Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

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 How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of 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. Notice of Funding Opportunity Description

Purpose / Research Objectives

The purpose of this Notice of Funding Opportunity (NOFO) is to leverage NICHD clinical research network infrastructure relevant to infants, children, women, pregnant and lactating individuals, and persons with disabilities to conduct innovative, multisite, investigator-initiated clinical trials and observational studies. This NOFO will utilize a bi-phasic (UG3/UH3), milestone-driven mechanism consisting of a start-up phase of up to two years (UG3) and a full enrollment and clinical study implementation phase (UH3) up to a total of seven years. Applications submitted in response to this NOFO must address specific aims and milestones for both the UG3 and UH3 phases. A UG3 project (phase I) that meets its milestones will be administratively considered by NICHD and prioritized for transition to the UH3 award (phase II). This NOFO provides an opportunity to leverage NICHD clinical research Network infrastructure as a platform for investigator-initiated innovative hypotheses by any investigator in the extramural community. Applications must be submitted as investigator-initiated, multi-Project Director/Principal Investigator (PD/PI) grant applications in conjunction with the respective NICHD-supported Network Data Coordinating Center (DCC).

The NICHD has a long tradition of supporting multisite clinical research dating back to the mid-1980s. Since that time, the NICHD has continued to expand its infrastructure support of multisite clinical research by establishing additional Clinical Research Networks to address other areas of science relevant to its mission. Beginning in 2016, the NIH proposed, and subsequently implemented a series of reforms to enhance clinical trial stewardship and transparency, and thereby, further assure the success of the NIH clinical trial enterprise. As part of that initiative, individual NIH Institutes and Centers were asked to develop their own clinical trial funding opportunities to address their research priorities and strategic goals. In response, the NICHD re-affirmed its commitment to conducting rigorous multisite clinical trials and identified four guiding principles for such research delineated in NOT-HD-19-034: Infrastructure for NICHD Multisite Clinical Trials.

To operationalize those four guiding principles and avail this multisite clinical research infrastructure to a more diverse and wider range of investigators, NICHD published PAR-23-037 in November 2022. The cooperative (U01) mechanism provided an opportunity for non-Network investigators to work collaboratively with Network investigators to propose research projects to be conducted by and within participating NICHD-supported Clinical Research Networks. All applications submitted in response to PAR-23-037 first underwent a rigorous pre-application process to assess the scientific scope and overall feasibility of proposed projects incorporating the collective and collaborative input from the respective and applicable NICHD Network component(s) as well as from the NICHD during its pre-application review. Concept proposals approved via this pre-application process were developed by investigators into U01 applications and submitted via PAR-23-037 as investigator-initiated, multi-PD/PI grant applications with the respective DCC designated as the Contact PD/PI. Applications submitted in response to the funding announcement were reviewed by a NICHD-convened scientific peer review panel. This NOFO replaces that initial funding announcement (PAR-23-037) and incorporates feedback received during the first two years of operationalizing the four guiding principles described in NOT-HD-19-034.

Specific Areas of Research Interest

This NOFO continues to invite applications for multisite biomedical clinical trials and observational studies developed in conjunction with NICHD Networks that will be conducted using NICHD-supported Network infrastructure. The scientific scope of this funding opportunity is focused on specific areas of the NICHD mission and Strategic Plan, and the corresponding Networks (listed below) that support those areas of study. Although multisite pilot trials and observational studies will be considered responsive, preference will be given to large scale clinical trials.

This NOFO utilizes a bi-phasic (UG3/UH3), milestone-driven mechanism consisting of a start-up phase of up to two years (UG3) and a full enrollment and clinical study implementation phase (UH3) of up to a total of seven years for both phases. The implementation of a phased grant mechanism approach to funding is a key component of this new funding opportunity. A phased mechanism facilitates greater stewardship of clinical trials and observational studies and this NOFO aims to further the modernization of clinical research by supporting innovative projects that are flexible, cost-effective, incorporated into clinical care and of higher impact. Applications submitted to this NOFO should hold the potential to advance patient care, inform treatment guidelines, and/or provide new US Food and Drug Administration (FDA) indications and labeling for biomedical interventions by leveraging NICHD Clinical Research Network infrastructure relevant to infants, children, women, pregnant and lactating individuals, and persons with disabilities.

Applications submitted in response to this NOFO must address topics that align with one or more of the participating Networks and their corresponding scientific areas of interest. Strong preference will be given to studies that:

• Optimize diverse participant enrollment representative of the condition being studied
• Utilize innovative study designs to facilitate timely and informed study completion, including but not limited to, complex adaptive designs, embedded pragmatic trials, Bayesian statistical analyses, enriched enrollment, machine learning approaches, real-world data use and/or innovative follow-up methodologies
• Align with clinical practice and can be integrated into real-world clinical care in a timely manner
• Leverage electronic health records and other digital data for data collection
• Encourage and facilitate participation of junior investigators (e.g., Fellows, Assistant Professors, and NIH-defined early-stage investigators) of diverse backgrounds.

Applications submitted in response to this NOFO should address topics that align with one or more of the following Networks and their corresponding science:

Collaborative Pediatric Critical Care Research Network (CPCCRN)

The purpose of the CPCCRN is to investigate the efficacy of treatment and management strategies to care for critically ill and injured children, as well as to better understand the pathophysiological basis of critical illness and injury in childhood. Given the relatively small and widely heterogeneous pediatric critically ill and injured patient population, the vigorous use of appropriate scientific methodologies deployed across a network of sites will achieve the numbers of patients required to provide robust clinical answers more rapidly than any individual clinical site acting alone. The CPCCRN, consisting of 12 Clinical Sites and 12 ancillary sites with over 61,000 annual Pediatric Intensive Care Unit (PICU) admissions, maintains the infrastructure needed to conduct definitive, rigorous, and reproducible multisite research to enhance the understanding of critical illness in children, to advance the care of critically ill and injured children, and to improve outcomes for this most vulnerable population. NICHD expects the CPCCRN to be its primary and first-line infrastructure involved in implementing multisite pediatric critical care clinical research and trials. The Request For Applications (RFA) for the current cycle of the CPPCRN was RFA-HD-21-016.

Global Network for Women's and Children's Health Research (GN)

The purpose of the Global Network for Women’s and Children’s Health Research is to improve health outcomes for women and children in low- and lower middle-income countries by researching sustainable, cost-effective health interventions, and strengthening research infrastructure and public health intervention capabilities in developing countries. The objective is to improve maternal and child survival, focusing on high-need areas, such as preventing life-threatening obstetric complications, improving infant birth weight and nutrition, and reducing prematurity and complications from preterm delivery in rural and peri-urban communities. The Network will increase opportunities for scientific linkages, interaction, knowledge development and transfer, and collaborative partnerships among US and foreign investigators and institutions. The current GN includes seven international sites in Bangladesh, the Democratic Republic of Congo, Guatemala, India, Pakistan, and Zambia, with partner institutions in the United States. Scientists in these countries work with their peer and partner institutions in the United States to conduct clinical trials in these low-resource areas.  The RFAs for the current GN cycle were RFA-HD-23-008 and RFA-HD-23-009.

Maternal-Fetal Medicine Units (MFMU) Network

The purpose of the Maternal-Fetal Medicine Units (MFMU) Network is to improve obstetric care and outcomes for pregnant and lactating people and their babies by reducing maternal, fetal, and infant morbidity and maternal complications. This includes finding ways to reduce maternal mortality, complications, and morbidities related to pregnancy, such as preterm labor and pregnancy induced hypertension, labor, and postpartum recovery; reduce prematurity, low-birth weight, infant mortality, and morbidities; and expand the evidence base regarding the safety and efficacy of therapeutic products used during pregnancy and lactation. The MFMU Network serves as NICHD's primary and first-line infrastructure involved in implementing multisite obstetric clinical trials.  The MFMU focuses on clinical questions in maternal-fetal medicine and obstetrics, particularly with respect to the continuing problem of preterm birth. The Network provides an infrastructure to conduct multiple large studies simultaneously, in both a cost-effective and timely manner. The participating clinical centers cover over 170,000 deliveries a year and are racially, ethnically, and geographically diverse, allowing study results to be generalizable to the US population. Results from MFMU Network studies have impacted clinical practice, both by finding treatments that prevent poor pregnancy outcomes and by stopping ineffective, costly, and potentially harmful therapies by providing the rationale for evidence-based, cost-effective obstetric practice.  The 14 MFMU clinical centers with the DCC work collaboratively to implement common protocols to enroll and follow-up enough participants to achieve statistical power to answer protocol hypotheses more rapidly and definitively than individual clinical centers acting alone. Applications for the current MFMU funding cycle were submitted in response to RFA-HD-23-016 and RFA-HD-23-017. 

Neonatal Research Network (NRN)

The purpose of the NRN is to improve healthcare and outcomes for newborns. This includes finding ways to improve the chances for survival without neurodevelopmental impairment for infants born premature, low-birth weight, or babies of all gestational ages with serious conditions. The NRN currently consists of a DCC and 15 Clinical Centers encompassing 38 hospitals with more than 137,000 births per year. NRN Centers have more than 34,000 neonatal intensive care unit admissions per year; 2,300 of these babies are born at less than 29 weeks gestational age. Applications for the current NRN funding cycle were submitted in response to RFA-HD-23-001 and RFA-HD-23-002.

Pelvic Floor Disorders Network (PFDN)

The purpose of the PFDN is to study clinical and health aspects of pelvic floor disorders in women including pelvic organ prolapse, urinary urgency/frequency, urinary incontinence, and fecal incontinence. More specifically, relevant areas of study include understanding the etiology and pathophysiology of these conditions such that better preventative strategies as well as safe and efficacious treatments may be developed. Other relevant research areas include the development of novel and nonsurgical treatments to treat pelvic organ prolapse and urinary incontinence including regenerative medical techniques, projects that optimize the effectiveness of existing treatments and minimize harmful adverse events and studies focused on understanding the psychosocial consequences and alleviating the burden of living with pelvic organ prolapse, urinary incontinence, and fecal incontinence. The Network, currently consisting of seven Clinical Centers and a DCC, provides the infrastructure, the recruitment capabilities and the research expertise needed to perform definitive, rigorous, and reproducible multisite studies under common protocols that will provide efficient, high quality, evidence-based data to guide both the surgical and non-surgical care for these large and ever-growing clinical problems. Applications for the current PFDN funding cycle were submitted in response to RFA-HD-22-021 and RFA-HD-22-022.

Additional Resources

In addition to the Networks listed here, applications proposing to assess maternal and pediatric pharmacology interventions will be advised to utilize resources available via NICHD’s Maternal and Pediatric pRecisioN in Therapeutics (MPRINT) Hub and the Pediatric Trials Network (PTN). MPRINT resources include, but are not limited to curated summaries of published literature around specific drugs, innovative approaches to maternal and pediatric real-world evidence extraction, clinical pharmacology and pharmacometrics, and model informed clinical trial design. 

The Pediatric Trials Network (PTN) provides an environment and the appropriate infrastructure for conducting regulatory rigorous pediatric and lactation clinical trials that lead to updates in drug labels as directed by the Best Pharmaceuticals for Children Act (BPCA). The Network is designed to address the longstanding concern of a paucity of FDA labels for off-patent therapeutics commonly used “off-label” in children or during lactation. Data collected from PTN trials help regulators revise drug labels for safer and more effective use in neonates, children, adolescents, as well as lactating persons and their infants. In addition, and in accordance with the BPCA legislation, the BPCA Priority List of Needs in Pediatrics outlines key needs in pediatric therapeutics. Investigators who are interested in collaborating with the PTN on areas such as regulatory requirements for Investigational New Drug (IND) studies, methods developments or pharmacokinetic analyses of drugs, and/or are interested in proposing projects that align with the BPCA Priority List are encouraged to propose projects assessing medications and conditions that are a part of the BPCA mandate to improve knowledge in pediatric therapeutics. 

Further, NICHD anticipates adding more Networks to this initiative in the future. If an investigator is considering a project that aligns with another NICHD Network (including the PTN and MPRINT HUB) or another area of science not directly aligned with the Networks listed in this NOFO, please contact this NOFO Scientific/Research Contact.

PRE-APPLICATION PROCESS

Prior to application submission, all proposals must first undergo a rigorous pre-application process, during which the scientific scope and feasibility of potential projects will be assessed by the NICHD. Potential applicants are encouraged to start this process early to allow ample time to prepare and submit a competitive application in response to this NOFO. Longer timelines are likely for non-Network investigators. Timelines and instructions for the pre-application process can be found on the NICHD Pre-Application Process for NICHD Network Multisite Clinical Research website.

APPLICATION PROCESS: UG3/UH3 PHASED MECHANISM

This NOFO utilizes a different grant mechanism than PAR-23-037. Applications under this NOFO will operate under a two-phase, milestone-driven grant mechanism (UG3/UH3) consisting of a start-up phase of up to two years (UG3) and a full implementation, enrollment and follow-up phase of up to five years (UH3) for a maximum of seven combined years. Applications are expected to provide clear descriptions of overall project deliverables, timelines, and milestones and how they align with the goals of the study and the Network(s). The NICHD may negotiate changes to the study deliverables, timelines, and milestones as well as the process for their re-prioritization prior to award. Continued funding of the project will be dependent upon meeting milestones throughout the project including during both the UG3 and UH3 Phases, and it is expected that the study will be completed within the project period. The investigative team may be asked to re-prioritize and adjust activities, timelines, and milestones on a periodic basis based on feedback from the Network Steering Committee(s), External Scientific Matter Expert Committee, Community Engagement Board, Data and Safety Monitoring Board (DSMB), and/or NICHD staff.

Transition to the UH3 phase requires NICHD approval.

• Any study that fails to meet their UG3 milestones will NOT be approved to transition to the UH3 phase.
• In addition, it is not guaranteed that all projects that attain their UG3 milestones will be approved to advance to the UH3 Phase. That decision will be made by NICHD and only after review of the UG3 Phase results.

APPLICATIONS NOT RESPONSIVE TO THIS NOFO

Applications to this NOFO that do not propose to utilize a NICHD Network or that did not receive NICHD approval of the Concept Proposal will be considered non-responsive. Additionally, applications proposing single center, animal studies, basic science or basic experimental studies involving humans are beyond the scope of this NOFO. Projects that are seeking infrastructure support for another Network are also beyond the scope of this NOFO. Applications that are deemed non-responsive will not be reviewed for this NOFO.

NICHD DATA SHARING EXPECTATIONS AND REQUIREMENTS

The NIH Policy for Data Management and Sharing (Policy) expects that researchers maximize the sharing of scientific data and data be accessible as soon as possible and no later than the time of an associated publication or the end of the award period, whichever comes first. NIH requires all applications submitted in response to this NOFO to include a Data Management and Sharing Plan (DMS Plan).  The DMS Plan is expected to address the Elements as described in Supplemental Information to the NIH Policy for Data Management and Sharing: Elements of an NIH Data Management and Sharing Plan (NOT-OD-21-014). The DMS Plan will be reviewed and approved by NIH Program Staff prior to award. Awardees will be required to comply with their approved DMS Plan and any approved updates.

For human clinical trial data, NICHD expects the use of the Data and Specimen Hub (DASH), a centralized resource for researchers to store and access de-identified data from studies funded by NICHD. Information about DASH may be obtained at https://dash.nichd.nih.gov/. For projects generating large-scale human genetic data, applicants should provide a Provisional or Institutional Certification specifying whether the individual-level data can be shared through an NIH approved repository, such as dbGaP and the Sequence Read Archive, in line with the NIH Genomic Data Sharing Policy.

If use of DASH is not feasible for a given data type (e.g. non-clinical data), NICHD expects awardees to share data through other equivalent broad-sharing data repositories.

For applications that aim to analyze existing data, DMS Plans should describe where and how other researchers can access that data to enable reproducibility and reuse.

Additional information on the Data Management and Sharing Policy is available on the NICHD Office of Data Science and Sharing website.

Plan for Enhancing Diverse Perspectives (PEDP)

The NIH recognizes that teams comprised of investigators with diverse perspectives working together and capitalizing on innovative ideas and distinct viewpoints outperform homogeneous teams. There are many benefits that flow from a scientific workforce rich with diverse perspectives, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.

To support the best science, the NIH encourages inclusivity in research guided by the consideration of diverse perspectives. Broadly, diverse perspectives can include but are not limited to the educational background and scientific expertise of the people who perform the research; the populations who participate as human subjects in research studies; and the places where research is done.

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), which will be assessed as part of the scientific and technical peer review evaluation.  Assessment of applications containing a PEDP are based on the scientific and technical merit of the proposed project. Consistent with federal law, the race, ethnicity, or sex of a researcher, award participant, or trainee will not be considered during the application review process or when making funding decisions.  Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

The PEDP will be submitted as Other Project Information as an attachment (see Section IV).  Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP Guidance materials.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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 NOFO.

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 Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• 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.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; 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 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 their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

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 How to Apply-Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

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, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. 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 NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

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 NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity 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.

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- Application Guide must be followed.

Plan for Enhancing Diverse Perspectives (PEDP)

• In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of actionable strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity. 
• Applicants should align their proposed strategies for PEDP with the research strategy section, providing a holistic and integrated view of how enhancing diverse perspectives and inclusivity are buoyed throughout the application.
• The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured.
• The PEDP may be no more than 2 pages in length and should include:
  • Actionable strategies using defined approaches for the inclusion of diverse perspectives in the project;
  • Description of how the PEDP will advance the scientific and technical merit of the proposed project;
  • Anticipated timeline of proposed PEDP activities;
  • Evaluation methods for assessing the progress and success of PEDP activities.

Examples of items that advance inclusivity in research and may be appropriate for a PEDP can include, but are not limited to:

• Partnerships with different types of institutions and organizations (e.g., research-intensive; undergraduate-focused; HBCUs; emerging research institutions; community-based organizations).
• Project frameworks that enable communities and researchers to work collaboratively as equal partners in all phases of the research process.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as human subjects in clinical trials, including those from underrepresented backgrounds.
• Description of planned partnerships that may enhance geographic and regional diversity.
• Outreach and recruiting activities intended to diversify the pool of applicants for research training programs, such as outreach to prospective applicants from groups underrepresented in the biomedical sciences, for example, individuals from underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
• Plans to utilize the project infrastructure (i.e., research and structure) to enhance the research environment and support career-advancing opportunities for junior, early- and mid-career researchers.
• Transdisciplinary research projects and collaborations among researchers from fields beyond the biological sciences, such as physics, engineering, mathematics, computational biology, computer and data sciences, as well as bioethics.

Examples of items that are not appropriate in a PEDP include, but are not limited to:

• Selection or hiring of personnel for a research team based on their race, ethnicity, or sex.
• A training or mentorship program limited to certain researchers based on their race, ethnicity, or sex.

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see PEDP Guidance materials.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

R&R Budget

All instructions in the How to Apply- Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed. The following additional instructions apply:

The budget will be developed as part of the pre-application process and must include all study-related costs not covered by Network infrastructure awards. The application must provide detailed annual budgets that will enable the project to meet study milestones. Separate itemized budgets must be prepared for each subcontract. The services provided by the Network DCC and/or other Network components for these projects will be supported by their existing infrastructure awards and should not be included in the budget. These expenses should be described in the budget justification as being supported by these established grants.  A description of funded Network responsibilities may be found by reviewing the corresponding RFAs (links included above) for the respective Networks.

• Salary. The budget may include support for non-Network participating investigators, coordinators, and other necessary personnel. If additional Network infrastructure support is needed for a study, specific approval from NICHD will be required.
• Travel. The budget should include travel funds for non-Network PD(s)/PI(s) and other necessary personnel to attend face-to-face Network Steering Committee Meetings (at least 2/year) and other necessary project-related meetings for up to $1500 per person per trip.
  • The budget should also include travel costs for one junior faculty member ($3000 per year per site) from all participating sites to travel to Steering Committee Meetings.  A different junior investigator should be listed on each Network grant award such that the greatest number possible of junior investigators have the opportunity to participate in Network research.
• Other Direct Costs. The budget may include, but is not limited to, the following other cost categories:
  • Single IRB
  • Data Sharing. The budget should also include DMS Plan costs including those associated with the preparation and submission of data into the NICHD Data and Specimen Hub (DASH) and/or other appropriate repositories approved by NICHD. All DMS costs should be summarized in the budget justification.
• Consortium.
  • Subcontracts. The budget may include costs for subcontracts to non-Network sites.
  • Capitation. Recruiting sites will be reimbursed when participants are enrolled to cover study-related costs that are not part of usual patient care. These may cover, but are not limited to, screening, consent approaches, pre-eligibility testing (e.g., research echocardiograms), study intervention implementation, research tests (lab tests, radiographs, etc.), investigational drugs/devices/etc., and participant incentives.

The budget may include requests for funding to support the collection and storage of biospecimens (e.g. for mechanistic studies) as part of the protocol for subsequent study or sharing. It is anticipated that these projects will also lend themselves to ancillary studies and such projects are encouraged. Costs for biospecimen collection, storage during the award period, shipping to the NICHD Biorepository (for sharing through DASH), and cataloging submission to DASH should be included in the budget. Biospecimen sharing through the DASH/NICHD Biorepository will be based on a determination by NICHD. Investigators interested in conducting ancillary studies to Network projects should notify the Scientific Research Contact in Section VI. A list of projects being conducted by these Networks and supported via this funding mechanism can be found via the NICHD Network website or at any of the individual Network websites.

The budget may also include costs to perform secondary analyses of the proposed study data. However, given changes implemented with the NIH Data Management and Sharing Policy (NOT-OD-21-013), it is anticipated that most secondary analyses will be performed by individual investigators using NICHD clinical study data published on the NICHD DASH. For secondary analyses performed by the Network, a strong preference should be given to junior investigators serving as the lead investigator on those projects with mentorship being provided by more experienced investigators.

The NICHD may, at its sole discretion, decide to provide some of the requested elements of the budget as services provided by other NICHD or NIH contracts or cooperative agreement programs.

PEDP implementation costs:

Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7): https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm.

R&R Subaward Budget

All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply- Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

Specific Aims: Describe the potential impact of the proposed research.

• The hypotheses and specific aims of the research must be clearly and concisely stated.
• The primary and secondary outcomes to be measured must be defined. The inclusion of secondary aims should be justified.
• Specify how the primary and important secondary outcome variables will be collected, the duration of follow up and the criteria for measuring the outcomes.
• Delineate the projected goals to be accomplished within each phase of this two-phase funding mechanism.

Research Strategy:

Importance of the Research

The Research Strategy must present an overview of the state of the science, the rationale supporting the project, the current status of treatment for the disease/condition, the significance of the study including how the results will impact clinical care and/or public health. The need, rationale, timeliness, and scientific relevance of the proposed study should be addressed and supported by the following:

• Describe the potential for the study results (positive or negative) to inform and be integrated into clinical care practices, patient treatment guidelines, and/or inform FDA drug or device labeling for the disease/condition.
• Provide evidence that the intervention is ready for clinical development.
  • For trials of drugs and biologics, provide evidence that the investigational agent’s mechanism of action is expected to be of benefit in ameliorating a specific aspect of the disease in the target population and the rationale that the dose or proposed dose-ranging studies will modulate that mechanism of action.
• Describe any innovative aspects of the study (e.g. novel concepts, methods, technologies, study design, intervention, assessment tools, statistical analyses, etc.) within each phase of the project and their potential to:
  • Enhance the quality of the project
  • Facilitate enrollment
  • Augment participant diversity
  • Foster project completion in an efficient, timely, and cost-effective manner
  • Benefit the population under study.

Rigor and Feasibility

• Project Summary. Provide a concise summary of the planned clinical study including the items listed below. Information that is required as part of the PHS Human Subjects and Clinical Trials Information Form need not be described in detail in this section; specific details can be referenced to the PHS Human Subjects and Clinical Trials Information Form.
  • Describe the study population, sample size requirements, pertinent socio-demographic information, required health status or disease condition, and geographic distribution.
  • Describe the target sample size including the diversity needed to accurately answer the research question and to provide generalizable results.
  • Provide a detailed description of the milestones to be accomplished within both phases of the project (UG3 and UH3 phase individually).
• Study Design. Describe and provide the rationale for the study design and why it is the most effective approach to successfully complete the project in a timely and cost-effective manner.   
  • Describe the use of innovative study designs, including but not limited to complex adaptive designs, embedded pragmatic trials, Bayesian analyses, enriched enrollment, machine learning approaches, real-world data use and/or innovative follow-up methodologies.
  • Describe the alignment and integration of the study protocol with clinical practice.
  • If a traditional design is being proposed (e.g randomized, placebo-controlled trial with one to one allocation), explain in detail why it is superior to an innovative design in facilitating the efficient, timely and cost-effective completion of the project.
  • All applicants proposing a clinical trial involving drug(s) or therapeutic(s) are required to include the rationale for the initial selection of the dose, or equivalent, for the drug(s) or therapeutic(s) proposed for study. The rationale is not meant to discourage innovative approaches or designs. This rationale should include, for each drug and therapeutic proposed, the following:
    • A succinct description of the available information on dosing (or equivalent) for each drug and/or therapeutic in the proposed population;
    • The approaches used to select the doses (or equivalent) for each drug and/or therapeutic proposed in the application (e.g. information from drug labels, pharmacometric modeling, existing real-world data);
    • When applicable, an explanation of how dosing for each drug and/or therapeutic will be adjusted throughout the clinical trial.
  • Discuss the use of existing common data elements (CDEs) for the project or the development of new CDEs for subsequent research in the area.
• Feasibility. Describe the plan for timely completion of the trial/study and the dissemination of important study findings.
  • Describe the milestones to be accomplished for each of the two phases (UG3 and UH3 phase individually) of the project.  
  • In addition to the posting of results in clinicaltrials.gov, other examples of timely dissemination include, but are not limited to, the publication of the primary analysis in a peer review journal, presentation at national conferences, and a press release of results when appropriate.
  • Discuss potential biases or challenges in the proposed study and how they will be minimized and/or addressed. For clinical trials, provide evidence that there is equipoise among the investigators, a true willingness to randomize participants to the study interventions, as well as among the overall medical community and patient communities.
• Monitoring. Describe the processes to monitor study progress and safety issues for each phase of the project. 
  • Describe the processes to conduct follow up in an efficient and cost-effective manner highlighting any innovative techniques including the use of the electronic health record. 
  • Describe any plan to access and use patient reported outcomes as well as any non-traditional data collection approaches (e.g. telephone, mobile devices, electronic health record extraction, or web-based systems) to facilitate follow up in a cost-effective and efficient manner.
• Dissemination and Implementation Planning. Describe plans for the timely dissemination of important study results to a variety of different stakeholders (e.g. clinicians, researchers, patients, advocates).
  • In keeping with the principle of implementation science, a major goal of this initiative is the timely incorporation of evidence-based practices, interventions, and policies into routine health care and public health settings to improve the impact on population health.
  • Applications should include a description of methods incorporated into the protocol to identify potential barriers and facilitators to promote the timely implementation of pertinent study results into clinical care.
  • Applications should include a description of subsequent plans for the practical implementation of pertinent study findings into clinical care.

Expertise and Resources

• Network resources. All applications to the NOFO must use the infrastructure of at least one NICHD Network.
  • Provide a clear justification for conducting the research in the proposed NICHD Network(s) and what Network resources will be used.
  • Describe how Network resources will be used to accomplish milestones within each of the two phases of the project (UG3 and UH3 phase individually).
  • Describe the role of the Network Community Engagement Board or other patient input on the project (e.g. input on study design including outcomes of interest, dissemination of results, uptake of findings into clinical care).
• Personnel. Clearly describe the defined roles and responsibilities of the investigators and key personnel.
  • Describe the expertise of the PD(s)/PI(s) and study team and their ability to implement the study, conduct collaborative clinical research and to perform the appropriate analyses of data collected.
  • Identify a junior investigator (e.g., Fellows, Assistant Professors, and NIH-defined early stage investigators) at each of the Clinical Research Centers to serve as a co-investigator and clearly describe their role in the project.  The junior investigator may assume a variety of potential roles including being the site PI or site co-PI with an emphasis on being mentored in all aspects of that role by a senior investigator. The junior investigator should understand all aspects of the project and be poised to propose secondary analyses. Regardless of the role selected, it should be well-defined and clearly described. High priority will be given to projects that include junior investigators (e.g., Fellows, Assistant Professors, and any NIH-defined early stage investigator) as part of their research team. 
• Organizational structure. Describe the organizational structure and composition of the Network(s), including, if applicable, how non-Network sites will be integrated for the study.
• Non-network sites. If the application includes adding non-Network sites for recruitment and/or other purposes, provide rationale for adding the sites.
  • Describe the ability of the research teams to recruit and enroll patients and implement study procedures including 24 hours per day and seven days a week if necessary.
  • For recruiting sites, describe each site’s management structure, facilities, relevant available population, and ability to recruit, retain, and follow up participants.
  • For other, non-recruiting sites, describe their unique role (e.g., specimen or imaging analysis) and capabilities relevant to that role. 
  • Describe how non-Network site progress will be assessed both within the UG3 phase, and subsequently, within the UH3 phase.

Multiple PD/PI Leadership Plan: Applicants are required to provide a detailed Multiple PD/PI Leadership Plan delineating specific roles and lines of communication. The Network DCC PI will serve as the contact PI; on rare occasion, the DCC PI may request that the alternate DCC PI or another qualified member of the DCC team serve in that role. NICHD will determine if such an approach is acceptable. The Multiple PD/PI Leadership Plan must include a clear description for dispute resolution.

Letters of Support: All Network Clinical Research Centers should commit to participation in the study. In lieu of having each Network Clinical Research Center provide a Letter of Support, the Network Steering Committee Chairperson will provide a Letter of Support acknowledging that all Network Clinical Research Centers plan and have the ability to successfully participate in the proposed study, or the rationale for why any specific site is not participating. Each non-network institution participating in the project must provide a separate letter of support signed by their Institutional Signing Official.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

The following modifications also apply:

• Applications that propose collecting biospecimens should address whether and how residual biospecimens will be shared and if any biospecimens will be collected solely for the purpose of sharing. NICHD expects that biospecimens resulting from NICHD-funded research will be shared with the wider scientific community to the extent feasible and in a timely manner. Researchers are encouraged to submit study-related biospecimens to the NICHD Biorepository that integrates with DASH to enable sharing with the broad research community. Biospecimen sharing through the DASH/NICHD Biorepository is subject to NICHD approval. Biospecimen submission requirements are described at NICHD DASH - Submission Resources (nih.gov). If sharing through DASH is not feasible, NICHD encourages awardees to share biospecimens through other equivalent broad-sharing biospecimen repositories.
• NICHD expect that tools, workflows, and/or pipelines created or used with support from this NOFO will be shared with the wider scientific community in a timely manner that would enable other researchers to replicate and build on for future research efforts. Plans should align to open-source practices and other NIH Best Practices for Software Sharing (https://datascience.nih.gov/tools-and-analytics/best-practices-for-sharing-research-software-faq) as much as possible.

Other Plan(s): 

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

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 How to Apply- 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 How to Apply- Application Guide must be followed.

Section 2 - Study Population Characteristics 

2.7 Study Timeline

Study Milestones and Timeline

All applications (clinical trials and non-clinical trials) submitted in response to this NOFO must be driven by well-defined proposed milestones. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity (i.e. deliverable). Milestones may include, but are not limited to, the items in the sample table below and can be provided in a similar table.

Sample Milestone Table.

In addition, other metrics should also be considered. For example, targets for protocol adherence and retention of participants for the requisite follow up should be established from the start and monitored throughout. Further, the sustained enrollment of projected diverse populations representing the epidemiology and populations at risk for the condition being studied will be monitored closely. It should be anticipated that quarterly milestone updates including enrollment tables will be required of all projects supported via this NOFO.

Delayed Onset Study

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 How to Apply- Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

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

See Part 2. 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

4. Submission Dates and Times

Part I. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply-Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. 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 Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply - 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 form. 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 NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.

See more tips for avoiding common errors.

Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NICHD, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].

Post Submission Materials

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.

For this particular announcement, note the following: The expertise and resources of the Network Clinical Research Centers and Data Coordinating Center have already been reviewed as part of the application for their infrastructure awards. The following review criteria are focused on aspects of the personnel expertise and environment resources that are specific to this proposed study and/or augment the existing Network infrastructure (e.g. specialty expertise, recruiting sites that provide broader access to geographic, demographic, or socioeconomic diverse populations, etc.).

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 scored review criteria and additional review criteria (as applicable for the project proposed).  An application does not need to be strong in all categories to be judged likely to have a major scientific impact. As part of the overall impact score, reviewers should consider and indicate how the Plan for Enhancing Diverse Perspectives affects the scientific merit of the project.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score.

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NICHD Scientific Review Branch, in accordance with NIH peer review policies and practices, 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.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions, consistent with applicable law.

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

Please note that reviewers will not consider race, ethnicity, age, or gender of a researcher, award participant, or trainee, even in part, in providing critiques, scores, or funding recommendations. NIH will not consider such factors in making its funding decisions.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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 recipient 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

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.  Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and 
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

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 (HHS) grant administration regulations at 2 CFR Part 200, 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 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 NIH as defined below.

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

• Providing updates at least annually on progress in PEDP implementation, if applicable. 
• Providing scientific leadership for all aspects of the study, including planning, 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 PD(s)/PI(s) agree(s) to accept close coordination, cooperation, and participation of NICHD staff in those aspects of scientific and technical management of the study as stated in these terms and conditions;
• Convening or participating on teleconferences to facilitate collaboration and communication with the Network Steering and other appropriate Committees, non-Network investigators and with NICHD staff;
• Adhering to the NICHD Policy on Data and Safety Monitoring requiring that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study;
• Upon implementation of the study, following the procedures required by the protocol regarding study conduct and monitoring, participant management, data collection, and quality control;
• Managing involvement of industry or any other third party in the study. Except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by the NICHD;
• Acquiring an Investigational New Drug (IND) Application / Investigational Device Exemption (IDE) from the FDA if an investigational agent or device is to be used;
• Identifying barriers and facilitators to the implementation of pertinent study results;
• Sharing scientific data and associated documentation through the NICHD Data and Specimen Hub (DASH) and other appropriate data repositories, in alignment with the NIH DMS Policy and the approved DMS Plan. 
• Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NICHD/NIH and Network infrastructure awards (DCC and Clinical Research Centers);
• Obtaining prior written approval of the NICHD Grants Management Specialist, in consultation with the NICHD Program Official, for changes in any of the key personnel identified in the Notice of Grant Award.
• Recipients(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding 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:

• 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.
• NICHD Project Scientist: The NICHD Project Scientist will have substantial programmatic involvement that is above and beyond the typical stewardship role in other awards. As described below, the Project Scientist will:
  • Provide scientific/programmatic support and input for study design, implementation, results analysis, publication, study closeout, and development of solutions to major problems, such as insufficient participant enrollment. The Project Scientist will work closely with the study investigators, both within and outside the Network, to design protocols, manage study implementation, and analyze and publish results;
  • Assist in the development and review of study budgets, including the identification of capitation costs and special institutional needs;
  • Have access to study data and periodically review the data and administrative progress reports. For these purposes, any individual-level data should be de-identified, and data from ongoing trials should be blinded until it is time to analyze study results. Program staff may use information obtained from the data for the preparation of internal reports on the activities of the study;
  • Oversee the adequacy of adverse event management and reporting;
  • Monitor study progress of each participating facility, and of the Network as a whole, through recipient's annual reports and interim (e.g. quarterly) milestone reports, Network study reports, site visits, screening logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting enrollment and participant follow-up targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting;
  • Consult with the PD(s)/PI(s) regarding the establishment and monitoring of milestones;
  • Participate on teleconferences with PD(s)/PI(s) and Network personnel to monitor study development and implementation progress, adherence to the study protocol, conduct of the study, and recruitment and retention of study participants.
• NICHD Program Official(s): In addition to general grant stewardship, the NICHD Program Official(s) will:
  • Monitor progress of study milestones to ensure that the objectives are being met and that all regulatory, fiscal, and administrative matters are handled according to NIH guidelines. Continuation of funding will be dependent upon the recipient's ability to show adequate progress towards milestone accomplishment;
  • Conduct site visits, as needed, to review/on-board new sites and monitor study implementation at existing sites. In conjunction with the Grants Manager, the Program Official(s) may withhold support of a recipient if technical performance requirements such as protocol compliance, enrollment targets, randomization and/or follow-up of subjects are not met;
  • Serve as the NICHD representative, or designate a NICHD representative, on the DSMB in the manner delineated in the NICHD Data and Safety Monitoring Policy;
  • For studies that utilize more than one Network, the NICHD expects that a Program Official will participate in programmatic oversight of the trial in the same manner as described above.
• Director of the NICHD:
  • NICHD reserves the right to terminate or curtail a study (or an individual award) under a range of scenarios including, but not limited to: 
    • failure to implement the study protocol; 
    • a substantial shortfall in subject recruitment, follow-up, data reporting and dissemination, quality control, or other major breach of the protocol; 
    • substantive changes in the agreed-upon protocol with which NIH does not concur; 
    • reaching a major study objective substantially ahead of schedule with persuasive statistical evidence; 
    • human subject safety or ethical issues that may dictate a premature termination; or
    • a change in the state of science that changes equipoise or has other significant impact on the relevance of the question under study. 
  • Studies in which recruitment and/or participant follow-up milestones are not met, or for which regulatory approval has not been met within one year, and are unlikely to improve sufficiently to bring the study to completion within an acceptable budget or time frame, may be closed for lack of progress. If the NIH or the recipient concludes that the study is no longer feasible, the PD(s)/PI(s) shall submit a close-out plan to the NIH within two months.
  • The NICHD Director retains responsibility for all NICHD-funded research. The NICHD Director receives the DSMB’s recommendations on whether Network studies should be continued or terminated and can make an independent decision on how to proceed. 
  • The NICHD Director can override the decisions of the Network Steering Committee when it is in the strategic interest of the NIH/NICHD, human subject protection, and/or dependent on funding availability.

Areas of Joint Responsibility include:

• The PD(s)/PI(s) will work collaboratively with the respective NICHD Network(s) DCC, and Clinical Research Center personnel and may be required to accept common development and implementation procedures, methodologies, training, clinical research data collection systems, and quality management processes necessary to develop and deploy studies;
• Network(s) DCC and Clinical Research Center personnel will be active participants on study teams in conjunction with the trial PD(s)/PI(s), and designated NICHD staff will participate on study team teleconferences regularly to monitor progress with study development and implementation of activities.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: 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 recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

• Awardees will provide updates at least annually on implementation of the PEDP.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

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: https://www.era.nih.gov/need-help (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: 301-480-7075

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

Robert Tamburro, MD, MSc
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-480-2619
Email: [email protected]

Elena K Gorodetsky, M.D., Ph.D.
ORWH - Office of Research on Women's Health
Phone: (301) 594-9004
E-mail: [email protected]

Joanna Kubler-Kielb, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6916
Email: [email protected]

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: [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 2 CFR Part 200.