SPECIALIZED CENTERS OF RESEARCH (SCOR) IN TRANSFUSION BIOLOGY AND MEDICINE

Release Date:  August 2, 1999

RFA:  HL-99-023

National Heart, Lung, and Blood Institute

Letter of Intent Receipt Date:  December 1, 1999
Application Receipt Date:  January 14, 2000

PURPOSE

The objectives of the Specialized Centers of Research (SCOR) program in
Transfusion Biology and Medicine are to improve the safety and efficacy of
blood and blood components, to determine the indications for their use, to
evaluate and possibly modify immunological responsiveness following their
administration, and to develop and evaluate alternative treatment strategies
that substitute for certain of their functions or stimulate their endogenous
production so as to reduce transfusion needs.  This initiative encourages the
use of new and innovative technologies to conduct quality basic research and
facilitate the transfer of the basic knowledge to the clinical area.  The
ultimate goals of this program are to make optimal use of blood and blood
components and to improve transfusion practice.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of "Healthy People 2000," a PHS-led national
activity for setting priority areas.  This initiative, Specialized Centers of
Research (SCOR) in Transfusion Biology and Medicine, is related to the
priority areas of heart disease and stroke, and cancer.  Potential applicants
may obtain a copy of "Healthy People 2000," (Full Report: Stock No. 017-001-
00474-0 or Summary Report: Stock No. 017-001-00473-01) through the
Superintendent of Documents, Government Printing Office, Washington, DC 20402-
9325 (telephone 202-512-1800).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and non-profit
institutions, public and private, such as universities, colleges, hospitals,
and laboratories.  This RFA is intended to support SCOR grants for basic and
clinical investigations.  Applications that include only basic or only
clinical research will not be responsive to this RFA.  In addition, clinical
research projects focused on large epidemiologic studies or large clinical
trials will be considered unresponsive to this RFA.  Foreign institutions are
ineligible from receiving awards under this solicitation. Under exceptional
circumstances, a foreign component critical to a project may be included as a
part of that project.  Racial/ethnic minority individuals, women, and persons
with disabilities are encouraged to apply as Principal Investigators or
responsible project investigators.

The Principal Investigator should be an established research scientist with
the ability to ensure quality control and the experience to administer
effectively and integrate all components of the program.  A minimum time
commitment of 25 percent is expected for this individual.  The Principal
Investigator must also be the project leader of one of the component research
projects.  If, through peer review, this project is determined to be of low
scientific merit, the overall SCOR application will not be considered further. 
If this project is judged by peer review to be of low scientific merit, it
will markedly reduce the overall scientific merit ranking assigned to the
entire application by the review committee.  Project leaders must agree to
commit at least 20 percent effort to each project for which they are
responsible.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) specialized centers
(P50) mechanism to support this research program. Responsibility for planning
the proposed project will be solely that of the applicant.  The total project
period for applications submitted in response to the present RFA may not
exceed five years.  The anticipated start date of award is January 2001.

Although multidisciplinary approaches are required, it is not the intent of
this announcement to solicit applications for large clinical trials or large
epidemiologic studies.  In general, funds will not be provided for the
purchase and installation of expensive, new equipment.

Upon initiation of the program, there will be required communications between
SCORs, usually in the setting of a biennial combined meeting of SCOR
participants.  Applicants should request travel funds for this purpose in
fiscal years 2002, 2004, and 2006 of the budget.  Applicants should also
include a statement in their applications indicating their willingness to
participate in these meetings.

Basic and Clinical Research

The overall concept of a SCOR program focuses on scientific issues related to
diseases relevant to the mission of the National Heart, Lung, and Blood,
Institute (NHLBI).  It is essential, therefore, that all applications include
both basic and clinical research projects.  Interactions between basic and
clinical scientists are expected to strengthen the research, enhance transfer
of fundamental research findings to the clinical setting, and identify new
research directions.  Plans for transfer of findings from basic to clinical
studies should be described.

Each SCOR grant application and award must include research involving human
patients/subjects, which is defined as research conducted with human
patients/subjects or on material of human origin such as tissue or other
specimens for which an investigator directly interacts with human
patients/subjects.  Support may be provided for human biomedical and
behavioral studies of etiology, pathogenesis, prevention and prevention
strategies, diagnostic approaches, and treatment of diseases, disorders or
conditions.  Small population-based epidemiologic studies, where the research
can be completed within five years, may also be proposed.  In addition, basic
research projects must be included that relate to the clinical focus.  A SCOR
may also contain one or more core units that support the research projects.

Length of SCOR Programs

Each NHLBI SCOR program is limited to ten years of support. Exceptions to this
policy will be made only if a thorough evaluation of needs and opportunities,
conducted by a committee composed of non-federal experts, determines that
there are extraordinarily important reasons to continue a specific SCOR
program.

Under this policy, a given SCOR grant is awarded for a five-year project
period following an open competition.  Only one five-year competing renewal is
permitted, for a total of ten years of support, unless the SCOR program is
recommended for extension.

The SCOR program in Transfusion Biology and Medicine is in the initial
five-year project period and this competition is for the second five-year
competition.  The comprehensive evaluation of this SCOR Program will be
conducted during the second project period according to the following
timetable.

Announcement of SCOR renewal competition   FY 1999

Project Period (Second Competition)        FY 2001 to FY 2005

Letter to SCOR Directors regarding SCOR    FY 2002 (mid-way through year -02   
evaluation plans                            of the second project period)

SCOR Evaluation Meeting                    FY 2002 (late in year -02 of the    
                                            second project period)

Notification of SCOR Directors of NHLBI    FY 2003 (mid-way through year -03   
Decision                                    of second project period)

The NHLBI does not limit the number of SCOR applications in a given SCOR
program from one institution provided there is a different SCOR principal
investigator for each application and each application is self-contained and
independent of the other(s).  This does not preclude cooperation, planned or
possible, among participants of SCORs after awards are made.  Scientific
overlap among applications will not be accepted.  If more than one application
is envisioned from an institution, the institution is encouraged to discuss
its plans with the NHLBI SCOR program administrator.

Consortium Arrangements

If a grant application includes research activities that involve institutions
other than the grantee institution, the program is considered a consortium
effort.  Such activities may be included in a SCOR grant application and can
provide scientific expertise in areas and topics that may not be readily
available at the applicant institution.  However, the consortium projects must
not constitute greater than 50 percent of the proposed projects.  It is also
imperative that a consortium application be prepared so that the programmatic,
fiscal, and administrative considerations are explained fully. Applicants
should exercise great diligence in preserving the interactions of the
participants and the integration of the consortium project(s) with those of
the parent institution, because synergism and cohesiveness can be diminished
when projects are located outside the group at the parent institution.

Facilities and Administrative costs paid as part of a consortium agreement are
excluded from the limit on the amount of direct costs that can be requested. 
The published policy governing consortia is available in the business offices
of institutions that are eligible to receive Federal grants-in-aid. Consult
the latest published policy governing consortia before developing the
application. If clarification of the policy is needed, contact Ms. Jane Davis,
Grants Operations Branch, NHLBI, (301) 435-0166.

FUNDS AVAILABLE

Applicants may request up to $1.28 million in direct costs, not including
Facilities and Administrative costs for collaborating institutions, in the
first year.  Competing renewal applicants may request an increase in their
budget in the first competing year (Year 06), not to exceed ten percent of the
costs awarded in the last noncompeting award year (Year 05) or $1.28 million,
whichever is greater (excluding Facilities and Administrative costs on
subcontracts).  Applicants may request up to a three percent increase for
subsequent noncompeting years.  The specific number to be funded will,
however, depend on the merit and scope of the applications received and on the
availability of funds.

Award of grants pursuant to this RFA is contingent upon receipt of funds for
this purpose.  Designated funding levels are subject to change at any time
prior to final award, due to unforeseen budgetary, administrative, and/or
scientific developments.

Equipment is included in the budget limitation.  However, requests for
expensive special equipment that cause an application to exceed this limit may
be permitted on a case-by-case basis following staff consultation.  Such
equipment requires justification.  Final decisions will depend on the nature
of the justification and the availability of funds.

BACKGROUND AND RESEARCH OBJECTIVES

Background

During the past two decades, significant scientific advances have been made in
transfusion medicine which have improved the safety and efficacy of blood,
blood components and plasma derivatives and have changed transfusion
practices. Advances have been made in detecting viral pathogens in donated
blood such as HIV-l, HIV-2, HTLV-I/HTLV-II and hepatitis C, thus preventing
such agents from entering the blood supply. Moreover, procedures have been
developed to inactivate viruses in plasma derivatives. Improved apheresis
technologies have been developed that permit more efficient collection and
manipulation of blood components and stem cells. Techniques have been
developed which may lead to the use of stem cells from umbilical cord blood
for bone marrow reconstitution. As a result, the importance of blood
transfusion has been greatly expanded through the use of components and
derivatives in increasingly specialized and effective forms of therapy.

The use of blood and blood components continues to increase. Improved patient
care, including aggressive cancer chemotherapy programs, bone marrow and
peripheral blood stem cell transplantation and sophisticated surgery
procedures have contributed heavily to this growth. Consequently, the
implementation of research programs to determine the optimal use of this
valuable resource is important and timely.

Blood centers, as well as medical centers with large transfusion services,
provide an important environment for research in transfusion medicine. These
centers also provide a variety of education opportunities aimed at several
groups, both within and outside the special blood bank community, including
laboratory technicians, undergraduate and graduate students, and practicing
physicians.

The SCOR mechanism is a very important and vital approach to address issues
and problems confronting transfusion medicine today. Some of the advantages of
this mechanism are listed below:

o The SCOR brings together multidisciplinary groups of investigators with
valuable expertise to transfusion medicine. With its mix of basic, applied,
and clinical research, the SCOR offers investigators invaluable resources for
research through coordinated interactions.

o The information that emerges from the research program of a SCOR may be
useful in addressing important national policy issues in transfusion medicine.
In the past, the SCOR program made important contributions to the NHLBI and
other federal agencies. This involvement was particularly important during the
turbulent times brought about by the AIDS epidemic. For example, investigators
in a SCOR research project were the first to demonstrate unequivocally the
value of hepatitis B core antigen antibody assay as a surrogate test for
screening blood donors at increased risk for HIV infection.

The Transfusion Medicine SCOR program, like the subspecialty which it serves,
is in a continually evolving state of development. Nevertheless, in the brief
history of the program there have been major accomplishments in basic and
clinical research which include:

o A series of knockout mice have been developed that contain deletions in one
or several members of the family of tyrosine kinases to determine what effect
these mutations have on hematopoietic cell development and function. These
studies are helping to define the roles played by tyrosine kinases in
hematopoietic signal transduction The potential to use this knowledge to
modulate immune responses, both in auto-immune disease or in relation to
transfusion-induced immunity, is enormous.

o Studies on the kinetics of clearance of donor leukocyte subpopulations in
transfusion recipients have shown a surprisingly prolonged, high-level
microchimerism in massively transfused trauma patients This long-term
multilineage microchimerism in trauma patients seems to be due to engraftment
of donor stem cells in recipients with mutual tolerance between recipient and
donor leukocytes. Preliminary clinical studies characterizing the survival of
specific donor leukocyte subsets in massively transfused trauma patients
revealed prolonged, high-level microchimerism. Multilineage persistence of
four donor leukocyte subsets for six months to 1.5 years has been observed,
suggesting engraftment of donor stem cells in recipients with mutual tolerance
between recipient and donor leukocytes. Studies are in progress to understand
the factors determining clearance versus chimerism of transfused leukocytes.
These studies should yield critical insights relevant to prevention of
alloimmunization and transfusion-induced graft-versus-host disease, as well as
approaches toward induction of tolerance for tissue and organ transplantation
and active immunotherapy.

o Mapping of the Plasmodium vivax binding site within the Duffy antigen on the
surface of red cells has enabled the synthesis of this epitope. Subsequent
creation of a transgenic mouse model expressing human Duffy in their red cells
has provided investigators with means to evaluate the potential therapeutic
value of the synthetic polypeptide to prevent in vivo P. vivax invasion of red
cells and interrupt the progression of malaria.

o Since inception of the Transfusion Medicine SCOR program in 1985, a large
proportion of studies in this program have dealt with transfusion-transmitted
infectious diseases, particularly AIDS. This focus on infectious disease was
in part a response to the recognition that HIV-l could be transmitted by blood
transfusion. The multidisciplinary configuration of the SCOR program was
ideally suited to meet the challenge of transfusion-associated AIDS. As a
consequence, significant contributions were made in the understanding of
HIV-l, HIV-2 and other human retroviruses. The knowledge gained from the
Transfusion Medicine SCOR program contributed significantly, for example, to
the selection, design and development of specific assays to detect the
presence of human retroviruses in blood donors.

Areas to be Addressed by this Initiative

With implementation of donor screening procedures that virtually eliminate
HIV-l and significantly reduce the likelihood of other transfusion-transmitted
viruses from entering the blood supply, the National Heart, Lung, and Blood
Institute (NHLBI) redirected its SCOR
program in 1996 to address other important areas of scientific need and
opportunity in Transfusion Biology and Medicine. Five areas of special
emphasis were identified that are essential for the optimal use and
improvement of transfusion therapy. Recent progress in
our understanding in such areas as immune regulation and hematopoiesis make
this an opportune time to encourage research in the following areas of
emphasis:

Immunomodulatory Aspects of Transfusion

The immune system occupies a central role in the safety and efficacy of
transfusion therapy. One of the major problems in transfusion therapy is
alloimmunization. In some situations, the occurrence may be of little
consequence, but as a general problem, alloimmunization is of great importance
as it limits the effectiveness of transfusions and in some cases results in
death of the patient. The target antigens to which these alloimmune responses
are directed have been well defined and include epitopes on red blood cells,
white blood cell specific antigens, platelet antigens, and HLA antigens. In
other instances, such as graft-versus-leukemia mediated by transfusion of
allogeneic T-cells, the target antigens are not known. Investigators in this
SCOR program are encouraged to pursue studies that focus on the mechanisms
involved in these alloimmune reactions. The ultimate goal is to develop better
strategies for the prevention and modulation when alloimmunity is undesired.
Alternatively, better approaches could be developed to enhance the efficacy of
alloimmune cellular therapies for graft-versus-tumor effect and cancer vaccine
development.

Development of Novel Cell Therapies and Cytokine Therapies

Recent developments in the understanding of hematopoiesis and stem cell
biology, in the identification of hematopoietic growth factors and cytokines,
and in cell culture technology hold promise for the creation of novel cellular
components and transfusion therapies. Studies are needed on the
identification, collection, purification, manipulation, and preservation of
hematopoietic stem cells for use in transplantation. Studies on the in vitro
expansion of hematopoietic stem cells are also encouraged. Significant
advances have been made which create realistic prospects for the establishment
of in vitro culture systems for production of stem cells for transplantation
and for the production of specific cell populations for transfusion therapy.
It is important to better understand the molecular and genetic events that
accompany stem cell proliferation and expansion, so that their manipulation
will allow the therapeutic use of the derivative cells. A further objective of
this SCOR program is to develop the requisite bioengineering and delivery
strategies to apply this new understanding to patient care, hopefully
minimizing the prolonged periods of severe pancytopenia that accompany modern
hematologic and oncologic therapies. In addition to the use of cytokines to
support the in vitro expansion of cells, studies are also needed to determine
the optimal use of cytokines in vivo to reduce transfusion needs. Studies
might address the identification of those disease states where cytokine
therapy might be of use. Studies are needed on the dose and timing of cytokine
therapy. Research studies on the regulation of endogenous cytokine production
are important and could eventually lead to clinical therapies.

Structure/Function Relationships of Human Blood Cell Surface Antigens

Studies are needed to better understand the relation of structure to function
in human blood cells, particularly red blood cells and platelets. There is a
need for studies on the characterization and biological significance of blood
cell surface antigens, particularly as they relate to the structural integrity
of the cells, to specific cell functions, and to specific disease processes.
Until recently, the major reasons for identifying blood group antigens and
antibodies have been their importance in assuring safe and effective blood
transfusions. In recent years, however, clinical information regarding the
relation of blood cell antigens to disease has accumulated, as has knowledge
of blood cell membrane structure and function. The primary structure of many
of the red cell membrane proteins have been deduced by cloning of genes that
encode these proteins. Significant progress has also been made in defining
polymorphisms in individual protein sequences responsible for various
antigenic determinants. These accomplishments have opened new research
opportunities in red cell and transfusion medicine. Platelet antigens are
known to be associated with functional glycoproteins on platelet membranes and
platelet antibodies have been shown to affect platelet function. Similar
studies are needed to determine what role antibodies may play in altering red
blood cell function. The emerging research issues in this area include: 1)
defining the physiologic function of cell membrane proteins, 2) identifying
the contribution of these membrane proteins and their homologues to various
disorders, hematological as well as nonhematological and, 3) using of novel
approaches such as phage-display systems, transgenic mice, and transfected
cell lines to develop monoclonal antibodies for use as typing reagents and for
use as therapeutic agents.

Blood Substitutes/Platelet Substitutes

Research on oxygen-carrying red cell substitutes could lead to the development
of products that provide short or even possibly long-term support for anemic
patients with the advantages of being universally compatible, pathogen free,
and without the requirement for cross-matching. They would ideally have a long
shelf-life and offer convenient storage. There are currently several human
safety trials of artificial oxygen carriers in various stages of study. Most
results reported thus far have been disappointing as unexpected toxicities
have been observed. Thus, studies are needed to understand the mechanisms of
toxicity of hemoglobin-based oxygen carriers. Projects might address the
apparent vasoactivity of these preparations. Animal models or in vitro models
need to be developed to reliably predict human toxic reactions. Furthermore,
the long-term (metabolic and pharmacologic) effects of oxygen carriers need to
be delineated. Studies on the efficacy of artificial oxygen carriers also need
to be conducted under the experimental conditions that reflect the intended
clinical use. Of particular importance are the function of artificial oxygen
carriers in the presence of red cells; the measurement of tissue and organ
function as an indication of efficacy; and the comparison of the efficacy of
artificial oxygen carriers with that of red cells. Much effort has also been
expended on the development of novel methods to prepare safer, hemostatically
efficacious platelet products or substitutes with longer shelf-lives than
currently provided by conventional liquid-stored platelets. These include
storage in the frozen state; storage in cold (4 degrees C) in the liquid
state; use of infusible platelet membrane fragments or microparticles; use of
rehydrated lyophilized platelets; as well as the use of photochemical methods
for the inactivation of viruses, bacteria, and protozoa. Other approaches have
attempted to make artificial platelet substitutes that are capable of in vivo
hemostasis. These include liposomes bearing hemostatically active agents on
their surface; fibrinogen-coated albumin microspheres; and red blood cells
bearing RGD peptides or fibrinogen on their surfaces. Considerable challenges,
however, still exist. The major problem is the lack of appropriate methodology
for assessing in vitro and in vivo the hemostatic function of such alternative
platelet products and substitutes. Thus, this program encourages the
development of definitive criteria to evaluate the hemostatic efficacy as well
as the mechanism of action of preparations with potential use as platelet
substitutes.

Indications for Red Blood Cell or Platelet Transfusion

Despite the obvious advantages of blood transfusion, there is concern that
blood components such as red blood cells and platelets are at times given to
patients who do not really need them, are given too frequently to patients who
do need them, and occasionally, either are not given or are given in
insufficient quantities when treatment is urgently required. Clinical
decisions regarding red blood cell and platelet transfusions are hampered by a
general lack of clinical studies, by imprecise methods of evaluating clinical
need and by uncertain methods for measuring effects. The time-honored and
useful measurements of hemoglobin concentration and hematocrit are clearly not
sufficient, by themselves, for many patients much of the time. Research
studies are clearly needed to improve knowledge in these areas. Studies might
focus on the development of predictors that better define the need for red
blood cell transfusion. The identification of organs that are specifically at
risk during acute anemia and the development of clinical monitors that measure
the state of perfusion and the presence of cellular hypoxia in those organs
that are specifically sensitive to low hemoglobin values may be promising
approaches. Studies are also needed to determine the appropriate indications
for platelet transfusions. The platelet levels that predispose
thrombocytopenic patients to hemorrhage and the efficacy of therapeutic
modalities other than transfusion are not well understood and require
investigation. The development of a practical test that predicts the
likelihood of clinically significant platelet-related bleeding would be
extremely useful.

An area in transfusion of special interest to the Institute is neonatal
transfusion therapy. Dramatic advances in the care of infants of low to
extremely low birth weight have resulted in survival beyond the immediate
intrapartum period. Current practice often includes transfusions with red
blood cells as part of the therapy for most of these infants. However,
adequacy of red blood cell transfusion in the premature infant is most often
assessed by measuring hemoglobin and hematocrit, two parameters that, as in
adults, have limited correlation with both the need to transfuse as well as
transfusion outcome. Research is needed to establish quantitative, clinically
useful criteria to be used in addition to or instead of hemoglobin and
hematocrit measurements in determining when to begin and end blood
transfusions in newborns. There is a need for new, innovative methods to
assess oxygen delivery in the newborn. Furthermore, studies to determine
transfusion outcomes in this population are also needed.

The different research topics and approaches described in the five areas of
emphasis are intended to provide potential applicants with examples of the
types of topics that are of interest to the NHLBI and worthy of pursuit. These
examples, however, are not meant to be all inclusive. Investigators are
encouraged to consider pursuing other important and innovative scientific
topics as well. It should be emphasized, however, that THE TOPICS CHOSEN MUST
RELATE DIRECTLY TO THE FIVE AREAS OF EMPHASIS IDENTIFIED IN THIS INITIATIVE.
Furthermore, the topics may address one or more than one area of emphasis. For
example, it would be appropriate for a SCOR applicant to propose projects that
address research issues pertaining to one area of interest such as
structure/function relationships of human blood cell surface antigens or a
combination such as structure/function relationships of human blood cell
surface antigens and immunomodulatory aspects of transfusion. Applicants
should also note that a SCOR program must meet the following criteria: (1)
address areas of significant national need and clinical importance; (2)
attract talented investigators who foster the development of a
multidisciplinary and collaborative synergistic approach; (3) include both
basic and clinical components with at least one of the projects in the SCOR
dealing exclusively with clinical issues or in which clinical parts of two or
more projects would, in aggregate, constitute at least one project relative to
resources and personnel; and, most importantly; (4) have the potential to
accelerate the transfer of basic research to clinical application. APPLICANTS
ARE REQUESTED TO CONTACT THE PROJECT OFFICER OF THIS INITIATIVE PRIOR TO
PREPARING A SCOR APPLICATION TO MAKE CERTAIN THAT THEIR PROPOSED PROGRAM IS
COMPATIBLE WITH THE OBJECTIVES OF THIS SOLICITATION.

The major emphasis of this SCOR program is on basic, applied and clinical
research in transfusion biology and medicine, 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 SCOR support should have a basic range of competence and potential
that will enable it to develop a program addressing the objectives and goals
of this initiative. SCORs should also provide a challenging environment for
attracting talented young scientists into biomedical research -and offering
opportunities for career development.

SPECIAL REQUIREMENTS

Special features of SCOR grants are:

o They provide opportunities for young and established investigators with
mutual or complementary interests to engage in multidisciplinary basic and
clinical research in a synergistic fashion such that major therapeutic
advances will be realized.

o A SCOR has a central theme to which all research projects pertain.  In
addition, a SCOR may include core units to provide services to the various
research projects and to support the organizational and administrative aspects
of the program.

o  Inherent in the SCOR program is a special interaction between the SCOR
director, the grantee institution, and the Division of Blood Diseases and
Resources (DBDR).  Upon initiation of the program, DBDR will hold periodic
meetings to encourage exchange of information among investigators who
participate in this program and to stimulate collaboration.  Applicants should
include travel funds for a two-day meeting every other year, most likely to be
held in Bethesda, Maryland.  Applicants should also include a statement in
their applications indicating their willingness to participate in these
meetings.

o  The Division's overall SCOR program and each SCOR grant undergo periodic
evaluation.  The progress reports are prepared for the information of the
National Heart, Lung, and Blood Advisory Council, the Division of Blood
Diseases and Resources staff, and ad hoc members of SCOR evaluation groups.

Requirements of SCOR grants:

o  The overall concept of a SCOR program focuses on scientific issues related
to the mission of the NHLBI.  It is essential, therefore, that all
applications include both basic and clinical research projects.  Interactions
between basic and clinical scientists are expected to strengthen the research,
enhance transfer of fundamental research findings to the clinical setting, and
identify new research directions.  Plans for transfer of findings from basic
to clinical studies should be described.

o  Each SCOR must have a well-delineated organizational structure and
administrative mechanism that foster interactions between investigators,
accelerate the pace of research, and ensure a productive research effort.

o  Each SCOR grant application and award must include research involving human
patients/subjects, which is defined as research conducted with human
patients/subjects or on material of human origin such as tissue or other
specimens for which an investigator directly interacts with human
patients/subjects.  Support may be provided for human biomedical and
behavioral studies of etiology, pathogenesis, prevention and prevention
strategies, diagnostic approaches, and treatment of diseases, disorders, or
conditions.  Small population-based studies, where the research can be
completed within five years, may also be proposed.  In addition, basic
research projects must be included that relate to the clinical focus. Each
component project requires a well-described hypothesis, preliminary data and a
time-table for conducting the proposed investigations.  A SCOR may also
contain one or more core units that support the research projects.  The
relationship between each research project and one or more core units should
be described.

o  Applications from institutions which have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research Resources may
wish to identify the GCRC as a resource for conducting the proposed research. 
In such a case, a letter of agreement from the GCRC program director/principal
investigator could be included with the application.

o  The principal investigator should be an established scientist with the
ability to ensure quality control and the experience to administer effectively
and integrate all components of the program.  A minimum time commitment of 25
percent is expected for this individual.  The principal investigator must also
be the project leader of one of the component research projects.  If, through
peer review, this project is not recommended for further consideration, the
overall SCOR application will not be considered further.  If this project is
judged by peer review to be of low scientific merit, it will markedly reduce
the overall scientific merit ranking assigned to the entire application by the
review committee.

o  Project leaders must agree to commit at least 20 percent effort to each
project for which they are responsible.  Investigators with minimal research
experience, but promising credentials, may participate; however, it is
expected that most of the project directors will be investigators with
significant research experience.

o  If a project director transfers to another institution, support for the
project will normally not be continued as a consortium.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and
their subpopulations must be included in all NIH supported biomedical and
behavioral research projects involving human subjects, unless a clear and
compelling rationale and justification is provided that inclusion is
inappropriate with respect to the health of the subjects or the purpose of the
research.  This new policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43).

All investigators proposing research involving human subjects should read the
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research", which have been published in the Federal Register of March 28, 1994
(F59 14508-14513), and in the NIH Guide for Grants and Contracts of March 18,
1994, Volume 23, Number 11.

Investigators may obtain copies from these sources or from the program staff
or contact person listed under Inquiries.  Program staff may also provide
additional relevant information concerning the policy.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that children (i.e., individuals under the age of
21) must be included in all human subjects research, conducted or supported by
the NIH, unless there are scientific and ethical reasons not to include them. 
This policy applies to all initial (Type 1) applications submitted for receipt
dates after October 1, 1998.

All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for
Grants Contracts, March 6, 1998, and is available at the following URL
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent by December 1,
1999, that includes a descriptive title of the proposed research; the name,
address, and telephone number of the Principal Investigator, the identities of
other key personnel and participating institutions; and the number and title
of the RFA in response to which the application may be submitted.  Although a
letter of intent is not required, is not binding, and does not enter into the
review of subsequent applications, it assists the NHLBI staff to estimate the
potential review workload and to avoid conflict of interest in the review.

The letter of intent is to be sent to:

Dr. C. James Scheirer
Division of Extramural Affairs
National Heart, Lung and Blood Institute
6701 Rockledge Drive, Suite 7093, MSC 7924
Bethesda, MD 20892-7924
Telephone:  (301) 435-0266
FAX:  (301) 480-3541
Email: js110j@nih.gov

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in
applying for these grants.  These forms are available at most institutional
business offices of sponsored research or may be obtained from the Division of
Extramural Outreach and Information Resources, National Institutes of Health,
6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910; telephone: (301) 435-
0714; Email: GrantsInfo@nih.gov, and from the NIH program administrator listed
under INQUIRIES.  Specific instructions for preparing a SCOR application are
also available from the program contact listed under INQUIRIES.

The RFA label included in grant application PHS 398 (rev. 4/98) must be
affixed to the bottom of the face page of the application.  Failure to use
this label could result in delayed processing of the application such that it
may not reach the review committee in time for review.  In addition, the RFA
title, SCOR in Transfusion Biology and Medicine and number, HL-99-023 must be
typed on line 2 of the face page of the application form and the "YES" box
must be marked.

Send or deliver a signed, typewritten original of the application, including
the Checklist, and three signed photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)

Send two additional copies of the application to the Chief, Review Branch, at
the address listed under LETTER OF INTENT.  It is important to send these two
copies at the same time as the original and three copies are sent to the
Center for Scientific Review (CSR).

Applications must be received by January 14, 2000.  If an application is
received after that date, it will be returned to the applicant without review. 
The CSR will not accept any application in response to this RFA that is
essentially the same as one currently pending initial review, unless the
applicant withdraws the pending application.  The CSR will not accept any
application that is essentially the same as one already reviewed.  This does
not preclude the submission of substantial revisions of applications already
reviewed, but such applications must include an introduction addressing the
previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by CSR and
responsiveness by the NHLBI staff.  Incomplete applications or applications
deemed not responsive to the RFA will be returned to the applicant without
further consideration.

Applications that are complete and responsive to the RFA will be evaluated for
scientific and technical merit by an appropriate peer review group convened by
the NHLBI in accordance with the review criteria stated below.  Applicants
should submit the highest quality applications possible to CSR as no site
visits or reverse site visits will be held.  As part of the initial merit
review, a streamlined process may be used by the initial review group in which
the scientific merit of applications relative to other applications received
in response to the RFA will be determined.  Applications judged to be of high
scientific merit will be discussed and be assigned a priority score, and will
also receive a second level of review by the National Heart, Lung, and Blood
Advisory Council.  Applications determined to be of low scientific merit will
be withdrawn from further consideration and the principal investigator and the
official signing for the applicant organization will be notified.

Factors to be considered in the evaluation of each application will be similar
to those used in review of traditional research grant applications and, in
addition, will include overall proposed interactions among basic and clinical
research projects.  Major factors to be considered in the evaluation of
applications include:

o  Scientific merit of the proposed basic and clinical research projects
including significance, importance, and appropriateness of the theme;
innovation, originality, and feasibility of the approach; and adequacy of the
experimental design.

o  Leadership, scientific stature, and commitment of the program director;
competence of the investigators to accomplish the proposed research goals and
their time commitment to the program; and the feasibility and strength of
consortium arrangements.

o  Collaborative interaction among basic and clinical research components, the
balance between them, and plans for transfer of potential findings from basic
to clinical studies.

o  Adequacy of the environment for performance of the proposed research
including clinical populations and/or specimens; laboratory facilities;
proposed instrumentation; quality controls; administrative structure;
institutional commitment; and, when needed, data management systems.

o  Appropriateness of the budget for the proposed program.

o  Appropriateness of the central theme and coordination and interrelation of
the research projects and core units.

AWARD CRITERIA

The anticipated date of award is January 1, 2001, for the SCORs in Transfusion
Biology and Medicine.  Awards will be made according to priority score,
availability of funds, and programmatic priorities.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.  The
opportunity to clarify any issues or questions from potential applicants is
welcome.

Direct inquiries regarding programmatic issues and requests for supplemental
instructions to:

George Nemo, Ph.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, MSC 7950
Bethesda, MD  20892-7950
Telephone:  (301) 435-0075
FAX:  (301) 480-1046
Email:  nemog@nih.gov

Direct inquiries regarding fiscal and administrative matters to:

Ms. Jane Davis
Division of Extramural Affairs
National Heart, Lung and Blood Institute
6701 Rockledge Drive, Suite 7174, MSC 7926
Bethesda, MD 20892-7926
Telephone:  (301) 435-0166
FAX:  (301) 480-3310
Email:  davisj@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.839, Blood Diseases and Resources.  Awards will be made under the
authorization of the Public Health Service Act, Title IV, Part A (Public Law
78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered
under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part
74.  This program is not subject to the intergovernmental review requirement
of Executive Order 12372 or Health Systems Agency review.  All current
policies and requirements that govern the research grant programs of the NIH
will apply to grants awarded under this RFA.

The PHS strongly encourages all grant and contract recipients to provide a
smoke-free workplace and promote the non-use of all tobacco products.  In
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking
in certain facilities (or in some cases, any portion of a facility) in which
regular or routine education, library, day care, health care or early
childhood development services are provided to children.  This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.


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