Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Heart, Lung, and Blood Institute (NHLBI)
Funding Opportunity Title	Translational Research Centers in Thrombotic and Hemostatic Disorders (TRC-THD) (U54)
Activity Code	U54 Specialized Center- Cooperative Agreements
Announcement Type	New
Related Notices	None
Funding Opportunity Announcement (FOA) Number	RFA-HL-12-008
Companion FOA
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestics Assistance (CFDA) Number(s)	93.839
FOA Purpose	The National Heart, Lung, and Blood Institute (NHLBI) solicits grant applications to participate in the Translational Research Centers in Thrombotic and Hemostatic Disorders (TRC-THD). The primary objective of this new Centers program is to enhance the translation of basic research discoveries that could lead to improved prevention, diagnosis, and treatment for thrombotic and hemostatic disorders. The TRC-THD will advance early stage translation research, integrating applied and basic science to move research discoveries toward clinical application. The individual multiple project Centers will address important clinical questions and must have at least one assay, method, procedure, or agent in early phase translation. Each Center will have a translational research skills development component and include collaborations with their Clinical and Translational Science Awards (CTSA) programs or institutional programs with similar capabilities to leverage existing resources to accelerate the translational research process. Additional Information Available at http://www.nhlbi.nih.gov/funding/inits/faq-hl-11-008.htm

Posted Date	November 16, 2010
Open Date (Earliest Submission Date)	Not Applicable
Letter of Intent Due Date	March 1, 2011
Application Due Date(s)	April 1, 2011
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	October 2011
Advisory Council Review	January 2012
Earliest Start Date(s)	April 1, 2012
Expiration Date	April 2, 2011
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Purpose

The primary objective of the Translational Research Centers in Thrombotic and Hemostatic Disorders (TRC-THD) is to enhance the translation of basic research discoveries that would lead to improved prevention, diagnosis, and treatment. The TRC-THD program will bring together clinical, translational, and basic investigators for a highly interactive, multi-disciplinary environment to address important clinical questions. The research focus will be on early translation of basic research discoveries, testing their applicability, feasibility, and possible clinical benefit. A translational research skills development component will provide a mentored research experience to young investigators to acquire the competencies needed for translational and clinical studies. To enhance the potential success of this new program, the Centers will be required to leverage existing infrastructure and resources at their institutions through collaborations with their CTSA or comparable institutional programs to enable timely and cost-effective completion of proposed translational and clinical research. Expected outcomes from this program are the identification of predictive markers of risk, the development of improved diagnostic tools, and the discovery of new therapeutic agents.

Background

NHLBI supports a strong program of mechanistic studies on the coagulation and fibrinolytic systems, platelet biology, and cell signaling. Transgenic mouse models have been developed that identified new proteins, pathways, and cellular interactions for potential therapeutic targets. The challenge is translating the information gained from in vitro and animal studies to human conditions and diseases. Conversely, a better understanding of the clinical challenges is needed to develop more predictive animal models and improved diagnostic tools.

Thrombotic disease or treatment to prevent thrombosis will affect most people in the United States at some point in their life. Thrombosis is the critical event in myocardial infarction and stroke, and antithrombotic agents are widely used for preventive therapy in high-risk populations. There is significant risk of venous thrombosis and pulmonary embolism associated with many orthopedic procedures, and it is a serious complication of diabetes, metabolic syndrome, sickle cell disease, hereditary diseases of the clotting system, pulmonary arterial hypertension, bone marrow disorders, and certain cancers or cancer therapies. Increasing age is independently associated with a dramatic increase in venous thrombosis. The aging US population, especially with multiple co-morbidities, escalates this serious health concern.

Maintaining hemostatic control and treatment of bleeding events is a challenge for hereditary and nonhereditary bleeding disorders such as hemophilia and platelet disorders. Acquired bleeding states represent a major complication of trauma, gastrointestinal ulcers, and adverse drug effects. In addition, patient genetic variation can contribute to unpredictable therapeutic dosing resulting in acquired bleeding diathesis. Hemorrhagic stroke can be the fatal result of high blood pressure, aneurysms, arteriovenous malformations, or medications. A better understanding of the mechanisms of thrombosis and hemorrhage, and the regulatory systems that normally maintain the balance between the two, is needed to develop safer hemostatic and anti-thrombotic agents.

Currently available knowledge and tools to assess individual risk in a particular situation or response to hemostatic or antithrombotic therapy can lead to over-treatment of some and under-treatment of others. There is a clear need to identify and validate biomarkers to diagnose and predict disease risk and to monitor therapy. Individualized proteomic and genetic characterization will enable personalized clinical management. Multi-disciplinary scientific teams with balanced basic and clinical expertise are needed to determine the impact of hemostatic and thrombotic mechanisms in the pathology of diverse disease entities and clinical conditions, develop efficient, cost effective diagnostic tools, and determine individual risks for bleeding, thrombosis or both.

General Program Design

The TRC-THD program will consist of up to five Centers addressing different clinical questions, exploring multiple approaches to improve prevention, diagnosis and treatment for thrombotic and hemostatic disorders. The interaction between the Centers will be enhanced through meetings and conference calls to exchange information, encourage collaborations, and maximize resources. Each Center will: (1) have at least one assay, method, procedure or agent in early phase translation;

(2) collaborate with their CTSA or similar Institutional program to maximize intellectual and physical resources; and (3) have a translational research skills development component to prepare young investigators for translational research.

The individual Centers, which may be multi-institutional, must have a minimum of three thematically unified interactive research projects and two mandatory cores. Collectively the research projects must have basic, translational, and clinical research components addressing important clinical questions. The required clinical research component may include observational studies, proof of concept studies, small or early Phase clinical trials. The two mandatory cores in the applications are an Administrative Core and a Translational Research Skills Development Core. The Administrative Core will serve the administrative needs for the Center and coordinate its activities with NHLBI, the Administrative Coordinating Center (ACC) and other TRC-THDs. A Translational Research Skills Development Core should provide the necessary competencies to two or more young investigator(s) interested in translational and clinical hemostasis/thrombosis research. Additional Center specific cores that provide service to at least two research projects may be included. Each Center must collaborate with their CTSA or similar Institutional program. The Centers should define the resources and capabilities to be provided, which match the needs of the proposed translational and clinical research projects. These could include: clinical resources, clinical study/trial design, clinical laboratory analysis, biostatical support, biomedical informatics, regulatory guidance, specific technical cores, and skills development of clinical research investigators.

Translational Research Skills Development Core:

A skills development core for new investigators interested in translational hemostasis/thrombosis research is mandatory. The TRC-THD, which brings together basic, translational and clinical research scientists addressing important clinical questions, presents a rich environment for young investigators to be exposed to a broad range of research skills. The individual Centers are expected to include among their research staff personnel who are newly trained and relatively inexperienced in research. The skills development core should augment the developmental environment by supporting activities to assist two or more new investigators in progressing to more senior status by enhancing their research skills. Innovative strategies should be proposed for cross-disciplinary career development to achieve the goal of exposing new investigators to additional research techniques and opportunities. In addition to developing the research skills, the Core must ensure that the participating new investigators receive the mentoring they need to foster their research careers. The Core is intended for staff investigators with limited translational research experience, including fellows and junior faculty members. 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. Participation or interaction with existing institutional programs is encouraged. The Translational Research Skills Development Core 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 TRC-THD is strongly encouraged.

Administrative Coordinating Center (ACC):

There will be one ACC to serve all the TRC-THDs which will perform a range of administrative functions including organizing investigator and External Panel meetings, arranging conference calls, and designing and maintaining a website for the program. A proposal for the ACC, which will service all the TRC-THDs, must be included in each TRC-THD application.

Specific Programmatic Requirements:

Translational Research Scientific Team: Each TRC-THD should focus on bringing together a multidisciplinary team with expertise in basic, translational and clinical research interested in applying this integrated knowledge to address important clinical questions in thrombotic and hemostatic disorders. Scientific partnerships between investigators who have not collaborated in the past are encouraged so that new interdisciplinary research teams can be formed that will have the required capacity to address common research goals. Plans for enhancing the abilities and opportunities for investigators to work across disciplinary boundaries should also be included in the Research Strategy component of the Program Overview and Statement of Objectives section.

Basic, Translational and Clinical Research Components: Collectively the research projects must have basic, translational, and clinical research components addressing important clinical questions. The required clinical research component may include observational studies, proof of concept studies, small or early Phase clinical trials. The TRC-THD must have at least one assay, method, procedure, or agent in early phase translation.

Collaboration with CTSA or other Institutional Programs: Each TRC-THD must demonstrate collaboration with their CTSA or other Institutional programs that will maximize intellectual and physical resources. The TRC-THD should define the resources and capabilities to be provided and how they contribute to the proposed research goals.

Translational Research Skills Development Core: Applications must include a description of plans to develop and direct a translational research skills development component. The core should be directed by an investigator with research and mentoring credentials. To facilitate multidisciplinary developmental activities, active involvement by other senior investigators in the TRC is encouraged. Each TRC must budget for providing skills development for two or more new investigators.

Administrative Core: Each TRC-THD should have an administrative core to coordinate activities within the program, the Administrative Coordinating Center and the NHLBI Program Director.

Administrative Coordinating Center (ACC): All applicants must include a proposal for an ACC with a description of how they would carry out its functions and a separate budget for those functions. The ACC will serve all the TRC-THD centers and will perform a range of functions including organizing investigator meetings and External Review Panel meetings, arranging conference calls, and designing and maintaining a website to support the TRC-THDs. One AAC site will be selected from the TRC-THDs and will receive additional funds to support these activities.

Internal Advisory Committee: Each TRC-THD will establish its own Internal Advisory Committee to evaluate progress and the effectiveness of interaction among participants.

Steering Committee: The Steering Committee composed of the TRC-THD Principal Investigators or their representative and the NHLBI Program Director will meet quarterly by conference call. The Steering Committee will plan the annual investigators meeting, and identify areas of shared interest and potential for collaboration in order to further the goals of the program.

Investigators Meetings: Investigators from individual TRC-THDs will meet annually in Bethesda, MD, to present updates on progress, to exchange ideas, and to discuss problems encountered. The agenda for the meetings will be determined by the Steering Committee composed of the Principal Investigators of the TRC-THDs and the NHLBI Program Director. The TRC-THD budget should include provisions for investigators to attend the investigators meeting.

External Review Panel: In order to maintain close scientific oversight of the TRC-THDs, an External Review Panel (ERP) consisting of eminent scientists in appropriate fields will be established by NHLBI. The ERP will meet periodically to review the progress of each TRC-THD and to assess the overall programmatic goals of the initiative. The ERP will make recommendations on structural and functional changes that should be made to enhance the TRC-THD program

Selected Research Examples

The following are examples of possible topics for the TRC-THD, but there are many other important challenges that would be responsive:

• Thrombotic risk associated with metabolic syndrome and diabetes; evaluate benefit of prophylaxis to reduce thrombotic events.
• Thrombotic risk associated with pregnancy, hormonal methods of birth control, and post menopausal hormone therapy.
• Identification of a biomarker(s) of in vivo platelet activation with which to assess platelet activation in human disease and evaluate the effectiveness of anti-platelet therapy.
• System biology and unbiased -omics (proteomic, genomic, lipidomic, metabolomic) approaches to understand bleeding/thrombotic set point or response to disease or therapy.
• Diagnostic tools to evaluate platelet function, understand integration of agonist-induced pathways of platelet aggregation, monitor efficacy of anti-platelet agents.
• Risk of thrombotic or bleeding events in children; improved therapies to treat or prevent thrombosis in children.
• Biomarkers or imaging methods to assess bleeding and thrombotic tendency; monitor response to therapy with current and new pharmaceuticals.
• Biochemical or imaging methods to monitor thrombosis progression and resolution; thrombosis associated with erosion or rupture of atherosclerotic plaques; and the role of the vasculature in thrombosis.
• Diagnostic criteria to evaluate bleeding risk with antithrombotic therapy or thrombotic risk to surgical procedures.
• Evaluate animal model discoveries (biomarkers, potential drug targets, etc.) in human populations; refine animal models to better reflect arterial and venous thrombosis in humans.
• Projects outside the scope of this FOA:
• Programs that do not address important clinical questions for thrombotic and hemostatic disorders.
• Programs that only focus on product development and do not contain basic and clinical research components.
• Programs that include Phase III clinical trials.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New The OER Glossary and the PHS398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The following NIH component intends to commit the following amounts in FY 2012: NHLBI, $14,000,000, up to 5 awards
Award Budget	Application budgets are limited to $1.8 million direct costs per year for each Center. An additional $150,000 in direct costs per year will be available for one Center selected to serve as the Administrative Coordinating Center (ACC).
Award Project Period	5 Years

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions:

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American tribal organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization 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 support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

It is critical that applicants follow the instructions in the PHS398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

Descriptive title of proposed research
Name, address, and telephone number of the PD(s)/PI(s)
Names of other key personnel
Participating institutions
Number and title of this funding opportunity

The letter of intent should be sent to:

Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7214, MSC 7924
Bethesda, MD 20892-7924 (Express mail zip: 20817)
Telephone: 301-435-0270
Fax: 301-480-0730
Email: [email protected]

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. 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 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the appendix files must be sent to:

Director, Office of Scientific Review
Division of Extramural Research Activities
National, Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7214, MSC 7924
Bethesda, MD 20892-7924 (Express mail zip: 20817)
Telephone: 301-435-0270
Fax: 301-480-0730
Email:[email protected]

All page limitations described in the PHS398 Application Guide must be followed, with the following exceptions or additional requirements:

• Research Strategy section is limited to 12 pages.

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS) as provided in the PHS398 Application Guide.

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide.

Part I. Overview Information contains information about Key Dates. 

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by NHLBI, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

CHARACTERISTICS OF TRC-THD PROGRAM

A. A Center must have a clearly defined, unifying, central theme to which each component project relates and to which each research investigator contributes.

• The NHLBI expects the applicants to define the integrating theme and to develop multidisciplinary approaches used to accomplish the objectives of the proposed research.
• The central theme must be clearly developed and the clinical questions being addressed clearly defined in the introduction. The integration of the required basic, translational and clinical research components should be described with regard to advancement of the central theme.
• The target goals anticipated on completion of the 5-year program should be outlined carefully in the introduction with special reference to contributions expected from the multidisciplinary team.
• The plan for interaction between the basic, translational and clinical investigators and the strategy for advancing the translational of basic research discoveries toward clinical application should be provided.

B. Component research projects that are interrelated and contribute scientifically to the central theme of the program.

• The relationship of hypotheses and goals of each component project to the central theme should be described.
• Each component project requires a well described research plan, preliminary data, and a timetable for conducting the proposed investigations.
• Component projects may be basic research, translational research, clinical research, or a combination. Population-based research is acceptable as a component of a project or one of several projects in the program if the objectives of the project can be completed in a 5-year project period. A TRC-THD may not be used to support Phase III clinical trials. The usual NIH policies concerning research on human subjects apply. Instructions for Form PHS 398 should be followed for addressing use of human subjects.
• An Administrative Core and a Translational Research Skills Development Core are required. If additional core facilities are included, the scientific and fiscal relationship of each component project to each core should be described and fully justified.
• A TRC-THD requires a minimum of three interrelated component research projects, each of which is funded for 5 years.
• Each individual project in a TRC-THD should have a different project leader.

C. A principal investigator (PI) who is a research scientist of recognized stature in his/her scientific discipline and has the demonstrated ability to ensure quality control and to administer and integrate all components of the translational research program.

• The principal investigator must devote a minimum of 3 person-months/year commitment to the grant.
• The principal investigator must also be the project leader of one of the component research projects.

D. Project leaders who provide expertise from several disciplines.

• Project leaders must be individuals whose scientific publications demonstrate their potential to contribute to the overall theme of the program project.
• Project leaders must agree to commit at least 2.4 person-months/year to the project for which they are responsible.
• Investigators with excellent research training, who have not yet achieved established investigator status, may participate.

E. Core leaders who have appropriate expertise.

• Core leaders must be qualified for their role(s) in the core unit.
• Core leaders should dedicate time and effort commensurate with the complexity of the core unit's function.

F. A plan to ensure extensive interaction among all participants and the communication of ideas and results.

• A compelling justification must be presented for how the proposed program structure will encourage and enable extensive interactions among investigators and accelerate the acquisition of knowledge.
• An internal advisory committee should be established to evaluate progress, the effectiveness of interaction among participants, and the collaboration with other institutional programs (e.g. CTSA).

G. A section titled "Synergy and Interactions Among Projects and Project Leaders." The section must address:

• Collaborative aspects, inter-relatedness of research, and the contribution of each project to both the central theme of the application and the other projects included in the application.
• A description of inter-project use of resources and research findings.
• A proposed schedule of seminar series, monthly group meetings, or other features that will stimulate collaboration and interaction among investigators included in the application.
• The role of the internal advisory committee, their interactions with each other and with the project leaders

The exceptions and additions noted below are the only changes from the general requirements provided in the instructions for PHS Form 398 that apply to each project and core unit of a TRC-THD application.

Specific Instructions

Face page

There is one face page for entire application. Applications must not repeat face page for components.

Table of Contents

• Provide a detailed table of contents that will enable readers to find specific information readily. List program introduction, each project, the budget for each project, each core unit, and the budget for each core unit, TRC-THD Administrative Center and supply the page number for each item. Identify each project by title, assign each project a number that reflects the order in which the projects are presented in the application, and provide the name of the project leader or responsible investigator.

Detailed Budget for Initial Budget Period

• Provide a detailed categorical budget for EACH PROJECT AND EACH CORE UNIT in their respective sections of the application. In addition, provide and identify a complete budget for each consortium project.
• Incorporate a detailed budget for all requested support for the first year. For each category, such as "Personnel," "Equipment," "Supplies," "Travel," and "Other Expenses," give the amount requested for EACH PROJECT AND CORE UNIT with subtotals. If contractual arrangements or "purchased services" involving other institutions or organizations are anticipated, include total (direct and facilities and administrative) costs associated with each third party participation in the " Consortium/Contractual Costs" category.

Budget for Entire Proposed Period of Support.

• Prepare a detailed categorical budget that provides totals for each year of requested support. Requests for any increases in succeeding years must be clearly stated and any changes in percent effort and funds must be justified in the individual project and core unit budgets.

Research Plan

• FOLLOW THE FORMAT OF THE PHS FORM 398 for each project.

Additional Format Instruction - The following sections must precede the portion of the application that contains the details of the individual projects.

Program Overview and Statement of Objectives (Limit of 12 pages)

• A TRC-THD should be viewed as a group of interrelated research projects, each of which is not only individually meritorious scientifically but also complementary to and interrelated with the other projects in the research program and contributes to the integrating theme. The theme of a proposed program and the clinical questions being addressed should be established in the first few sentences of the general introduction. Translational components should be identified and how the program will advance basic discoveries toward clinical application.
• Describe the rationale for the proposed total research program. Explain the strategy for achieving the objectives of the overall program and how each research project and core unit relates to that strategy and to each other.
• Describe the collaboration with the CTSA or similar institutional programs; explain the relationship and benefits to the TRC-THD.
• The general overview of the overall program description is the appropriate place to indicate the planned interactions and collaborations between investigators in the group, to predict the anticipated unique advantages that would be gained by the research within the proposed program, to describe how the projects are synergistic and mutually interrelated.
• Briefly describe the features of the institutional environment that are relevant to the effective implementation of the overall program. As appropriate, describe available resources such as clinical and laboratory facilities, participating and affiliated units, patient populations, geographic distribution of space and personnel, and consultative resources. The information requested here supplants the "Resources" page in the PHS Form 398 grant application, which is NOT to be used in this section.
• CHAIN OF RESPONSIBILITY. Describe in detail, and by diagram if appropriate, the chain of responsibility for decision making and administration, beginning with the principal investigator and including the leaders of the research projects and core units. Indicate where, in the chain of responsibility, advisory groups (internal consultants) would be used, and describe their function in ensuring quality control in the research efforts.
• INTERNAL ADVISORY BOARDS. Every TRC-THD should have plans for an internal advisory board. The internal advisory board should consist of three to five members outside of the program but within the applicant institution (or within participating institutions) who are able to assist in frequent, ongoing reviews.
• SPECIFIC MANAGERIAL RESPONSIBILITIES: Indicate who would be responsible for assisting the principal investigator with day-to-day administrative details, program coordination, and planning and evaluation of the program.
• CONSORTIUM ARRANGEMENTS: Applications that include research activities involving institutions other than the applicant institution are considered consortia. Foreign consortia with specific relevance to the objectives of the program may be included. Consortia applications must be prepared so that the programmatic, fiscal, and administrative considerations are explained fully. The published policy governing consortia is available in the business offices of institutions that are eligible to receive Federal grants-in-aid. Consult the latest published policy governing consortia before preparing an application. If clarification of the policy is needed, contact the Chief of the Grants Operations Branch, Division of Extramural Affairs, NHLBI, at 301-435-0144.

Individual Projects

1. Title and number each research project so that it can be readily distinguished from any other project in the program. An individual description should be prepared for each project. Provide the name and academic title of the project leader and each participating investigator.

2. Present the budget for each research project according to the instructions for PHS Form 398. A detailed categorical budget is required for the first and all subsequent years. Include budget requests and explicit detailed budget justifications for all years.

3. Describe in detail the facilities to be used by each project. This is to be accomplished by completing the "Resource and Environment" page included in the PHS Form 398 grant application packet.

4. Specific Aims: List the specific aims of the research project for the total period of requested support. Indicate the general priority of each aim in the overall research plan. (Limited to 1 page.)

5. Research Strategy: State the overall objective for each proposed research project and explain how it relates to the central theme of the program and how it interrelates with and complements and/or supplements, the other research projects and core units. Organize the Research Strategy in the specified order using the instructions for PHS Form 398. In addition, describe the overall expected biomedical significance of the proposed research. (Limited to 12 pages.)

6. The Human Subjects and Vertebrate Animals sections should be included for each individual project (see PHS Form 398 Instructions). The usual NIH policies concerning research on human subjects and/or Vertebrate Animals apply.

Individual Core Units

In addition to the two mandatory cores, a core unit is defined as a resource for the program that provides centralized services to more than one of the research projects.

1. Title and assign a LETTER designation to each core unit so that it can be readily distinguished from any other core unit.

2. Provide the name and academic title of the core unit leader and each participating investigator.

3. Describe the function of the core unit as a resource to the program. This section must present clearly the facilities, techniques, and professional skills that the core unit would provide to the program and explain why its inclusion is essential to two or more of the individual research projects and to the overall research program. (Limited to 6 pages.)

4. Describe in detail the facilities to be used by EACH core unit. This is to be accomplished by completing the "Resource and Environment" page included in the PHS Form 398 grant application packet.

5. Present the budget for each core unit in the format and according to the instructions for Form 398. A budget for the entire proposed project period is required for all subsequent years of support (direct costs only). Include explicit and detailed categorical budget justifications for all years and fully describe how the costs interrelate with those of the projects serviced by the core unit.

6. Relation of the Core Units to the Research Projects: Provide in tabular form information concerning the research projects that each core unit would serve and the proportion of the cost of the core unit associated with each research project involved. (Limited to 6 pages.)

Administrative Coordinating Center (ACC):

A proposal for the ACC, which will service all the TRC-THDs, must be included in each TRC-THD application. The ACC will perform a range of functions including organizing investigator meetings, External Review Panel meetings, arranging conference calls, and designing and maintaining a website to support the TRC-THDs. A description should be provided of how the ACC would carry out its functions and a separate budget for those functions. The ACC director should have qualifications necessary to manage the facility and devote at least 5 % effort. In addition to costs associated with arranging annual meetings, four to six conference calls per year and design and maintenance of a TRC-THD website, travel costs for three External Review Panel members and two to three guest speakers to an annual meeting should be included within the $150,000 direct costs per year limit. The AAC proposal will be reviewed and scored independently from the rest of the TRC-THD. One AAC site will be selected from the TRC-THDs and will receive additional funds to support the ACC activities. (Limited to 6 pages.)

Summary Table of TRC-THD page limits

Section Page Limit

ProgramOverview and Statement of Objectives 12

Individual Research Projects (each) 12 + 1 Specific Aims Page

Cores (each) 6

TRC-THD Administrative Coordinating Center 6

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Each application will be reviewed in its entirety and receive a single impact/priority score. The individual research projects will not receive separate scores. The ACC component will be scored independently from the rest of the TRC-THD.

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the application address an important clinical question(s) to improve prevention, diagnosis or treatment for hemostatic or thrombotic disorders? Would successful completion of the proposed projects advance a basic research discovery toward clinical application?

Investigator(s)

Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? 

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? What is the quality of the strategy to evaluate the feasibility, applicability or possible clinical benefit of the translational component?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Will the program's collaboration with their CTSA or other institutional program(s) assist in achieving the objectives of the proposed research?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.

In addition to the above review criteria, the following criteria will be applied to applications in the determination of scientific merit and the impact/priority score.

Review Criteria for Translational Research Skills Development Core:

The Core will be evaluated in terms of its potential effectiveness in developing the skills and research capabilities of new investigators as reflected in the following required elements of the application:

• A summary of the types of skills that would be developed and a description of proposed project-specific activities;
• A detailed discussion of how mentoring and the professional development of the new investigators will be achieved, including their progression to more independent status;
• The credentials and track records of the Core Leader, the Principal Investigator, and other participating senior staff in developing new investigators;
• A plan for coordinating the activities of participating senior investigators;
• A plan for monitoring the progress of the new investigators;
• A description of existing opportunities within the applicant's institution for supporting investigator development, participation or interaction with these programs and added benefit of the Core to enhance experience for new investigators;
• 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.

Review Criteria for Administrative Coordinating Center:

The ACC will receive a separate impact/priority score based on the review criteria below, but that score will not be factored into the overall impact/priority score for the TRC-THD.

• What are the expertise, training, and experience of the investigators and staff, including the administrative abilities of the Principal Investigator, co-investigator(s)?
• Is the time they plan to devote to the ACC sufficient to provide for coordination and collaboration?
• Do the administrative, supervisory, and collaborative arrangements provide for achieving the goals of the program, including a willingness to cooperate with the participating TRC-THDs and the NHLBI?
• What is the quality of the facilities, equipment, and organizational structure to coordinate TRC-THDs activities?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NHLBI (assignments will be shown in the eRA Commons), in accordance with NIH peer review policy and procedures, using the stated review criteria.

As part of the scientific peer review, all applications will:

• Receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center and will compete for available funds with all other recommended applications submitted in response to this FOA . Following initial peer review, recommended applications will receive a second level of review by the NHLBI Advisory Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Maintenance of programmatic balance within the TRC-THD program.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. 

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.   

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. . More information is provided at Award Conditions and Information for NIH Grants.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• All aspects of the proposed research studies, including study design, conduct of the study, analysis and interpretation of research data, and preparation of publications.
• Coordinating interactions and collaborations of investigators within their TRC-THD and with investigators across the TRC-THDs.
• Attendance and participation in Steering Committee activities and annual investigator meetings.
• Maintaining career development opportunities to encourage new investigators to work in translational research.
• Providing information to the NIH Project Scientist regarding the progress of their TRC-THD.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The NHLBI Project Scientist will:

• Serve on the Steering Committee and may serve on other study committees, when appropriate.
• Establish an External Review Panel and convey the recommendations of the Panel to the TRC-THD investigators.
• Assist in the interactions between Centers to promote collaborations, in coordination of collaborative research efforts involving multiple Centers, and in avoiding unwarranted duplication of effort.
• Review and comment on critical stages in the research program before subsequent stages are implemented.
• Retain the option of recommending modification of the research plan if the technical performance falls below acceptable standards, or when specific lines of research cannot be effectively pursued in a timely manner.
• Retain the option to recommend additional research endeavors within the constraints of the approved research and negotiated budget.
• Implement adjustments to the TRC-THD program based on recommendations from the External Review Panel.
• An agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• Awardees agree to governance, through voting and decision making, of the program through a Steering Committee. Steering Committee voting membership shall consist of the Principal Investigators (i.e., the Cooperative Agreement Awardees) and the NHLBI Project Scientist. Quarterly meetings of the Steering Committee will ordinarily be held by telephone conference call. In person meetings will be held once yearly in Bethesda, MD.
• Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.FSRS.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.  

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]

Rebecca P. Link, Ph.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 9268, MSC 7950
Bethesda, MD 20892-7950 (Courier service zip: 20817)
Telephone: 301-435-0071
Email: [email protected]

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Patricia Reyes
Office of Grants Management
Division of Extramural Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7140, MSC 7926
Bethesda, MD 20892-7926
Telephone: 301-435-0166
Fax: 301-451-5462
Email:[email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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 Part 52 and 45 CFR Parts 74 and 92.