SPECIALIZED CENTERS OF CLINICALLY ORIENTED RESEARCH (SCCOR) IN HEMOSTATIC AND 
THROMBOTIC DISEASES                                

RELEASE DATE:  January 30, 2004        

RFA: RFA-HL-04-016 

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATION:
National Institutes of Health
 (http://www.nih.gov)

COMPONENT OF PARTICIPATING ORGANIZATION:
National Heart, Lung, and Blood Institute (NHLBI) 
 (http://www.nhlbi.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.938, 93.939
 
LETTER OF INTENT RECEIPT DATE:  August 24, 2004
APPLICATION RECEIPT DATE:  September 21, 2004 

THIS RFA CONTAINS THE FOLLOWING INFORMATION
o Purpose of this RFA
o Research Objectives
o Mechanism 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 Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA

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 will focus
on diseases and function related to hemostasis and thrombosis.  It is expected 
that the results from these SCCOR grants will have a positive impact on the 
prevention, diagnosis, and treatment of thrombotic and bleeding disorders. 

RESEARCH OBJECTIVES

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. The 
original SCOR program required both basic and clinical research, but the 
preponderance of funded projects were 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 clinical settings. 
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.  

Formation of a blood clot and the resulting ischemia leading to tissue damage 
is the major cause of disability or death in the United States. The application 
of innovative technologies in molecular biology, immunology, genetics and 
protein chemistry has contributed to elucidation of the regulatory pathways of 
hemostasis and the risk factors related to thromboembolic disease.  Further 
research is necessary to translate these advances to clinical care.  The long 
term goal of this SCCOR program is integration of science and clinical medicine 
in the prevention and treatment of thrombotic and hemostatic disorders.  Five 
specific areas of emphasis are detailed below. 

Arterial and Venous Thrombosis

The molecular basis of the involvement of inflammation and immune mediators in 
thrombosis remains unclear and methods of predicting thrombotic disease 
associated with abnormalities of these interactive pathways remain to be 
determined.   Many proteins, which are integral components of the coagulation 
cascade, are also potent activators of leukocytes and endothelial cells. 
Platelets are key mediators of inflammation.  Microparticles from 
platelets/leukocytes/endothelium may be an important source of tissue factor 
for thrombus formation.  Thus, studies that address the interaction of 
inflammation and thrombosis, and the associated clinical sequelae are timely.

Thrombosis and Cancer  

Thrombosis in cancer remains a significant problem in clinical medicine. 
Coagulation mechanisms appear to be involved in metastasis and cancer 
progression. The basic mechanisms underlying cancer related thrombosis, the 
optimal treatment of the hypercoagulable state associated with malignancy, and 
the role of the hemostatic system in cancer progression remain to be defined.
Despite prospective clinical trials suggesting that anticoagulants alter the 
course of cancer, the nature of this effect remains uncertain. Better 
understanding of the relationship between the coagulation system, fibrinolysis, 
angiogenesis and their roles in tumor progression and host resistance to 
thrombosis is needed.

Thrombotic Stroke

Ischemic stroke involves thrombosis, inflammation and reperfusion injury.  
Little is known about the interactions of blood cells and proteins, the vascular 
structures and the neuronal/glial compartment in normal and ischemic conditions.  
New insights into mechanisms and risk factors may come from studies of genetic 
polymorphisms linked to stroke and the level of expression of different genes. 
The development of coagulant activity and the interaction of platelets with the 
brain vasculature is a priority area of study.   

Better means of intervention for acute stroke and stroke prophylaxis are needed. 
Clinical studies of aspirin resistance in ischemic stroke patients may give 
insights into both mechanisms and improved therapeutics for stroke.  
Thrombolytic therapy with tissue plasminogen activator (t-PA) has proved 
beneficial, but, only a small group of patients qualify and the treatment may 
increase the risk of bleeding and neuronal damage. Decreased levels of 
circulating activated protein C (APC), compared with controls, may be a marker 
for increased risk for post-infection ischemic stroke. Recombinant APC, approved 
for treating severe sepsis, exerts important biologic activities in vivo in 
addition to its known anticoagulant activity.  Studies in animal models show 
that APC may have anti-inflammatory and anti-apoptotic activities, and it is 
neuroprotective in ischemic stroke.  Anti-platelet agents, such as an ecto 
ADPase (CD39), and chimeric agents that block P-selectin and complement, have 
been reported to produce beneficial results after stroke.  These agents, as well 
as the t-PA inhibitor, neuroserpin, are attractive candidates for combination 
therapy of ischemic stroke.

Disorders of fibrinolytic system 

Fibrinolysis plays an important role in the regulation and limitation of clinical 
thrombosis.  Hereditary deficiencies in these pathways are poorly defined.  The 
fibrinolytic system also has broad functions and its components may be involved 
in angiogenesis and obesity-related thrombosis. Significant opportunities for 
clinical studies might include in the development of more efficient and specific 
thrombolytics, cell-based and targeted delivery of these agents, and the 
efficacy/safety of catheter-directed thrombolysis.  The interrelated roles of 
fibrinolysis and inflammation require further investigation.  
   
Bleeding Disorders

The molecular definition of the defects in the VWF gene or the protein in Von 
Willebrand Disease (VWD) remain unclear.  Gene therapy trials are continuing in 
patients with hemophilia.  Opportunities for additional patient-oriented 
research include novel sites of FVIII/FIX synthesis or inducing synthesis of 
modified factors that increase survival or efficacy of the expressed gene 
product.  Factors that affect the incidence or prevalence of inhibitors and 
modulating their clinical impact are also important areas of investigation.   

Defects in platelet function are diagnosed using assays that are essentially 
similar to those that were in place 25-30 years ago.  We have not developed 
clinically-relevant measures of platelet function with the exception of 
structural definitions of glycoprotein receptor deficiencies such as Glanzmann 
Thrombasthenia and Bernard-Soulier syndrome.  With the advent of proteomics and 
gene arrays, opportunities exist to define new clinical syndromes and novel 
therapeutics for platelet disorders.  Studies on the bleeding complications of 
uremia are also encouraged.  

Research Topics

The objective of the SCCOR in Hemostatic and Thrombotic Diseases is to stimulate 
multidisciplinary collaborations leading to clinical and basic science research 
efforts in thrombotic and bleeding disorders.   The following examples of 
research topics are intended to provide a perspective on the scope of research 
that could 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 this new SCCOR program.  Large clinical 
trials will not be supported under this program.

o Study genetic and environmental risk factors, modifier genes, and disease 
outcome in thrombotic  and / or bleeding disorders utilizing  proteomic, 
genomic and other tools;  

o Perform translational studies on anticoagulant and antiinflammatory agents; 
evaluate pharmacogenetics, biomarkers, and monitoring of drugs;  

o Define the molecular properties of the brain vasculature, its expression of 
coagulant activity and platelet adhesion mechanisms; potential markers of 
ischemic injury and methods to prevent neuronal damage;
 
o Explore age-dependent regulation of  hemostasis, identify genetic switches, 
and possible development of hypercoagulable state; 

o Elucidate molecular and signal transduction processes involved in the 
activation of platelets; develop assays of platelet function, and perform 
translational studies on platelet inhibitors as potential therapeutic agents;

o Define the role of the fibrinolytic enzymes, their activators and inhibitors 
in thrombosis / bleeding with special attention to obesity and diabetes;

o Elucidate the underlying pathophysiology of immune-mediated thrombosis or 
bleeding and develop new approaches to its diagnosis and treatment;

o Develop imaging tools, assays and identify biomarkers of the subclinical  
prothrombotic state  that can be useful in early detection and diagnosis of the 
disease process;

o Study the role of thrombosis in cancer and  malignancy; evaluate drug therapy 
targeted to hemostatic factors in the prevention of cancer-related morbidity and 
mortality. 

The SCCOR mechanism provides both the incentive and the structure to maintain 
critical collaborative cores or other resources necessary for translational 
research.  

Clinical Research Skills Development Core

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 new SCCOR to request up to 
$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.  

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.

MECHANISM OF SUPPORT

This RFA will use the NIH P50 award mechanism. As an applicant you will be solely 
responsible for planning, directing, and executing the proposed project.  This RFA is 
a one-time solicitation.  Future unsolicited, competing – continuation applications 
based on this project will compete with all investigator – initiated applications and 
will be reviewed according to the customary peer review procedures.  The anticipated 
award date is February 1, 2006.  Applications that are not funded in the competition 
described in this RFA may be resubmitted as NEW investigator-initiated applications 
using the standard receipt dates for NEW applications described in the instructions of 
the PHS 398 application.

This RFA uses just-in-time concepts.  It also uses the modular budgeting as well as 
the non-modular budgeting formats (see 
http://grants.nih.gov/grants/funding/modular/modular.htm.  Specifically, if you are 
submitting an application with direct costs in each year of $250,000 or less, use the 
modular budget format.  Otherwise follow the instructions for the non-modular budget 
research grant applications.  This program does not require cost sharing as defined in 
the current NIH Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm. 

FUNDS AVAILABLE

The NHLBI intends to commit approximately $8,000,000 in fiscal year 2006 to fund two 
to four new grants in response to this RFA.  An applicant may request a project period 
of up to five years and a budget for direct costs up to $2.5 million, not including 
Facilities and Administrative (F&A) costs for collaborating institutions, in the first 
year.  In addition, applicants for a new 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.  Because the nature and scope of the proposed research will 
vary from application to application, it is anticipated that the size of each award 
will also vary.  Although the financial plans of the NHLBI provides 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. 

ELIGIBLE INSTITUTIONS

You may submit (an) application(s) if your institution has any of the following 
characteristics:

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

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

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 underrepresented racial and ethnic groups as well as 
individuals with disabilities are always encouraged to apply for NIH programs.   

SPECIAL REQUIREMENTS

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 tissue.

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, minorities and children to conduct valid analyses of subgroup effects.  Human 
biomedical and behavioral studies of etiology, pathogenesis, prevention and prevention 
strategies, diagnostic approaches, and treatment of thrombotic and bleeding disorders 
or conditions are responsive.  However, 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 to 
oversee one or more clinical projects in a SCCOR program. 

8. The principal investigator 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, 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.  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 the programmatic, fiscal, and administrative considerations are 
explained fully.  At least 50 percent of the 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. Anthony Agresti, Grants Operations Branch, NHLBI, (301) 435-0171.  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 the 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.

WHERE TO SEND INQUIRIES            

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:

Pan Ganguly, Ph.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
Rockledge II, Room 10176
Bethesda, MD  20892 -7950 (20817 for courier / express service)
Telephone:  (301) 435-0070
FAX:  (301) 480-1046
Email:  gangulyp@nhlbi.nih.gov

o Direct your questions about peer review issues to:

Anne Clark, Ph.D.
Chief, Review Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Dr., Room 7214 (MSC 7924)
Bethesda, MD 20892-7924 (20817 for express/courier service)
Telephone:  (301) 435-0270
FAX:  (301) 480-0730
Email:  ClarkA@nhlbi.nih.gov

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

Ms. Mary Baylor
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Rockledge II, Room 7126
Bethesda, MD  20892
Telephone:  (301) 435-0152
FAX:  301-480-3310
Email:  baylorm@nhlbi.nih.gov
 
LETTER OF INTENT

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

o Descriptive title of the proposed research
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 IC 
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 to Dr. Anne Clark at the address listed 
under WHERE TO SEND INQUIRES.

SUBMITTING AN APPLICATION

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 DUNS number can be obtained 
by calling (866) 705-5711 or through the web site at http://www.dunandbradstreet.com/. 
The DUNS number should be entered on line 11 of the face page of the PHS 398 form. The 
PHS 398 document is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format.  For 
further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: 
GrantsInfo@nih.gov.

SUPPLEMENTARY INSTRUCTIONS:

Because of the size and complexity of a SCCOR, prospective applicants are urged to 
consult with the staff of the Division of Blood Diseases and Resources early in the 
preparation of the application. Special instructions for preparing a SCCOR application 
are available from the program contact listed under WHERE TO SEND INQUIRIES or at 
http://www.nhlbi.nih.gov/funding/policies/sccor_desc.htm .

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 Hemostatic and Thrombotic Diseases 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 2011

Program Reannounced:                FY 2009

Project Period (Second Competition):FY 2011 through FY 2016

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

SCCOR Evaluation Meeting:           FY 2013 (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 listed 
under Where to Send Inquiries.

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: 
http://grants.nih.gov/grants/funding/phs398/labels.pdf.

SENDING AN APPLICATION TO THE NIH: 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 and all copies of 
the appendix material must be sent to Dr. Anne Clark at the address listed under WHERE 
TO SEND INQUIRES.

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 weeks.

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 application.  

PEER REVIEW PROCESS  

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NHLBI.  Incomplete and/or nonresponsive applications will not be 
reviewed.  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 National Heart, Lung, and Blood Advisory 
Council.

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 evaluate the application in order to judge the likelihood 
that the proposed research will have a substantial impact on the pursuit of these 
goals.  The scientific review group will address and consider each of the following 
criteria in assigning the application’s overall score, weighting them as appropriate 
for each application. 

o  Significance
o  Approach
o  Innovation
o  Investigator
o  Environment

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.

o 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?

o 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?

o INNOVATION: Does the project employ novel concepts, approaches or methods?  Are the 
aims original and innovative?  Does the project challenge existing paradigms or 
develop new methodologies or technologies? 

o 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?  

o 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 the unique features of the scientific environment or employ useful collaborative 
arrangements?  Is there evidence of institutional support?  

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.

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 investigators.  

o Methods by which new investigators are to be recruited and selected including plans 
to recruit women, minorities and children.   

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.   

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK:  The involvement of human subjects 
and protection from research risk relating to their participation in the proposed 
research will be assessed.  (See criteria included in the section on Federal 
Citations, below) 

INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH:  The adequacy of plans to 
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 
included in the section 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.

DATA SHARING:  The adequacy of the proposed plan to share data.

ADDITIONAL REVIEW CONSIDERATIONS

Sharing Research Data 

Applicants requesting more than $500,000 in direct costs in any year of the proposed 
research must include a data sharing plan in their application. The reasonableness of 
the data sharing plan or the rationale for not sharing research data will be assessed 
by the reviewers. However, reviewers will not factor the proposed data sharing plan 
into the determination of scientific merit or priority score.  See 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html for guidance.

BUDGET:  The reasonableness of the proposed budget and the requested period of support 
in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE 

Letter of Intent Receipt Date:  August 24, 2004
Application Receipt Date:  September 21, 2004
Peer Review Date:  January / February, 2005                    
Council Review:  September, 2005
Earliest Anticipated Start Date:  February 1, 2006

AWARD CRITERIA

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.
 
REQUIRED FEDERAL CITATIONS 

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.  
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

DATA AND SAFETY MONITORING PLAN:  Research Components involving Phase I and II 
clinical trials must include provisions for assessment of patient eligibility and 
status, rigorous data management, quality assurance, and auditing procedures. In 
addition, it is NIH policy that all clinical trials require data and safety 
monitoring, with the method and degree of monitoring being commensurate with the risks 
(NIH Policy for Data Safety and Monitoring,  NIH Guide for Grants and Contracts, June 
12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

SHARING RESEARCH DATA;  Starting with the October 1, 2003 receipt date, 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.  http://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.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH:  It is the policy of the NIH 
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 103-43).

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 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy 
of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. 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: a) 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 b) 
investigators must report annual accrual and progress in conducting analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: The NIH 
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. 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 is available at 
http://grants.nih.gov/grants/funding/children/children.htm. 

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:  
NIH policy 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 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. 

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 
http://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. 

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION
ACT: The Office 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 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA 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.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  The 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 (HIPPA) of 1996 that governs the protection of 
individually identifiable health information, and is administered and enforced by the 
DHHS Office for Civil Rights (OCR).  Those who must comply with the Privacy Rule 
(classified under the Rule as “covered entities”) must do so by April 14, 2003 (with 
the exception of small health plans which have an extra year to comply).

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 HIPPA 
Privacy Rule on NIH processes involving the review, funding, and progress monitoring 
of grants, cooperative agreements, and research contracts can be found at 
http://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 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 
http://grants.nih.gov/grants/policy/policy.htm. 

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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