SCOR:  MOLECULAR MEDICINE AND ATHEROSCLEROSIS

Release Date:  July 17, 2000

RFA:  HL-00-015

National Heart, Lung, and Blood Institute
  http://www.nhlbi.nih.gov/index.htm

Letter of Intent Receipt Date:  March 16, 2001
Application Receipt Date:       June 15, 2001

PURPOSE

The objective of this initiative is to establish new or to continue to support 
closely interacting, multiproject Specialized Centers of Research (SCORs) to 
study the etiology and pathophysiology of atherosclerosis at the molecular 
level.  The goals of this second cycle of the SCORs are to focus on studies on 
the pathobiology of the atherosclerotic lesion at the level of the arterial 
wall.  Such studies may include investigations of the mechanisms for lesion 
susceptibility and initiation; the mechanisms of lesion progression, 
complication, and regression; and the interactions of the vessel wall with 
systemic factors promoting atherogenesis.  The current SCOR program was funded 
in 1997 and therefore, this initiative represents the recompetition of an 
existing SCOR program and covers the second five-year funding period of a ten-
year program.

A SCOR provides the opportunity for investigators to engage in 
interdisciplinary and collaborative research which is focused on a specific 
disease or an area within a disease category.  It is required that SCOR 
applications include studies of human subjects and/or human materials as well 
as basic studies clearly related to a disease area.  The foundation of the 
clinical component should be strongly linked to the basic science projects; 
the basic science studies should be driven by the needs of the clinical 
projects.  Thus, 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.  

Coronary Heart Disease (CHD) accounts for the largest share of deaths from 
diseases of the heart.  CHD rates are particularly high in blacks perhaps due 
to the higher prevalence of major CHD risk factors such as hypertension, 
diabetes and obesity.  Differences in the nature of the
atherosclerotic process leading to CHD in blacks may also be a contributory 
factor.  The National Heart, Lung, and Blood Institute (NHLBI) wishes to 
encourage research into the pathogenesis of the atherosclerotic lesion in 
blacks as part of this SCOR program. 

In addition, to encourage women, under represented minority investigators, and 
persons with disabilities to work within a SCOR project, to facilitate 
recruitment of new women and under represented minority scientists and those 
with disabilities to this area of research, and to foster cutting edge and 
innovative research directions, each SCOR program may support up to two 
investigators by utilizing up to $50,000 per year per investigator to fund 
pilot and feasibility projects. This will allow women, under-represented 
minority investigators and those with disabilities to acquire skills and data 
to make them more competitive in seeking independent research support (e.g. 
R01).  These funds will not be supplements, but rather specific dollars 
identified in the SCOR budget and restricted to be used for this purpose.  The 
recipients would be chosen based on a proposal written by a SCOR investigator 
and reviewed by an internal review committee at the parent institution.

HEALTHY PEOPLE 2010
The Public Health Service (PHS) is committed to achieving the health promotion 
and disease prevention objectives of "Healthy People 2010," a PHS-led national 
activity for setting priority areas. This Request for Applications (RFA), 
SCOR: Molecular Medicine and Atherosclerosis, is related to one or more of the 
priority areas. Potential applicants may obtain a copy of "Healthy People 
2010" at http://www.health.gov/healthypeople/.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by for-profit and non-profit domestic 
institutions, public and private, such as universities, colleges, hospitals, 
laboratories, units of state or local governments, and eligible agencies of 
the Federal government.  This RFA is intended to support SCOR grants for basic 
and clinical investigations; therefore, applications that include only basic 
or only clinical research will not be responsive to this announcement.  In 
addition, clinical research projects focused on large epidemiologic studies or 
large clinical trials will be considered unresponsive to this RFA.  Awards 
will not be made to foreign institutions.  However, 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.

The Principal Investigator should be an established research scientist with 
the ability to ensure high quality research and the experience to administer 
effectively and integrate all components of the program.  A minimum time 
commitment of 25 percent is required 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.  Project leaders must agree 
to commit at least 20 percent effort to each project for which they are 
responsible.

EXCLUSIONS

This RFA is intended to support Specialized Centers of Research grants.  
Therefore, applications that include only basic or only clinical research will 
not be responsive to this announcement.  In addition, clinical research 
projects focused on large epidemiological studies or large clinical trials 
will be considered unresponsive to this RFA. 

Applicants should be aware that applications for administrative supplemental 
funds will be accepted only under unusual and well defined circumstances.  The 
Institute staff should be consulted prior to submission of an application.  
Supplemental grants will not be awarded for the first 18 months or the last 12 
months of a total project period.

MECHANISM OF SUPPORT

This RFA will use the Specialized Centers of Research (SCOR, P50) grant award 
mechanism.  Responsibility for the planning, direction, and execution of the 
proposed project will be solely that of the applicant.  All current policies 
and requirements that govern the research grant programs of the NIH will apply 
to grants awarded under this RFA.  The anticipated award date is April 1, 
2002.

Basic and Clinical Research

The overall concept of a SCOR program focuses on scientific issues related to 
diseases relevant 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.

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.

Applicants from institutions that have a General Clinical Research Center 
(GCRC) funded by the National Center for Research Resources may wish to 
identify the GCRC as a resource for conducting the proposed research.  If so, 
a letter of agreement from either the GCRC program director or Principal 
Investigator could be included with the application.

Length of SCOR Programs

Each NHLBI SCOR program is limited to 10 years of support. The current SCOR 
program on Molecular Medicine and Atherosclerosis was funded in 1997 and, 
therefore, this RFA covers the second five-year funding period.  Under this 
policy, SCOR grants funded in response to this RFA will only be for five years 
without the possibility of renewal.  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.

The NHLBI comprehensive evaluation of the Molecular Medicine and 
Atherosclerosis SCOR program will be conducted during the second project 
period according to the following timetable:

Program Announced                    July/August, 2000

Project Period 
(Second Competition)                 April 1, 2002 to March 31, 2007

Letter to SCOR Directors		      	
Regarding SCOR Evaluation Plans      October, 2003		

SCOR Evaluation Meeting              January, 2004

Notification of SCOR Directors	
of NHLBI Decision                    October, 2004

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.

FUNDS AVAILABLE

The NHLBI intends to commit approximately $ 8.5 million in FY 2002 to fund 
five new and/or competitive continuation SCOR grants in response to this RFA. 
Applicants may request a project period of up to five years. New applications 
may request a first year budget for direct cost of up to $1,350,000. 
Applicants applying for competitive renewal may request a first year budget 
not to exceed 10% over the final year budget of the last funding period.  The 
facilities and administrative costs for collaborating institutions are 
excluded from this ceiling and a maximum increase of no more than three 
percent is allowed in each additional year requested in the application.  
Although the financial plans of the NHLBI provide support for this program, 
awards pursuant to this RFA are contingent upon the availability of funds and 
the receipt of sufficient number of meritorious applications.

Equipment is included in the budget limitation.  However, requests for major 
equipment that cause an application to exceed this limit may be permitted on a 
case-by-case basis following staff consultation.  Such equipment requires in-
depth justification.  Final decisions will depend on the nature of the 
justification and the Institute's fiscal situation.

Consortium Arrangements

When a grant application includes research activities that involve 
institutions other than the grantee institution, it is considered a consortium 
effort.  Such activities may be included in a SCOR grant application, but it 
is imperative that a consortium application be prepared so that the 
programmatic, fiscal, and administrative considerations are explained fully.  
Applicants of SCOR grants 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 of 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 Kevin Keating, Grants Operations Branch, NHLBI, 301-435-0177.

RESEARCH OBJECTIVES

Background

Atherosclerosis underlies most coronary heart disease, a major cause of death 
(500,000 per year) and disability, as well as much peripheral vascular 
disease, many cases of stroke and several other diseases.  Atherosclerosis is 
a multifactorial process with a complex and incompletely understood etiology. 
An inter-disciplinary approach integrating basic sciences with the clinical 
aspects of the disease is required to study this disorder, and the NHLBI 
adopted the SCOR mechanism for that purpose.  

Since their inception, the SCORs in Arteriosclerosis have promoted 
multidisciplinary research on the relationships of hyperlipidemia, 
hypertension, thrombosis, diabetes, smoking, and other systemic risk factors 
to the etiology and pathogenesis of atherosclerosis. Despite the significant 
progress achieved, however, there remain many unresolved questions in 
atherosclerosis research, which are well suited for the comprehensive and 
multidisciplinary nature of the SCOR mechanism.  The past accomplishments of 
the SCOR program and the potential for continued advances in understanding and 
averting atherosclerosis and coronary artery disease through an integrated 
program of clinical and basic research are the basis for continuation of this 
avenue of support.  

Significant progress has been made in elucidating the structure and function 
of lipoproteins and apoproteins, the generation of useful animal models for 
nutrition and metabolic studies, and the definition of factors influencing 
localization of atherosclerotic lesions.  Other ongoing activities have 
considerably expanded insight into relevant processes in the arterial wall.  
An explicit pathogenesis is emerging and the development of new modes of 
intervention to show the progression of the disease is now possible.  However, 
much of the pathobiology involving the arterial wall is incompletely defined, 
and this is believed to be especially important in the clinical expression of 
atherosclerosis.

CRITICAL AREAS OF RESEARCH OPPORTUNITY  

To optimize the impact of the SCOR program, an emphasis needs to be placed on 
the processes that result in the initiation, progression, complication, and 
regression of atherosclerosis.  Studies on systemic factors promoting 
atherogenesis and its complications acting at the level of the vessel wall 
also need to be addressed.  To delineate the mechanisms responsible for 
atherosclerosis and its complications in humans, sophisticated and state-of-
the-art methodologies and approaches of molecular medicine such as gene 
regulation, gene transfer and therapy, three-dimensional structural biology, 
vascular imaging techniques, gene mapping and identification, and genetically 
modified animal models would be required, as well as the more standard 
research approaches. 

Because of the interdisciplinary nature of the research, collaboration among 
investigators of varied expertise is strongly encouraged.  Specifically, 
"Networking" (i.e., shared biologic and information resources, reagents, 
patients, genetically altered animals, and the like), are needed to maximize 
benefits in the most cost-efficient manner possible. 

The following are examples of methods, approaches, and areas of opportunities 
for research into lesion susceptibility and initiation; progression, 
complication, and regression of atherosclerotic lesions; and systemic factors 
promoting atherogenesis and its complications.  The list is not to be regarded 
as complete or exclusive and other research proposed by applicants that meets 
the objectives of this program will be considered by the NHLBI. 

Mechanisms Involved in Lesion Susceptibility and Initiation

Hemodynamic factors influence the localization of the atherosclerotic lesion. 
The role of shear stress in affecting the site of early lesions is 
controversial in view of the demonstrated existence of selective ion channels 
that may signal changes in the local hemodynamic environment in vascular 
cells.  In addition, there exists a newly discovered Shear Stress Response 
Element and DNA binding proteins in the promoter regions of certain genes that 
encode growth factors or adhesion molecules which are thought to play a role 
in lesion initiation.  This type of work provides a framework for novel 
molecular approaches to the study of atherosclerotic lesion initiation that 
promise to provide insight into the critical links among well-defined risk 
factors, hemodynamics, and locally altered arterial wall biology.  Another 
important gap in our knowledge of lesion initiation in humans relates to the 
formation of the arterial intima and the heterogeneity of smooth muscle and 
endothelial cells in the human arterial wall.  New concepts of vascular 
developmental biology and molecular tools for distinguishing subpopulations of 
arterial cells are currently emerging.  An opportunity thus exists to approach 
key issues in the initiation of human atherogenesis that previously have 
remained elusive.  

The effects of the well established risk factors on CHD events in the 
population at large have been shown to apply also to blacks, and most studies 
show that hypertension, glucose intolerance, and obesity may contribute 
disproportionately to CHD in black populations.  The contribution of these 
risk factors to lesion initiation and progression would shed light on devising 
approaches for interventions targeted to black populations.

Mechanisms Involved in Lesion Progression, Complication, and Regression

Recent clinical and pathological data show that, in human coronary 
atherosclerosis, rupture or erosion of the plaque, rather than gradual 
closure, underlies many acute myocardial infarctions and episodes of unstable 
angina, and that non-occlusive plaque rupture may constitute an important mode 
of episodic lesion progression. 

Valvular and aortic stenosis and arterial calcification are prominent features 
of CVD and coronary atherosclerosis and correlate with increased risk of 
myocardial infarction and may play an important role in plaque rupture.  
Calcification of the arterial wall has been shown to result from the 
expression of the same genes that are involved in bone formation.   Further 
research into the molecular mechanisms of arterial calcification may yield new 
insights into the aging of the vasculature and the stability of the 
atherosclerotic plaques, and may present new targets for clinical 
intervention.

Normal hemostasis and vascular patency are maintained by a dynamic equilibrium 
between the fibrinolytic and coagulation systems.  Endothelial cells play a 
central role in hemostatic regulation by producing components of the 
coagulation and the fibrinolytic systems and inhibitors of platelet 
aggregation.  Hence, several issues implicating the hemostatic system in 
atherogenesis merit consideration.  These may include interactions of the 
coagulation factors with blood lipids and their impact on the function of the 
endothelial cells and blood cells; mechanisms regulating the interaction of 
the blood components with the vascular endothelium in thrombosis and 
atherogenesis; factors regulating endothelial functions such as macromolecular 
transport, abnormal permeability, and endothelial cell relaxing factor; and 
mechanisms controlling arterial endothelial thrombo-resistance processes. 

Potential specific areas of new research might include studies of apoptosis of 
cells within plaques, matrix accretion and dissolution, studies on the origin 
of the calcifying cells of the arterial wall, regulation of prothrombotic 
factors such as tissue factor within complex lesions, and formation of plaques 
in microvessels which are sources of intraplaque hemorrhage.   

Emerging vascular imaging modalities provide a major opportunity to probe, in 
vivo, the nontraditional mechanisms of plaque progression and complication.  
Human tissue, such as that obtained at atherectomy, can be utilized to shed 
light on the alterations in cellular and molecular regulatory mechanisms of 
atherogenesis.  The use of these technologies may provide information on the 
structure of the intima, media, and adventitia of coronary arteries, which may 
elaborate on the vascular remodeling and compensatory responses to atheroma.  
Such observations may provide insight into how profiles of risk factors in 
humans influence these pathophysiological mechanisms.

As stenotic but stable plaques seldom cause lethal clinical manifestations, a 
biological approach to understanding the mechanisms of plaque destabilization 
should suggest novel therapies aimed at reversing this process, a target newly 
envisioned in cardiovascular therapeutics.  One potential avenue to this end 
could involve local gene therapy using newly developed vectors and 
endovascular delivery systems.

Systemic Factors Promoting Atherogenesis and its Complications Acting at the 
Level of the Arterial Wall

Many systemic factors associated with atherosclerosis have been identified.  
However, understanding how these risk factors interact with vascular cells has 
lagged.  An important area in this regard involves the complex interactions of 
insulin resistance, dyslipidemia, hypertension, and central obesity with 
coronary heart disease.  These risk factors are particularly prevalent in the 
black population where studies of these complex interactions and their 
association with race would be desirable.  The advent of genetically altered 
animals such as mice provides a new avenue to explore the integrative 
metabolic and local arterial wall aspects of such systemic factors that 
promote atherogenesis.  

For example, an area of interest that could be used to probe the link of 
systemic factors with atherosclerotic lesions would be the generation of 
compound mutants of insulin-resistant mice with atherosclerosis prone animals. 
Once established, such newly created animal models could be used for 
systematic evaluation of the effect of dietary and other environmental 
variables on atherogenesis.  Likewise, such compound mutant animal strains 
could be used to test potential preventive and therapeutic measures.  Various 
compound mutant animals could be applied to advantage to probe polygenic risk 
factors that promote atherogenesis (e.g., crosses with animals over-expressing 
or with gene knockouts involving growth factors, cytokines, coagulation 
factors, and apolipoproteins).  

New fundamental knowledge in immunobiology has added new insight to our 
understanding of the cellular and humoral immune responses, and our ability to 
manipulate elements of these basic mechanisms.  The advances have encompassed 
structural biology (molecular details of MHC/antigen complexes in antigen 
recognition and presentation), delineation of co-stimulatory molecules, 
development of new concepts of helper T cell subtypes (TH1, TH2), 
characterization of numerous cytokines, their receptors, and signaling 
pathways, and the precise molecules involved in immune-mediated cytolysis and 
cell death.  Such advances have begun to yield dividends in new approaches to 
infectious diseases and malignancies, but the opportunities they afford to 
atherogenesis remain less well explored.  Significant knowledge would 
doubtless accrue from application and extension of these recent advances to 
studying the initiation, progression and complication of the atherosclerotic 
lesions.

Molecular Medicine Methods and Approaches

Responses to this RFA should apply modern methods and approaches of molecular 
medicine to studies of the pathogenesis of atherosclerosis in the arterial 
wall and should emphasize the molecular and cellular bases of atherogenesis 
and the molecular genetics of atherosclerosis.  The methodology to be used may 
include, among others, the following approaches:

Genetics/Gene Manipulation

Several recent advances in technology and analytical methods, together with 
the rapid construction of genetic and physical maps in animals and humans, 
have substantially improved the likelihood of detecting some genetic 
contributors to atherogenesis and for studying the molecular and physiological 
consequences of gene variation.  For example, large-scale surveys of human 
genomic variation are now possible with efficient high-throughput methods 
using hybridization to high-density DNA probe arrays.  Furthermore, 
polymorphism screening can serve to identify single-nucleotide polymorphisms 
in the identification of complex disease genes.	

The power to map and identify genes responsible for disease, the capability of 
delivering exogenous genes to cells and organs, and the ability to manipulate 
gene expression and regulation all provide opportunities to investigate the 
role of various factors on vessel wall biology.  Examples of methods and 
approaches include:

o Methods to Prevent Specific Gene Expression (e.g.antisense)  
o Understanding Gene Expression in the Developing Animal.
o Gene Transfer and Therapy.   
o Generation of Genetically Altered Animals.
o Gene Mapping and Identification.

Structural Biology

Elucidation of the fine structure of the key enzymes, receptors, growth 
factors, cytokines, etc., at the three-dimensional level is an important step 
toward understanding their mechanisms of action on the vessel wall and 
designing agonists or antagonists to perturb their activity.  Examples of the 
methodology to be used include:

o X-Ray Crystallography
o NMR
o New Electron and Laser Microscopy Techniques

Vascular Imaging Techniques


The imaging of arterial lesions can be used to investigate the 
pathophysiological basis for the development and progression/ regression of 
atherosclerosis and to predict the impact of intervention on progression/ 
regression.  The use of improved methods for invasive and noninvasive imaging 
of lesions, especially plaque rupture and acute occlusion, is a high priority. 
Examples of the methods that can be used include:

o Quantitative Angiography
o B-Mode Ultrasound
o Intravascular Ultrasound
o NMR

Biennial Research Meetings

Upon initiation of the program, the NHLBI will sponsor periodic meetings to 
encourage exchange of information among investigators who participate in this 
program and to stimulate collaboration. Applicants should request additional 
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.

STUDY POPULATIONS

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 was first published in the Federal Register of March 28, 1994 
(FR 14508-14513) and in the NIH Guide for Grants an Contracts, Vol. 23, No. 
11, March 18, 1994, available on the web at: 
http://grants.nih.gov/grants/guide/notice-files/not94-100.html

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of 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 and Contracts, March 6, 1998, and is available at the following URL 
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html
Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRIES. Program staff may also provide additional relevant 
information concerning the policy.

URLS IN NIH GRANT APPLICATIONS OR APPENDICES
All applications and proposals for NIH funding must be self-contained within 
specified page limitations. Unless otherwise specified in an NIH solicitation, 
internet addresses (URLs) should not be used to provide information necessary 
to the review because reviewers are under no obligation to view the Internet 
sites. Reviewers are cautioned that their anonymity may be compromised when 
they directly access an Internet site.

LETTER OF INTENT

Prospective applicants are asked to submit, by March 16, 2001, a letter of 
intent 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, the information that it 
contains allows NHLBI staff to estimate the potential review workload and plan 
the review.

The letter of intent is to be mailed to Chief, Review Branch at the address 
listed under inquiries.

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 
offices of sponsored research and 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.

Instructions for the preparation of grant applications for SCORs are the same 
as those used for the preparation of Program Project Applications and are 
available at: http://www.nhlbi.nih.gov/funding/policies/ppg.htm

The RFA label available in the PHS 398 (rev. 4/98) application form must be 
affixed to the bottom of the face page of the application. Type the RFA number 
on the label. 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 and number must be typed on line 2 of the 
face page of the application form and the YES box must be marked.
The sample RFA label available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to 
allow for this change. Please note this is in pdf format.  Submit 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)

At the time of submission, two additional copies of the application must be 
sent to the Chief, Review Branch at the address listed under INQUIRIES.  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), otherwise the NHLBI 
cannot guarantee that the application will be reviewed in competition for this 
RFA.

Applications must be received by June 15, 2001.  If an application is received 
after that date, it will be returned to the applicant without review. The 
Center for Scientific Review (CSR) will not accept any application in response 
to this announcement that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  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 the CSR and 
responsiveness by the NHLBI. Incomplete and/or non-responsive applications 
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. As part of the 
initial merit review, all applications will receive a written critique and 
undergo a process in which only those applications deemed to have the highest 
scientific merit, generally the top half of the applications under review, 
will be discussed, assigned a priority score, and receive a second level 
review by the National Heart, Lung, and Blood Advisory Council (NHLBAC).

Review Criteria:

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments reviewers will be asked to discuss the following aspects 
of the application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals.  Each of these 
criteria will be addressed and considered in assigning the overall score, 
weighting them as appropriate for each application.  Note that the application 
does not need to be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score.  For example, an 
investigator may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward.

(1) Significance
Does this study address an important problem? If the aims of the application 
are achieved, how will scientific knowledge be advanced? What will be the 
effect of these studies on the concepts or methods that drive this field?

(2) Approach

Are the conceptual framework, design, methods, and analyses adequately 
developed, well integrated, and appropriate to the aims of the project? Does 
the applicant acknowledge potential problem areas and consider alternative 
tactics?

(3) Innovation 
Does the project employ novel concepts, approaches or method? Are the aims 
original and innovative? Does the project challenge existing paradigms or 
develop new methodologies or technologies?

(4) Investigator 
Is the investigator appropriately trained and well suited to carry out this 
work? Is the work proposed appropriate to the experience level of the 
principal investigator and other researchers (if any)? Does the Program 
Director have the appropriate scientific statue and proven leadership to serve 
in such capacity?

(5) Environment
Does the scientific environment in which the work will be done contribute to 
the probability of success? Do the proposed experiments take advantage of 
unique features of the scientific environment or employ useful collaborative 
arrangements? Is there evidence of institutional support?

(6) Collaboration
Does the submitted proposal represent collaborative research among 
investigators from basic and clinical research with necessary disciplines? 
What are the likelihood of effective collaboration among the investigators, 
and the likelihood of success of the research objectives proposed?

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

o  The adequacy of plans to include both genders, minorities and their 
subgroups, and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 
evaluated.

o  The reasonableness of the proposed budget and duration in relation to the 
proposed research

o  The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project  
proposed in the application.

AWARD CRITERIA

Applicants should be aware that, in addition to scientific merit, program 
priorities and program balance, the total costs of the proposed project and 
the availability of funds will be considered by NHLBI staff as well as NHLBAC 
in making funding recommendations.  In circumstances in which applications 
have similar scientific merit, but vary in cost competitiveness, NHLBI is 
likely to select the more cost competitive application for funding.

SCHEDULE

Letter of Intent Receipt Date:    March 16, 2001
Application Receipt Date:         June 15, 2001
Peer Review Date:                 October, 2001
Review by NHLB Advisory Council:  February, 2002
Anticipated Award Date:           April 1, 2002

INQUIRIES

Inquiries concerning this RFA are encouraged. The opportunity to clarify any 
issues or questions from potential applicants is welcome.

Direct inquiries regarding scientific issues to:

Momtaz Wassef, Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung and Blood Institute
6701 Rockledge Drive, MSC 7956
Bethesda, MD  20892
Telephone:  (301) 435-0550
FAX:  (301) 480-2858
E-mail: Wassefm@nih.gov

Direct inquiries regarding review matters to:

C. James Scheirer, Ph.D.
Chief, Review Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7216, MSC 7924
Bethesda, MD 20892-7924
Telephone: (301) 435-0266
FAX: (301) 480-3541
Email: js110j@nih.gov.

Direct inquiries regarding fiscal and administrative matters to:

Mr. Kevin Keating
Grants Operations Branch
National Heart, Lung and Blood Institute
6701 Rockledge Drive, MSC 7926
Bethesda, MD  20892
Telephone:  (301) 435-0177
FAX:  (301) 480-3310
E-mail: KeatingK@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.837.  Awards are made under authorization of Sections 301 and 405 of the 
Public Health Service Act as amended (42 USC 241 and 284) and administered 
under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 
74 and 92. This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.
The PHS strongly encourages all grant 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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