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

Comparison of Strategies to Study Pediatric Pulmonary Vascular Disease Outcomes Using Bioinformatics (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-HL-14-005

Companion Funding Opportunity

Not Applicable

Number of Applications

One Section III. 3. Additional Information on Eligibility.

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

93.838

Funding Opportunity Purpose

Under this Funding Opportunity Announcement (FOA), the National Heart, Lung, and Blood Institute (NHLBI) invites applications to support a comparison of the ability of two data sources, electronic health records and traditional prospective patient-based clinical and research data, to answer research questions regarding the natural history, longitudinal outcomes, and phenotypes of therapeutic response for pediatric pulmonary vascular disease (PVD).  There will be one award for a Bioinformatics Clinical Coordinating Center (BCCC).  Because PVD in children is rare and heterogeneous, the applicant will develop, implement, and evaluate the strengths and limitations of two data collection approaches to answer research questions regarding the natural history, longitudinal outcomes, and phenotypes of therapeutic response.  The prospective data collection strategies proposed should include utilizing: 1) electronic health records (EHR) and 2) traditional prospective patient-based clinical and research data.  Applicants should propose: 1) methods, plans, and expertise required to develop the two data sources; 2) at least three research pediatric PVD questions that the data collection strategies can address; and 3) a method to compare the usefulness of the two data sources to answer the research questions. This work will elucidate the value of EHR in answering real-world clinical management questions with the ultimate goal of improving health outcomes for children treated for PVD, and optimizing clinical trial design.  The work will require multidisciplinary and multi-institutional team coordination that includes expertise in bioinformatics and computational science and clinical knowledge and access to pediatric patients with PVD. 

Key Dates
Posted Date

June 1, 2012

Open Date (Earliest Submission Date)

January 21, 2013

Letter of Intent Due Date

January 21, 2013

Application Due Date(s)

February 21, 2013, by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

June-July 2013

Advisory Council Review

October 2013

Earliest Start Date(s)

December 2013

Expiration Date

February 22, 2013

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (R&R) 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. 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 the 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

Background

Pulmonary vascular disease (PVD) is a rare, progressive, and fatal disorder with a variety of presentations and causes.  Diagnostic criteria, treatment, and prognosis may differ substantially for the various phenotypes, particularly in children.  One type of PVD, childhood pulmonary arterial hypertension (PAH), has an estimated prevalence of 3.7-5.0 cases per million children. Once diagnosed, the disease burden of PAH is great as it is often irreversible, and there is no available cure. PVD in children occurs in heterogeneous populations (e.g., bronchopulmonary dysplasia, congenital cardiac disease, sickle cell disease, idiopathic).  Evaluation and treatment of suspected PVD cases are hampered by the lack of standardized methods for systematically collecting data on the natural history, longitudinal outcomes, and responses to available off-label medications. Pediatric randomized controlled trials to guide treatment decisions on safety, efficacy, and effectiveness are limited because there are no validated clinical endpoints appropriate for young children.  Endpoints commonly in use for adult populations are not suitable or possible to measure in many children (e.g, six-minute walk test).  The lack of validated clinical endpoints to measure severity of disease and efficacy of treatments limits the design of studies in the pediatric PVD population that would inform practice.  This program aims to address significant gaps in our knowledge about diagnostic criteria, natural history, and longitudinal outcomes including treatment response in the pediatric PVD population.  Existing data in health records could potentially fill this gap, if the information could be gathered electronically into one database.  Traditional methods of data collection for prospective observational cohort studies can be very informative, but may limit research questions that can be tested in a timely way.

Research Objectives

This initiative will support a comparison of the ability of two data sources, electronic health records and traditional prospective patient-based clinical and research data, to answer research questions regarding the natural history, longitudinal outcomes, and phenotypes of therapeutic response for pediatric PVD.

Applicants should propose:

1.    Methods, plans, and the necessary expertise to develop the two new data sources. This expertise should include experience with EHR and traditional data collection methods and implementation.

2.    At least three pediatric PVD research questions that the data collection strategies can address.

3.    A method to compare the usefulness of the two data sources to answer the research questions.

This work will elucidate the value of EHR in answering real-world clinical management questions with the ultimate goal of improving health outcomes for children treated for PVD, and optimizing clinical  trial design.  The short-term objective is to distinguish pediatric PVD phenotypes, their longitudinal outcomes, and differential responses to current therapies.  This initiative will result in one award for a Bioinformatics Clinical Coordinating Center (BCCC) to develop two new cohorts in partnership with clinical investigators:

The BCCC will propose a method to evaluate the advantages and disadvantages of both data collection strategies (EHR vs. prospective cohort) for addressing knowledge gaps in phenotyping and outcomes of children with pulmonary vascular disease.

The BCCC will coordinate the collection of data from at least three participating clinical centers over a minimum of one year for each enrolled patient.   The BCCC with partnering clinical investigators will propose at least three research questions that will be answered by the data sets.   These research questions should be relevant to clinical practice and should help to enlighten future hypothesis-based mechanistic research or clinical study design. The BCCC will require a multidisciplinary team, which should include expertise and experience in bioinformatics, computational modeling, ontology and prospective observational data collection development, and content expertise in pediatric PVD.

EHR-based Cohort:

Researchers should provide detailed plans for establishing the EHR cohort including:

BCCC applicants will demonstrate the expertise needed to facilitate communication and research design implementation with PVD clinical experts, develop or apply a modern and powerful data management system for heterogeneous data integration, and validate data mapping across EHR systems in the study.  The BCCC will also be responsible for developing and testing a user interface suitable for clinical pediatric PVD researchers, computational and information frameworks for integrating clinical and/or biological data, query algorithms, and epidemiologic analysis and modeling. Applicants are encouraged to use or adapt currently available EHR processing tools, such as those available from NIH Common Fund National Centers for Biomedical Computing (NCBC, http://www.ncbcs.org/) or from Clinical and Translation Science Awards (CTSA, http://www.ncrr.nih.gov/clinical_research_resources/clinical_and_translational_science_awards/).

The BCCC will need to demonstrate the feasibility of case identification, capture and transfer of usable longitudinal data, and will develop strategies to identify additional clinical teams that could contribute to the cohort.  In addition, plans for EHR data harmonization, quality control assessment, and analysis should be provided. As data for the EHR cohort are transferred from participating sites to the BCC data system, preliminary queries will be conducted in years 1 and 2 across the coded EHR cohort, so that algorithms for phenotype categorization and sub-categorization among clinical disease diagnoses can be refined. The BCC will propose milestones for evaluation of the quality and usefulness of data and procedures for improving data collection. 

Pediatric PVD Prospective Observational Cohort:

Simultaneous with development of the EHR cohort, the BCCC will work with clinical experts to implement a parallel pediatric PVD prospective observational cohort based on more traditional clinical data extraction.  This cohort should use observational study methods to collect uniform data (clinical and other) to evaluate specified outcomes for a PVD population that will answer one or more predetermined scientific questions.

This cohort should obtain a minimum of one year of prospective data from at least 500 children with PVD to compare with the EHR cohort and allow BCCC and clinical researchers to evaluate the natural history, longitudinal outcomes, and therapeutic responses of pediatric PVD phenotypes.  Data analysis should be proposed to answer clinically-relevant research questions across multiple sites.  The research team will develop, monitor, evaluate, and modify the data capture process, to optimize analysis of data and comparison of results with the EHR based approach.

Research Questions

In addition to describing the technical procedures for developing the two data bases, each application is expected to propose at least three research questions that may be answered by the two cohorts and a method for comparing the value of each data collection strategy to answer these questions.

Technical, Legal, and Ethical Issues

Technical, legal, and ethical issues for the EHR-based and prospective observational data cohorts will be described by the applicant, and procedures to address these issues must be provided as part of the human subjects section of the application.  Patient Identity Management strategies need to be provided in the application in order to link data collected during the course of the study.  The applicant will describe procedures to protect patient identity when collecting, transferring, linking, and analyzing their information. Plans to adhere to health information privacy rules should be described.  The applicant will describe oversight to detect and mitigate breach of confidentiality of information.  The BCC will describe plans for development of a centralized, web-based tool to access the EHR and prospective observational cohorts.  This tool will present information from participating sites and provide a centralized view of pediatric PVD data, allowing researchers to browse and query.  It is expected that this tool and the data therein will remain accessible to the research community following the completion of the research supported by this FOA.  The investigators should include a plan for continued sustainability and use of these resources post-award.

Analysis plan

The applicant should provide an analysis plan for the research questions to be tested, but also to evaluate the advantages and disadvantages of data collected by EHR vs. the prospective observational cohort.  Which approach is more effective for answering research questions that will advance our understanding and the evaluation and treatment of pediatric PVD?

SELECTED RESEARCH EXAMPLES:
Research topics of interest include, but are not limited to, those listed below:

Research that would NOT be responsive to this FOA:

This FOA is intended to support only human studies.  Applications that include animal studies will not be considered responsive. Patient registries alone, without an EHR-based cohorts to be compared, will not be responsive.  Retrospective studies will not be considered responsive, and clinical trials are not the intent of this FOA. 

Section II. Award Information
Funding Instrument

Cooperative Agreement

Application Types Allowed

New

The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NIH intends to fund an estimate of one award, corresponding to a total of $1,800,000 in FY 2014.  NIH anticipates funding up to 1.8 million total costs each year for 4 years. Future year amounts will depend on annual appropriations.

Award Budget

Application budgets are limited to a maximum of $1.8M total costs per year, but must reflect actual needs of the proposed project.

Award Project Period

4 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

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) 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) (PDs/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 4-6 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 SF 424 (R&R) 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.

Section IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

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
6701 Rockledge Drive, Room 7214, MSC 7924
Bethesda, MD 20892 (express mail zip code: 20817)
Telephone: (301) 435-0270
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Required and Optional Components

The forms package associated with this FOA includes all applicable components, mandatory and optional.  Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

PHS 398 Research Plan Component

All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide, with the following modifications:

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Foreign Institutions

Foreign (non-US) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

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 submitted electronically following the instructions described in the SF 424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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.  

Additional requirements for submitting an application:

Applicants for the BCCC should present a description of plans to:

Qualifications and Experience.  The PD(s)/PI(s) must have the necessary experience and expertise to develop and coordinate the data collection strategies for observational clinical studies in patients.  Previous participation in clinical studies/trials should be detailed including name of study, role in study and number of patients recruited; participation in studies where recruitment was unsuccessful should also be included.

Provide a description of the expertise of the collaborating Clinical Center PD(s)/PI(s) to develop and refine ontologies for subject selection, recruitment, data collection, and submission to the BCCC.

When multiple PD(s)/PI(s) are designated by the applicant, the PD(s)/PI(s) must commit at least 2.4 person months effort to the clinical project and management of the program. A plan to ensure interaction among all investigators and the communication of ideas and results should be described. Multiple PD(s)/PI(s) are strongly encouraged.

Study Population.  Applicants should describe at least three participating clinical sites and demonstrate access to a sufficient number of patients to accomplish the data collection strategies by providing specific, objective sources of data on the size of the available population.  This can include documentation of participation in previous clinical studies/trials of similar patients over the last 5 years.

Describe plans for identifying additional clinical centers that may be needed to assure enrollment targets are met.

Patient access may be accomplished by establishing links with other groups in addition to the applicant’s institution. It is strongly recommended that recruiting centers with a demonstrated record of successful subject recruitment and retention be included.   If links with other groups are anticipated, the application should include a plan with appropriate letters of support that describe (1) how the applicant will link to and operate with the other groups and (2) how the PD(s)/PI(s) will monitor the quality of the other group’s performance (recruitment and data quality. 

Links with NIH Clinical and Translational Science Award (CTSA) Centers. Applications from institutions that have a CTSA funded by the NIH should identify the resources that would be available to support the proposed research.  Examples of resources include cost sharing, “in-kind” support of personnel or facilities, assay performance, statistical or regulatory support, etc.  A description of the CTSA and how the applicant proposes interacting with it should be included, as well as letter of agreement from either the CTSA Program Director or participating PD/PI. Applications from institutions without CTSAs will not be disadvantaged.

The Protection of Human Subjects Section should include a detailed data and safety monitoring (DSM) plan (as described in the 398 instructions) that will include the roles and responsibilities of an Observational Safety Monitoring Board  (OSMB) and procedures to protect subject confidentiality.  http://www.nhlbi.nih.gov/funding/policies/dsmpolicy.htm  The DSM plan should describe the background of potential OSMB members that would be recruited.  They should not be named in the application.  The budget for the clinical study should include costs associated with preparation and logistics for OSMB meetings.

Feasibility is an important aspect of these applications. Applicants must demonstrate the ability to enroll the required numbers of patients.  Patient availability and a record of successful subject recruitment and retention at clinical sites proposed to assist with enrollment must also be documented.  Additional recruiting site(s) are highly recommended.

A detailed time line for milestones in the study must be provided. This time line must account for IRB and OSMB approval, realistic goals for patient recruitment and follow up, and data analysis and preparation.  Progress will be administratively assessed annually before non-competing awards are made. It is expected that no more than six months from the funding date will be required before patient recruitment begins.

Communication: Communication in this program is essential.  Applicants must propose a plan to describe how communication and interactions will be maintained between clinical sites and the BCC.  Any costs for meetings and teleconferences should be included in the budget.

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

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.

For this particular announcement, note the following:

The purpose is to elucidate the value of EHR in answering real-world clinical management questions for a rare disease with the ultimate goal of improving health outcomes for children treated for PVD, and optimizing clinical trial design. Applicants are expected to propose: 1) methods, plans, and experience to develop two data sources for pediatric pulmonary vascular disease (EHR and prospective observational clinical and research data), 2) a method to compare the usefulness of the two data sources, and 3) at least 3 specific research questions that will be answered from the data.

Overall Impact

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

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? What is the quality of the three research questions proposed in terms of significance?. Are the research questions meaningful?

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? Is the expertise of pulmonary vascular disease collaborators appropriate?    

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?  What is the quality of both data collection strategies? Is the analysis plan for the research questions to be tested sound, and will it support evaluation of the advantages and disadvantages of data collected by EHR vs. the prospective observational cohort? Is there a realistic plan to recruit the required number of patients?  Will the applicant be able to identify pediatric pulmonary vascular disease cases by each data collection strategy? What is the likelihood the applicant and the clinical sites will be able to collect data by the two methods for comparisons? Does the applicant have the ability to access and utilize electronic health records from different sources and formats? Will the applicant be able to link clinical data from different sources and protect patient confidentiality? Does the application have the ability to make comparisons and evaluate the data collection strategies to answer relevant research questions for rare disease? Does the applicant propose milestones for evaluation of the quality and usefulness of data and procedures for improving data collection?

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

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

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

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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:

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications 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(s)/PI(s) 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 U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

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

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

Areas of Joint Responsibility include:

Dispute Resolution:

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

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

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)

Carol J. Blaisdell, M.D.
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 10166, MSC 7952
Bethesda, MD 20892-7952
Telephone: 301-435-0222
Email: blaisdellcj@mail.nih.gov

Peer Review Contact(s)

Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7214, MSC 7924
Bethesda, MD 20892 (express mail zip code: 20817)
Telephone: 301-435-0270
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Financial/Grants Management Contact(s)

Renee Livshin
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7156, MSC 7926
Bethesda, MD 20892-7926
Telephone: 301-435-0166
Email: tjarosiknhlbi.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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