Key Dates

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from 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.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

This Funding Opportunity Announcement (FOA) invites applications for clinical or community sites to be part of a multi-center group- or cluster-randomized trial under the NIH Early Intervention to Promote Cardiovascular Health of Mothers and Children (ENRICH) program. ENRICH will aim to test the effectiveness of an implementation-ready intervention designed to promote cardiovascular health (CVH) and address CVH disparities in both mothers and children (0-5 years old) who are of low socio-economic status (SES), live in low-resource rural or urban communities, or who are in diverse geographic regions of the U.S. with high burden of cardiovascular disease (CVD) risk factors. Specifically, this initiative will support multi-site interventions designed to determine if a CVH module delivered within the context of a home visiting program can enhance maternal and early childhood CVH. The overall estimated number of mother-child dyads needed for the trial is about 3,000.This FOA uses a bi-phasic, milestone-driven, cooperative agreement mechanism (UG3/UH3).

Awards made under this FOA will support a milestone-driven planning phase, including feasibility studies and pilot activities for up to 2 years (UG3), with possible transition to an implementation phase (UH3) for up to five additional years. Only UG3 trials that meet the scientific milestones and award requirements of the UG3 phase may transition to the UH3 phase. Applicants are expected to be familiar with the requirements of the UG3/UH3 mechanism. Applications submitted in response to this FOA are expected to address both the UG3 and UH3 phases. Applications are also expected to include plans for project management, including participation in the development of a common protocol for the UH3 phase during the UG3 phase, subject recruitment and retention, scientific conduct of the trial including its design, randomization and power analysis; intervention, measurement, and statistical analysis of study results. Inclusion of performance-based milestones for each phase is a critical component of the application.

This FOA runs in parallel with a companion U24 FOA (RFA-HL-22-008) which seeks applications for a research Resource Coordinating Center (RCC) for the Early Intervention to Promote Cardiovascular Health of Mothers and Children (ENRICH) program.

Background

Maternal morbidity and mortality rates in the U.S. have risen in recent years. Racial disparities in maternal mortality are particularly alarming, with African Americans having more than 3-fold and American Indians/Alaskan Natives more than 2-fold higher rates compared with non-Hispanic Whites. More women at older ages, or with chronic conditions, such as diabetes, hypertension, or obesity are becoming pregnant-- all risk factors for maternal morbidity and mortality. In addition to adverse pregnancy outcomes and poor peri-partum health, maternal obesity, pre-eclampsia and gestational diabetes are also associated with long-term risk of CVD in the mother. Many research reports have noted that women who had pre-eclampsia had significantly higher risk of adverse cardiovascular health (CVH) outcomes 15 years later compared to controls who did not have pre-eclampsia, and maternal pre-eclampsia, gestational diabetes, or hypertension, are associated with risk of high blood pressure in mothers post pregnancy and in their children as early as 3 years of age. There are also evidence-based guidelines recommending both behavioral and pharmacological interventions targeted at cardiovascular and maternal risk factors and chronic conditions such as obesity, hypertension, and diabetes.

Epidemiologic studies in children support the conclusion that the development of cardiometabolic risk factors begins in utero and early childhood, progresses from childhood through adolescence and into adulthood, and results in adverse clinical CVH outcomes. Beginning prenatally and in childhood, unhealthy behaviors such as poor diet and nutrition, sedentary behavior and lack of physical activity, sleep timing and disruptions, and smoking exposures (e.g., second-hand smoke exposures); health factors such as obesity, elevated blood pressure, glucose and lipids in the mother; and social determinants of health (e.g., poor access to health care) all contribute to the loss of ideal CVH. The associated loss of CVH prenatally and postpartum is accelerated by poor lifestyle behaviors and inadequate adherence to evidence-based guideline recommendations such as the treatment of hypertension or smoking cessation. The loss of CVH is also exacerbated by adverse social determinants of health indicators, including poverty, poor access to or utilization of health services, and contextual factors within the home and in social and community environments. These adverse exposures have direct effects on CVH and constrain behavioral options leading to further deterioration in CVH. Strategies that optimize and promote CVH and reduce the adverse effects of social determinants of health indicators have the potential to reduce health disparities, reduce maternal morbidity, and improve the health and well-being of infants and children in a way that could be sustained across the lifespan.

Research Scope

Scientific Knowledge to be Achieved
Interventions that are shown in randomized trials to be effective in promoting maternal health by preventing the development of cardiovascular risks or ensuring their adequate treatment and preserving CVH in the child would help provide clinicians, policy makers and other entities with means to promote CVH in both mother and child. Interventions designed to preserve or promote CVH during critical periods (e.g., pregnancy, postpartum, early childhood) could similarly have the potential to set individuals on the best trajectories for lifelong CVH. Trials that stimulate ancillary studies to perform assessment of markers of subclinical CVD (e.g., inflammatory markers) or measures of critical developmental changes (e.g., in circadian biology, microbiome, epigenetics) and maternal CV morbidity would inform the understanding of this potentially critical time period when interventions may have great impact to preserve or promote CVH.

This FOA focuses on addressing CVH risks of both mothers and children via home visiting. Studies to date of home visiting models or home visiting plus mHealth or telehealth have not comprehensively targeted composites of CVH behavior metrics (diet and nutrition, physical activity, obesity, smoking exposures of mother-child dyads), nor has research on home visiting assessed a comprehensive set of CVH risk factors (including hypertension, diabetes or dyslipidemia). Therefore, research that would demonstrate the effectiveness of promoting CVH in home visiting would contribute to the scientific knowledge and improve the ability of home visiting programs to address CVH risk factors with the families with whom they work.

Applicants must be familiar with evidence-based home visiting models (https://homvee.acf.hhs.gov/) and must leverage their proposed intervention with such programs. HRSA, in collaboration with AC, administers DHHS Maternal, Infant, and Early Childhood Home Visiting (MIECHV) Program, which funds evidence-based home visiting in 50 states, 5 territories, 23 tribes and tribal organizations, and the District of Columbia. Home visiting programs are integrated into comprehensive care systems to help families adopt healthy lifestyle and to follow appropriate medical recommendations such as treatment of hypertension. This funding opportunity has the potential to integrate CVH preservation and promotion strategies into evidence-based home visiting. Many home visiting models are designed to begin during pregnancy or shortly after birth and typically continue through early childhood, up to 5 years old. This FOA supports the use of trained home visiting delivery staff (e.g., social workers, nurses or community health workers) and models that meet DHHS criteria for evidence of effectiveness (see HomVEE [https://homvee.acf.hhs.gov/] and https://homvee.acf.hhs.gov/effectiveness) and encourages the engagement of community members across the country, including community health workers, coalitions of community-campus partnerships for health (CCPH) and local and state home visiting organizations.

The Health Resources and Services Administration (HRSA) and the Administration for Children and Families (ACF) will provide the infrastructure and in-kind support to awardees investigators to gain access to evidence-based home visiting programs already being supported by HHS. Investigators will leverage this support to obtain access to home visiting staff to implement interventions in the home. Investigators must partner with at least one evidence-based home visiting program to gain access to evidence-based home delivery programs and must obtain approval for any adaptations or enhancement to an evidence-based home visiting model. Investigators must leverage in-kind support already provided by HHS to local implementation sites for the home visiting program. HRSA and ACF staff, along with NIH staff will provide staff-level scientific and technical input for ENRICH. HRSA and ACF staff along with NIH staff may serve as project scientists on the Steering Committee and various subcommittees (e.g., intervention, measurement, publications, ancillary studies subcommittees).

Skills development: This FOA also supports skills development of home-visiting staff professionals and early stage investigators (ESIs), particularly those underrepresented in the biomedical research, to develop and prepare the next generation of researchers in early CVH. Preserving or promoting ideal CVH will need a broad understanding and skills in clinical trials, behavioral interventions, and implementation science. Creating this kind of knowledge base will require a cross-disciplinary team approach to facilitate the ability of the next generation of investigators to create new knowledge and a more rapid approach to translation of evidence to the clinical and community settings. This initiative provides an opportunity for investigators to support skills development of both ESIs and professionals to develop and maintain a workforce focused on preserving and promoting CVH and preventing CVD.

Design, Analysis, and Sample Size for Studies to Evaluate Group-Based Interventions: Investigators who wish to evaluate the effect of an intervention on a health-related biomedical or behavioral outcome may propose a study in which (1) groups or clusters are assigned to study arms and individual observations are analyzed to evaluate the effect of the intervention, or (2) participants are assigned individually to study arms but receive at least some of their intervention in a real or virtual group or through a shared facilitator. Such studies may propose a parallel group- or cluster-randomized trial, an individually randomized group-treatment trial, a stepped-wedge design, or a quasi-experimental version of one of these designs. In these studies, special methods may be warranted for analysis and sample size estimation. Applicants should show that their methods are appropriate given their plans for assignment of participants and delivery of interventions. Additional information is available at https://researchmethodsresources.nih.gov/.

Specific Areas of Research

Investigators are expected to conduct research to accomplish the following:

• Identify clearly-defined study population(s) that include at-risk mother and child (e.g., low SES, low-resource rural or urban communities, or populations residing in diverse geographic regions of the U.S. (e.g., South Eastern, Stroke Belt, Mississippi Delta, Appalachia) or those with high burden of CVD risk factors (obesity, hypertension, diabetes); or those with risk of developing pre-eclampsia or gestational diabetes.
• Design and implement interventions which enhance ongoing evidence-based home visiting programs to test implementation-ready approaches and examine their impact on CVH measures in mother and child, including a focus on mediators and moderators of the intervention effect (e.g., social determinants of health indicator such as access to healthcare).
• Support skills development of home-visiting staff professionals and at least one ESI, particularly those underrepresented in biomedical research, in life-course approaches, intervention methods, adherence to prevention and treatment recommendations by team-based approaches involving the health care team, and implementation science focused on preserving and promoting ideal CVH.
• Leverage evidence-based home visiting models (https://homvee.acf.hhs.gov/HRSA-Models-Eligible-MIECHV-Grantees) that have been ascertained as meeting the HHS established criteria of evidence of effectiveness including the following:
  • Evidence of HHS support of home visiting staff to implement interventions in the home.
  • Assessed as moderate or high-quality impact using evidence-based criteria
  • Favorable impact on primary and secondary health outcomes as defined by Home Visiting Evidence of Effectiveness (HomVEE) review (https://homvee.acf.hhs.gov/)
  • Favorable sustained impacts >1-year post program inception on maternal or child health outcomes
  • Favorable impacts on maternal or child health that have been replicated

Investigators must partner with at least one evidence-based home visiting program (i.e., local implementing agency) to gain access to evidence-based home delivery programs, and must obtain approval for any adaptations or enhancement to an evidence-based home visiting model. Investigators must leverage in-kind support already provided by HHS to local implementation sites for the home visiting program.

Applicants may propose working with home visiting models that have not yet been determined by HomVEE to meet HHS criteria for evidence of effectiveness as long as they adhere to the above established evidence-based criteria, provide compelling justification for their proposed inclusion, and obtain approval from supporting agencies along with a commitment of in-kind support.

Phases of Award

UG3 Phase

This two-year phase of the FOA consists of supporting planning and establishment of community partnerships and collaboration with home visiting organizations, development of the UG3 protocol, staff training, and feasibility and pilot studies. This phase will support the development of a manual of operations, and other necessary resources; Data and Safety Monitoring Board approval of the trial protocol and informed consents; activation of clinical/community sites; and initiation of study participant recruitment for the UH3 phase. During this phase, multiple clinical/community sites that receive the UG3 awards will work together with the ENRICH RCC (RFA-HL-22-008) and project office staff to develop one common protocol (including study design, analytic plan, sample size) to be used across multiple sites in the UH3 phase. Toward that end, community/clinical sites may need to conduct pilot studies in Year 2 of this phase to refine the development of the common protocol. Applicants will be expected to submit proposals for the study design and analytic plan to be used in the UH3 to evaluate the intervention and use information gathered in the UG3 phase that would inform the analytic plan for the UH3 phase. Attention to key design features including those related to sample size, effect size, and power are expected in the applications.

Transition from UG3 to UH3

Award of the UG3 does not guarantee subsequent UH3 funding. An NHLBI-appointed Data and Safety Monitoring Board (DSMB) and NIH program staff will provide administrative review of the UG3 phase to ascertain the extent to which peer-reviewed milestones have been met in the UG3 phase. DSMB and NIH program staff recommendation to transition into the UH3 phase will be considered by the NHLBI prior to the issuance of the UH3 award and subject to NHLBI funding availability.

UH3 Phase

This phase consists of implementation of one common protocol across multiple sites/programs, with coordination and support provided by the ENRICH RCC. A common protocol in the UH3 phase would allow for a consistent intervention (including incorporation of mHealth or telehealth approaches) and common data collection elements. Applicants must provide a detailed proposal for both the UG3 and UH3 phases of the study (including study aims, design, approach, etc.).

Key Elements

The study population must include vulnerable populations, such as families with low incomes, families living in low-resourced rural or urban areas, or those in geographic regions with high prevalence of CV risk factors. Inclusion criteria should identify women with one or more CV risk factors. High-risk mothers may include those with obesity, pre-eclampsia, gestational diabetes, age >40 years old, or excessive pregnancy weight gain. The overall estimated number of mother-child dyads needed for the trial is about 3,000. Each UG3/UH3 applicant is expected to enroll and retain about 500 to 600 dyads in the UH3 phase and should plan for about 3 years of average follow-up following randomization, or provide justification for alternative approach.

Study Design: The FOA seeks applications that use Types 1 and 2 hybrid effectiveness/implementation intervention designs. Applicants are expected to specify the unit of randomization, unit of assessment, and sample size estimation. Considerations regarding the unit of randomization should include protection from contamination, feasibility, generalizability, and fidelity of the intervention delivered to a specific mother and child dyad. Study designs that use interventions which are behaviorally sound for CVH promotion and intervene on and measure key components of CVH metrics (e.g., Life Simple 7 indicators), and moderating effects such as social determinants of health indicators (e.g., poverty, access to healthcare), and psychosocial indices of both mother and child are considered responsive. Additionally, partnership with the mothers primary care providers to identify and/or manage their CV risk factors per appropriate clinical guidelines are also considered responsive. Other study designs may be proposed with justification.

Intervention: A primary goal would be to move the study population across the continuum of CVH, for example, from poor to intermediate to ideal or from intermediate to ideal (for mothers) or to maintain ideal CVH trajectories (e.g., for children). [CVH metrics include weight/height/length, diet, sedentary behavior, physical activity, smoking exposures, sleep; and biomedical measures including blood pressure, glucose, and lipid levels]. A detailed intervention plan is expected and applicants must propose interventions that would target a composite of CVH metrics in both mothers and children. It is expected that the interventions would be delivered via home visiting or in combination with virtual delivery. Additional partnerships and/or integrations with OBGYN and primary care (maternal) and pediatric care (through pediatrician) for components that benefit from additional medical care are encouraged. All interventions including enhanced home visiting virtual delivery with mHealth or telehealth approaches must be age- and developmentally appropriate and applicants are expected to target both mother and child, and where appropriate, other care givers (e.g., fathers, grandparents), and to be tailored to socioeconomic or social determinants of health risk. Collection of data (e.g., retrospective chart reviews and self-reports) on pre-pregnancy, pregnancy and postpartum conditions associated with CVD risks (e.g., pre-pregnancy BMI, weight gain during pregnancy, hypertension, pre-eclampsia, gestational diabetes, adherence to medications, type of delivery, postpartum health status) will be expected. Such information would be useful in examining their associations with maternal and child health outcomes post intervention.

Measurement: Both mothers and children (0-5 years) must be assessed with respect to CVH outcomes. Ideally, the primary outcome would be a composite of CVH metrics i.e., measured blood pressure, glucose, and lipids, as well as adherence to prescribed mediation as appropriate; BMI; diet/nutrition; sedentary behavior/physical activity; smoking exposure (including second hand smoking) and sleep (duration, circadian measures) separately for mothers and for the children. However, at a minimum, a composite of several of the CVH metrics must be proposed as the primary outcome. Secondary outcomes may include the components of the CVH metrics that were not used as primary outcomes or other indicators of risk (e.g., ascertainment of maternal morbidity through retrospective chart reviews), implementation assessment and outcomes including service delivery, medication adherence, and client outcomes, social determinants of health indicators (e.g., family economic self-sufficiency, access to quality health care), or resilience factors (e.g., social support). Other potential measures may include psychosocial factors (e.g., depressive symptoms), child feeding practices (e.g., breast or bottle feeding, introduction of solid foods), and contextual factors within the home, social and community environments. The goal is to provide the strongest evidence for causal inference, as well as strategies for implementation across a broad spectrum of families.

Due to budget constraints, genetics and other biological biomarkers aside from serum glucose and lipids will not be measured using this award. However, it is anticipated that future opportunities will permit investigators to propose ancillary studies and use other funding mechanisms (such as investigator-initiated grants) to collect such measures on ENRICH study participants.

Examples of Research

The following are provided as research examples. Applicants may propose to use more than one of these and are not limited to those listed here:

• Test community-based implementation-ready effectiveness intervention that uses home visiting model to promote CVH in mothers (e.g., from poor to intermediate to ideal) and preserve CVH in children 0-5 years of age
• Test interventions in high-risk mothers with pre-eclampsia, gestational diabetes or excessive weight gain and assess cardiovascular risk and health during and post-pregnancy and in the children.
• Test whether linking and integrating home visiting with primary care providers enhance participants adherence to guideline-based medical recommendations, adoption of healthy behaviors, improve cardiometabolic health of mothers and children, and reduce maternal morbidity.
• Conduct home visiting intervention studies, including use of telehealth approaches, to test what works best, for which families, under what conditions, and that assess ideal CVH metrics for both mothers and children and important effect modifiers such as social determinants of health indicators.
• Conduct family-based home visiting trials, including virtual multi-component interventions in low resourced communities, (e.g., rural communities and Federally Qualified Health Centers) with the goal of maintaining ideal CVH metrics in children and improving CVH metrics in mothers.
• Test the combined effects of various CVH modalities using digital health tools and mobile technologies to enhance intervention adherence.

Applications Not Supported by this FOA

The following types of applications will be considered non-responsive to this FOA and will be returned without review. Please refer to the Frequently Asked Questions (FAQ) page for additional guidance.

• Applications that do not include vulnerable populations, such as families with low incomes, families living in low-resourced rural or urban areas, or those in geographic regions with high prevalence of CV risk factors. Inclusion criteria should identify women with one or more CV risk factors.
• Applications that do not propose interventions delivered via home visiting or in combination with virtual delivery
• Applications that do not use Types 1 and 2 hybrid effectiveness/implementation intervention designs.
• Single site clinical trials
• Multi-site epidemiologic or observational studies that do not meet the NIH definition of a clinical trial (see NOT-OD-15-015) and mechanistic clinical trials
• Applications that propose to conduct preclinical/vertebrate studies with animals

Diversity Statement

Every facet of the United States scientific research enterprise from basic laboratory research to clinical and translational research to policy formation requires superior intellect, creativity and a wide range of skill sets and viewpoints. NIH’s ability to help ensure that the nation remains a global leader in scientific discovery and innovation is dependent upon a pool of highly talented scientists from diverse backgrounds who will help to further NIH's mission.

Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

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

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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 PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

NHLBI strongly encourages inclusion of early stage investigators (ESIs).

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.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

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

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

The letter of intent should be sent to:

Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung and Blood Institute (NHLBI)
Email: [email protected]

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Describe the experience of the multidisciplinary team including the required expertise and/or specialized training and/or experience with evidence-based home visiting models (https://homvee.acf.hhs.gov/). Describe how the team will leverage their proposed intervention with evidence-based home visiting models. Describe experience of the PD(s)/PI(s) with leading or building the necessary collaborations for research. Roles and responsibilities, including coordination of the responsibilities of all team members, must be well-defined and a description of the depth of involvement/levels of effort commitment of each of the multidisciplinary team members must be included. Describe the experience of key personnel in the conduct of clinical trial coordination and management, including success in meeting milestones and timelines, expertise in the content area of the proposed clinical trial, and expertise in biostatistics and clinical trial design. The experience of each PD/PI and all Key Personnel must be carefully documented, and roles and responsibilities must be well defined. In addition, the respective responsibilities and authority of each PD/PI must be specified. The application must ensure that a multidisciplinary team of appropriate personnel (clinician, statistician, data manager, study coordinator(s), etc.) are proposed to facilitate the implementation of all aspects of the clinical trial, including recruitment of subjects, design/implementation of the clinical protocol, and coordination of roles/responsibilities.

R&R Budget

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

A detailed budget must be presented for activities to be conducted under this FOA. The operational budget should include, but not be limited to the following items:

• With respect to the proposed intervention(s) that leverage existing home visitation programs, describe what will be covered by the existing home visitation program and what will be funded through this FOA.
• Funds for developing skills of home visiting delivery personnel in the common protocol. This may start in year two of the UG3 phase. The skills development activities may be organized by the RCC in a central location, so funds may be needed for home visiting personnel and should be included in the budget.
• Funds in year 1 and 2 for ESIs, PD/PI, and one additional key personnel to participate in up to three two-day steering committee (one of these would be in Bethesda, MD) and other committee meetings including meeting with Institute-appointed Data and Safety Monitoring Board beginning at the start of award and in subsequent years until the completion of the study. In the UH3 phase, these meetings will likely be reduced in frequency to two per year for the steering committee and working groups.

Note: even if selected for award, subsequent budget reallocations may be needed in year 2 of the UG3 phase as a common protocol is being developed in order to facilitate any further refinement, pilot testing, and initial implementation of the common protocol by the RCC and the clinical/community site grantees.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims

• Applicants must provide a concise description of the disparities in cardiovascular disease in the U.S. population that the proposed research plan will address, including the developmental origins of health and cardiovascular disease as related to maternal and child health. A description of the implementation-effectiveness research to be conducted and the hypotheses driven study aims must be clearly provided. A discussion of the contribution of the anticipated study results to improving of CVH and clinical care of mother and child must be included.

Research Strategy

The Research Strategy must present an overview of the state of the science and relevance of the proposed clinical trial, a detailed discussion of the specific protocol, and the approach to data collection, analysis, and dissemination. Both the UG3 and the UH3 phases must specify the milestones to be accomplished.

UG3 Phase

The clinical/community sites that receive the UG3 awards will work together with the ENRICH RCC and NIH staff to develop one protocol (including study design, analytic plan, sample size, etc.) to be used across multiple sites in the UH3 phase. The following must be addressed:

• Describe the Home Visiting Model selected for this study, the rationale for selection and how effectiveness implementation research will be accomplished to enhance cardiovascular health in both mother and child.
• Without duplicating the information in the Retention and Recruitment Plan (section 5) of the PHS Human Subjects Clinical Trials Information Form, clearly describe the study population, rationale for selection and ability to recruit and retain the study population (e.g., low SES, underserved urban or rural, populations in diverse geographic regions, at risk mothers (e.g., history of hypertension, pre-eclampsia, obesity, gestational diabetes).
• Describe the anticipated specific duties and tasks of study personnel. Detail the planned feasibility studies and the roles of project staff. Include plans to work collaboratively with other awardees in other clinical/community sites and with the Coordinating Center.
• Describe how the anticipated pilot testing of study procedures (e.g., e-delivery) will contribute to the development or refinement of the common protocol, and how the design and approach will meet the developmental needs of children and of the mother from pregnancy through the post-delivery period.
• Describe the proposed study design including unit of randomization, unit of assessment, inclusion criteria, sample size, effect size, and power for the primary outcome (s) and description of the secondary outcomes to be used in the UH3 phase.
• Without duplicating the information in the Retention and Recruitment Plan (section 5) of the PHS Human Subjects Clinical Trials Information Form, provide a recruitment and retention strategy for approximately 500-600 mother-child dyads, as well as the plan for an average follow-up of 3 years, or provide justification for alternative approach.
• Describe the intervention design and measurement of intervention dose, quality and fidelity, and moderators (e.g., indicators of social determinants of health).
• Describe measurement procedures including CVH health metrics and other measurements. Include a discussion of the role of primary care and other relevant health care providers in the design of the project and in the implementation of the intervention.
• Provide an organizational plan that consists of project management staff, their roles and responsibilities, and percent effort for each.
• Describe plans to involve ESIs in the proposed project, including those underrepresented in biomedical research and planned process for developing skills in home visiting providers and ESIs in conducting clinical trials related to maternal and child cardiovascular health
• Propose and justify milestones that will be subject to peer review. Core milestones that are of particular interest include, but are not limited to
  • Complete and finalize protocol and informed consent documents
  • Conduct of feasibility and pilot studies
  • Approval by DSMB of a common protocol.
  • Provision of a template for consent(s) and/or assent(s), and data and safety monitoring plan
  • IRB approval of final protocol and consent and/or assent
  • Enrollment of the first participant/site during the UG3 phase
  • At least 25% of clinical or community sites activated

UH3 Phase

This phase consists of implementation of a DSMB approved common protocol among all the grantees in the ENRICH FOAs.

• In addition to the above requirements in the UG3, an applicant must provide processes for retention, intervention, and measurement (including process measures dose, fidelity, reach) for the 5-year period.
• Describe how the full enrollment of study participants will be supported.
• Provide details on the intervention to be implemented and rationale for the proposed intervention
• Describe processes to work with other sites to implement a common and developmentally appropriate intervention and trial protocol.
• Identify key intervention components for both mother and child. Discuss the planned approach to ongoing monitoring of the trial implementation, including recruitment and retention milestones, completeness of data, and adherence to the data safety monitoring plan.
• Describe how data on primary and secondary outcomes for both mother and child will be collected.
• Describe the measures to be used and their developmental appropriateness including reliability of questionnaires..
• Describe processes to work collaboratively with other awardees in other clinical/community sites and with the Coordinating Center.
• Provide clearly defined milestones. Core milestones include, but are not limited to these examples:
  • Enrollment of 100% of the projected recruitment for all study participants, including pregnant women, minorities and children, 0-5 y
  • Study closure and completion of implementation
  • Collection of data related to primary and secondary endpoints and public access data transfer to Resource Coordinating Center (RCC)
  • Submission of primary manuscript to peer-reviewed scientific journal(s) and dissemination of results

Letters of Support

• To be considered complete, applications must include letter(s) of support from collaborating home visiting organization or partners, and other relevant entities (e.g., Native American Tribal Organizations, Federally recognized tribal governments) and their relevant commitment to participate. Letters must specify the in-kind resources that will be used to compensate home delivery staff. Applications without the required letter(s) of support will not be reviewed. If partial funding is to be provided by sources other than NHLBI, provide letter(s) of support from the source(s) signed by an authorized representative.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

Data Sharing:

• It is expected that data from this study will be made available to the public two years after publication of the primary outcome paper, or no later than 3 years after the end of the clinical activity (final patient follow-up, etc.), whichever comes first. Data will be transferred to the RCC by the clinical/community sites and the RCC will prepare public access data files for distribution through the NHLBI biodata repository.
• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Applicants should describe how they will work with the RCC to share data and resources.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Section 5 - Other Clinical-Trial Related Attachments

5.1 Other Clinical Trial-related Attachments

Applicants must provide a detailed table listing the characteristics of trials they have been involved in that demonstrate experience in trial coordination in the last 5 years. The table must be provided as an attachment called "Clinical Trial Research Experience.pdf" and may not exceed 3 pages. The table columns for each study record should include:

• Column A: clinical study title
• Column B: applicant's role in the study
• Column C: a brief description of the study design
• Column D: planned enrollment
• Column E: actual enrollment
• Column F: whether the studies completed on schedule or not
• Column G: publication reference(s)

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to 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. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission. Each application of a collaborative set must be on-time. Considerations for late applications that are based on the institution or PD/PI apply only to his/her individual application.

Applicants are responsible for viewing their application before the due date 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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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

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

Applications must be submitted electronically following the instructions described in the SF424 (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 How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

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 SF424(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. See Section III of this FOA for information on registration requirements.

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 System for Award Management. 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 and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? 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?

Specific to this FOA:

• How likely are the proposed interventions able to shift current practices in maternal and child health?
• In what ways will the results of this study, if effective, change clinical or community practice?
• How will the anticipated study results contribute to the improvement of CVH of mother and child?

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

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

Specific to this FOA:

• How experienced are the members of the multidisciplinary team, and is the described experience appropriate to the proposed study? How well developed is the team structure and how appropriate is the experience of the study personnel, including PDs/PIs in leading and building collaborative research? Have personnel been identified for specific tasks at UG3 and UH3 phases?
• How adequate is the organizational plan in describing the project management staff, their roles and responsibilities and the percent efforts for each?
• How well described are the roles and responsibilities of study personnel and ESIs including those underrepresented in biomedical research, within the organizational plan?
• What is the likelihood of success of the plans to provide skills development training in clinical trials related to maternal and child health?
• Are home delivery staff included as paid staff (i.e., with in-kind resources from HHS) and are there training for the providers in maternal and child cardiovascular health?
• How feasible are the plans to work collaboratively with other clinical sites and with the coordinating center?

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA

• How adequately does the proposed research link the current state of the science on maternal morbidity and mortality and disparities in maternal cardiovascular risk to the study aims?
• To what extent do the planned research activities address the developmental origins of disease, particularly cardiovascular disease as related to maternal and child health?
• How appropriate to the hypothesis-driven study aims is the proposed implementation-effectiveness research to be conducted?
• How reasonable is the Data Sharing Plan?
• How adequate is the plan to share data and resources with the RCC

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

Specific for this FOA:

• How appropriate are the available facilities and resources to adequately coordinate a multi-site clinical trial?
• How strong is the evidence that the institutions have the available resources needed to conduct a multi-site trial?
• Are the partnerships with home visiting model agencies and community partners strong enough to support the protocol?
• Does the proposed plan for active involvement in the ENRICH Steering Committee and sub-committees exhibit strong potential for effective contribution and collaboration?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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 score, but will not give separate scores for these items.

Study Timeline

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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 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 Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

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

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

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 recipient'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 terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 Part 75, 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 recipients 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

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

All aspects of their study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators. The recipient agrees to accept close coordination, cooperation, and participation of NHLBI and other NIH staff in those aspects of scientific and technical management of the study. Upon implementation of the protocol, each clinical/community site, whether a single institution or a consortium of institutions, will follow the procedures required by the protocol regarding study conduct and monitoring, patient management, and data collection. Support or other involvement of industry or any other third party in the study--e.g., participation by the third party; involvement of project resources or citing the name of the project or the NHLBI support; or special access to project 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 with the concurrence by NHLBI Program Officer to ensure objectivity of research.

Obtaining prior written approval of the NHLBI Grants Management Specialist in consultation with the NHLBI Program Officer for a change in any of the senior/key personnel identified in the Notice of Award.

Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

Have access to data generated under this Cooperative Agreement and will periodically review the data and progress reports. NHLBI staff may use information obtained from the data for the preparation of internal reports on the activities of the study.

Serve as a resource to provide scientific/programmatic support during the accomplishment of the ENRICH program by participating in the design of the activities, advising in the selection of sources or resources, advising in management and technical performance, or participating in the preparation of publications.

Participate in the monitoring of issues relating to recruitment, retention and follow-up of study participants, and monitoring of data integrity and quality control through consideration of the annual reports, site visits, patient logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting patient enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting. Assist in the development and modification of study protocols.

Additionally, an agency program official or IC Program Officer will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

Participate actively and collaboratively in a Steering Committee (SC), anticipated to be chaired by an independent chair and composed of the principal investigator of the coordinating center, as well as the principal investigators of the various field clinical centers, and NHLBI and other scientific staff from co-funding Institutes or offices. The SC will have primary responsibility for facilitating the conduct and monitoring of studies and reporting study results. As the components of the SC may be geographically dispersed, the SC should meet with at least monthly conference calls, supplemented as deemed necessary by face to face meetings. Each full member of the SC will have one vote, except NIH staff, who will have one collective vote. Recipient members of the Steering Committee will be required to accept and implement all policies governing the study conduct approved by the Steering Committee.

Additionally, participate actively and collaboratively in the ENRICH subcommittees that may be established, such as the Design Committee, Recruitment Committee, Quality Control Committee, Publications and Presentations Committee, Ancillary Study Committee, and others.

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

A final RPPR, 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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Charlotte A. Pratt, MS, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0382
Email: [email protected]

Jamie Marshell White
Office Of Research On Women's Health (ORWH)
Phone: (301) 496-9200
E-mail:[email protected]

Priscah Mujuru, DrPH, MPH, RN
National Institute on Minority Health and Health Disparities (NIMHD)
Phone: 301-594-9765
E-mail:[email protected]

Elizabeth Neilson, PhD, MPH, MSN
Office of Disease Prevention (ODP)
Telephone: 301-827-5578
Email: [email protected]

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: [email protected]

Allison Moyal
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8036
Email: [email protected]

Priscilla Grant, JD
National Institute on Minority Health and Health Disparities (NIMHD)
Phone: 301-594-8412
E-mail:[email protected]

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.

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 Part 75.