Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Heart, Lung, and Blood Institute (NHLBI)

Funding Opportunity Title

Regional Clinical Centers for the Cardiovascular Cell Therapy Research Network (CCTRN) (UM1)

Activity Code

UM1 - Cooperative Agreements - Multi-Component Research Project Cooperative Agreements

Announcement Type

Reissue of RFA-HL-06-001

Related Notices
  • April 29, 2011 - Corrections to RFA-HL-12-026, Section II. Award Information, Section IV. Application Submission Information, and Section V. Application Review Information. See NOT-HL-11-141.
Funding Opportunity Announcement (FOA) Number

RFA-HL-12-026

Companion FOA
RFA-HL-12-025, UM1 Multi-Component Research Project Cooperative Agreements
Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

 93.837

FOA Purpose

The purpose of this FOA is to request applications for participation as a Regional Clinical Center (RCC) in a continuation of the Cardiovascular Cell Therapy Research Network (CCTRN).  A separate solicitation (RFA-HL-12-025) seeks applications for a network Data Coordinating Center (DCC).

The goal of the CCTRN is to promote evaluation of novel stem cell-based treatment strategies for individuals with cardiovascular disease. The network provides support to maintain an infrastructure to develop, coordinate, and conduct multiple collaborative clinical trials designed to improve cardiovascular disease outcomes.

 
Key Dates
Posted Date
Letter of Intent Due Date

May 22, 2011

Application Due Date(s)

June 22, 2011

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

October/November 2011

Advisory Council Review

January 2012

Earliest Start Date(s)

April  2012

Expiration Date

June 23, 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.

Table of Contents

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Nature of the Research Opportunity

This solicitation requests applications for Regional Clinical Centers (RCCs) to support a Renewal of the Cardiovascular Cell Therapy Research Network (CCTRN). A separate solicitation (RFA-HL-12-025) seeks applications for a Data Coordinating Center (DCC) that will support the network.  The CCTRN provides a unique environment for academic leaders in the field to form collaborative partnerships to develop and implement well-designed cell-based clinical studies.

The CCTRN was initiated in January, 2007, to provide the organizational, technical and clinical infrastructure necessary to conduct early, proof-of-concept studies designed to provide new knowledge in the field of cell-based therapies for the treatment of cardiovascular diseases.  Currently, the CCTRN consists of a DCC and five RCCs, some of which have added satellite centers to enhance patient recruitment.  The CCTRN also maintains a biorepository and core labs to manage imaging data (MRI, SPECT, and echocardiography), plus a training program for clinician-scientists interested in cell-therapy research.  Beginning in 2012 with the next funding period, it is anticipated that the network will expand to 6 RCCs and up to 12 satellite centers.  As this is a Renewal, applications from the current DCC and RCCs will be evaluated in addition to applications from institutions not presently in the network.

RCCs participate in development and implementation of network studies, recruit patients and disseminate research findings.  The RCC must have demonstrated excellence in performing clinical research in general, with a strong background in both basic and clinical cardiovascular research, and a proven ability to recruit patients with cardiovascular disease from various racial and ethnic groups. RCCs will propose, develop, and conduct protocols, recruit patients, and disseminate research findings. Each RCC will be expected to take part in multiple concurrent protocols and participate in a cooperative and interactive manner with other RCCs and the DCC.  Awards may be restricted at sites unable to successfully participate in network protocols and meet patient enrollment goals. 

Background

Heart disease is the leading cause of death in North America. In 2006, cardiovascular diseases caused 831,000 deaths, representing 34 percent of all deaths in the United States.  Each year about 785,000 Americans have a first heart attack, and another 470,000 have a second (or higher) attack.  Approximately 500,000 new heart failure cases are diagnosed every year, and an estimated five million Americans suffer from heart failure. The estimated cost of cardiovascular disease for 2010 is approximately $503 billion: $324 billion in direct health expenditures, $42 billion in indirect cost of morbidity and $137 billion in indirect cost of mortality (Source: NHLBI Disease Statistics).

Recently published data from multiple epidemiologic studies show that about 8 million Americans above the age of 40 have peripheral arterial disease (PAD).  Prevalence increases dramatically with age and disproportionately affects blacks (Source: American Heart Association).

Improved medical and surgical management in the past 30 years has produced a decline in the death rate due to cardiovascular heart disease. In certain groups, left ventricular assist device (LVAD) implantation may provide short- to intermediate-term benefit.  However, damage from hypertension, myocardial infarction, valvular disease, and cardiomyopathy often leads to remodeling of cardiac tissue, which can progress to heart failure. Accelerated ventricular remodeling is a probable contributor to the increased mortality observed after myocardial infarction in hypertensive patients. Current therapy cannot reverse the harmful remodeling and loss of myocytes that accompanies injury. In light of the limited efficacy and poor side effect profile of current treatment options, there is an unmet need for alternative long-term therapeutic strategies. If therapies could be developed to reverse or repair heart damage, an enormous public health burden would be ameliorated.

During the past ten years there has been a growing body of evidence suggesting that regeneration strategies such as cell-based therapies may provide viable approaches to repairing damaged myocardial tissue and restoring cardiac function.  A variety of adult stem cells, including bone marrow mononuclear cells, endothelial progenitor cells and mesenchymal stem cells have demonstrated improved ventricular function in animal models of acute myocardial infarction.  However, the mechanism(s) by which regeneration may occur in humans remain largely unknown, with the possibilities including both direct (e.g., stem cell differentiation) and indirect (paracrine) effects.  Investigators are working to understand stem cell plasticity, mechanisms of stem cell engraftment and survival, and effects on organ function in order to refine approaches that can be utilized in clinical settings.

Research aimed at preventing the progression and consequence of cardiovascular disease, and reversing the disease process through repair and regeneration of damaged tissues, has provided the basis for a new and exciting paradigm of cardiovascular disease treatment.  Small exploratory studies and larger randomized clinical trials of cell therapy in patients with myocardial infarctions or chronic heart failure currently are underway in the CCTRN and elsewhere.  Both animal and human studies indicate that cell therapy may be able to improve cardiac function and replace damaged or diseased tissue.  Early clinical studies suggest that infusion of autologous bone marrow cells is safe and may improve cardiac function in human disease as well.

Thus, three major factors – a compelling clinical need, supportive preclinical data, and promising early clinical experience – underscore the opportunity for cell-based therapy to dramatically alter the treatment of cardiovascular disease.

Ongoing Clinical Trials

Currently the CCTRN is supporting three clinical trials, which are expected to complete randomization of patients by the end of 2011:

1.    TIME: Transplantation in Myocardial Infarction Evaluation .  A Phase II, Randomized, Controlled, Double-Blind Trial Evaluating the Effect of Timing on the Administration of Bone Marrow Mononuclear Cells versus Placebo in Patients with Acute Myocardial Infarction.

2.    LateTIME: A Phase II, Randomized, Controlled, Double-Blind Trial Evaluating the Safety and Effect of Administration of Bone Marrow Mononuclear Cells Two to Three Weeks Following Acute Myocardial Infarction.

3.    FOCUS: A Randomized, Controlled, Phase II, Double-Blind Trial of Intramyocardial Injection of Autologous Bone Marrow Mononuclear Cells under Electromechanical Guidance for Patients with Chronic Ischemic Heart Disease and Left Ventricular Dysfunction.

These studies are expected to provide new scientific knowledge regarding the feasibility and effectiveness of delivering cells to cardiac tissue for the purpose of improving cardiac function and patient outcomes. Additional scientific knowledge is expected from studies of patient samples stored in a network biorepository, and from other patient-related data.

Specific Areas of Research Interest and Experimental Approaches Being Sought

The primary goal of the Network is to conduct multiple network-wide clinical trials to evaluate cell-based therapies for the treatment of cardiovascular diseases and related syndromes such as angina and peripheral arterial disease. Secondary objectives of the Network are to:

The CCTRN emphasizes early Phase I and II clinical investigations. Studies may involve autologous or allogeneic cells, new strategies for cell delivery, techniques for screening and localizing transplanted cells, and standardization of cell and therapeutic procedures. Phase III trials are outside the scope of this program.  The Network is expected to be able to manage multiple trials concurrently, and complete five to eight trials during the seven-year funding period. 

Potential research protocols include, but are not limited to, randomized clinical trials that:

Study endpoints that include pulmonary function measurements in addition to cardiac function are encouraged.

Network Organization

The CCTRN will be funded as a Cooperative Agreement consisting of a DCC and up to six RCCs with associated satellites, a biorepository, up to four core laboratories and up to four skills-development training programs for investigators and nurse coordinators.  Funds will be provided for up to 12 satellite centers within the network.  Inclusion of satellite centers in RCC proposals is encouraged, but optional.  Failure to include satellite centers will not adversely affect proposal scoring. Foreign sites are not allowable due to the logistics of cell processing.

The network will use a governance structure consisting of a NHLBI-appointed steering committee Chair, a steering committee comprised of RCC principal investigators, and NHLBI staff.

Scientific and Performance Requirements for the RCC

RCCs will be evaluated on the strength of their scientific application as well as their record of success supporting previous cardiovascular clinical trials, especially with regard to proper trial conduct (Good Clinical Practices) and meeting enrollment targets.

RCCs propose protocols, participate in development of network studies, recruit patients, implement protocols, and disseminate research findings. All individual RCCs are required to participate in a cooperative and interactive manner with one another and with the DCC in all aspects of the CCTRN.  RCC applicants must demonstrate excellence in clinical science, ability to isolate and prepare Good Manufacturing Practices (GMP)-grade cell products in a clinical setting, ability to perform clinical interventions on the range of cardiovascular diseases and conditions that the network may address, and a proven ability to recruit patients with these diseases and conditions from various racial/ethnic groups into clinical trials of the type that will be done in this network.  The latter requirement includes demonstrating access to sufficient numbers of eligible patients and might necessitate forming partnerships with local primary care practice groups and hospitals (“satellite” organizations). Potential applicants should review the additional information contained in Section IV, Application Submission Instructions.

The PD/PI of the RCC is expected to have demonstrated scientific leadership in the conduct of cardiovascular cell therapy-based clinical research.  The PD/PI is responsible for proposing protocols, estimating costs, participating in proposal development and implementation, conducting the research, overseeing standardized cell isolation and preparation procedures, including the submission of samples of cellular products to a central quality control laboratory, assuring quality of patient care and protocol adherence, assuring the accurate and timely transmission of data collected to the DCC and core laboratories, and collaborating with other CCTRN investigators in the publication and dissemination of research findings.

RCC applications must include up to two research protocols for a randomized clinical trial or proof of concept furthering the understanding of the diagnosis, management, or treatment of cardiovascular disease using cell therapy, suitable for implementation by the Network.  Protocols describing a small to intermediate-sized trial that can be completed by the Network within 2-5 years will be considered responsive.  Proposed studies should provide clinically relevant pathophysiologic information and move the field forward.  Protocols should be outlined in 1-2 pages and include objectives, rationale, research aims, outcome measures, study design, and description of the patient population with an estimate of the expected distribution of minority and female patients and ages.

The RCC must demonstrate both clinical science excellence and specialized expertise in cardiovascular disease management, a strong background in research, and a proven ability to recruit patients from various racial and ethnic groups.  RCCs will propose, develop, and conduct protocols, recruit patients, and disseminate research findings.  Each RCC will be expected to take part in multiple concurrent protocols.  All individual RCCs will be required to participate in a cooperative and interactive manner with one another and with the DCC.

RCC applicants should submit benchmark data from any cardiovascular-related clinical trials conducted at the site during the past five years. Benchmark data should include information (compared to the overall trial average) on: 1) the number of patients recruited, 2) timeliness of enrollment (time from site activation to first enrollment), 3) endpoint completion (submission of primary and secondary endpoint data), 4) patient retention (subjects completing final study visit, and 5) data quality and timeliness. Such information should be verified as much as possible by the DCC of the trial.  

Each RCC applicant must demonstrate the ability to produce clinical grade cell products in a manner compliant with regulatory requirements (Good Manufacturing Practices; GMP) and consistent with commonly agreed upon standards and procedures for Network protocols. Clinical cell processing laboratories must scale up the processes developed in the research laboratory using reagents approved for use in humans and using GMP. The establishment of cellular processing facilities within each RCC is necessary to combine the consulting, manufacturing, and regulatory duties that are necessary for the development of novel cellular therapies.  RCC-based cell processing facilities are expected to provide the actual, clinical grade cellular products utilized by investigators and must be produced in a standardized manner that allows comparability with cellular products from other RCCs when subjected to quality control testing. Some of the preclinical tasks of a cell processing facility include the qualification and testing of reagents, scale-up of methods, development of Standard Operating Procedures (SOPs), ongoing process validation, and the provision of controlled GMP infrastructure. RCC applicants may utilize existing cell processing facilities at their institution, or subcontract with an appropriate cell processing facility within close geographical proximity. Applicants should be aware of a resource that may be utilized for these purposes. NHLBI supports three NHBLI Somatic Cell Therapy Processing Facilities (RFP under BAA-HB-03-06) and for the development of clinical, Good Manufacturing Practices (GMP) grade cell products (http://www.nhlbi.nih.gov/funding/inits/archive/hb03-06a1.htm). More information regarding the NHLBI facilities for Production Assistance for Cellular Therapies (PACT) can be obtained from the PACT website (http://www.pactgroup.net).

RCC applicants must have demonstrable experience and expertise to conduct complex multi-center clinical studies in cardiovascular diseases and a history of previous successful clinical research. Prospective Clinical Centers must have an established research program in the scientific areas of interest and demonstrated access to a sufficient number of patients to accomplish their portion of the proposed protocols. The applicant must have an established program with experience in identifying and treating cardiovascular disease patients and a designated facility for this purpose. RCC applicants should also discuss clinical studies and trials conducted in last two years, particularly those related to cell therapy. Applicants should be well-versed in the science of cellular therapy and represent an institution (or partner with such an institution) able to manufacture quality-controlled cell-based products in compliance with FDA regulations and preparation standards defined for Network protocols.

RCC applicants also are required to provide a description of relevant patient demographics, and evidence of previous success recruiting patients for similar or related cardiovascular research programs.  Examples of strategies and best practices for patient recruitment are requested, and priority will be given to institutions with demonstrated success in meeting recruitment targets.  A detailed recruitment plan, including the proportion of patients expected to be supplied by the network, should be provided for each submitted protocol.  Applicants also should indicate whether they have prior success using satellite offices or institutions to refer patients willing to participate in clinical trials.

A minimum time commitment of 3 person-months is expected from the physician leadership (Program Director/Principal Investigator and any Co-investigators) at each Clinical Center. The Program Director/Principal Investigator or another member of the physician investigative team is expected to be readily available to respond directly to questions about CCTRN matters on a daily basis, preferably through e-mail, and should indicate this in the application. The Program Director/Principal Investigator must have a demonstrated track record of successful leadership of a multi-disciplinary team, including the ability to communicate with and ensure collaboration among cardiologists, cardiothoracic surgeons, nurses, and other related sub-specialists. Each RCC must designate a research coordinator with adequate effort as described below. A description of this individual's training, experience and involvement in clinical research should be provided.

The RCC is subject to annual administrative review.  Also, it is anticipated that the entire CCTRN program, including the DCC and RCCs, will be reviewed by a panel of experts during year -04.

Committees

Steering Committee (SC)

The SC is the main governing body of the network. Voting members of the SC include, at a minimum, the Network Chair, the PD/PIs of the DCC and RCCs (or their designated alternates), and the NHLBI Program Officer. The network Chair is independent of the DCC and RCCs, and will be appointed by NHLBI. The network Chair will plan network activities, oversee its functions, conduct SC meetings, and be a voting member of the Steering Committee. The SC will develop and ensure compliance with network policies and procedures, identify and prioritize topics for investigation, evaluate protocols proposed by the RCCs, and develop consensus protocols for submission to protocol review committees (PRCs). The SC also participates in the selection and oversight of Network core laboratories and biorepositories.  The SC will ensure that studies are properly conducted and monitored, that data are analyzed and interpreted appropriately, and that study results are reported in the scientific literature in a timely manner and disseminated to those directly involved in the care of cardiovascular disease patients. The SC typically meets three times per year, with bi-weekly conference calls and ad hoc meetings as required.  All major scientific decisions will be determined by majority vote of the SC, subject to final approval by NHLBI. The SC has final responsibility for approving the protocol before review by the PRC or Data and Safety Monitoring Board (DSMB). 

Subcommittees of the SC, such as the Executive Committee, and subcommittees for Publications and Presentations, Research Coordinators, Cell Processors, and Quality Control, have been established and may be continued or added to at the discretion of the SC.  The Publications and Presentations Subcommittee facilitates and supervises preparation of manuscripts prior to submission for publication. The Research Subcommittee recommends research ideas and develops network research protocols for review identified by the SC. The Quality Control Subcommittee is responsible for developing standards for specific laboratory tests and other measures to be used in the network protocols.

Protocol Review Committee (PRC)

An independent PRC is appointed by and advisory to the NHLBI. It consists of a chairperson and scientists with expertise in basic and clinical cell therapy research, clinical trial design, biostatistics, enabling technologies, outcome measures, and other areas of expertise as needed.  The PRC will evaluate protocols proposed by the SC based on the following criteria: importance of the question to be addressed, the scientific merit of the experimental design and approach, feasibility, appropriateness for the network, and consistency with NHLBI missions and policies. All new study protocols performed by the network must be approved by the PRC before referral to the DSMB.  Minor protocol amendments or low-burden ancillary studies or secondary analyses of approved trials may be submitted directly to the DSMB for consideration.

Data and Safety Monitoring Board (DSMB)

An independent DSMB is appointed by and advisory to the NHLBI in accordance with established policies to ensure data quality and participant safety.  All network protocols must be approved and monitored by the DSMB, generally after their approval by the PRC (except in cases of minor protocol amendments, low-burden ancillary studies or secondary analyses of approved trials).  The DSMB will be responsible for providing independent advice to the NHLBI regarding the progress of each trial and the appropriateness of continuing each study.  The DSMB will meet approximately every six months, with interim meetings as necessary.    

Section II. Award Information
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 number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.   Up to six (6) RCCs will be funded by this award

The total amount of funding (direct and indirect costs) that will be available through this and the companion announcement (RFA-HL-12-025) is up to $63 million over a seven-year period to support the CCTRN. 

Award Budget

Each RCC may request direct costs up to $300,000, not including F&A for first tier consortia.  RCCs will be provided additional funds to support satellite centers contributing patients to network studies. RCCs may propose training programs for scientists and/or nurse coordinators that will be supported by the network.  Funding for core laboratories (imaging, echocardiology, etc.) and biorepositories, and protocol reimbursement will be administered separately by the DCC.  Future year amounts will depend on annual appropriations.

Award Project Period

The total project period for an application submitted in response to this funding opportunity may not exceed seven 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.

Section III. Eligibility Information

1. Eligible Applicants
 
Eligible Organizations

Higher Education Institutions:

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

Nonprofits Other Than Institutions of Higher Education

For profit Organizations

Governments

Other

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

Required Registrations

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.

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.

Eligible Individuals (Project Director/Principal Investigator)

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.

Eligible PD/PIs include those with the experience and expertise to conduct clinical studies in cardiovascular diseases.  The disciplines and expertise that may be appropriate for this program are cardiology, cardiovascular surgery, cardiovascular imaging, cardiovascular nursing, cardiovascular physiology, stem cell biology, clinical trials management, project management, regulatory affairs and biostatistics.   To ensure that data analysis is performed independently of data acquisition, the PD/PI for a DCC may not be a PD/PI for a RCC, and vice-versa.  The same institution may apply for both a RCC and DCC award, but the applications must identify different and independent groups of investigators for each.              

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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.     

Section IV. Application and Submission Information

1. Address to Request Application Package

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

2. Content and Form of Application Submission

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.

Letter of Intent

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 Affairs
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214, MSC 7924 
Bethesda, MD 20892-7924 (Express: 20817)
Telephone: (301) 435-0270
FAX: (301) 480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Application Submission

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 Affairs National Heart, Lung, and Blood Institute
National Institutes of Health
 6701 Rockledge Drive, Room 7214, MSC 7924 
Bethesda, MD 20892-7924 (Express: 20817)
Telephone: (301) 435-0270
FAX: (301) 480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Page Limitations

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

Research Plan

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

General Requirements for the RCC

The Network is a collaborative effort requiring RCCs to participate in a cooperative and interactive manner with all components. Applicants should explicitly indicate their willingness to:

Additionally, departmental and institutional commitment to supporting cardiovascular cell therapy research and to prioritization of Network research should be clearly documented by the leadership in the form of letters or memoranda provided to the PD/PI, and by citing evidence of past support. These assurances to provide support should address areas such as fiscal administration, personnel management, space allocation, procurement, planning, equipment, and budgeting and should include Institutional Review Board (IRB) assurance of a willingness to consider participation in cell therapy research.

Satellite Centers

RCCs may choose, but are not required, to include geographically proximate partners or satellite sites, such as other academic centers and/or private and community hospitals and clinics. Such satellite centers could be venues for additional patient enrollment or might provide access to patient populations not traditionally cared for at the RCC. The RCC will be responsible for providing scientific leadership and regular communication to satellite centers regarding protocols and study progress and for providing administrative and budget support for protocol initiation.  The potential productivity of the partners and satellites will be considered part of the RCC’s contribution to the Network.  Funding for satellite centers will be provided as a separate line item up to $45,000 annual direct costs per satellite for the 7-year grant period).  There is no limit to the number of partner or satellite sites that may be proposed by an individual RCC, however, non-domestic (foreign)  sites will not be considered due to the logistics of cell processing.  Failure to include satellite sites will not adversely affect the scoring of RCC proposals.  A maximum of 12 satellite sites (across all RCCs) will be funded by this award. 

Clinical Research Skills Development Programs

The CCTRN has the potential to provide a rich training experience for investigators and nursing staff.   Accordingly, this FOA will provide funding to support skills development programs for each of two training tracks: clinical research investigators and clinical research coordinators.

RCC applicants are not required to submit proposals for skills development programs, and the absence of such will not adversely affect scoring.  Applicants may request up to $100,000 per year in direct costs for each training program.  Not more than one of each program may be requested by a single applicant, and not more than two of each program (total of 4) will be funded each year.

Developmental opportunities that provide experience with new technologies and skills are encouraged for inclusion in the training programs. Innovative strategies should be proposed for cross-disciplinary career development to achieve the goal of exposing investigators and/or nursing staff to additional research techniques and opportunities. Examples include direct participation in various components of the trial (e.g., case report form screening, triaging, recruitment, informed consent, test article preparation, patient logistics and follow-up care, etc.).  Participants should be encouraged to participate in writing groups and make presentations both to internal network staff and external organizations/societies.   Applicants are expected to ensure that participants will receive the mentoring needed to foster their careers.

The skills development programs are intended for investigators or nurses with limited clinical research experience.  Candidates for the clinical research investigator skills development program should include MD and/or PhD 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.

Candidates for the clinical research coordinator skill development program should include individuals with a nursing degree, regardless of experience or skill level, provided that they have less than one year of prior experience in stem cell clinical trials research.

Leaders for these programs must be identified and should have strong educational and mentoring credentials and be able to contribute a minimum of 0.6 calendar months).  To facilitate mentoring and multidisciplinary developmental activities, active involvement by the principal investigator and other senior investigators within the Network is strongly encouraged.

Training program applications will be evaluated on the basis of how well they address the following elements:

Attaining independent status should be an objective of the Core activities so participating new investigators should be encouraged to apply for 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.

The scientific and performance requirements must follow the requirements listed above and the instructions in the PHS 398 application Continuation Format Page form http://grants.nih.gov/grants/funding/phs398/phs398.html#fp3.  The total length of the Clinical Research Skills Development Program section should not exceed 6 pages. These pages will not be counted against the 12 page Research Strategy limit and should not be included in the Research Strategy Section of the application. Rather this optional section should be placed immediately before the Checklist in the application and pages must be numbered sequentially with the rest of the application. The presence of a Clinical Research Skills Development Program must be noted at the beginning of the Abstract.

The Research Strategy, and scientific and performance requirements must follow the instructions in the PHS 398 application form, http://grants.nih.gov/grants/funding/phs398/phs398.html and should not exceed 12 pages total.

Budget guidelines for the RCC

Applicants should prepare operating budgets for seven one-year periods with initial direct costs not to exceed $300,000 per year.  The budget is expected to maintain the infrastructure required to perform multiple clinical trials and should include a minimum of (3 calendar months) for the PD/PI. Other key personnel should include the study coordinator(s), and appropriate administrative support.

Applicants proposing satellite centers may budget an additional $45,000 total direct costs per year for each satellite center as a separate, additional line item in the budget.  RCCs proposing satellites should consider how best to apportion FTEs to facilitate trial implementation, patient recruitment, and enrollment at the constituent sites. Costs not directly linked to patient enrollment at any satellite sites must be budgeted in the RCC application. Ongoing monitoring, training and contract management of clinical trials at any satellite sites will be performed by the Coordinating Center and need not be budgeted by the RCC.  Note: satellite costs are in addition to the RCC maximum allowable total costs (see above).

Applicants proposing skills development programs may budget an additional $100,000 direct costs per year as a separate, additional line item in the budget.  Note: this line item is in addition to the RCC maximum allowable direct costs (see above).

Appropriate effort for other key personnel and travel costs for two or more people to attend SC meetings and other travel related to Network operations should be included with appropriate justification. 

It is expected that actively enrolling sites will use per-patient protocol-specific payments to supplement the RCC budget for the support of additional personnel and activities.  These payments should not be included in the application budget.  

Estimated protocol implementation costs should  be included in the budget justification section but are not included in the maximum infrastructure ceiling, although the proposed trial should be feasible for implementation in the described Network structure.  Proposed protocols which will test or use patented pharmaceuticals or devices should include plans for in-kind industry support.  Applications should clearly identify the potential source for any drugs or substances being considered for clinical protocols that are currently unavailable commercially. It should be noted that funds will not be provided for the purchase of expensive medical equipment, such as echocardiographic, cardiopulmonary exercise testing, magnetic resonance imaging or ultrafiltration systems.

If any of the protocols proposed by RCC applicants include obtaining blood or tissue samples, the applicant should delineate how such specimens will be handled and analyzed. If a central laboratory is required to analyze specimens, the RCCs will be responsible for obtaining the sample and the cost of obtaining and shipping them will be part of the  per patient payments.

CCTRN and Clinical and Translational Award (CTSA) Organizations

The NHLBI encourages academic centers participating in the CCTRN to partner with a CTSA, if one exists at the applicant institution, to enhance the scientific and operational aspects of the Network.

There are many potential ways that a CCTRN RCC could interface with a CTSA structure. Specific examples include utilizing some of the educational and mentoring programs within the CTSA organization to enhance a Clinical Research Skills Development Core. Since one of the goals of the CTSA network is to establish strong and interactive relationships with local communities and clinics, there may be potential for enhanced recruitment of clinically and ethnically diverse patient populations through the CTSA.  RCCs might partner with translational investigators in the CTSA to create state-of-the art mechanistic and translational sub-studies that could be conducted within the Network’s clinical protocols.

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, with the following modifications:

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.

Foreign Organizations

Foreign (non-US) organizations are not eligible for this funding opportunity.

3. Submission Dates and Times

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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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.

6. Other Submission Requirements and Information

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.

This FOA is open to all applicants with experience in cardiovascular research, regardless of whether  they have previously participated in CCTRN clinical trials.  RCC applicants must be at an institution with an existing cardiovascular research program and demonstrated access to a sufficient number of patients for CCTRN protocols.

Proposed studies should be novel and should not replicate or merely extend clinical trials already undertaken by the current CCTRN.  The proposals should estimate the number of patients available from the applicant’s institution and if appropriate should address inclusion of children and minorities as participants, and any relevant ethical issues.  Applicants should indicate if additional NHLBI resources must be leveraged or collaborations initiated to ensure feasibility of the proposed study.

Please note that decision to fund a particular RCC does not necessarily commit the CCTRN to initiate proposed studies from that RCC. 

Regarding investigator qualifications, applicants should provide evidence of productivity and relevant past performance in previous or ongoing clinical trials evaluating cell therapies, including those with a cooperative or multicenter design.  Applicants should indicate whenever applicable (1) where their participation in a single institution study led to the implementation of a multicenter study; (2) contributions in key areas of protocol development and design, accrual planning and monitoring, patient recruitment, retention and study completion, data collection and analysis; and (3) relevant publications.  

Applicants who are current CCTRN RCCs should include a description of their participation and contribution to the Network, including:

a.     Recruitment targets and percent of target achieved

b.    Number of patients enrolled in studies

c.     Screening approaches to identify subjects for CCTRM trials within the applicant’s institution

d.    Specific roles of the applicant(s) in CCTRN trials (principal investigator, co-investigator, SC member, etc.).

e.    Other contributions to Network activities (standing subcommittees, elected roles in Steering Committee, and publications). 

Applicants who are not current CCTRN RCCs should include a description of their recent experience and participation in Phase I/II clinical trials, including:

a.     Recruitment targets and percent of target achieved

b.    Number of patients enrolled in these studies.

c.     Screening approaches to identify subjects for clinical protocols within the applicant’s institution

d.    Specific roles of the applicant(s) (e.g., principal investigator, participation in clinical trial design and development, analysis and dissemination of data).

e.    Number of centers involved and the proportion of patients enrolled from the applicant’s center in multicenter studies.

f.      Contributions to cooperative group or multi-site clinical trial activities, as appropriate.

Sites that have experience with satellite centers (consortiums) should describe coordination, communication and management plans among the investigative teams.  If a multicenter application has a long-standing, well-documented collaboration and interaction among institutions, this should be clearly indicated in the application.  Participation of the consortium in previous clinical trials should be indicated.  Any unique accomplishments or strengths of the consortium advantageous to the CCTRN should be described.  

The RCC must ensure complete, accurate, and timely submission of cell preparations, biospecimens and data to the appropriate collaborating sites, including cell processing laboratories, imaging laboratories, biorepositories and the DCC.  Applicants should describe their experience with and internal processes for performing these activities as required by previous or ongoing protocols. 

Applicants must clearly express their intent to participate in a cooperative manner in the CCTRN as outlined in this FOA.  Letters of Departmental support should be included.  RCCs are expected to place high priority on CCTRN clinical trials over studies supported by other sources and should provide a strategy for allocating patients to CCTRN trials versus other trials.   

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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.

Overall Impact - Overall

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).

Scored Review Criteria - Overall

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?   

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?   Does the application provide evidence of investigator success in carrying out cardiovascular clinical trials, as measured by meeting study recruitment goals and producing peer-reviewed publications? Does the RCC demonstrate that staff has the expertise, training, and experience to conduct multiple protocols effectively in a Network?   Is adequate medical and regulatory expertise available to handle the highly regulated area of cell therapy?  

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?  Are the proposed studies consistent with the specific areas of research being sought?     

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? 

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?

Does the research plan demonstrate understanding of the scientific, statistical, logistical, and technical issues underlying multi-center clinical trials, including the assessment of outcomes relating to treatment and management of cardiovascular patients? Does the RCC demonstrate leadership in study design, data acquisition and management, data quality, and data analysis?

Does the RCC management demonstrate that an administrative framework has been developed and implemented to facilitate the design, implementation, review and management of cell therapy trial protocols? Are adequate expertise, time and effort devoted for effective Network functions?

Does the RCC demonstrate an ability to participate in collaborative research and cooperate with a Network Steering Committee, RCC staff, and the NHLBI?

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?

Does the RCC demonstrate the presence of adequate facilities, equipment, sponsorship and organizational structures to effectively implement the CCTRN study protocols? This includes but is not limited to conducting studies, obtaining study and investigational agents and devices, and meeting the recruitment requirements.

Additional Review Criteria - Overall

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.

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

Additional Review Considerations - Overall

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. 

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group convened by the Office of Scientific Review, Division of Extramural Research Activities, 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:

Applications will be assigned to the NHLBI 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:

3. Anticipated Announcement and Award Dates

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.

Section VI. Award Administration Information

1. Award Notices

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.

2. Administrative and National Policy Requirements

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.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS 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:

The Clinical Center PD/PIs will have the primary responsibility in all aspects of CCTRN studies, including proposing protocols, participating in their overall development, preparing protocol budgets in collaboration with the DCC, modifying proposals if indicated, recruiting study participants, conducting the research, assuring quality of study participant care and protocol adherence, assuring the accurate and timely transmission of data collected in conjunction with the DCC, analyzing and interpreting data, preparing publications, and working with the DCC and NHLBI to disseminate research findings.  Clinical Center PIs will also be responsible for working with the DCC to develop common definitions and standardization across protocols wherever appropriate.  Awardees must agree to the governance of the study through a Steering Committee.   

Support or other involvement of industry or any other third party in the study -- e.g., participation by the third party; involvement of study resources or citing the name of the study or NHLBI support; or special access to study results, data, findings or resources -- may be advantageous and appropriate.  However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NHLBI.

Study investigators are encouraged to publish and to release publicly and disseminate results and other products of the study in accordance with study protocols and governance.  For applicable studies, data not previously released and other study materials or products not previously distributed are to be made available to individuals who are not study investigators, within three years of the end of the period of NHLBI support, provided such release is consistent with the study protocol and governance.

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 HHS, PHS, and NIH policies.

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

The NHLBI Project Scientists will monitor patient recruitment and study progress, ensure disclosure of conflicts of interest, and ensure adherence to NHLBI policies.  NHLBI will appoint the Network Chair, all members of the Protocol Review Committee (PRC), and the Data and Safety Monitoring Board (DSMB).  The Network Chair will be responsible for ensuring that there are well-documented policies, procedures, and bylaws to guide all aspects of Network activities and operations. 

The NHLBI Project Scientists will serve on the Steering Committee and other study committees, when appropriate, and will have one vote.  The NHLBI Project Scientists may work with awardees on issues coming before the Steering Committee and, as appropriate, other committees, e.g., recruitment, intervention, follow-up, quality control, adherence to protocol, assessment of problems affecting the study and possible changes in protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems such as insufficient participant enrollment.

The NHLBI reserves the right to terminate or curtail the study (or an individual award) in the event of  (a) failure to develop or implement a mutually agreeable collaborative protocol; (b) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control; (c) major breach of the protocol or substantive changes in the agreed-upon protocol with which NHLBI cannot concur; (d) attaining of a major study endpoint before schedule with persuasive statistical significance; or (e) human subject ethical issues that may dictate a premature termination.

In addition to the Project Scientis, a separate NHLBI Program Official will be responsible for the normal program stewardship of the cooperative agreement, and will be named in the Notice of Award.

Areas of Joint Responsibility include:
Awardee(s) agree to the governance of the study through a Steering Committee.   The Steering Committee will have primary responsibility for the conduct of protocols and the preparation of publications. Steering Committee voting membership shall consist of all Principal Investigators (i.e., cooperative agreement awardees), one NHLBI Project Scientist, and the Chairperson.  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.

An independent Protocol Review Committee, established by the NHLBI, will provide peer review for each network protocol.  A Data and Safety Monitoring Board will be appointed by the Director, NHLBI to provide overall monitoring of interim data and safety issues.  An NHLBI scientist, other than the NHLBI Project Scientist, shall serve as Executive Secretary to the Boards.  Because the Boards serve as independent groups advisory to the NHLBI, study investigators will not communicate with Board members regarding study issues, except as authorized by the Board’s Executive Secretary.  

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 regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

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. 

Section VII. Agency Contacts

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

Application Submission Contacts

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

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: commons@od.nih.gov

Scientific/Research Contact(s)

Sonia Skarlatos, PhD, FAHA
Deputy Director, Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 8124, MSC 7940
Bethesda, MD 20892-7940
Telephone: 301-435-0556
FAX: 301-480-7971
Email: skarlats@nhlbi.nih.gov

Peer Review Contact(s)

Director, Office of Scientific Review
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214, MSC 7924 
Bethesda, MD 20892-7924 (Express: 20817)
Telephone: (301) 435-0270
FAX: (301) 480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Financial/Grants Management Contact(s)

Ms. Beckie Chamberlin
Grants Management Specialist
Division of Extramural Affairs
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health
6701 Rockledge Drive, Room 7144, MSC 7926
Bethesda, MD 20892-7926
Telephone: (301) 435-0166
FAX: (301) 451-5462
Email: chamberr@nhlbi.nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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.


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