CDC Chronic Fatigue Research Program -External Peer Review

[Guest guest]

~

Although the suffering of ME/CFS patients is

going on, because NOTHING has changed since the

CDC started their very expensive research in the

Eighties - the *Panel of External Reviewers*

concluded:

*....The CDC should continue to support the CFS

program so that it can continue its successful

work....*

~jvr

``````````

From: Tom Kindlon

CDC Chronic Fatigue Research Program -

External Peer Review

On the criteria issue, no criticism based on a quick

skim:

" In particular, CDC has led the world in defining the

illness, including improving the quantitative

precision with which the illness is defined-through

development of a standardized case definition. While

some have recently criticised the recent

standardization of the research criteria for CFS, the

panelists believed that the CDC's work on

psychometric operationalization of the existing 1994

case definition should improve the reliability of

research. "

http://www.cdc.gov/cfs/pdf/cdc_cfs_research_program-external_review.pdf

CDC Chronic Fatigue Research Program

External Peer Review

5-7 November 2008

Panel of External Reviewers:

Boulton, MD, MPH,

L. Komaroff, MD (Chair),

Gudrun Lange, PhD,

Oleske, MD (excused),

White, MD

The external review panelists visited the CDC Chronic

Fatigue Research Program from November 5 to 7,

2008. The Chronic Fatigue Syndrome (CFS) team is

charged both with conducting research and

educational programs. The visit included initial and

exit briefings with Stephan Monroe, PhD, the Director

of the CDC Division of Viral and Rickettsial Diseases

in the National Center for Zoonotic, Vector-borne,

and Enteric Diseases, Reeves, MD, the

Director of the CDC Chronic Fatigue Research

Program, as well as program team leaders. Several

opportunities were provided to interact with all

program staff through PowerPoint and poster

presentations and a facilities tour over the three

days of the review.

Executive Summary

Both the research and education teams presented an

informative overview of their mission, goals, and

accomplishments in an integrated format of

presentations and poster presentations. We

summarize here our responses to the primary

questions posed to the panelists by Dr. Monroe:

1* " Are the current mission and goals of the program

appropriate and consistent with the public health

mission of CDC? " The review panelists felt that the

efforts of the CDC have highlighted the public health

importance of CFS, through CDC's documentation of

the high prevalence and substantial functional and

financial burden imposed by this illness. The

panelists felt that the CDC was uniquely positioned

to conduct a broadly based research program derived

from the population, a large-scale educational

outreach program, particularly to healthcare

professionals, and to be an expert web based

resource for patients, their families and

non-healthcare professional bodies. The panelists

also believed that the CDC was the best placed

institution to lead the establishment of both

research and educational networks, both nationally

and internationally.

2* " What should be the specific goals and objectives

of the program over the next 3-5 years (i.e., what

should be the target(s) that the program is aiming

for? " The review panelists felt that they were better

positioned to evaluate the goals and objectives

articulated by the leadership of the program than to

propose their own goals and objectives. In general,

the panelists felt that the accomplishments of the

research program thus far have been substantial, and

that all of the current research projects address

important issues. The panelists' judgement was that

the CDC team currently leads the world in both the

breadth and depth of their research into CFS. At the

same 1 time, time, the panelists felt that a written

articulation of a five-year plan for both research and

education needed to be created and shared widely.

3* " Given the recommendations above, what

research and programmatic activities should the

program be engaged in now and in the coming years

in order to be on track to achieve the desired goals

and objectives?

a. -Current activities that should be continued or

expanded

b. -Current activities that should be reduced or

eliminated

c. -New activities that should be initiated:

intramural, or via extramural collaboration "

A compilation of the review panelists' detailed

responses to these questions appears below.

Research Program

Strengths to be further encouraged

1* The review panelists judged that over the past

decade, the CDC team has amassed a very important

body of research work on CFS. In particular, CDC has

led the world in defining the illness, including

improving the quantitative precision with which the

illness is defined-through development of a

standardized case definition. While some have

recently criticised the recent standardization of the

research criteria for CFS, the panelists believed that

the CDC's work on psychometric operationalization of

the existing 1994 case definition should improve the

reliability of research.

2* The CDC also has played a key role in elucidating

the heterogeneity of CFS, measuring the prevalence

of the illness, assessing the cost to society from

both lost productivity and from medical care

expenses, identifying possible psychosocial

underpinnings of the illness, identifying possible

genetic polymorphisms that render a patient

vulnerable to the illness, and more broadly studying

pathophysiology (such as its studies of gene

structure and expression in CFS). The panelists

believed that CDC had done much to elucidate the

pathophysiology of CFS and in particular the links

between biological and psychosocial risk markers.

3* An objective marker to assess the impact of the

group's research activities was provided in the form

of number of research publications and impact

factors. The group has published 115 peer reviewed

papers since 2000 and the consequent ISI citations

were the highest in the world for a single institution

in the area of CFS.

4* Although there is much talk about approaching

the study of complex chronic illnesses by using a

" biopsychosocial model " , the CDC research team has

actually " walked the walk. " CDC has organized a

broad array of disciplines in its studies of

CFS-including epidemiology, biostatistics,

demography, psychology, and molecular diagnostics.

5* Moreover, those efforts have been shared beyond

CDC with great success. For example, through the C3

and CAMDA programs, extremely large data sets,

containing clinical, demographic, psychological,

laboratory, and molecular diagnostic data, have been

openly shared with external colleagues, which has

resulted in a paradigm shift in how CFS is now

regarded. The decision to seek speedy publication in

public access electronic journals also results in

sharing information with the research community at

the earliest possible time. The panelists would

encourage further data sharing at the appropriate

times.

6* The CDC has taken advantage of its proximity to

Emory University to engage talented clinical

investigators, particularly in behavioral sciences,

neurology, neuroimaging and endocrinology, in the

study of patients recruited as part of CDC's studies.

It also is working with the University of Miami.

7* The panelists were impressed by the program's

scientific and intellectual rigor.

8* The loyalty, commitment, enthusiasm, intellectual

rigor and dedication of team members was

impressive. Staff meetings occur weekly, lasting two

hours, the open nature of communication was

obvious, and the importance and emphasis on

making consensual decisions was clear. It was

similarly clear that when there are differences of

opinion, Dr. Reeves does not hesitate to make a

final decision.

9* The review panelists were particularly impressed

with the group morale, given that there has been a

sustained organizational ambivalence about the

placement of the CFS program within CDC, which

could have been confusing and disheartening to

some. Solid backing and commitment by CDC would

further enhance group cohesion and productivity.

Potential areas for development

1* Five year plan: The panelists were disappointed

not to see a carefully articulated 5-year research

strategy that integrates current epidemiologic,

laboratory, and educational activities of the program.

While recognizing that research results and external

events almost always cause some alteration in such

plans, the panelists strongly felt that such a plan,

incorporating contingencies, would bring focus to the

effort, and share vision and direction both within the

team itself and with external interested parties. It

would also help the program leadership to better

determine how best to use limited research dollars.

2* Links to public health: The reviewers were

disappointed with the absence of any research

linkages to other public health institutions. For

example, the CDC group should consider whether it

can collaborate in the use of established

databases-such as the Behavior Risk Factor

Surveillance System (BRFSS) in which all states

participate--to better elucidate risk markers.

3* EIS officers: A related concern was the absence of

Epidemic Intelligence Service (EIS) officers in the CFS

research program for many years now, and the

apparent lack of any recent attempts by the program

leadership to recruit EIS officers. Team leadership

should make a serious effort to recruit an EIS officer

through active recruiting practices. An EIS officer

would bring additional scientific expertise and would

speak to the internal credibility and importance of

the program within CDC.

4* External collaborators: Although the program has

collaborated with medical schools in its research, the

reviewers thought that this kind of collaboration

could be expanded. In particular, the reviewers

suggested that the CDC could galvanize the

development of both international and national

research (and educational) networks comprising

academic researchers, providers, public health

practitioners, and community based groups. These

networks might be used to consider in particular the

creation of registries and/or special surveillance

programs.

There is a notable lack of engagement with

governmental public health (i.e. state and local

public health department) by the program.

Epidemiology units in state health departments and

state public health laboratories have a long standing

tradition of active involvement with the CDC in the

conduct of joint applied research. That research

collaboration has played a critical role in initiating

enhanced surveillance and improved characterization

of many emerging diseases and conditions. The

program should also consider more active

involvement with national public health practice

professional organizations such as CSTE, APHL,

NACCHO and ASTHO. These organizations have a

critical role to play in defining CFS as an important

public health issue.

Organizations that face the financial burden of

dealing with complex chronic illnesses, such as

prepaid group practices and health insurance

companies, might also have an interest in supporting

the CDC's efforts to prevent and control CFS. CDC

should consider discussion with such organizations.

5* Research networks: The CDC is ideally placed to

organize detailed planning of an international CFS

research network-identification of institutions that

could be involved, specification of common data

definition and data collection techniques. To this

end, group leadership might want to consider

identifying one or two members of the team who

could be delegated to conduct the planning and

implementation of these networks.

6* GWA studies: Some mention was made of

undertaking genome-wide association (GWA) studies

of CFS. Such an undertaking requires a very large

sample size to be scientifically valid, and should not

be considered until there is a national or

international network in place that could deliver the

required samples.

7* Gene expression studies: Gene expression

studies, on the other hand, are not so dependent on

large sample sizes, and already have led to

interesting results. One important new area relating

to gene expression has not been pursued-microRNA

expression patterns in patients with CFS-and should

be considered. Some of the panelists were also

concerned about the variability in the results of gene

expression studies by the CDC and other groups, and

would encourage the program to work with other

investigators to standardize the conduct of these

studies.

8* Pathophysiology and endophenotypes: While

impressed with the scientific discoveries of the

pathophysiology associated with CFS, and the goal of

identifying " endophenotypes " , the panelists had two

concerns:

The panelists were not convinced that time series

alone would be enough to elucidate whether the

abnormalities found were causal or simply the effects

of having CFS. The panelists recommend that the

CDC program urgently consider intervention studies

to help to elucidate the direction of causality in the

several pathophysiologies identified by the CDC. This

strategy was not articulated clearly. For example,

since both cognitive behavior therapy and graded

exercise therapies are known to address some of the

abnormalities found, and since both these therapies

have been shown to be efficacious for CFS, these

behavioral interventions should be seriously

considered. Collaborations with providers and

medical schools practised in randomised controlled

trials might provide the best means to achieve this.

The group should articulate a clearer strategy for

addressing the issue as to how heterogeneity is

going to confound the establishment of risk markers

and pathophysiology.

9* Pharmacotherapy: Some discussions have been

had with the pharmaceutical industry, which has a

growing interest in medications to treat fatigue. This

kind of interest should be fostered and nurtured.

Educational Program

The review panelists were not asked to review the

effectiveness of the public education program funded

by the CDC, and conducted by a contractor. Instead,

they focused on CDC's efforts at professional

education about CFS and the Web site information it

has created to educate the general public.

Strengths to be encouraged

1* The professional education program began by

attempting to identify professionals in multiple

communities who would become trainers of their

peers. The CDC concluded that this program did not

have sufficient impact. The decision to " cut its

losses " and take a new approach was the mark of

firm leadership and impressed the panelists.

2* The CFS booth at multiple professional

conferences drew over 12,000 visitors. Although no

formal assessment could be conducted of the impact

of this effort, the level of interest was impressive.

3* The 31 Grand Rounds presentations given by CDC

MDs have been attended by over 1,500 physicians

and other health professionals, and impressed the

panelists. The panelists noted with approval that

these contacts had a great potential for establishing

extramural collaborations.

4* The online CME programs on CFS have led to

nearly 1,000 course completion certificates.

5* The visibility and credibility of CDC as an

institution has been an important partner in making

CFS a visible illness.

6* A particularly impressive professional education

effort has been the DocStyles programs in which a

sample of 142,000 physicians assessed their

knowledge about and attitudes toward CFS. The

ability to conduct a survey that large, with a 60%

response rate, is impressive. Moreover, the survey

documents an enormous growth in the understanding

of CFS by practicing physicians over the past 10-20

years-some of it due to the efforts of the CDC in

studying and publicizing the illness.

7* The CDC intends to lead the development of

clinical guidelines for the management of CFS for use

in the USA, and to disseminate these widely. The

review panelists applaud this plan and regard this as

an urgent priority for CDC.

Potential areas for development

1* Public health contacts: As with the research

component of the program, the panelists felt that

the CDC had not reached out to the public health

practitioners in its public and professional education

activities. There should be a focus to identify,

contact, and collaborate with traditional public health

agencies to promote understanding of CFS as a

public health issue. For example, the existing

network of over 3000 local health departments could

be engaged in helping to develop and distribute

information sheets about CFS.

2* Web sites for professionals: The program's web

sites for professionals and for the general public has

not had a lot of traffic. The program should

systematically assess whether major web sites for

health professionals-such as Medscape-include

content about CFS, and links to the pertinent pages

on the CDC Web site. If not, the CDC would likely be

effective in working with these web sites in creating

these links.

Web sites for the public: Likewise, the program

should systematically assess whether the major

health Web sites for the general public-such as

WebMD, MSN, AOL.body, EverydayHealth.com, and

About.com-contain content about CFS and links to

the pertinent pages for the public on the CDC Web

site.

A summary of strategic recommendations

1* The CDC should continue to support the CFS

program so that it can continue its successful

work.

2* Dr. Reeves should create a 5-year strategic action

plan with clear milestones and performance

measures, focused on how the plan hopes to achieve

improved prevention and control. The plan would

identify the strengths and risks of each of the current

major projects underway, how the results of one

project might influence the conduct of another

project, and establish the likely route map between

current projects and the mission aim of control and

prevention of CFS. A progress report that refers to

the written plan should be reviewed by an external

panel in 2 years, although this might not necessarily

require a site visit.

3* The program should establish closer relationships

with traditional public health agencies (i.e. state and

local health departments) for the purpose of

enhancing both research and education

collaborations.

4* The program should consider utilizing already

existing database resources to further the

understanding of CFS in regard to its risk markers

and its standing as a significant public health issue.

5* Clinical guidelines on management should be

developed for use in the USA, by the CDC team in

collaboration with others, and disseminated for CFS.

6* The team needs to consider studies that test the

direction of causality of pathophysiology, such as

using interventions.

Potential conflicts of interest of panelists

Dr Komaroff, Dr. Lange, and Dr. White have

collaborated in research with the CDC program,

published research papers with staff members, and

attended meetings hosted by CDC. They have never

received financial payments from the CDC beyond

travel and accommodation expenses.