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)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Funding Opportunity Title

Limited Competition: Pregnancy as a Window to Future Cardiovascular Health:  Adverse Pregnancy Outcomes as Predictors of Increased Risk Factors for Cardiovascular Disease (U10)

Activity Code

U10 Cooperative Clinical Research – Cooperative Agreements

Announcement Type

New

Related Notices
  • October 30, 2012 - See Notice NOT-OD-13-007. Deadline Extended for Applications Due on October 29 and 30, 2012.

  • September 18, 2012 - Corrections to RFA-HL-13-014. See Notice NOT-HL-12-154.
Funding Opportunity Announcement (FOA) Number

RFA-HL-13-014

Companion FOA

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

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

93.837; 93.838; 93.839; 93.233

FOA Purpose

This Limited Competition Funding Opportunity Announcement (FOA) encourages applications from the current “Nulliparous Pregnancy Outcomes Study:  Monitoring Mothers-to-be (NuMoM2b)” clinical research sites and Data Coordinating and Analysis Center (DCAC) to propose a prospective follow-up study of the existing NuMoM2b cohort to examine the cardiovascular (CV) risk profile of women with a history of preeclampsia and other adverse pregnancy outcomes (APOs) at approximately two years postpartum.

 
Key Dates
Posted Date

August 10, 2012

Letter of Intent Due Date

September 30, 2012

Application Due Date(s)

(Extended to October 31, 2012 per NOT-OD-13-007) , Originally October 30, 2012

AIDS Application Due Date(s)

Not Applicable.   

Scientific Merit Review

February/March 2013

Advisory Council Review

May 2013

Earliest Start Date(s)

July 1, 2013     

Expiration Date

(Extended to November 1, 2012 per NOT-OD-13-007) , Originally October 31, 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

Purpose

This Limited Competition Funding Opportunity Announcement (FOA) encourages applications from the current “Nulliparous Pregnancy Outcomes Study:  Monitoring Mothers-to-be (NuMoM2b)” clinical research sites and Data Coordinating and Analysis Center (DCAC) to propose a prospective follow-up study of the existing NuMoM2b cohort to examine the cardiovascular (CV) risk profile of women with a history of preeclampsia and other adverse pregnancy outcomes (APOs) at approximately two years postpartum.

Background

Current medical practice is based on the assumption that women return to normal health following a pregnancy complicated by preeclampsia or other APOs, although several retrospective epidemiologic studies indicate that they remain at an increased risk for subsequent hypertension, CV disease, and diabetes. A recent meta-analysis found that women with a history of preeclampsia have approximately four times the risk of developing hypertension, and double the risk of subsequent ischemic heart disease, stroke, and venous thromboembolic events within 5 to 15 years after pregnancy1. These findings, primarily based on retrospective studies, highlight the need for prospective research to systematically elucidate the aspects of CV risk associated with APOs in order to improve the health of women with a history of APOs. 

This FOA draws upon the recommendations of a 2010 workshop convened by the NHLBI, along with the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine, to examine the possible associations between preeclampsia and future CV disease across different domains, including basic science and clinical practice.  The goal was to identify knowledge gaps and research opportunities that could facilitate the prevention of CV disease outcomes long term. This FOA proposes to address this important gap by performing a prospective CV risk assessment at approximately two years postpartum in women with and without APOs during their first pregnancy by leveraging the existing NuMoM2b cohort.

Objectives and Scope

The purpose of this FOA is to fund a prospective observational follow-up study of the existing NuMoM2b cohort to examine the CV risk profile of women with a history of preeclampsia and other APOs at approximately two years postpartum. The NuMoM2b cohort of 10,000 ethnically and geographically diverse nulliparous participants provides a unique combination of a rich depth of phenotypic information about APOs, including clinical data and biospecimens starting in early pregnancy in a large, prospective cohort.  Prospective characterization of elevated CV risk profiles in women with a history of APOs, and elucidation of clinically relevant mechanisms coupling APOs with early CV risk, would provide scientific direction to develop future strategies for follow-up and medical management of CV risk factors in the early postpartum years.  

This FOA addresses the need for research to identify the population of women with preeclampsia and other APO-related postpartum CV risk, to define the phenotype of CV risk in the early years postpartum, to delineate the relative contributions of predisposing factors evident in early pregnancy versus effects of later pregnancy complications, and to identify possible underlying mechanisms coupling APOs to early CV risk.  Clinically important and potentially actionable measurements relevant to CV risk are an important component of the proposed study.  When appropriate, longitudinal assessment is strongly encouraged, considering not only existing comparable NuMoM2b measurements, but also potential testing of existing NuMoM2b biospecimens as part of the application.   

Key elements of this FOA are the following:

Example measurements to address these key elements include, but are not limited to, a brief physical exam including height, weight, waist and hip circumference, and blood pressure; a fasting blood-draw; and urine collection. Example laboratory tests would include, but are not limited to, blood total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, hemoglobin A1c, creatinine, and urine creatinine and protein.  Proposed laboratory testing (e.g., traditional or novel biomarkers) may include analysis of samples collected during the original NuMoM2b study. A set of questionnaires that facilitate the application’s aims may be included.  An assessment of health behaviors relevant to CV risk, with emphasis on modifiable factors that could be translated into future interventions within the health care system or broader public health context may be incorporated.

A one-time assessment of objectively measured breathing during sleep at two years postpartum should be part of the proposed study, with the goal of delineating the contribution of SDB (e.g., obstructive sleep apnea) to early CV risk in women with and without previous APOs. The postpartum sleep breathing assessments should be comparable with the measurements collected during pregnancy in the existing NuMoM2b cohort to allow for a prospective assessment of SDB trajectory (incidence and severity) between pregnancy and postpartum in relation to CV risk. The sub-group of women who received at least one SDB assessment in the NuMoM2b parent study would be eligible for the breathing assessment at two years postpartum.

An additional element of this FOA is to investigate factors that contribute to recurrence risk of APOs. The proposed study should include a method for identification and ascertainment of APOs in subsequent pregnancies throughout the project period. Verification of APOs should be performed consistent with the NuMoM2b definitions.  

Evaluation of Responsiveness

Prior to the peer review process, NHLBI program staff will determine whether applications are responsive to this FOA.  All applications should include letters of support from 1) the NuMoM2b Steering Committee, and 2) the business officials of each grantee institution (clinical sites and DCAC) in the NuMoM2b study.  NHLBI staff will determine whether the letters adequately address the required components described in Section III.3, Additional Information on Eligibility. Applicants should refer to Section III.3  for a description of the information to include in the required letters of support.

Selected Research Examples

A variety of hypotheses could potentially advance understanding of APOs and CV risk. Some examples of research questions appropriate for this FOA include, but are not limited to, the following:

Program Organization and Coordination

This FOA solicits applications from the current NuMoM2b clinical research sites and the current Data Coordinating and Analysis Center (DCAC) to form a cooperative network in scientific partnership with NHLBI to pursue the goals described above.

The clinical research sites will be responsible for development of the study protocol (in conjunction with the DCAC and Steering Committee), recruitment of human subjects, collection of relevant clinical information, entering data onto case report forms and/or a web-based data collection system, and collection/temporary storage of biological specimens. All individual clinical research sites will be required to participate in a cooperative and interactive manner with one another and with the DCAC and NIH. The clinical research sites will also be expected to have multidisciplinary expertise such that, when combined, their expertise is sufficient to accomplish the research objectives.  These areas of expertise may include but not be limited to cardiovascular medicine, obstetrics and gynecology, sleep disorders, internal medicine/primary care, preventive medicine/epidemiology, biostatistics, health behavior change, and laboratory medicine. 

The DCAC will be responsible for development of the study protocol (in conjunction with the clinical research sites and Steering Committee), development of study materials (case report forms, questionnaires, Manual of Operations, recruitment tables), central data collection, quality control, management and analysis. The analytic plan will be developed by the Steering Committee. The DCAC will maintain a study website with features that include communications for study investigators, participants, and the public research community (e.g., regarding process for ancillary studies), and support other centralized functions (see below).      

The DCAC will identify a Sleep Reading Center (SRC) with a demonstrated track record of coordinating, managing, and analyzing sleep data in multi-center studies. SRC responsibilities include facilitating the DCAC and Sleep Subcommittee (see below) with protocol and Manual of Operations development; training field site personnel and implementing protocols at field sites; expediting review of sleep data for medical alerts; overseeing site performance, quality control, data collection and data management; and coordinating data management with the DCAC and field sites. The SRC should have previous experience with the breathing assessment equipment that will be used in the follow-up study. The SRC Chair will participate as a member of the Sleep Subcommittee (see below). 

A Steering Committee will be assembled and will consist of the PD/PI of each awarded grant (clinical research sites and DCAC), the Chair of the Sleep Subcommittee, and NIH staff. The Steering Committee will be charged with the task of combining multiple perspectives and research agendas across clinical research sites into a coherent plan of action, to include the development of the study protocol and the analytic plan.

Plans for sleep breathing study governance should be clearly presented. The Steering Committee will constitute a ‘Sleep Subcommittee’ with representation from each participating clinical research site, DCAC, SRC, and the NHLBI Program Office. Appropriate expertise is to be included for effective leadership and operational oversight of the sleep breathing assessment study protocol development, clinical research site implementation, recruitment, performance, data quality management, and data analysis and interpretation. The Sleep Subcommittee Chair will be a member and will report directly to the Steering Committee.

An independent Observational Study Monitoring Board (OSMB) will be appointed by the NHLBI. Members of the OSMB will advise the Institute regarding protocol safety, participant burden and successful achievement of milestones.  OSMB meetings (e.g., travel costs) will be supported through the DCAC.

Investigators should indicate in their application their plans for the processing and storage of biospecimens, laboratory testing (including processes to facilitate consistency in laboratory methods across samples), and aliquoting of samples for future analysis.  A central biorepository will be supported through the DCAC.

A process for reviewing ancillary study proposals (not funded by this FOA) will be developed by the DCAC and Steering Committee.  A process will be needed for coordination with approved and funded ancillary studies, including tracking sample inventory, and making relevant data and biospecimen samples available to the ancillary study investigators (e.g., including coordinating in sample selection, shipping of samples, receiving unused samples, and receiving ancillary study data). While the general processes and inventory tracking are part of this FOA, additional costs related to a specific ancillary study (e.g., aliquotting, shipping) are expected to be funded by the ancillary study.

Inquiries About This FOA

Potential applicants are strongly encouraged to contact NHLBI program staff regarding the content of this FOA.  Please refer to Section VII for agency scientific/research contacts.

References

1.    Bellamy L, Casas JP, Hingorani AD, Williams DJ.  Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ. 2007;335:974.

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

NIH intends to commit approximately $11.26 million in total costs over a 4-year period; NHLBI’s commitment is approximately $10.58 million and NICHD’s commitment is $680,000.  It is anticipated that 9 new awards will be made; One of these awards will fund the Data Coordinating and Analysis Center (DCAC), including centralized functions as appropriate (e.g., laboratory assays/reading center/equipment).

Awards issued under this FOA are contingent upon the availability of funds.

Award Budget

Budget submissions should clearly delineate between the DCAC and each clinical research site for application purposes. 

The DCAC may request up to $3.5 million in aggregate direct costs over the four-year duration.  This includes centralized costs for specialized assessments (e.g., laboratory assays/reading center/equipment) anticipated to be approximately $2.6-2.8 million.

Clinical research sites should use the following metrics for Direct Costs commensurate with expected patient enrollment levels from the parent award.  Clinical research sites with:

  • 500 patients can request up to $240,000 Directs Costs for all years combined.
  • 1200 patients can request up to $550,000 Direct Costs for all years combined.
  • 1900 patients can request up to $830,000 Direct Costs for all years combined.

Direct cost limits exclude first-tier consortium/contractual facilities and administrative (F&A) costs when determining if an applicant is in compliance with the direct cost limitation.  While consortium F&A costs may be requested and awarded, applicants should not consider these costs when determining if a budget exceeds the direct cost limits.

Award Project Period

 Project period is limited to 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

Eligible Applicants

1.A. Eligible Organizations

Only those institutions in the NuMoM2b parent study funded by the Eunice Kennedy Shriver NICHD at the date of issuance of this FOA are eligible to apply.

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.

1.B. 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.

Only researchers in NuMoM2b parent study institutions at the date of issuance of this FOA are eligible to apply as a PD/PI. Any eligible individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with the invited institutions 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.

More than one PD/PI, or multiple PD(s)/PI(s), may be designated on the application for projects that require a “team science” approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans, policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PD(s)/PI(s) must be registered in the NIH eRA Commons prior to the submission of the application (see http://grants.nih.gov/grants/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PD(s)/PI(s) is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PD(s)/PI(s) will require additional information, as outlined in the instructions below. When considering multiple PD(s)/PI(s), please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application.  Multiple PD(s)/PI(s) on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

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 not submit more than one application.

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. 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
6701 Rockledge Drive, Room 7214, MSC 7924
Bethesda, MD 20892-7924 (Express zip: 20817)
Telephone: 301-435-0270
FAX: 301-480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Application Submission

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

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

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

Page Limitations

All page limitations described in the PHS398 Application Guide and the Table of Page Limits must be followed.

Research Plan

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

All applications should have the same Specific Aims and Research Plan.

Intent to Participate

Budget Preparation

Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information." The instructions for budget requests provided with the research grant application form PHS 398 (rev 5/01) should be followed. F&A costs will be awarded in the same manner as for research project grants.  Budgets will be reviewed on the basis of appropriateness for the work proposed. Allowable costs and policies governing the research grants programs of the NIH will prevail. In planning the budget section of the application, each applicant should submit budget estimates for all years exclusive of escalation for reoccurring costs.

Supplemental Instructions

Please address the following topics briefly in the Research Plan section of your application then include a parenthetical reference to the Human Subjects section for details:

Required Letters of Support

Resource Sharing Plan

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

Appendix

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

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 date 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.  

Awards will be made as cooperative agreements (U10s). Therefore, awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI. "Award Administration Information." Interaction among the participating investigators will be required, as well as significant involvement from NHLBI to accomplish the program aims.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

Overall Impact - Overall

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

Scored Review Criteria - Overall

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? 

Investigator(s)

Are the PD(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?

For the Clinical Research Sites

For the DCAC application

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?

For the DCAC application

Does the DCAC provide administrative, supervisory, and collaborative interactions with the clinical research sites necessary for achieving the goals of the Program?

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable.

Renewals

Not Applicable.

Revisions

Not Applicable.

Additional Review Considerations - Overall

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

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(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 response to this FOA.

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

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:

Awardees will have primary and lead responsibilities for the project as a whole, including research design and protocol development, participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, as well as collaborations with other awardees. Upon completion of the project funding, or at a later date if authorized in writing by the NHLBI Grants Officer, awardees are expected to put their data into the public domain and/or make them available to other investigators, according to the approved plan for making data and materials available to the scientific community and the NIH for the conduct of research at no charge other than the costs of reproduction and distribution. (See collaborative responsibilities below.)

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

NHLBI Program Official: The NHLBI Program Official is responsible for the programmatic, scientific and/or technical aspects of the award.

The NHLBI Program Official will have the following substantial involvement:

S/he will provide technical assistance, advice, coordination, and other functions above and beyond the levels normally required by for program stewardship without dominating the relationship. S/he will serve on the Steering Committee and other study committees as a voting member along with other NHLBI scientists when appropriate.

Likewise, if generated, the Program Official will assure that the Steering committee will establish guidelines to make biologic samples available to outside investigators after a reasonable period of analyses by the network.   Finally, if a GWAS study is executed through the network, the Program Official will assure that the Steering committee will develop a plan for submission of GWAS data to the NIH-designated GWAS data repository. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

NHLBI Project Scientist: The NHLBI Project Scientist(s) is responsible for the scientific technical assistance and advice to Awardees and the Steering Committee.

The NHLBI Project Scientist will have the following substantial involvement:

S/he will provide advice and assistance to the Awardees on issues coming before the Steering Committee and, as appropriate, other committees, e.g.: recruitment, intervention, follow-up, quality control, adherence to protocol, assessment of problems affecting the study and potential changes in the protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems such as insufficient participant enrollment. 

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.

Final decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property issues is assigned to NHLBI staff other than the Project Scientists. The responsibility for final decision making may reside with Senior Institute management, separate organizational components and/or oversight committees.  Because it is anticipated that the Project Scientist will participate in activities that rise to a level of involvement that results in conflicts of interest, for example, co-publication, etc., other staff members such as direct line supervisors and/or other Senior NHLBI Program management staff will serve as agency Program Officials and will be responsible for the normal scientific and programmatic stewardship of the award.  The NHLBI policy on authorship and manuscript review of NHLBI sponsored extramural research protects against conflicts of interest with the Program Officer.

The NHLBI reserves the right to phase out or curtail the study (or an individual award) in the event of (a) failure to develop or implement a mutually agreeable protocol, (b) substantial shortfall in subject recruitment, consortium participation and collaboration with other awardees, (c) substantive changes in the agreed-upon methodologies and tools with which NIH cannot concur, (d) human subject ethical issues that may dictate a premature termination, or (e) results that substantially diminish the scientific value of study continuation.

Areas of Joint Responsibility include:

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. The Principal Investigator of this award will be required to participate in periodic meetings and telephone conference calls with other investigators. These meetings and calls will be arranged by NHLBI staff to promote sharing of information among investigators regarding state of science technologies, data management techniques, analytical strategies and tools, and data sharing. Support or other involvement of industry or any other third party in the study -- e.g., participation by the third party; involvement of study resources or citing the name of the study or NHLBI support; or special access to study results, data, findings or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NHLBI. Study investigators are encouraged to publish and to release publicly and disseminate results, tools, resources and other products of the study, in accordance with the study protocols and governance. It is expected that all methods, analyses, software, and algorithms will be made available in a timely matter to the scientific community. A plan for dissemination of study results will be developed by the awardee and approved by the NIH Project Scientist and will be in accordance with the NHLBI Data Sharing Policy available at http://www.nhlbi.nih.gov/funding/datasharing.htm.

Awardees agree to the governance of the study through a Steering Committee. Steering Committee voting membership shall consist of the PI for each awarded grant (clinical research sites and DCAC), the Chair of the Sleep Subcommittee, the NHLBI Project Scientist, and the NICHD Project Scientist. The Chair of the Sleep Subcommittee will vote on issues related to the sleep breathing assessment and the NICHD Project Scientist will vote on issues related to the parent study and issues related to ascertainment of subsequent pregnancy outcomes. 

The Steering Committee will be charged with the task of combining multiple perspectives and research agendas across sites into a coherent plan of action (policies and procedures that govern operations) to include the development of the study protocol and the analytic plan. The Steering Committee will also be charged with developing a data management and quality assurance plan in collaboration with the DCAC to support the NIH data sharing goals and develop methodologies to encourage public access and availability.

An outside Chairperson, who is not participating as a Principal Investigator, will be selected by the NHLBI. Each full member will have one vote and NHLBI will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

Observational Study Monitoring Board

An independent Observational Study Monitoring Board (OSMB) will be appointed by NHLBI to provide overall monitoring of interim data and safety issues. Meetings of the OSMB will ordinarily be held in Bethesda, MD. An NHLBI scientist other than the NHLBI Program Official or Project Scientist will serve as Executive Secretary to the Board. Because the OSMB serves as an independent group advisory to the NHLBI, study investigators shall not communicate with OSMB members regarding study issues, except as authorized by the Board's Executive Secretary.

Dispute Resolution:

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

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)

Megan Mitchell, MPH
Clinical Trials Specialist
Vascular Biology and Hypertension Branch
Division of Cardiovascular Sciences
National Heart, Lung and Blood Institute
6701 Rockledge Drive
Room 8113, MSC 7940
Bethesda, MD 20892
Tel: 301-594-4335

Dale Burwen, MD, MPH
Medical Officer
Women’s Health Initiative Branch and Epidemiology Branch
Prevention and Population Sciences Program
Division of Cardiovascular Sciences
National Heart, Lung and Blood Institute
6701 Rockledge Drive
Room 9186, MSC 7940
Bethesda, MD 20892
Tel: 301-594-1354

Aaron D. Laposky, PhD
Program Officer
Director, Sleep and Neurobiology Program
National Center on Sleep Disorders Research
Division of Lung Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Room 10042, MSC 7952
Bethesda, MD  20892
Tel: 301-435-0193

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 20892-7924
Bethesda, MD 20817 (express/courier service 20817)
Telephone: 301-425-0270
Fax: 301-480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Financial/Grants Management Contact(s)

Mrs. Tammi Simpson
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7170
Bethesda, MD 20892-7926
Telephone: 301-435-0166
Email: simpsontl@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.


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