Subject: RFA HL-90-15-B.082490
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Thu, 23 Aug 90 07:47 EST

Hello,
   This is the second of several coming down the wire from the
NIH Guide 8/24/90.  Please post this to the NIH Listserver as:
    RFAHL-90-15-B.082490
    Thanks.
           Dottie
 ---------------------------- Text of forwarded message -----------------------
 
REQUEST FOR
APPLICATIONS
 
RFA:  HL-90-15-B
 
P.T. 04; K.W. 0715032, 0745020, 0745027, 0745070, 0403004
 
COMPREHENSIVE SICKLE CELL CENTER PROGRAM
 
National Heart, Lung, and Blood Institute
 
Letter of Intent Receipt Date:  January 4, 1991
Application receipt date:  September 16, 1991
 
The Division of Blood Diseases and Resources (DBDR), National
Heart, Lung, and Blood Institute (NHLBI), invites
applications for the support of Comprehensive Sickle Cell
Centers to focus on multidisciplinary programs of basic,
applied, and clinical research, and also to include relevant
service activities in diagnosis, counseling, and education
concerning sickle cell disease and related disorders.
 
Comprehensive Sickle Cell Centers provide the environment in
which resources, facilities, and manpower can be coordinated
in order to pursue research and demonstration activities
related to sickle cell disease.  In the setting of a Center,
it should be possible to bridge the gap between fundamental
and clinical research and patient care by taking advantage of
interactions between various research disciplines, by
encouraging the development of demonstration and education
programs to expedite the transfer of new knowledge, and by
providing local capabilities which can serve the needs of
affected individuals and families.
 
Sickle cell anemia, first described in this country in 1910
by Dr. James B. Herrick, is an hereditary blood disorder
characterized by the presence of recurrent episodes of pain
called "crises," a chronic anemia related to accelerated
destruction of red blood cells, increased susceptibility to
certain infections, and acute and chronic damage to various
organs.  This blood disorder results from the presence of
genes for sickle hemoglobin inherited from both parents.  In
the United States, sickle cell anemia is predominantly, but
not exclusively, found in persons of African ancestry.  The
prevalence of sickle cell anemia within this group is
approximately one in 500 at birth, affecting more than 50,000
individuals.  This disorder is also found in Greeks, Southern
Italians, Eti-Turks, Arabs, Egyptians, Southern Iranians, and
Asiatic Indians at incidence rates often equal to or greater
than that found in Blacks.  In addition, sickle cell
hemoglobin also occurs in combination with other abnormal
hemoglobins and thalassemia.  Thus sickle cell anemia and
related hemoglobinopathies are among the most common genetic
blood disorders seen in this country.  The medical costs for
caring for a patient with these conditions can be extremely
high.  This expense, when added to the loss of time from
school and employment and the resultant psychosocial and
educational problems, makes this disorder one of high
psychologic, social, and economic importance.
 
ADMINISTRATIVE BACKGROUND
 
The National Institutes of Health established the
Comprehensive Sickle Cell Center Program in 1972, in response
to a Presidential initiative and Congressional mandate.
After an open competition, ten Centers were funded in 1972
and five additional Centers in 1973.  Subsequent requests for
applications in 1977, 1978, 1983, and 1988 resulted in the ten
Comprehensive Sickle Cell Centers that are currently funded.
The Sickle Cell Disease Branch, DBDR, NHLBI,
announces its plan to fund, for the period 1993-1998, 10
Comprehensive Sickle Cell Centers, each capable of a wide-
range of activities emphasizing basic and clinical research.
These Centers also provide facilities for bringing improved
medical services to the community.
 
DESCRIPTION OF COMPREHENSIVE SICKLE CELL CENTERS
 
A Center should be an identifiable unit within the sponsoring
institution, usually a university or research-oriented
hospital.  It should be organized around a group of
investigators and health care workers engaged in ongoing
basic and clinical research and community service related to
sickle cell disease.  Each Center must be affiliated with an
established medical institution with facilities and patient
populations available for clinical investigations in sickle
cell disease.  While a Center must devote its major effort to
basic and clinical research, it must also support quality
programs in diagnosis, education, and counseling related to
sickle cell disease.
 
A Center is headed by a Program Director who may also be a
principal investigator on one or more of the projects
contained within the Center.  Committees, internal and
external, which provide scientific and fiscal overview of
Center activities are required.  In addition, a formal,
ongoing agreement among the sponsoring institution and the
Center must be developed specifying the commitment of each
to the other. Because of the diversity and complexity of the
components of a Sickle Cell Center, the Program Director must
pay particular attention to coordination, communication, and
interaction among the various activities which constitute
the whole.  The Program Director must be involved not only in
the management of the basic and clinical research efforts but
must also provide overall leadership to the service-oriented
activities provided by the diagnostic, counseling, and
educational components of the Center.  The Program Director
must maintain close contact with NHLBI program
administrators and grants management officers responsible for
each program.
 
Individual components, including core projects, must have
their own director, comparable to the principal investigator
of a research project grant.  While individual components may
enjoy a certain amount of autonomy in the conduct of a
specific project, each is directly accountable to the Center
Program Director, who has overall responsibility for program
coordination, implementation, and evaluation.
 
Projects conducted at collaborating institutions under
contractual or consortial agreements shall be directed by a
project director who is responsible to the Center Program
Director for conduct of project activities in compliance with
approved protocols.  Although these contractual agreements
are between the grantee and collaborating institutions, they
must be reviewed and approved by NIH staff before they can be
implemented and grant funds expended for their conduct.
 
Under the guidance of the Program Director, activities within
each of the required program components (research, education,
diagnosis, and counseling) should be coordinated and
integrated to enhance and strengthen interrelated activities
and to facilitate communication and information exchange
among components.  Such interaction should be frequent,
formalized, and documented to facilitate continuous exchange
of relevant information between projects and components, thus
contributing to greater program productivity and
effectiveness.  Regular meetings of project directors,
seminars, poster sessions, and staff lectures are excellent
mechanisms for fostering communication and interaction among
Center staff.
 
Finally, each Program Director will be expected to develop a
mechanism for the ongoing evaluation of the effectiveness and
impact of the activities constituting the Center program.
While NHLBI will continue to assess the quality and
performance characteristics of the program through periodic
peer review and staff evaluation, each of the Centers must
consider approaches by which it can demonstrate how the local
program has influenced understanding and practice in matters
related to sickle cell disease.  Only by establishing and
validating the benefits of the Center program can the long-
term support of this approach be justified.
 
OBJECTIVES AND SCOPE
 
The following broad goals of the National Sickle Cell Disease
Program are directly applicable to the Center concept:
 
1. To foster research and development at both the fundamental
and clinical levels.  Examples are listed below to indicate
research investigations considered appropriate for
Comprehensive Sickle Cell Centers. The list is neither
exclusive nor all-inclusive.  Applicants may propose work in
related areas which bear directly or indirectly on any of
the problems of sickle cell disease.
 
.  The role of hematopoietic growth factors on the
    reactivation of Hb synthesis in erythroblasts.
 
.  Reperfusion lung injury in sickle cell disease.
 
.  Development of animal and cellular model systems.
 
.  Genetic and molecular control of globin gene expression.
 
.  Nutrition in sickle cell disease.
 
.  Bone marrow transplantation.
 
.  Hemostatic and thrombogenic abnormalities.
 
.  Endothelial function.
 
.  Non-invasive techniques for monitoring CNS events.
 
.  The micro-environment in sickle cell disease,
    hemodynamics and rheology.
 
.  Immune dysfunction.
 
.  Interaction of genetic modifiers.
 
.  Drug development.
 
.  Haplotype analysis-clinical severity.
 
.  Improved therapy and clinical management of patients with
    sickle cell disease.
 
.  Membrane defect-lipid and protein abnormalities,
    transport studies.
 
.  Adherence factors-plasma, red cell adherence molecules.
 
.  Auto-oxidation in sickle erythrocytes.
 
.  Improved therapy and clinical management.
 
.  Gene therapy.
 
.  Structure of sickle hemoglobin fibers.
 
.  Sociological and psychological effects of sickle cell
    anemia, including coping mechanisms and interfamilial
    dynamics and relationships.
 
2. To develop educational programs to serve the
needs of:
 
   .   medical and allied health professionals to ensure
       that an adequate supply of appropriately trained
       personnel is available to manage patients with sickle
       cell disease; and
 
   .  patients, family members, and social agencies where
     community education programs can affect the daily
     lives of the patient with sickle cell disease.
 
3. To provide facilities where accurate diagnosis, including
hemoglobin genotyping, can be performed.  Although mass
screening efforts are inappropriate for Center
applications, targeted screening programs, e.g., newborn
diagnosis, diagnosis of couples-at-risk of producing
offspring with sickle cell disease, and efforts to refine
techniques for prenatal diagnosis could be supported.
 
4. To provide genetic counseling based on accurate diagnosis
of hemoglobin genotypes.  All counseling should be non-
directive.  Adequate information should be provided
counselees to enable them to make informed decisions about
health-related and/or family planning issues affecting
their lives.
 
5. To develop improved clinical care of patients with sickle
cell disease.
 
Comprehensive Sickle Cell Centers should be in an excellent
position to make major contributions toward achieving these
aims because of their multidisciplinary programs of research
at both the fundamental and clinical levels.  While each
Center should be responsive in some measure to all of the
above goals, the major emphasis of the Center should be on
the basic and clinical research aspects of the program, the
nature of which will depend upon the interests and areas of
expertise of its investigators, as well as on the physical
resources and population available.  However, each
institution requesting Center support should have a basic
range of competence and potential that will enable it to
develop a program addressing all of the Center goals.
 
Centers should also provide a challenging environment for
attracting talented young minority scientists into biomedical
research and offering opportunities for career development.
 
COLLABORATION
 
Active cooperation among Centers is required.  Collaborative
efforts among Center projects and between Centers enhance
productivity and facilitate technology transfer between
research and clinical application.  Therefore, multi-
institutional projects are encouraged, if deemed necessary to
achieve specific, identified program goals.  Center program
directors shall meet annually to review their progress and to
plan new approaches for future collaborative work.  Thus, the
accomplishments of Centers will be shared freely and
expeditiously.
 
ELIGIBILITY CRITERIA
 
In addition to the established eligibility criteria for
Public Health Service grants, applicant organizations must be
associated with a major medical institution with appropriate
facilities and must have available the patient population
needed for the proposed research and service activities.
 
Universities and medical schools, hospitals and public or
private research institutions, alone or in collaborating
arrangements, are encouraged to apply for a Comprehensive
Sickle Cell Center grant.  Minority health professional
institutions are also encouraged to apply.  It is our
intention to support at least one or more such minority
institutions that propose a program that is approved by peer
review and can fulfill the needs and requirements of the
Sickle Cell Centers program.  All applications must
demonstrate competence in appropriate basic and clinical
research and in diagnosis, education, and counseling to meet
the objectives of this RFA.
 
EXCLUSIONS
 
Studies of the clinical course ("natural history") of sickle
cell disease are currently being conducted in a multi-
institutional collaborative Cooperative Study of Sickle Cell
Disease.  Therefore, applications to pursue such
investigations are not appropriate to this Comprehensive
Sickle Cell Center competition.  Applications lacking any of
the required components (research, education, diagnosis, and
counseling) will be considered as non-responsive to this RFA
and will not be accepted.
 
INCLUSION OF FEMALES IN STUDY POPULATIONS
 
In proposed studies involving humans, females should be
included in the study population, otherwise a clear rationale
for their exclusion must be provided in the application.
 
MECHANISM OF SUPPORT
 
Although the support mechanism will be the grant-in-aid, it
differs from the traditional research project grant in the
goal orientation of the Center and in the degree of
participation by the Institute's program staff.  The grant
may provide funds to support core resources, fundamental
and/or applied research, clinical applications, demonstration
projects to improve community services, and certain
educational activities.  It is anticipated that a minimum of
approximately two-thirds of the support funds shall be
devoted to the research and development aspects of the
Center program, the remaining amounts may be devoted to
demonstration activities in education, testing and
counseling.  The actual balance between research and
demonstration will vary from Center to Center and will depend
on local circumstances and competencies.  The programs to be
supported and their funding levels in FY 93 will be
determined by the scientific merit of applications received
and adjudged by established peer review procedures.  The FY 9l
fiscal support for the Centers program is $l4.9 million.
Although the Institute will consider a modest expansion of
this program, the availability of FY 93 funding is
contingent on the provision of money through the
appropriation process.  Awards in response to this
announcement will not be made to foreign institutions.
Subprojects to foreign institutions will be considered only
for high-quality research of very unusual merit, programmatic
need, a unique potential, and documented evidence of
effective collaborative arrangements.
 
NHLBI POLICIES RELATED TO CENTERS
 
1. NEW CENTER APPLICATIONS:
 
New applications may request up to $1.0 million direct costs
(exclusive of indirect costs on subcontracts) in the first
year with a maximum increase of no more than 4 percent in
each additional year requested in that application.
APPLICATIONS WHICH EXCEED THESE LIMITS WILL BE RETURNED TO
THE APPLICANT.
 
Requests for special equipment that cause the applications
to exceed these limits, however, will be permitted and
considered on an individual basis.  Applicants should make
every attempt to include all equipment in the ceiling amount
and to discuss the equipment request with NHLBI staff early
in the planning phase of their application.  All requests for
equipment that cause the application to exceed the limits
will require in-depth justification and will be carefully
considered throughout the review process.  Final decisions
will depend on the nature of the justification and the
Institute's fiscal situation.
 
2. COMPETING RENEWAL CENTER APPLICATIONS:
 
Competing renewal applications may request up to $1.0
million direct costs (exclusive of indirect costs on
subcontracts) or a 10 percent increase over the recommended
amount shown on the Notice of Grant Award for the last non-
competing year, whichever is greater, with a maximum increase
of no more than 4 percent in each succeeding year.  The same
policy regarding equipment which is stated above under "New
Applications" applies to competing renewals.  APPLICATIONS
WHICH EXCEED THESE LIMITS WILL BE RETURNED TO THE APPLICANT.
 
3. MODIFICATIONS TO AN APPLICATION FOLLOWING SUBMISSION:
 
Center grant applications may not be modified by the
applicant after submission or at any stage during the review
process.
 
All projects, core units, and budgetary requests presented in
the application will be reviewed by the Center Parent Review
Committee and the NHLBI Advisory Council.
 
COMMITMENT OF THE GRANTEE ORGANIZATION AND CENTER STAFF
 
It is expected that each Center will have the flexibility to
plan, direct, and execute its own program reflecting local
interests and resources.  However, each Center must also be
responsive to the identified objectives of the Sickle Cell
Disease Program as to both program content and direction.
The Center will be requested to provide documentation
concerning progress and effectiveness on an annual basis.
Overall activities will be reviewed periodically by the
staff of the Sickle Cell Disease Branch.  This review will
involve assessment and evaluation of progress and plans for
future project activities.  Facilities and resources must be
available for all of the primary needs of the Center.  Funds
for new construction cannot be provided; therefore, the
facilities must be adequate for the purpose of the Center
with either no, or only very minor, alterations and
renovations.  The applicant organization must be willing to
make a long-term commitment of these physical resources to
the Center.  Both the physical facilities and the human
resources of a Center should serve to foster effective
interaction among individuals representing many different
disciplines.
 
Key staff members must also be willing to make a long-term
commitment.  In the administration of the Center, the Program
Director should be able to provide leadership for all aspects
of the program.  The Program Director shall be responsible
for the organization and operation of the Center, for
communication with the National Institutes of Health on
substantive and operational matters, and for effective
exchange of information with other Centers.
 
REVIEW MECHANISM AND CRITERIA
 
Initial scientific merit review of applications for
Comprehensive Centers solicited in this announcement will be
conducted by the Division of Extramural Affairs, NHLBI,
using a Parent Committee of
expert consultants.  The review may involve a reverse site
visit or an on-site visit.  Final review will be by the
National Heart, Lung, and Blood Advisory Council.  Criteria
for evaluation of the application will include:
 
a.  Qualifications, experience, and commitment of the
Center Director and the ability to devote adequate time
and effort to provide effective leadership.
 
b.  Scientific merit and quality of the proposed
projects.  Each project will be assigned a priority score
based on scientific merit and relevance to the goals of
the Center.
 
c.  Competence of the senior personnel to accomplish the
proposed goals of the Center, their commitment, and time
they will devote to the project.
 
d.  Adequacy of the facilities to conduct the proposed
research including laboratory and clinical facilities,
access to patients, instrumentation and data management
systems, when needed.
 
e.  Nature of the overall structure and management of the
Center, including scientific and fiscal management,
integration of the parts, and quality control.
 
f.  Appropriateness of the budget in relationship to the
proposed program.
 
g.  Committee structure, both internal and external, and
projections for ongoing evaluation of the Center's
effectiveness.
 
h.  Institutional commitment to the program as evidenced
by provision of resources, and the appropriateness of the
institutional resources and policies for the
administration of a center program of the type proposed.
 
i.  Willingness of the Center leadership to work
cooperatively with other Sickle Cell Centers and with the
NHLBI.
 
METHOD OF APPLYING
 
Letter of Intent
 
Applicants are requested to send a letter of intent by
January 4, 1991, addressed to:
 
Charles L. Turbyfill, Ph.D.
Chief, Center and Special Projects Section Review Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Westwood Building, Room 553A
Bethesda, Maryland  20892
Telephone:  (301) 496-7351
 
To facilitate Institute planning, applicants are requested to
submit a letter of intent to the NHLBI on or before January
4, 1991.  The letter should indicate a descriptive
title, investigators who might be involved, and any
participants outside the applicant institution.
 
The Institute requests such letters only for the purpose of
providing an indication of the number and scope of
applications to be received and, therefore, usually does not
acknowledge their receipt.  A letter of intent is not
binding; it will not enter into the review of any application
subsequently submitted, nor is it a necessary requirement.
 
Format for Applications
 
Form PHS-398 (revised 10/88) should be used.  Since this
form is designed primarily for the traditional
research-project grant application, several sections have
been modified and/or expanded to more effectively suit the
needs for adequate description of components of a Center.
SPECIFIC GUIDELINES FOR PREPARATION OF APPLICATIONS FOR
COMPREHENSIVE SICKLE CELL CENTER GRANTS ARE AVAILABLE FROM
DR.  WELLS (address below) AS A SUPPLEMENT TO THIS DOCUMENT.
 
To identify the application as a response to this RFA, check
"yes" on Item 2 of page 1 of the application and enter the
title "Comprehensive Sickle Cell Center" and the RFA number
HL-90-15-B.
 
Application Procedure
 
Send or deliver the completed original application and four
(4) signed, exact copies of it, on or before September 16,
1991, to:
 
Division of Research Grants
Westwood Building, Room 240
National Institutes of Health
Bethesda, Maryland  20892**
 
AT THE SAME TIME, SEND AN ADDITIONAL TWO (2) COPIES OF THE
APPLICATION TO DR. CHARLES L. TURBYFILL AT THE ADDRESS UNDER
LETTER OF INTENT.  THE NHLBI CANNOT GUARANTEE THAT THE
APPLICATION WILL BE REVIEWED IN COMPETITION FOR THIS RFA
UNLESS THESE TWO COPIES ARE ALSO RECEIVED ON OR BEFORE
September 16, 1991.
 
THE RFA LABEL (AVAILABLE IN THE 10/88 REVISION OF APPLICATION
FORM 398) MUST BE AFFIXED TO THE BOTTOM OF THE FACE PAGE OF
THE ORIGINAL COPY OF THE APPLICATION.  FAILURE TO USE THIS
LABEL COULD RESULT IN DELAYED PROCESSING OF YOUR APPLICATION.
 
Timetable
 
Letter of Intent........................January 4, 1991
Receipt of Applications.................September 16, 1991
Advisory Council Review.................September 10-11, 1992
Awards..................................April 1, 1993
 
INQUIRES
 
Inquiries regarding this announcement may be directed to the
program administrator:
 
Charles A. Wells, Ph.D.
Federal Building, Room 504
National Institutes of Health
Bethesda, Maryland 20892
Telephone:  (301) 496-6931
 
The programs of the Division of Blood Diseases and
Resources, National Heart, Lung, and Blood Institute, are
identified in the catalog of Federal Domestic Assistance,
number 13.839.  Awards will be made under the authority of
the Public Health Service Act, Section 301 (42 USC 241) and
administered under PHS grant policies and Federal
regulations, most specifically 42 CFR Part 52 and 45 CFR part
74.  This program is not subject to the intergovernmental
review requirements of Executive Order 12372, or to Health
Systems Agency Review.