RELEASE DATE:  August 17, 2004
RFA Number:  RFA-HL-05-001  

EXPIRATION DATE:  May 12, 2005

Department of Health and Human Services (DHHS)
National Institutes of Health (NIH)

National Heart, Lung, and Blood Institute (NHLBI)


o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations


The primary objective of the Specialized Centers of Clinically Oriented Research 
(SCCOR) programs is to foster multidisciplinary research on clinically relevant 
questions enabling basic science findings to be more rapidly applied to clinical 
problems. The clinical and basic research supported through this RFA must focus on 
vascular injury, repair, and remodeling. It is expected that the results from the 
SCCOR grants will have a positive impact on the prevention, diagnosis, and 
treatment of vascular diseases. This program has three major goals: 
(1) to stimulate interdependent clinical and multidisciplinary basic research 
projects that investigate molecular and cellular mechanisms of vascular injury, 
repair, and remodeling, (2) to promote patient-oriented research that will improve 
our ability to prevent, detect, characterize, manage, and treat vascular diseases, 
and (3) to develop the skills and research capabilities of new clinical 

The National Heart, Lung, and Blood Institute (NHLBI) revised the Specialized 
Centers of Research (SCOR) program, based primarily on recommendations from the 
National Heart, Lung, and Blood Advisory Council.  The new program is called the 
Specialized Centers of Clinically Oriented Research (SCCOR) program 
http://www.nhlbi.nih.gov/funding/policies/sccor_desc.htm.  The original SCOR 
program required both basic and clinical research, but the preponderance of funded 
projects was in the basic science arena.  The new title and the revisions to the 
program reflect the Institute's desire to capitalize on basic research advances by 
encouraging their translation to the clinical arena.  The guiding principle of the 
new SCCOR program is the central focus on clinically relevant research, and the key 
change to achieve this goal is the requirement that at least one-half of funded 
projects be clinical.  The specific components of the new SCCOR program are 
detailed in this RFA.  Special instructions for preparing a SCCOR application are 
available from the program contact listed under WHERE TO SEND INQUIRIES or at 
Vascular Injury, Repair, and Remodeling

Vascular diseases are responsible for the major causes of morbidity and mortality 
in the United States.  They comprise disorders of arteries, veins, microvessels, 
and lymphatics.  These disorders include coronary, peripheral, visceral and 
cerebral vascular occlusive diseases, restenosis, aortic coarctation, aneurysms and 
dissection, vasospasm, vasculitis, arterial and venous thrombosis, venous 
insufficiency, and lymphedema.  Although vascular disorders are heterogeneous in 
their causes and orientation, they share the common denominator of pathological 
vascular repair and remodeling in response to underlying injury due to 
dyslipidemia, hypertension, mechanical forces, diabetes, obesity, 
hypercoagulability, oxidative stress, inflammatory or immunological processes, 
advanced age, gender or genetics. 

Vascular injury, repair, and remodeling are regulated by a myriad of local events 
and stimuli.  Repair and remodeling mechanisms are influenced by local availability 
and activity of mitogens, differentiation factors, cytokines/chemokines, adhesion 
molecules, proteases, matrix components, and vasoactive agents.  All of these 
factors may represent potential targets for improved diagnosis, patient 
stratification, and therapeutic intervention.  
The vascular repair can be successful and complete, in which case the systemic 
reaction may resolve; but in many situations, the repair is incomplete and 
unsuccessful and leads to remodeling of the vascular wall.  For some patients the 
remodeling of the vascular wall may be functional, while for others it may lead to 
enlarging or narrowing of the lumen or thromboembolic complications.  For example, 
pathological remodeling can lead to aneurysm formation, stenosis, restenosis, or 

While circulating cytokines and growth factors can lead to accelerated inflammation 
of the injured vascular wall, such molecules can also promote the recruitment of 
bone marrow-derived progenitor vascular cells, endothelial progenitor cells in 
particular, with intrinsic capacity to repair the vascular wall.  Such cells are 
produced by the marrow in response to signals derived from the injured vascular 
wall, released in the systemic circulation and anchored at the level of vascular 
lesions.  They appear to contribute to the repair of the arterial wall, as their 
absence results in more vascular lesions, and their administration to animals 
deprived of vascular progenitor cells can retard the onset of vascular disorders.  
Understanding the production of cells involved in the repair of the vessel wall 
from a distance (bone marrow) is nascent, potentially important and a great 
opportunity for advancing the field of vascular disorders.  

Both the susceptibility of blood vessels to injury and their amenability to repair 
and/or remodel are profoundly affected by vascular cell heterogeneity.  Vascular 
cell morphology can differ dramatically from one vascular bed to another, according 
to specific functional requirements.  Endothelial cells destined to reside within 
the arterial or venous vascular beds, moreover, follow diverging differentiation 
pathways, and those assigned to these specific locations express characteristic 
molecular markers.  Vessel size, anatomic location, and geometry, in addition, 
determine the quality and magnitude of hemodynamic forces to which vascular cells 
are exposed.  Finally, vascular cells are subject to regional molecular cues and 
signals derived from specialized surrounding tissues.  As a result, vascular cell 
gene expression profiles and functional responses vary significantly from one 
setting to another and profoundly influence the cell’s remodeling and repair 

While normal tissues maintain equilibrium between vascular growth and cellular 
demands, the loss of such balance may lead to either excessive or insufficient 
angiogenesis and neovascularization.  Although numerous pathways and molecular 
players that relate to vascular proliferation have been identified, their 
integrated function and co-regulation are poorly understood.  Further studies in 
this area are expected to reveal a host of opportunities for defining the molecular 
basis and treatment of ischemic myocardium and limbs and to prevent the progression 
of atherosclerosis. 

A complication of vascular inflammation is thrombosis and thromboembolic 
complications.  The occlusion of an arterial vessel by a thrombus can lead to the 
damage of end-organs, such as myocardial infarction and stroke.  While hemostasis 
at the level of sectioned vessels can be lifesaving, the coagulation system was not 
designed to differentiate vascular wall disruption resulting from a traumatic 
injury versus the spontaneous fracture of an atherosclerotic plaque at the level of 
a coronary vessel.  Hence, excess and misguided coagulation can be detrimental, 
whereas some degree of thrombosis may enhance the repair process.  The dual role of 
platelets and coagulation in the process of vascular injury and repair represents 
another opportunity for investigations. 

This dual role is perhaps particularly true at the level of branching vessels, 
where atherosclerotic lesions occur earlier, and hemodynamic conditions are 
particularly stringent.  Such hemodynamic strain might prevent the successful 
repair of vascular injuries.  For example, it might be challenging for progenitor 
cells to anchor on the surface of damaged arteries.  The presence of adhering 
platelets might facilitate the attachment of progenitor cells, and further 
participation into the repair process. 

Hypertension exerts a profound effect upon blood vessel structure and function.  
Vascular alterations that occur in this setting may include reconfiguration of 
vessel wall matrix components, dysregulation of cellular proliferation profiles, 
arterial stiffening, and microvessel rarefaction.  A detailed appreciation of these 
mechanisms, particularly as they relate to individual genomic and proteomic 
profiles, will likely lead to new opportunities for diagnostic and therapeutic 

Measures of the functional and structural properties of blood vessels can be used 
to assess preclinical vascular disturbances such as endothelial dysfunction and 
increased vascular stiffness.  Abnormalities of endothelial function have been 
identified in patients with dyslipidemia, hypertension, diabetes, metabolic 
disorders, obesity and atherosclerosis, and have been shown to predict future 
vascular events.  Vascular compliance decreases with aging and is altered in 
patients with hypertension.  Moreover, increased vascular stiffness contributes to 
systolic hypertension and adversely affects cardiac function.  The relationship 
between vascular stiffness and arterial diseases is not well defined. 

Aortic aneurysms and dissections are examples of vascular diseases characterized by 
serious distortions in arterial architecture due to remodeling.  Recent research on 
the pathophysiology of abdominal aortic aneurysms (AAAs) has highlighted the 
importance of chronic inflammation and immune responses, enzymatic destruction of 
aortic elastin and collagen, and depletion of vascular smooth muscle cells from the 
aortic media.  Numerous therapeutic opportunities may exist to influence the 
biology and natural history of AAAs, as well as the development of non-surgical 
treatments for small AAAs.  

A variety of established and emerging imaging technologies will be important in 
providing qualitative and quantitative measures of vascular wall dysfunction that 
will be especially applicable to clinical studies.  Applications of nanotechnology 
and molecular imaging are encouraged as a means to facilitate longitudinal studies 
in patients, both in detecting and stratifying vascular disease, assessing the 
functional characteristics of vascular lesions over time, and in assessing the 
results of various interventions.
Translation of basic science findings into improvements in the diagnosis and 
treatment of vascular disease is important.  It is apparent that there is 
significant human variability in the rate of vascular disease or its progression, 
for example, in the growth of aortic aneurysms or in atherosclerotic plaque burden.  
Furthermore, clinical heterogeneity exists in the response to treatment, whether 
pharmacological, endovascular or surgical.  Improved methods for detecting those at 
increased risk for vascular disease progression will permit initiation of 
preventive and therapeutic measures at an earlier, sub-clinical stage.  Better 
stratification of individuals into those likely to respond versus those likely to 
fail therapy will permit more effective therapy and tailored approach in the 
management of vascular disease in the individual patient. 

The need for clinical trials to investigate the efficacy, safety and durability of 
new treatment methods for vascular disease is critical.  Examples include cell- and 
gene-based therapies, endovascular and novel pharmacological interventions, as well 
as development of durable bioprosthetic devices to treat vascular disorders such as 
coronary, peripheral, visceral, and cerebral vascular occlusive diseases. 


The objective of the SCCOR in vascular injury, repair, and remodeling is to 
stimulate clinically relevant, multidisciplinary collaborations leading to clinical 
and basic science research efforts on important public health problems for 
individuals with vascular diseases.  The translation of knowledge into clinical 
practice should be a goal of applications submitted in response to this initiative.  
Recent advances in understanding the genetic, molecular, and physiologic 
underpinnings of vascular function and pathophysiology of disease offer new 
directions to study normal and abnormal vascular function, to develop early 
diagnostic tools and markers, and to stratify patients based on genetic and 
molecular markers.

The research encompassed by this program will (1) emphasize the development and 
translation of basic discoveries to understand the mechanisms of vascular disease; 
(2) improve the detection, characterization, staging, and management of vascular 
disease by using cutting-edge methodologies, such as nanotechnology, molecular 
imaging, genomics, proteomics, quantitative systems analysis; and (3) develop new 
methods to treat vascular diseases such as cell- and gene-based therapies for 
regenerative medicine.  

The SCCOR mechanism provides both the incentive and the structure to maintain 
critical collaborative cores or other resources necessary for translational 
research.  For example, the SCCOR mechanism affords the ability to establish and 
maintain a large clinical/DNA sample database of patients with various types of 
vascular disease.

The following examples of research topics are intended to provide a perspective on 
the scope of research that would meet the objectives of this program.  It is not 
required that all or any of these topics be included.  Applicants are encouraged to 
consider other topics that are relevant to the goals of the Vascular Injury, 
Repair, and Remodeling SCCOR program.  A unified program of clinical and basic 
research is needed to address such topics as:

o Define cellular and molecular factors and signals involved in vascular injury, 
repair, and remodeling including inflammatory, immune and humoral responses, high-
blood-pressure and lipid effects, and biochemical and biomechanical interactions

o Study mechanisms involved in the vascular injury, repair, and remodeling due to 
diabetes, the metabolic syndrome, and obesity

o Identify the origin of cells and mechanisms that contribute to the repair and 
remodeling of vascular lesions, and examine the use of stem or progenitor cells to 
repair, regenerate, or replace defective or damaged vascular tissue

o Determine how vascular cell heterogeneity contributes to the susceptibility of 
blood vessels to injury, repair, and remodeling

o Investigate the role of blood components (e.g., platelets, leukocytes, red blood 
cells) in the process of vascular injury, repair, and remodeling 

o Determine biological mechanisms responsible for variation in human susceptibility 
and progression of vascular diseases, and response to therapy as it relates to 
vascular, injury, repair and remodeling

o Apply emerging noninvasive or minimally invasive technologies (e.g., 
nanotechnology and molecular imaging) to study vascular injury, repair, and 
remodeling, and use that knowledge and technology to detect and stratify vascular 
diseases, to assess the functional characteristics of vascular lesions over time 
and the results of therapeutic interventions

o Apply state-of-the-art global technologies such as proteomics and genomics to 
understand the mechanisms of vascular injury, repair, and remodeling, and how gene 
and protein variations influence therapeutic success. 

o Develop novel and improved markers of subclinical vascular disease, including 
genetic and proteomic determinants, that can enhance our ability to detect and 
diagnose vascular diseases early in the disease process.

o Develop and test: (1) novel drugs to prevent, treat or manage vascular diseases; 
(2) novel therapeutic approaches to treat vascular diseases, including cell- and 
gene-based therapies; and (3) novel surgical interventions.


o Studies that focus on basic or clinical science only

o Phase III clinical trials

o Epidemiological studies

o Studies that are focused purely on stem cell characterization without 
consideration of vascular repair and remodeling

o Studies in coronary artery disease that focus on the injury of the myocardium


The newly developed Specialized Centers of Clinically Oriented Research (SCCOR) 
program mechanism requires clinical and basic scientists with a broad range of 
skills to work together on a unified theme. It, therefore, presents a rich 
environment for young clinical investigators to be exposed to and develop 
additional research skills. The individual centers can be expected to include among 
their research staff clinical personnel who are newly trained and relatively 
inexperienced in research. To assist the SCCOR grants in enhancing the 
developmental environment for their new clinical investigators, the NHLBI will 
permit applicants for a SCCOR to request up to an additional $100,000 in direct 
costs per year for a Clinical Research Skills Development Core. The objective of 
the Core is to support activities to assist new clinical investigators in 
progressing to more senior status by enhancing their research skills. This support 
is in addition to the usual cap on the SCCOR mechanism that is updated annually. A 
Clinical Research Skills Development Core is not required, however, and its absence 
will not disadvantage an applicant. The quality of the Clinical Research Skills 
Development Core, if proposed, will be evaluated based on the specific components 
listed below. The priority score on the Core will have no effect on the overall 
score of an application. 

Developmental opportunities that provide experience with new technologies and 
skills are encouraged for inclusion in the Core. Innovative strategies should be 
proposed for cross-disciplinary career development to achieve the goal of exposing 
new clinical investigators to additional research techniques and opportunities. 
Examples include a program of seminars focusing on scientific topics that include 
an integration of basic and clinical studies or an "exchange" program, wherein 
clinical investigators spend time in basic science laboratories. In addition to 
developing the research skills of new clinical investigators, the Cores must ensure 
that the participating new clinical investigators receive the mentoring they need 
to foster their research careers. The Clinical Research Skills Development Core is 
intended for staff investigators with limited clinical research experience, 
including fellows and junior faculty members. Investigators who have had a previous 
K series award are not eligible to participate as new investigators under this 
program.  Individuals with an active K grant can participate until the end of the 
award period for the K grant, but may not receive salary on the Skills Development 
Core. The Core should also address other skills necessary for a successful research 
career, such as grant writing, ethical conduct of research, and clinical trial 
design. Additional information about the Clinical Research Skills Development Core 
can be found at http://www.nhlbi.nih.gov/funding/policies/sccor_skill.htm

If a Clinical Research Skills Development Core is proposed, it must be directed by 
an investigator with strong educational and mentoring credentials who will devote a 
minimum of 5 percent effort as its Leader. To facilitate mentoring and 
multidisciplinary developmental activities, active involvement by the principal 
investigator and other senior investigators within the SCCOR is strongly 
encouraged. An application for a Clinical Research Skills Development Core will be 
evaluated in terms of its potential effectiveness in developing the skills and 
research capabilities of new clinical investigators as reflected in the following 
required elements of the application: 

o   A summary of the types of skills that would be developed and a description of 
proposed project-specific activities. 

o   A detailed discussion of how mentoring and the professional development of the 
new clinical investigators will be achieved, including their progression to more 
independent status.  

o   The credentials and track records of the Clinical Research Skills Development 
Core Leader, the Principal Investigator, and other participating senior staff in 
developing new investigators.  

o   A plan for coordinating the activities of participating senior investigators.  

o   A plan for monitoring the progress of the new clinical investigators.  

o   A description of existing opportunities within the applicant's institution for 
supporting investigator development and steps taken to avoid overlap with or 
duplication of these efforts. 

o   A detailed development plan for each proposed new investigator (or a 
representative plan and proposals for tailoring it to needs of multiple new 
investigators) including required course work and scientific enrichment activities 
such as special lectures, visiting scientist symposia, seminars, and workshops.  

Costs allowable for inclusion within the $100,000 direct costs per year limit for 
the Clinical Research Skills Development Core include salary support for the Core 
Leader and other participating senior investigators and staff, travel costs for new 
investigators, supplies and equipment to be used in support of developmental 
activities, and costs for courses, seminars, workshops, and other activities 
directly related to the development plan. All costs requested in this Core must be 
justified with respect to developmental activities and may not be used to 
supplement the costs of research proposed in the rest of the SCCOR.

Since the Core is intended to serve new clinical investigators who occupy positions 
and receive salary support from the SCCOR grant, salary support for the new 
investigators is neither needed nor allowable as a Core cost. All new clinical 
investigators supported by the SCCOR grant should be eligible to participate in 
Core-sponsored activities so long as they have not attained independent status. 
However, attaining independent status should be an objective of the Core 
activities. So, participating new investigators should be encouraged to apply for 
either a Career Development Award, a patient-oriented regular research grant, or 
any other source of independent research or career development support. Although 
the participating new investigators will be expected to devote essentially full-
time effort to research during this period, they may devote an appropriate 
percentage of their time to maintaining clinical skills.

An application for a Clinical Research Skills Development Core will be evaluated in 
terms of its potential effectiveness in developing the skills and research 
capabilities of new clinical investigators as reflected in the required application 
components identified above.

This RFA will use the NIH P50 award mechanism.  All applications received in 
response to the Vascular Injury, Repair, and Remodeling SCCOR program will be 
considered as new applications and must meet the requirements for the new SCCOR 
program (please see http://www.nhlbi.nih.gov/funding/policies/sccor_desc.htm).  As 
an applicant, you will be solely responsible for planning, directing, and executing 
the proposed project.  The anticipated award date is April 1, 2006.  

Applicants should request a 5-year project period when responding to this 
announcement. Each NHLBI SCCOR program is limited to 10 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 SCCOR 
program. Under this policy, a given SCCOR grant is awarded for a 5-year project 
period following an open competition. Only one 5-year competing renewal is 
permitted, for a total of 10 years of support, unless the SCCOR program is 
recommended for extension.

The NHLBI comprehensive evaluation of the Vascular Injury, Repair, and Remodeling 
SCCOR program will be conducted during the second project period according to the 
following timetable: 

Program Announced:                    FY 2004

Project Period (First Competition):   FY 2006 through FY 2010

Program Re-announced:                 FY 2008

Project Period (Second Competition):  FY 2011 through FY 2015

Letter to Principal Investigators 
Regarding SCCOR Evaluation Plans:     FY 2012 (mid-way through year 02
                                               of 2nd project period)

SCCOR Evaluation Meeting:             FY 2012 (late in year 02 of 2nd
                                               project period) 

The NHLBI does not limit the number of applications for a given SCCOR program from 
one institution. However, each SCCOR application from the institution must have a 
different Principal Investigator and must be self-contained and independent of 
other SCCOR applications from the same institution. Institutions envisioning more 
than one application are encouraged to discuss their plans with the program contact 

This RFA uses just-in-time concepts and only non-modular budgeting formats. Follow 
the instructions for the non-modular budget research grant applications at 
https://grants.nih.gov/grants/funding/phs398/phs398.html. This program does not 
require cost sharing as defined in the current NIH Grants Policy Statement at 


The NHLBI intends to commit approximately $20.0 million in FY 2006 to fund 5 to 7 
new grants in response to this RFA. An applicant may request a project period of 5 
years and a budget for direct costs of up to $2.5 million per year not including 
Facilities and Administrative (F&A) costs for collaborating institutions in the 
first year (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-040.html).  
In addition, applicants for a SCCOR may request up to $100,000 in direct costs per 
year above the usual cap ($2.5 million direct costs) for a Clinical Research Skills 
Development Core. All applications will be considered as new applications. An 
increase of no more than 3 percent may be requested in each additional year. 
Because the nature and scope of the proposed research will vary from application to 
application, it is anticipated that the size and duration of each award will also 
vary. 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 a sufficient number of meritorious applications.

Consortium Arrangements
If a grant application includes research activities that involve institutions other 
than the grantee institution, the application will be considered a consortium 
effort. Such applications are permitted, but it is imperative that the application 
be prepared so that programmatic, fiscal, and administrative considerations are 
explained fully. At least 50 percent of projects (including at least one clinical 
project) and 50 percent of the cores must be located at the applicant institution. 
The NIH published policy governing consortia is available in the business offices 
of institutions that are eligible to receive federal grants-in-aid and should be 
consulted before developing the application. For clarification of the policy, 
contact Mr. Dave Reiter, Grants Operation Branch, NHLBI (301) 435-0177.  

Applicants for SCCOR grants should exercise great care in preserving the 
interactions of the participants and the integration of the consortium project(s) 
with those of parent institution, because synergism and cohesiveness can be 
diminished when projects are located outside the group at the parent institution. 
Indirect costs paid as part of a consortium agreement are excluded from the limit 
on the amount of direct costs that can be requested.

You may submit (an) application(s) if your institution has any of the following 
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges,             
hospitals, and laboratories
o Units of state and local governments
o Eligible agencies of the federal government
o Domestic institutions/organizations

o Foreign institutions are not eligible to apply.
o Faith-based or community-based organizations 

Any individual with the skills, knowledge, and resources necessary to carry out the 
proposed research is invited to work with their institution to develop an 
application for support.  Individuals from under-represented racial and ethnic 
groups as well as individuals with disabilities are always encouraged to apply for 
NIH programs.   

1. The overall concept of a SCCOR program focuses on clinical and basic scientific 
issues related to diseases and disorders relevant to the mission of the NHLBI. To 
be considered responsive to this announcement, all applications must include both 
clinical and basic research. In addition, interactions between clinical and basic 
scientists are expected to strengthen the research, enhance the translation of 
fundamental research findings to the clinical setting, and identify new research 
directions. Translation of findings from basic to clinical studies is an important 
focus of the SCCOR program. 
2. The number of clinical research projects in each NHLBI SCCOR must be equal to or 
greater than the number of basic science projects, at the time of submission, 
award, and throughout the 5-year project period. For example, if an application has 
a total of three projects, two of the projects must be clinical research projects. 
Neither a clinical component in a basic science project nor a clinical core 
fulfills the requirement for a clinical project. However, a single project can 
integrate basic and clinical research. If the majority of the research within a 
project is clinical, it will be considered a clinical project; if the majority of 
the research within a project is basic, it will be considered a basic project. 
Because a SCCOR grant is a 5-year program, an applicant should submit a 5-year plan 
for all the projects. 

3. In order for a project to be considered clinical research for the purposes of 
responsiveness to this RFA, the research must be patient-oriented research. 
Patient-oriented research is research in which an investigator (or colleague) 
directly interacts with patients having a disease or condition of interest. Normal 
healthy subjects may be included, but only in combination with studies involving 
patients. In studies involving the use of human specimens, the investigators must 
have direct interaction with the patient from whom the specimen is obtained and 
relate the research results to the patient status or outcome for this to be 
considered a clinical project. It is intended that the requirement for investigator 
interaction with the study participants will eliminate research involving archived 

Applicants are encouraged to pursue patient-oriented research on topics related to 
health disparities and the translation of this research to clinical practice for 
affected minority populations. At a minimum, clinical research projects must 
include women and minorities in the study population in representative numbers, 
unless such inclusion can be demonstrated to be inappropriate. Clinical studies 
involving interventions or treatments must give consideration to including 
sufficient numbers of women and minorities to conduct valid analyses of subgroup 
effects. Epidemiologic studies or Phase III clinical trials will be considered 
unresponsive to this RFA.

4. Each awarded SCCOR must consist of three or more projects, all of which are 
directly related to the overall clinical focus of the SCCOR. At least 50 percent of 
the projects and 50 percent of the cores must be located at the applicant 
institution, and at least one of the clinical projects must be at the applicant 
institution. Component projects not located at the applicant institution may be at 
a foreign institution, but must conform to NIH policy regarding the protection of 
human subjects. Each component project, whether clinical or basic, requires a well-
described, clinically relevant hypothesis, preliminary data, and a time-table for 
conducting the proposed investigations.

5. The relationship of each core to each component project should be described. A 
core must provide services to two or more projects. 

6. Each SCCOR must have a well-delineated organizational structure and 
administrative mechanism that foster interactions between investigators, accelerate 
the pace of research, enable translation of basic research findings to clinical 
applications, and ensure a productive research effort.

7. Applicants should provide a detailed data and safety monitoring plan for the 
clinical research proposed; the monitoring plan will be considered as part of peer 
review of the application. This plan should address informed consent, recruitment, 
reporting of adverse events, patient safety, oversight of clinical issues in the 
protocols, storage and analysis of confidential data, and dissemination of any 
research results. After a decision has been made regarding SCCOR awards, the 
Institute will determine whether to convene a Data and Safety Monitoring Board 
(DSMB) to oversee one or more clinical projects in a SCCOR program.  It is NHLBI 
policy to appoint DSMBs for Institute-funded intervention studies when an 
independent group is needed to evaluate the data on an ongoing basis to ensure 
participant safety and/or study integrity.  The decision to establish each board is 
made by the relevant Division Director with the concurrence of the NHLBI Director.  
In those cases where such interventional studies are proposed, applicants are 
encouraged to include funds in the budget for 5 DSMB members for 2 meetings a year 
to be held in Bethesda, Maryland.

8. The principal investigator (SCCOR Director) should be an established research 
scientist with the ability to ensure quality control and the experience to 
administer both clinical and basic research effectively and integrate all 
components of the program. A minimum time commitment of 25 percent is required for 
this individual. The Principal Investigator must be the Project Leader of one of 
the component research projects. If this project is not recommended by peer review, 
the overall SCCOR application will not be considered further. If this project is 
judged by peer review to be of low scientific merit, this will markedly reduce the 
overall scientific merit ranking assigned to the entire application. 

9. Project Leaders should have significant research experience and must agree to 
commit at least 20 percent effort to each project for which they are responsible. 
Leaders of clinical projects should have experience in clinical research as defined 
in Item 2, above. Investigators with minimal research experience, but promising 
credentials, may participate; however, it is expected that most of the project 
leaders will be investigators with significant research experience.

10. Applicants are encouraged to establish links and utilize existing resources, 
including the NHLBI Program in Genomic Applications 
(http://www.nhlbi.nih.gov/resources/pga/); NHLBI Proteomics Centers 
(http://www.nhlbi.nih.gov/resources/medres/proteomics/index.htm); Programs of 
Excellence in Gene Therapy for Heart, Lung, and Blood Diseases with National 
Service Cores for Pre-Clinical Grade Vector Production, Cell Morphology, 
Hematopoietic Cell Processing, and Non-Human Primate Hematopoietic Transplantation 
(http://www.med.cornell.edu/pegt/); NHLBI clinical research networks; and General 
Clinical Research Centers, as feasible and appropriate. If applicants propose to 
utilize such resources, a letter of agreement from the Program Director or 
Principal Investigator of the resource should be included with the application. 

11. The applicant should plan and budget for the SCCOR Director and the Project 
Leaders of the SCCOR to attend one annual grantee meeting per year in Bethesda, 

12.  NIH recently reaffirmed support for the concept of timely sharing and 
distribution of model organisms for biomedical research.  Applicants are expected 
to include in the application/proposal a description of a specific plan for sharing 
and distributing unique model organism research resources generated using NIH 
funding so that other researchers can benefit from these resources.  More 
information can be found at 
Applicants are encouraged to include funds in the budget for this purpose.

We encourage inquiries concerning this RFA and welcome the opportunity to answer 
questions from potential applicants.  Inquiries may fall into three areas:  
scientific/research, peer review, and financial or grants management issues:

o Direct your questions about scientific/research issues to:

H. Eser Tolunay, Ph.D.
Director, Vascular Biology Research Program
Division of Heart and Vascular Diseases 
National Heart, Lung, and Blood Institute
Rockledge Centre ll
6701 Rockledge Drive, Room 10190
Bethesda, MD 20892-7956
Telephone: (301) 435-0545
FAX: (301) 480-2858
Email: TolunayE@nhlbi.nih.gov

o Direct your questions about peer review issues to:

Valerie Prenger, Ph.D.
Chief, Review Branch
Division of Extramural Affairs 
National Heart, Lung, and Blood Institute 
Rockledge Centre ll
6701 Rockledge Drive, Room 7214 
Bethesda, MD  20892-7924
Telephone:  (301) 435-0270 
Fax: (301) 480-3541 
Email: prengerv@nhlbi.nih.gov

o Direct your questions about financial or grants management matters to:

David Reiter
Grants Operations Branch 
National Heart, Lung, and Blood Institute 
Rockledge Centre ll
6701 Rockledge Drive, Room 7172
Bethesda, MD 20892-7926
Telephone: (301) 435-0177
FAX:  301-480-3310
Email: reiterd@nhlbi.nih.gov

Prospective applicants are asked to submit a letter of intent that includes the 
following information:

o Descriptive title of the proposed research program
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does not enter 
into the review of a subsequent application, 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 sent by the date listed at the beginning of this 
document. The letter of intent should be sent by mail or email to Dr. Valerie 
Prenger at the address listed under “WHERE TO SEND INQUIRIES.”


Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001). Applications must have a DUN and Bradstreet 
(D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier 
when applying for federal grants or cooperative agreements. The D&B number can be 
obtained by calling (866) 705-5711 or through the web site at 
http://www.dunandbradstreet.com/. The D&B number should be entered on line 11 of 
the face page of the PHS 398 form. The PHS 398 document is available at 
https://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format.  
For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: 
SUPPLEMENTARY INSTRUCTIONS: Because of the size and complexity of a SCCOR, 
prospective applicants are urged to consult with the staff of the Division of Heart 
and Vascular Diseases early in the preparation of the application (see INQUIRIES 
Section).  Special instructions are needed for preparing a SCCOR application and 
are available from the program contact listed under WHERE TO SEND INQUIRIES or at 
http://www.nhlbi.nih.gov/funding/policies/sccor_supp.htm. To provide opportunity 
for such interactions, the time frame for implementation of this program includes 
an ample interval between the release of this RFA and the receipt date for 

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) 
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 RFA label is also available at: 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the 
application, including the Checklist and three signed photocopies in one package 
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 and all copies 
of the appendix material must be sent to:

Valerie Prenger, Ph.D.
Chief, Review Branch
Division of Extramural Affairs 
National Heart, Lung, and Blood Institute 
Rockledge Centre 11, Room 7214  
Bethesda, MD  20817 (express mail)
Telephone:  (301) 435-0270 
Fax: (301) 480-3541 
Email: prengerv@nhlbi.nih.gov

APPLICATION PROCESSING: Applications must be received on or before the application 
receipt date listed in the heading of this RFA.  If an application is received 
after that date, it will be returned to the applicant without review. 

Although there is no immediate acknowledgement of the receipt of an application, 
applicants are generally notified of the review and funding assignment within 8 
The Center for Scientific Review (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.  However, when a previously 
unfunded application, originally submitted as an investigator-initiated 
application, is to be submitted in response to an RFA, it is to be prepared as a 
NEW application.  That is, the application for the RFA must not include an 
Introduction describing the changes and improvements made, and the text must not be 
marked to indicate the changes from the previous unfunded version of the 

Principal Investigators should not send supplementary material without first 
contacting the Scientific Review Administrator (SRA). The SRA will be identified in 
the letter sent to you indicating that your application has been received. If you 
have not received such a letter within three weeks after submitting the 
application, contact Dr. Valerie Prenger at the address listed under “WHERE TO SEND 

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NHLBI. Incomplete or unresponsive applications will not be 
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:

o 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 and assigned a priority score.
o Receive a written critique.
o Receive a second level review by the NHLBI National Advisory Council or Board. 

The goals of NIH-supported research are to advance our understanding of biological 
systems, improve the control of disease, and enhance health.  Factors to be 
considered in the evaluation of each application will be similar to those used in 
the review of traditional clinical and basic research grant applications and, in 
addition, will include overall proposed interactions between clinical and basic 
research projects.  The review panel will include a majority of clinical 
researchers who will receive special instructions to place emphasis on strong 
clinical components.  Major factors to be considered in the evaluation of 
applications include:  

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

o Leadership, scientific expertise, experience, and commitment of the principal 
investigator; competence of the investigators to accomplish the proposed research 
goals and their time commitment to the program; clinical research experience among 
the investigators; and the feasibility and strength of consortium arrangements.

o Collaborative interaction between clinical and basic research components, 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; quality of the 
support cores; proposed instrumentation; quality controls; administrative 
structure; institutional commitment; and, when needed, data management systems. 

o Adequacy of the data and safety monitoring plan for the clinical research 

Each project will receive a priority score.  Each core (except the Clinical 
Research Skills Development Core) will be Recommended or Not Recommended based on 
whether the core is essential for the proposed research and has the capability to 
fulfill the proposed function.  Reviewers will evaluate the number of projects 
serviced by the core; strengths and weaknesses of the proposed approaches, 
resources, and interactions; whether the investigators are qualified for their 
role(s) in the core; and whether the proposed budget for the core is appropriate.  
Each application will receive an overall priority score based on the review 
criteria listed above.   

The Clinical Research Skills Development Core will receive a priority score based 
on the review criteria below, but the priority score will not enter into the 
overall priority score.    

Review Criteria for Clinical Research Skills Development Core:  

The Clinical Research Skills Development Core will be evaluated for its 
effectiveness in developing the skills and clinical research capabilities of new 
investigators.  This will include an evaluation of:   

o Credentials and track record of the Principal Investigator, Clinical Research 
Skills Development Core Project Leader, and other participating senior 

o Methods by which new investigators are to be recruited and selected including 
plans to recruit women and minority individuals.   

o Plans for developing the skills of new investigators; the types of skill and 
technologic development proposed.  

o Means by which the new investigators' professional development will be achieved.   

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following items 
will be considered in the determination of scientific merit and the priority score:

and protections from research risk relating to their participation in the proposed 
research will be assessed. (See criteria included in the section on Federal 
Citations, below.)
include subjects from both genders, all racial and ethnic groups (and subgroups), 
and children as appropriate for the scientific goals of the research.  Plans for 
the recruitment and retention of subjects will also be evaluated. (See Inclusion 
Criteria in the sections on Federal Citations, below.)

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to be 
used in the project, the five items described under Section f of the PHS 398 
research grant application instructions (rev. 5/2001) will be assessed.  


Letter of Intent Receipt Date: April 11, 2005
Application Receipt Date:  May 11, 2005
Peer Review Date: Sept/Oct 2005
Council Review: February 2006
Earliest Anticipated Start Date:  April 1, 2006


Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities

ANIMAL WELFARE PROTECTION:  Recipients of PHS support for activities involving 
live, vertebrate animals must comply with PHS Policy on Humane Care and Use of 
Laboratory Animals 
(https://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), as mandated 
by the Health Research Extension Act of 1985 
(https://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal 
Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), as 

HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that applications 
and proposals involving human subjects must be evaluated with reference to the 
risks to the subjects, the adequacy of protection against these risks, the 
potential benefits of the research to the subjects and others, and the importance 
of the knowledge gained or to be gained.

DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for all 
types of clinical trials, including physiologic, toxicity, and dose-finding studies 
(phase I); efficacy studies (phase II); efficacy, effectiveness and comparative 
trials (phase III).  The establishment of data and safety monitoring boards (DSMBs) 
is required for multi-site clinical trials involving interventions that entail 
potential risk to the participants.  (NIH Policy for Data and Safety Monitoring, 
NIH Guide for Grants and Contracts, June 12, 1998: 

SHARING RESEARCH DATA:  Investigators submitting an NIH application seeking 
$500,000 or more in direct costs in any single year are expected to include a plan 
for data sharing or state why this is not possible. 
https://grants.nih.gov/grants/policy/data_sharing  Investigators should seek 
guidance from their institutions on issues related to institutional policies, local 
IRB rules, as well as local, state and federal laws and regulations, including the 
Privacy Rule. Reviewers will consider the data sharing plan but will not factor the 
plan into the determination of the scientific merit or the priority score.

that women and members of minority groups and their sub-populations must be 
included in all NIH-supported clinical research projects unless a clear and 
compelling justification is provided indicating that inclusion is inappropriate 
with respect to the health of the subjects or the purpose of the research. This 
policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 

All investigators proposing clinical research should read the "NIH Guidelines for 
Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, 
October, 2001," published in the NIH Guide for Grants and Contracts on October 9, 
2001 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a 
complete copy of the updated Guidelines are available at 
The amended policy incorporates: the use of an NIH definition of clinical research, 
updated racial and ethnic categories in compliance with the new OMB standards, 
clarification of language governing NIH-defined Phase III clinical trials 
consistent with the new PHS Form 398, and updated roles and responsibilities of NIH 
staff and the extramural community.  The policy continues to require for all NIH-
defined Phase III clinical trials that: (1) all applications or proposals and/or 
protocols must provide a description of plans to conduct analyses, as appropriate, 
to address differences by sex/gender and/or racial/ethnic groups, including 
subgroups if applicable; and (2) investigators must report annual accrual and 
progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic 
group differences.

maintains a policy 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. 

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 is available at 

requires education on the protection of human subject participants for all 
investigators submitting NIH proposals for research involving human subjects.  You 
will find this policy announcement in the NIH Guide for Grants and Contracts 
Announcement, dated June 5, 2000, at 

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on 
hESCs can be found at http://stemcells.nih.gov/index.asp and at 
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only research 
using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry 
will be eligible for federal funding (see http://escr.nih.gov).  It is the 
responsibility of the applicant to provide, in the project description and 
elsewhere in the application as appropriate, the official NIH identifier(s) for the 
hESC line(s) to be used in the proposed research.  Applications that do not provide 
this information will be returned without review. 

of Management and Budget (OMB) Circular A-110 has been revised to provide public 
access to research data through the Freedom of Information Act (FOIA) under some 
circumstances.  Data that are (1) first produced in a project that is supported in 
whole or in part with federal funds and (2) cited publicly and officially by a 
federal agency in support of an action that has the force and effect of law (i.e., 
a regulation) may be accessed through FOIA.  It is important for applicants to 
understand the basic scope of this amendment.  NIH has provided guidance at 

Applicants may wish to place data collected under this RFA in a public archive, 
which can provide protections for the data and manage the distribution for an 
indefinite period of time.  If so, the application should include a description of 
the archiving plan in the study design and include information about this in the 
budget justification section of the application. In addition, applicants should 
think about how to structure informed consent statements and other human subjects 
procedures given the potential for wider use of data collected under this award.

Department of Health and Human Services (DHHS) issued final modification to the 
“Standards for Privacy of Individually Identifiable Health Information,” the 
“Privacy Rule,” on August 14, 2002.  The Privacy Rule is a federal regulation under 
the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that 
governs the protection of individually identifiable health information and is 
administered and enforced by the DHHS Office for Civil Rights (OCR).  

Decisions about applicability and implementation of the Privacy Rule reside with 
the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) 
provides information on the Privacy Rule, including a complete Regulation Text and 
a set of decision tools on “Am I a covered entity?”  Information on the impact of 
the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress 
monitoring of grants, cooperative agreements, and research contracts can be found 
at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

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.   Furthermore, we caution reviewers that 
their anonymity may be compromised when they directly access an Internet site.

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 RFA is related to one or 
more of the priority areas. Potential applicants may obtain a copy of "Healthy 
People 2010" at http://www.healthypeople.gov/.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal 
Domestic Assistance at http://www.cfda.gov/ and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health Systems 
Agency review.  Awards are made under the authorization of Sections 301 and 405 of 
the Public Health Service Act as amended (42 USC 241 and 284) and under Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the 
terms and conditions, cost principles, and other considerations described in the 
NIH Grants Policy Statement.  The NIH Grants Policy Statement can be found at 

The PHS strongly encourages all grant recipients to provide a smoke-free workplace 
and discourage the 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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