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

Cardiovascular Research Network (CVRN) Limited Competition (U54)

Activity Code

U54 Specialized Center- Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-HL-13-004

Companion FOA

None

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 Funding Opportunity Announcement (FOA) is to invite new applications for a five-year Cooperative Agreement (U54) award that will transition the current Cardiovascular Research Network (CVRN) to a research center.  When the CVRN was initially funded in 2007 (RFA-HL-07-011) applications were limited to those submitted by domestic healthcare delivery organizations. As the current Network has developed significant databases that will be expanded by the new Center, applications responding to this FOA are limited to grantees funded under RFA-HL-07-011. The overarching goals of the CVRN are to support high-quality cardiovascular disease (CVD) research in community-based care, with a particular focus on intervention and comparative effectiveness research; accelerate knowledge of how electronic health data systems across multiple, integrated healthcare organizations can contribute to intervention and comparative effectiveness research; expand the Network's ability to serve as a resource to NHLBI; and increase research collaborations between healthcare provider organizations and researchers affiliated with organizations outside the Network. The program will support principal research projects to carry out studies that focus on important topics in CVD intervention and comparative effectiveness research.  One such project will pilot both pragmatic and cluster randomized trials and develop metrics to evaluate their efficiencies.  Targeted infrastructure and other research activities will also be supported to advance CVD science.  Expansion of Network membership to non-members will commence under this solicitation.

Key Dates
Posted Date

November 3, 2011

Letter of Intent Due Date

January 30, 2012

Application Due Date(s)

February 29, 2012

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

August 31, 2012

Advisory Council Review

October 2012

Earliest Start Date(s)

December 2012

Expiration Date

March 1, 2012

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

1.  Research Objectives

Nature of the Research Opportunity

The National Heart, Lung, and Blood Institute (NHLBI) invites applications for a five-year Cooperative Agreement (U54) award to transition the Cardiovascular Research Network (CVRN) to a research center.  During this transition, NHLBI will continue to support collaborative cardiovascular disease (CVD) research among multiple healthcare provider organizations that are oriented toward community care; are located in geographically diverse areas; have access to large, stable and diverse patient populations;  have existing integrated health data systems  (e.g., laboratory, pharmacy, outpatient, hospitalization and specialty care sources); provide comprehensive longitudinal care, including prevention, diagnosis and treatment of CVD; and can provide patient, provider, and system-level information relevant to CVD research.  Enhanced support will expand the understanding of the utility of large, integrated health data systems in CVD research; expand the Network's ability to serve as a resource to NHLBI; and increase research collaborations between healthcare provider organizations and researchers affiliated with organizations outside the Network.

Need for the Research

Despite advances in reducing the incidence, prevalence, and burden of cardiovascular disease, much remains unknown about the effectiveness of many screening, diagnostic, and therapeutic strategies to address CVD.  CVD remains the number one cause of death among adults in the U.S.  Electronic health data systems are a resource that hold promise to help address the gap in knowledge and evidence about the effectiveness of approaches to reduce CVD.  Yet, the capacities of these systems for research are relatively early in their development, and even less known is their value for intervention and comparative effectiveness research (CER). 

Validity of electronic health data systems for CVD research

The quality of data from real world medical settings differs from data rigorously and prospectively collected for clinical trials or cohorts, leading others to question its value for research.

While observational studies generated from electronic health data systems have frequently addressed data quality and validity on a study-by-study basis, the assessment of the validity of electronic health data has received relatively little attention in research, much less CVD research.  Addressing the important issue of validity of electronic data systems and doing so in a more systematic fashion in the CVRN is needed to better understand the extent electronically generated data can produce valid results and ways to address limitations.  This aspect of the FOA is an important foundation for other research pursuits using electronic health data.

Electronic health data systems in intervention research

The NHLBI has funded randomized controlled trials (RCTs) that have significantly advanced our understanding of CVD and its treatment.  However, clinical trials are often costly and can require prolonged timelines to plan, launch, and disseminate findings in clinical practice.   Even with the provision of adequate resources and careful planning, the success of clinical trials can be challenged by important factors, such as inaccurate estimates of event rates among eligible patient subgroups and the number of potential participants that meet defined inclusion and exclusion criteria.  Traditional RCTs will always have a prominent place in medical research.  Exploring mechanisms to enhance the planning of clinical trials through electronic health data systems is warranted.  Additionally, while relatively unexplored, understanding the utility and careful documentation of integrated electronic health data systems in the conduct of trials would bolster our understanding of the potential roles and limitations of these systems.  The availability of large, integrated health data systems also affords the opportunity to assess their capabilities in alternative and novel trial designs such as cluster randomized trials.  

Electronic health data systems in comparative effectiveness research

For the purposes of this FOA, comparative effectiveness research (CER) will be defined as "the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care. The purpose of CER is to assist consumers, clinicians, purchasers, and policy makers to make informed decisions that will improve health care at both the individual and population levels."  (http://www.annals.org/content/151/3/203.full.pdf+html)

Although often considered the gold standard, clinical trials are not appropriate for all medical research questions and may be cost prohibitive or unable to yield timely results.   Hence, exploration of potentially more efficient, cost-effective research approaches that utilize observational and quasi-experimental data to address questions about effective CVD preventive, diagnostic and therapeutic strategies is needed.  The increasing adoption of electronic health data (EHD) systems also offers the opportunity to integrate information from a variety of sources, and the potential for such aggregation can be far-reaching.   However, the selection of appropriate CER questions is critical when utilizing electronic health data due to (1) potential limitations such as confounding by indication and the challenges of statistical methods to address it; (2) the need for innovation in methodology to maximize efficiency; and (3) poor data standardization.  Investment in assessing the capabilities, quality, limitations and methods to address the limitations of electronically-generated observational data for CER is an important endeavor to determine the extent that EHD-based research can ultimately help improve the care and outcomes of patients.

Objectives

The overarching goals of the CVRN are to support high-quality CVD intervention and comparative effectiveness research in community-based care; accelerate our knowledge of the use of integrated health data systems across multiple healthcare organizations in CVD research, and intervention and comparative effectiveness research in particular; facilitate increased research collaboration; enhance the use of the CVRN as a resource; and begin expansion of Network membership.  Targeted infrastructure and other CVD research activities will also be supported. 

The CVRN will serve as a research center and its specific objectives are as follows:

The objectives will be pursued through two primary vehicles:  the Principal Research Projects and five Cores as described in more detail below. 

Principal Research Projects

The CVRN will support three types, or components, of principal research projects: 

Each project should include the participation of a minimum of two health plans.  

Component 1:  Comparison of Randomized Controlled Trial Outcomes to Observational Studies Generated from Electronic Health Records

To help leverage NHLBI’s investment in the CVRN, this project seeks to determine the extent that electronic health databases in the Network, constructed for comparison to randomized clinical trials, can produce valid results to assess therapeutic effectiveness.  Applicants should propose 5-7 completed randomized trials with cardiovascular disease outcomes for comparison.  The outcomes of these trials will be compared with findings of those that can be generated from electronic health records to help determine the extent that these databases can be utilized for CVD, intervention, and comparative effectiveness research.  Advantages and limitations should be documented, and importantly, a method(s) to overcome the limitations, such as confounding variables, should be tested and reported. 

Examples of randomized trials with CVD outcomes that might be considered for inclusion in these comparisons are: Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial, Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH) Trial, The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), Bypass Angioplasty Revascularization Investigations 2 - Diabetes (BARI 2D) Trial, Clinical Outcomes Utilization Revascularization and Aggressive Drug Evaluation (COURAGE) Trial, Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial, Occluded Artery Trial (OAT), and Surgical Treatment for Ischemic Heart Failure (STICH) Trial.  

Component 2:  New Comparative Effectiveness Research that Maximizes Use of Electronic Health Data Systems

Electronic data systems and the databases they can yield may afford an opportunity to address important CER questions about health care such as quality and patterns of care and options in treatment decisions. The NHLBI July 2010 workshop on Future Directions of Cardiovascular Disease Comparative Effectiveness Research highlighted the following strengths of such databases pertinent to CER:

The CER conducted under this renewal of the CVRN can take advantage of these strengths and pursue compelling CVD CER questions while simultaneously exploring innovation in methodology (e.g., statistical approaches to address confounding by indication) and efficiencies pertinent to CER (e.g., efficiencies in identifying and consenting patient populations, outcomes assessment, or data concatenation). Non-randomized approaches for CER including quasi-experimental designs that capitalize on natural experiments may allow for the evaluation of the impact of new technology adoption or existing interventions or strategies not yet tested in clinical trials.  It is expected that the application propose at least two new comparative research projects.

Some selected research examples include:

Component 3:  Pilot Pragmatic and Pilot Cluster Randomized Trials to Prevent or Treat Cardiovascular Clinical Outcomes

Practical trials “are primarily designed to determine the effects of an intervention under the usual conditions in which it will be applied, whereas explanatory trials are primarily designed to determine the effects of an intervention under ideal circumstances.” (http://www.jclinepi.com/article/S0895-4356(09)00048-1/fulltext ).  A cluster randomized trial is a trial in which individuals are randomized in groups (i.e. the group is randomized, not the individual).  For the purposes of this research project, NHLBI seeks preparatory work to develop protocols and test feasibility for practical/pragmatic and cluster randomized trials that meet the following criteria:

It is expected that at least three pilot pragmatic and pilot cluster randomized trials will be conducted under this solicitation.  Of these, at least one must be a pragmatic and one a cluster randomized trial. Importantly, this solicitation also requires that metrics be developed to carefully assess the efficiency of the CVRN in its ability to plan and conduct these pilot trials, e.g., identify groups of potentially eligible patients/clinicians/sites (via access to lab results, pharmacy data, diagnoses, surgeries); ease of recruitment; follow-up; and interventions in the real world (e.g., tracking specific types of care).  Metrics should be developed to carefully evaluate and document efficiencies of these trials.

Any trials requiring data safety monitoring should propose a grantee-appointed Data Safety Monitoring Board when necessary.

Research Infrastructure and Other Activities

The CVRN will fund five cores that will serve a variety of functions to support the principal research projects.  These cores will also offer several activities to advance CVD, intervention, and comparative effectiveness research, including the following: facilitate and streamline multisite research, enhance access to the CVRN by non-CVRN researchers and organizations, increase its ability to serve as a resource for clinical trial planning, provide training and education, and commence expansion of the Network.

Administrative Core:

The Administrative Core will be responsible for the overall coordination of the activities of the CVRN, including the financial aspects of the CVRN collaboration.  The core will also be responsible for facilitating effective communication and collaboration between the research projects and other cores of the CVRN, and across participating CVRN member research organizations and external research collaborators.  It will particularly focus on streamlining processes for planning, implementing and completing multi-site studies in shorter time periods.  It will also provide support (including travel) for the Steering and an external advisory committee.   The Administrative Core application must contain a written plan for the management of the CVRN.  The plan should address in detail how the CVRN will be governed, and roles of the key staff in the governance of the CVRN.  Members of the external advisory committee need not be selected and identified for the application.  The application will be required to request Administrative Core support for a web designer to develop, maintain and support a CVRN public access website, as well as a secure website.  The secure website will be accessed by CVRN project staff and investigators to provide real time communications and post key study documents, provide multi-author document management, and support other miscellaneous uses to be defined by the Steering Committee.  The core will also organize reviews of competing proposals for free analyses of completed CVRN data sets and expanded VDW.

Statistics Core:

The Statistics Core will provide statistical support for each of the principal research projects and other new CVRN projects and activities, in addition to supporting ongoing CVRN-wide data standardization efforts.  This core will include expertise in advanced statistics, implementation science, clinical trials, epidemiology and health economics as well as dedicated senior programmer/analysts who will be available to conduct analyses on datasets from new and completed CVRN projects.  Activities and new projects of the core will include:

Knowledge Development Core:

This core will expand opportunities for career development, and collaboration with existing and non-CVRN researchers and other organizations by offering specific educational and informational activities:

Evaluation Core:

The Evaluation Core will provide real-time and regular feedback from CVRN and collaborating non-CVRN researchers and organizations.  The aim is to help improve functioning, efficiencies, and communication across the cores and research projects.  Results of the evaluations should be shared across the CVRN and to NHLBI.  The core should help oversee progress implementing recommendations resulting from the evaluations. 

Expansion Core:

This core will begin expansion of CVRN membership to non-HMOs to help advance the interoperability of electronic health records for research purposes and provide increased diversity to the CVRN.  Requisite characteristics, and interested U.S. health care delivery organizations and their capabilities will be identified during the first year of funding.  A new protocol for a federated data model designed to link electronic health record data from one system with insurance claims from another system to create virtual integrated delivery data capability will then be planned.  Site specific VDW protocols for data linkage will be developed, and at least two pilot studies linking electronic health records and claims data from non-HMO entities to those data of selected CVRN sites will be conducted.

Section II. Award Information
Funding Instrument

Cooperative Agreement

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 NHLBI intends to commit the following amounts for one award:

FY2013-2017 $24,000,000 (FY13:  $4,200,000; FY14: $5,400,000; FY15:  $6,300,000; FY16:  $5,300,000; FY17:  $2,800,000)

NHLBI intends to commit $4,200,000 in FY2013.

Award Budget

Application budgets are limited to direct costs of $3,570,000 in year 1, $4,590,000 in year 2, $5,355,000 in year 3, $4,505,000 in year 4, $2,380,000 in year 5.    

Award Project Period

Five 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

The eligibility to apply in response to this FOA is limited to the current Cardiovascular Research Network (CVRN) grantee as funded under RFA-HL-07-011

Networks must include a sufficient number of healthcare organizations such that total patient enrollment is stable (i.e., the majority of patients can be followed for a combined retrospective and prospective period of five years) and is at least seven million adults (ages 18 and over) in a given year.  Also, Network-covered populations should approximate the demographics of the general U.S. population, and must include diverse populations with respect to gender, race/ethnicity and, to the extent that it is practical, rural/urban populations and a range of geographic locations.  The majority of healthcare organizations must have integrated health data systems and Virtual Data Warehouse.   

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, 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 Director(s)/Principal Investigator(s) (PD(s)/PI(s)) 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 least4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) 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 PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.

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:

The letter of intent should be sent to:

Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924
Bethesda, MD 20817 (express/courier service)
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 Research Activities
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924
Bethesda, MD 20817 (express/courier service)
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 requirements:

Section of Application

Notes

Page Limits

Overview of CVRN

(Includes items listed in 6.A below)

12

Introduction to Resubmission and Revision Applications

For each component and core

1

Specific Aims

For each component or core

1

Research Strategy

Component 1

12

Component 2: each  CER project

12

Component 3: each pilot trial

6

Each Core

6

Biographical Sketch

Each investigator

4


Research Plan

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, with the following modifications:

Foreign Institutions

Foreign (non-US) Institutions may not apply.

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 components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Supplemental Instructions for the Preparation of a Network Application with Multi-Components

The following section supplements the instructions found in Form PHS 398.  Additional instructions are required because the Form PHS 398 is designed primarily for individual, free-standing research project grant applications, and has no specific instructions for multi-project applications, nor research network infrastructure development.

The order of presentation should be as follows:

PHS 398 Form pages as described below:

Research Plan

A) CVRN Overview

B)  Individual Principal Research Projects

Component 1:  Comparison of Randomized Controlled Trial Outcomes to Observational Studies Generated from Electronic Health Records

Component 2:  New Comparative Effectiveness Research that Maximizes Use of Electronic Health Data Systems 

Component 3:  Pilot Pragmatic and Pilot Cluster Randomized Trials to Prevent or Treat Cardiovascular Clinical Outcomes

 C.   Individual Cores:

Appendix

Special Requirements that must be addressed in the application

Budget Information

The pilot pragmatic and pilot cluster randomized trials should not exceed $1,275,000 per trial in direct costs, including the development and application of metrics to evaluate each trial's efficiencies.  No more than $425,000 in direct costs should be allocated to emerging research over the five-year budget period.  Evaluation functions of the Evaluation Core should not exceed $425,000 in total costs over the five-year period.  At least $637,500 in direct costs should be devoted to free analytic support and $637,500 in direct costs for expansion of the CVRN Virtual Data Warehouse to incorporate high priority cardiovascular data elements.   No salary support for mentors of career development positions will be provided.  Applications must include estimates for travel costs for a two-day, in-person Steering Committee meeting each year, which will occur in Bethesda, Maryland.  Applications should also include travel costs for one in-person meeting per year for an external advisory committee meeting, of 8-10 members, which will occur in Bethesda, Maryland. This external advisory committee meeting should also include travel costs of the CVRN executive committee to Bethesda, Maryland.

Cooperative Agreements: Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2. "Award Administration Information." 

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

Data Sharing Plan: Regardless of the amount requested, applicants are expected to include a brief 1-paragraph description of how final data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

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

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the CVRN, as an integrated effort,  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 CVRN 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(s)/PI(s), 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(s)/PI(s), 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?

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?

 Additional Review Criteria - Overall

As applicable for the Network 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.

CVRN as an Integrated Effort

Will there be coordination, interrelationships, and synergy among the research projects and core components as they relate to the objectives of the Network?  What are the advantages of conducting the proposed research projects and activities as a Network rather than through separate research efforts?  Will the research efforts taken together have more impact on the field than separate projects and activities conducted in isolation? Will the research proposed in the individual projects be enhanced by the Network?  Are there mechanisms posed for regular communication and coordination among investigators within and outside the Network?  Are mechanisms in place for the day-to-day management of the Network, including arrangements for internal quality control of ongoing research?  Are there adequate plans to document activities, products and procedures?

Governance

Does the application propose procedures to maximize research capacity, capability and collaborations across Network members?  Are the organization and administrative structure appropriate to the complexity of the work, and does the proposed governance promote constructive collaborations among committees and non-Network organizations?

Cores

Will the utility and quality of the services (including procedures and techniques) of each core enable the CVRN to achieve its goals?  Are the qualifications, experience, and commitment of the personnel involved in each core appropriate?  Is the budget realistic and does it appear to reflect the core director's understanding of the scope of the work?  Is the budget appropriate and can the distribution of costs to projects be accounted for?  For the Administrative Core:  Does the core director have experience in multi-site, scientific research administration in community-based settings?  Is there a decision process within the proposed core for the evaluation of research productivity, for the allocation of funds, and for the management of the resources?   

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

NotApplicable.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

NotApplicable..

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

NotApplicable.

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(s),convened by the NHLBI in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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 National Heart, Lung, and Blood Advisory Council (NHLBAC) . 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’s 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 Program Director(s)/Principal Investigator(s) will have the primary responsibility for: all aspects of the study, including study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by action of the Steering Committee.

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

An NIH Project Scientist (or “Project Coordinator,” or “Project Collaborator,” or “Intramural Scientist”) will 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; NHLBI scientist(s) may serve on other study committees, when appropriate.  The NHLBI Project Scientist (and other cited NHLBI scientists) may work with awardees on issues before the Steering Committee, and as appropriate, other committees, for example: development and implementation of data and sample sharing plans, informed consent issues, sample collection, protocol development, quality control, data analysis and publication, and preparation and development of solutions to major problems such as efficiency and yield of iPS differentiation protocols.

Additionally, 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:

Awardee agrees to governance, through voting and decision making, of the program through a Steering Committee.  Steering Committee voting membership shall consist of the principal investigator, site principal investigators, and the NHLBI Project Scientist.  Monthly meetings of the Steering Committee will ordinarily be held by telephone conference call.  In person meetings should be held twice yearly, once in Bethesda and once at a national conference.

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 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 the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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)

Barbara Wells, PhD
Division of Cardiovascular Diseases
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 10112
Bethesda, MD 20892-7936
Bethesda, MD 20817 (express/courier service)
Telephone: 301-435-0417
Email:wellsb@mail.nih.gov

Peer Review Contact(s)

Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924
Bethesda, MD 20817 (express/courier service)
Telephone: 301-435-0270
Fax: 301-480-0730
Email:nhlbichiefreviewbranch@nhlbi.nih.gov

Financial/Grants Management Contact(s)

Robert Tarwater
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health
6701 Rockledge Drive, Room 7150
Bethesda, MD 20892-7926
Bethesda, MD 20817 (express/courier service)
Telephone: 301-435-0166
Email:tarwater@mail.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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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