate cognitive behavioral therapy and graded exercise in participants
• Stratify impact of intervention by various parameters including duration of illness, onset type, early life stress, psychiatric comorbidity, cortisol responsiveness, and fMRI changes

Results from the CFS adolescent foster care study will be used to plan a large-scale longitudinal intervention study that will occur through 2013.

• Identify and target specific risk factors for CFS

Pharmacologic intervention trials will be conducted in collaboration with partners that may include pharmaceutical companies and academia. Anticipated protocol development will begin in 2010-2011 and studies could occur through 2013.

• Target pathophysiologic pathways involved in CFS

Data Sharing

The CFS Public Health Research Program embraces the philosophy of transparency in the preparation, dissemination, and use of scientific information, including large datasets. A recent example of this approach resulted in the publication of a collection of findings and advances that could not have been made by any one research organization alone. The CFS Public Health Research Program is committed to working with the Office of Science and Technology Policy, the Department of Health and Human Services, CFS research colleagues, and others, to develop working policies and procedures to implement these data-sharing goals while maintaining appropriate protection for all research study participants.

Educational Intervention and Research

DocStyles

DocStyles is a CDC sponsored national survey to aid in understanding healthcare providers´ knowledge, attitudes, and beliefs concerning CFS. CDC anticipates receiving an analysis database in October 2009, based on questions in the current DocStyles survey, and publishing the results in early 2010.

• Design educational interventions and evaluate their efficacy
• Develop questions for next DocStyles survey

CDC CFS Website

Based on statistical and data mining analysis of website utilization patterns, a new CDC CFS website is under design and should be operational in late 2009, with two additional major revisions anticipated by 2013. Beginning in late 2009, CDC will also explore links with other websites including those of state and city health departments, Medscape, and WebMD.

• Detailed analyses of public and professional user needs

CFS Provider CME

CDC anticipates continuing the CME component of provider education for primary care physicians, nurse practitioners, physician assistants, and allied health professionals. In 2010-2011, the current courses will be revised.

• Design and implementation of a more focused set of CFS continuing education courses

Pilot Health Care Provider Education

Partnerships formed with healthcare providers participating in the patient registry in Bibb County will provide an opportunity to conduct a focused community health care provider education and intervention study.

• Engage CSTE and state and local health departments in the development of a CFS toolkit and orchestrate its dissemination to public health agencies
• Engage national public health practice organizations, state and local health departments, and HMOs

Workshops and International Research Networks

International Workshop - Clinical Management of CFS

The aim of this workshop, anticipated to be held in 2010, is to establish a collaborative international consortium of investigators who will present and discuss evidence- and practice-based findings related to the treatment, and management of CFS.

• Publish management guidelines applicable to practicing health care professionals in the treatment of CFS
• Establish a network of investigators, clinicians, and others who will meet regularly to discuss clinical management issues pertinent to CFS and related illnesses

International Workshop - CFS Case Definition

CDC convened an International CFS Study Group that met in 2000, 2001, and 2002, and in 2003, published recommendations to guide systematic and reproducible application of the case definition. In 2010, CDC anticipates convening an international workshop to discuss research and clinical CFS diagnostic criteria for adults and children.

• Develop consensus as to status of the published 2003 Study Group recommendations
• Develop consensus as to an appropriate CFS case definition for health care providers