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 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.

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. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

PURPOSE

The purpose of this funding opportunity announcement (FOA) is to invite applications for multisite clinical trials and large scale observational studies developed in conjunction with NICHD Networks that will be conducted using NICHD-supported Network infrastructure. The goal of this FOA is to operationalize the previously reported NICHD guiding principles for multisite clinical trials delineated in Notice NOT-HD-19-034.

• Enhancing the rigor and reproducibility of clinical trial protocols. NICHD is committed to this trans-NIH goal, and will ensure that multisite clinical trial protocols are submitted through the peer review process and that NICHD staff members have the tools to provide oversight of milestone planning, progress review, and ongoing risk management. This effort will include the identification of methods to minimize staff exposure to real and perceived conflicts of interest, ensure stewardship of public funds, increase accountability, and maintain public trust.
• Promoting greater availability of multisite clinical trial infrastructure to support trials from a wider range of investigators. Maximizing the availability of research resources facilitates open access and potentially enhances fair competition. NICHD invests in the training of well-qualified, clinically trained scientists with many innovative ideas. The institute will find ways to make vital infrastructure for multisite clinical trials more available to the research community to help secure its continued growth.
• Facilitating data sharing and access to biospecimens to efficiently expand research capacity for all investigators. This effort will maximize NICHD’s infrastructure investment by promoting secondary analysis, reproducibility of results, and enhanced data/specimen aggregation and sharing. Incorporating FAIR principles and enhancing data harmonization will allow NICHD and the scientific community to capitalize on artificial intelligence and other enhanced analytic techniques. These principles are becoming the gold standard across NIH, and NICHD will incorporate them to better address the public health needs of its populations.
• Facilitating greater involvement of diverse populations in multisite clinical trials. Health disparities and inclusion in clinical trials are significant concerns for the populations and conditions that are priorities for NICHD. Infrastructure for multisite trials needs to reach racially and geographically diverse populations to advance our scientific mission.

Multisite clinical trials and observational studies proposed to be conducted by and within the participating NICHD-supported Clinical Research Networks will be submitted as investigator-initiated, multi-Principal Investigator (PI) grant applications by any qualified investigator in the extramural community (including NICHD Network investigators) in conjunction with the respective NICHD Network Data Coordinating Center (DCC). It is the intent of this FOA to invite applications developed collaboratively with NICHD Networks that will utilize the NICHD Clinical Research Network infrastructure in a manner that will promote the funding and support of the best science in a timely, transparent, equitable and cost-effective manner. Although the goal is to progressively include additional NICHD Networks, the initial NICHD Networks to be included in this initiative are:

• • Maternal-Fetal Medicine Units Network
  • Neonatal Research Network
  • Global Network for Women's and Children's Health Research
  • Collaborative Pediatric Critical Care Research Network
  • Pelvic Floor Disorders Network.

If an investigator is considering a project that aligns with another NICHD Network or another area of science not directly aligned with the five Networks listed, they are advised to contact this FOA Scientific/Research Contact.

BACKGROUND

The NICHD has a long tradition of supporting multisite clinical research. Dating back to the mid-1980s, the NICHD formed its first two Clinical Research Networks, the Neonatal Intensive Care Units (the current Neonatal Research Network) and the Maternal-Fetal Medicine Units, with the explicit goal to perform large scale clinical trials and to provide faster, more effective systems of evaluating neonatal intensive care and maternal-fetal treatments. In the ensuing 35 years, these Networks conducted seminal research that has advanced these fields and impacted and informed clinical care and practice. The NICHD also continued to expand its infrastructure support of multisite clinical research during that time by creating additional Clinical Research Networks to address other areas of science relevant to its mission. This infrastructure has supported hundreds of clinical research projects and trials over the years informing care, changing clinical practice and advancing outcomes for populations within the mission of the NICHD including infants, children, adolescents, pregnant and lactating individuals and those with disabilities.

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, and to provide NIH Institutes and Centers flexibility across their different scientific areas, individual 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 the four guiding principles of that research.

To operationalize these guiding principles, and after soliciting widespread public input (NOT-HD-19-041), the NICHD asserted its commitment to a centralized approach in which Network infrastructure is provided to support clinical research. Although the NICHD Network structure and processes vary slightly from one Network to another, the basic framework of a centralized approach is relatively consistent across the NICHD Networks. For example, infrastructure support is commonly provided for both a Network Data Coordinating Center (DCC) as well as Network Clinical Research Centers. In this model, the DCC provides biostatistical expertise, computer programming, and project management to design protocols, develop statistical analysis plans, develop data management systems, manage study funds, monitor data integrity and study safety, and work with study investigators to analyze and publish study results. The Network Clinical Research Center infrastructure tends to include a full-time equivalent (FTE) research coordinator position (sometimes shared among multiple individuals), a data entry clerk (50% FTE), a PI and an alternate PI (each with up to a 10% FTE). The Network operational structure tends to include a Steering Committee with representation from the DCC PI, each Clinical Research Center PI, a chairperson and the NICHD Project Scientist. Other Network operational components generally include some form of an External Scientific Matter Expert Committee, a Community Engagement Board and a Data and Safety Monitoring Board (DSMB). It is the Steering Committee with input from these other components and a variety of subcommittees that has the primary responsibility for implementing the objectives of the Network. Traditionally, Networks receive capitation dollars that are managed and distributed to the Clinical Research Centers by the DCC to conduct clinical research proposed and developed by Network investigators.

However, to avail this multisite clinical research infrastructure to a more diverse and wider range of investigators, the NICHD now invites any qualified investigator in the extramural community (including participating Network investigators) to work collaboratively with Network investigators to propose research projects to the NICHD for utilizing Network(s) resources. After a rigorous pre-application process to assess the scientific scope and overall feasibility, with collective and collaborative input from the respective and appropriate NICHD Network components, and with the requisite NICHD endorsement, multisite clinical study proposals to be conducted via the participating NICHD-supported Clinical Research Networks will now be submitted as investigator-initiated, multi-PI grant applications using this funding opportunity with the DCC PI designated as the Contact PI. Applications received in response to this funding opportunity will be reviewed by a NIH-convened scientific peer review panel. Applications submitted in response to this FOA must propose large scale biomedical clinical research projects that require multisite participation to be successfully completed. The intent of this initiative is to solicit applications that hold the potential to advance patient care, inform treatment guidelines and/or to provide new US Food and Drug Administration (US FDA) indications and labeling for biomedical interventions for the patient populations of interest to the respective Networks.

SCIENTIFIC SCOPE

This funding opportunity will support large scale, multisite biomedical clinical trials and observational studies that will leverage participating NICHD Network resources (listed below). The scientific scope of this funding opportunity is focused on specific areas of the NICHD mission and Strategic Plan, and the corresponding Networks that support those areas of study. Thus, applications submitted in response to this FOA must address topics that align with one or more of the following Networks and their corresponding science:

Maternal-Fetal Medicine Units (MFMU) Network

The purpose of the MFMU Network is to improve obstetric care, pregnancy health, and outcomes for pregnant and lactating people and their babies. This includes finding ways to: reduce maternal mortality, complications, and morbidities related to pregnancy, labor, and post-partum recovery; reduce prematurity, low-birth weight, infant mortality, and morbidities; and expand the evidence base about the safety and efficacy of therapeutic products used during pregnancy and lactation. NICHD expects the MFMU Network to be its primary and first-line infrastructure involved in implementing multisite obstetric clinical trials.

The objective of the MFMU Network, therefore, is to conduct definitive, rigorous, and reproducible, multisite clinical trials and observational studies in pregnant and lactating people, providing evidence to guide obstetrics, obstetric pharmacology, and lactation clinical practice. This Network of research institutions will work collaboratively to implement common protocols to enroll and follow-up enough patients to achieve statistical power to answer protocol hypotheses more rapidly and definitively than individual centers acting alone.

MFMU Network Request for Applications (RFA) links:

NICHD Maternal-Fetal Medicine Units (MFMU) Network: Data Coordinating Center (RFA-HD-23-017)

NICHD Maternal-Fetal Medicine Units (MFMU) Network: Clinical Centers (RFA-HD-23-016)

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 with other serious conditions. NICHD expects the NRN to be its primary and first-line infrastructure involved in implementing multisite neonatal clinical trials.

The objective of the NRN, therefore, is to conduct definitive, rigorous, and reproducible, multisite clinical trials and observational studies in newborns and lactating people, providing evidence to guide neonatology, pediatric pharmacology, and lactation clinical practice. This Network of research institutions will work collaboratively to implement common protocols to enroll and follow-up enough patients to achieve statistical power to answer protocol hypotheses more rapidly and definitively than individual centers acting alone.

NRN Network RFA links:

NICHD Neonatal Research Network (NRN): Data Coordinating Center (RFA-HD-23-001)

NICHD Neonatal Research Network (NRN): Clinical Centers (RFA-HD-23-002)

Global Network for Women's and Children's Health Research

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 (as defined by the World Bank) by researching sustainable, cost-effective health interventions, and strengthening research infrastructure and public health intervention capabilities in developing countries. The Network will increase opportunities for scientific linkages, interaction, knowledge development and transfer, and collaborative partnerships among US and foreign investigators and institutions.

The objective of the Global Network, therefore, is to conduct high-impact clinical trials and observational studies of sustainable, cost-effective health interventions and their implementation in women and children in low- and lower middle-income countries, while simultaneously building sustainable professional capacity and infrastructure in obstetric, neonatal, and pediatric research in those countries.

Global Network RFA links:

NICHD Global Network for Women’s and Children’s Health Research: Data Coordinating Center (RFA-HD-23-009)

NICHD Global Network for Women’s and Children’s Health Research: Research Units (RFA-HD-23-008)

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 objective of the CPCCRN, therefore, is to maintain 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.

CPCCRN Network RFA link:

Collaborative Pediatric Critical Care Research Network (RFA-HD-21-016)

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. Relevant areas of study in pelvic floor disorders include surgical and nonsurgical treatments, social and behavioral contributions, pharmacologic therapies, any outcomes from the broad array of treatments available, and prevention efforts, among others. The Network aims to provide evidence-based data to guide both surgical and non-surgical care for this large and growing clinical problem.

The objective of the PFDN, therefore, is to facilitate interactions between a network of academic centers with the recruitment capabilities and research expertise needed to perform definitive, rigorous, and reproducible multisite studies under common protocols that will provide efficient, high quality, evidence-based clinical answers to both providers and women.

PFDN Network RFA links:

NICHD Pelvic Floor Disorders Network (PFDN): Data Coordinating Center (RFA-HD-22-022)

NICHD Pelvic Floor Disorders Network (PFDN): Clinical Centers (RFA-HD-22-021)

Further information regarding these Networks may be found by reviewing their most recent RFAs (links included above), all of which are now or will soon be expired (November 30, 2022) or their respective NICHD webpages (links also embedded above). It is anticipated that additional NICHD Networks and Consortia will be progressively added to this initiative. If an investigator is considering a project that aligns with another NICHD Network or another area of science not directly aligned with the Networks listed in this FOA, please contact this FOA Scientific/Research Contact.

PRE-APPLICATION PROCESS AND PLANNING PHASE

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 (e.g., approximately 4-6 months prior to application due date) to allow ample time to prepare and submit a competitive application in response to this FOA. Any investigator wishing to submit an application in response to this funding opportunity will first be required to submit a Letter of Inquiry at a minimum of 120 calendar days prior to the application due date (NIH Application Standard Due Dates for U01). The investigator should send this Letter of Inquiry to the NICHD Scientific/Research Contact for this FOA by secure e-mail. After review of the Letter of Inquiry by the NICHD, the investigator will either be invited to submit a more detailed Concept Proposal or be advised to pursue alternative funding opportunities.

The intent of the Concept Proposal is to provide an overview of the project such that the feasibility of performing the project within the Network(s) can be assessed and the importance and relevance of the science to the field and to the mission of the Network(s) and to the NICHD can be evaluated. Details for the information to be included in the Concept Proposal and other details regarding the pre-application process may be found at: https://www.nichd.nih.gov/health/clinical-research/clinical-trial-preapplication-process or obtained from this FOA Scientific/Research Contact.

The extensive period of time from the submission of the Letter of Inquiry until the estimated application submission due date is designed to allow ample time for the pre-application process and the collaborative development and refinement of a grant application by the extramural investigator and the Network. It is the intent that the investigator proposing the trial will work with the Network(s), and potentially other NICHD supported resources, and utilize that extensive expertise to collaboratively develop a final grant application.

APPLICATION PREPARATION IN RESPONSE TO THIS FOA

After the rigorous and collaborative pre-application process, and only with NICHD endorsement of the final Concept Proposal, the project investigator will continue to work collaboratively with the respective Network(s) to jointly prepare a grant application in response to this funding opportunity that will undergo NIH peer review. The application will be submitted in response to this FOA as a multi-PI, investigator-initiated application with a Network DCC PI as the Contact PI, and the DCC institution/organization being the recipient of the Notice of Grant Award (if the application receives a meritorious score and is able to be funded). The investigator who initially proposed the project will be a PI as part of the multi-PI application. The funding requested to support that investigator’s role in the project and their institution will be awarded as a subcontract from the DCC award. A non-Network PI may propose additional sites (including another network) to participate in the project and those sites will initially be vetted as part of the pre-application process, and will also be part of the application submission and review. If the investigator who proposes the trial is a Network investigator, their support will be provided from the Network infrastructure award that they have previously received unless additional expenses are required and delineated in the budget justification.

Applications may propose a variety of clinical study designs, but must utilize Network(s) infrastructure. The potential to complete projects and disseminate results in a timely manner that hold the potential for widespread and expedient implementation to advance care and outcomes will be a priority of this funding opportunity. Consequently, projects that propose clinical trials will be a priority, although non-trial observational projects that hold similar potential for impact are also encouraged. Investigators representing other networks that will work with these NICHD Networks are encouraged to apply.

Applications submitted in response to this FOA must propose large scale biomedical clinical research projects that require multisite participation to be successfully completed. The intent of this FOA is to invite applications that hold the potential to obtain results that will inform patient care and treatment guidelines and/or provide new US FDA indications and labeling for biomedical interventions for the patient populations of interest to the respective Networks. Applications proposing to assess maternal or pediatric therapeutic interventions are encouraged to utilize resources available via the NICHD’s Maternal and Pediatric pRecisioN in Therapeutics (MPRINT) Hub. Those resources include, but are not limited to six core resources:

• Knowledge and Portal Core
• Pharmacometrics and Clinical Trial Design Core
• Real-world Evidence Core
• Phenotyping Core
• Milk Analytics Core
• Pharmacometrics and Analytical Chemistry Core.

To align with the NICHD’s guiding principles to promote greater availability of multisite clinical trial infrastructure to support trials from a wider range of investigators, applicants should strive to compose teams richly diverse in perspectives, backgrounds, and academic disciplines. In addition, to facilitate greater involvement of diverse and underrepresented subject populations in multisite clinical trials, projects must also propose a study population (e.g., geographic, race/ethnicity, and sociodemographic diversity) to meet the scientific needs of the project.

Milestones

Applications submitted in response to this FOA 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. 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 reprioritization prior to award. Continued funding of the project will be dependent upon meeting milestones, and it is expected that the study will be completed within the project period. The investigative team may be asked to reprioritize and adjust activities, timelines, and milestones on a periodic basis based on feedback from the Network Steering Committee, External Scientific Matter Expert Committee, Community Engagement Board, Data and Safety Monitoring Board, and / or the NICHD staff.

Examples of milestones include, but are not limited to:

• Study activation
• Registering project on ClinicalTrials.gov, if applicable
• Enrollment of the first participant
• Enrollment of 25%, 50%, 75% and 100% of the projected study population
• Retention target for the study population
• Completion of data collection
• Completion of primary outcome data analyses
• Reporting of results in ClinicalTrials.gov, if applicable

APPLICATIONS NOT RESPONSIVE TO THIS FOA

Applications to this FOA that do not utilize a NICHD Network or that did not receive NICHD endorsement of the Concept Proposal will be considered non-responsive. Additionally, single center, animal studies, basic science and basic experimental studies involving humans are beyond the scope of this initiative and will not be considered responsive. Applications that are deemed non-responsive will not be reviewed for this FOA.

NICHD DATA AND RESOURCE SHARING EXPECTATIONS AND REQUIREMENTS

NICHD expects that data, biospecimens, and results of NICHD-funded research will be shared with the wider scientific community to the extent feasible and in a timely manner. NIH Data Management and Sharing Policy (NOT-OD-21-013) expects scientific 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 FOA/RFA to include a Data Management and Sharing Plan (Plan). The 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 Plan will be reviewed and approved by NIH Program Staff prior to award. Awardees will be required to comply with their approved Plan and any approved updates.

Specifically, for human data, the NICHD encourages 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. They can also submit information about the location and availability of biospecimens to DASH, if applicable. Information about DASH may be obtained at https://dash.nichd.nih.gov/.

For applications that aim to co-analyze already archived and shared data with data that have not yet been shared with the broader research community, applicants must describe their Plans for sharing such primary with the broad research community for example through DASH or another established repository.

If use of DASH is not feasible, NICHD expects awardees to share data and/or biospecimens through other equivalent broad-sharing data and/or biospecimen repositories. 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, in line with the NIH Genomic Data Sharing Policy (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-124.html).

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

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

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)

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 Government

• 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 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 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.

• 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 registration; 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 his/her 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.

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.

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, per 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 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 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

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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.

R&R or Modular Budget

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 the Network Clinical Research Centers for these projects will be supported by their existing infrastructure awards and should not be included in the budget. These expenses may be described in the budget justification as being supported by these established grants. In addition, variations among the services provided by the five participating Network DCCs and their Clinical Research Centers as well as available Network capacity will be addressed in budget determinations developed during the pre-application process. A description of funded Network responsibilities may be found by reviewing the corresponding RFAs (links included above) for the respective Networks although Network capacity may require budgeting for additional support for these services.

The budget should include support for non-Network participating investigators and their site-specific study coordinators and other necessary personnel. 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, DSMB Meetings and other necessary project-related meetings, up to $1500 per person per trip and as often as four times per year. The budget should also include a provision for the costs associated with the preparation and submission of data and biospecimens into the NICHD Data and Specimen Hub (DASH) or another appropriate data/biospecimen repository.

R&R Subaward Budget

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: 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.

Research Strategy:

Significance

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, and the significance of the study. The need, rationale, timeliness, and scientific relevance of the proposed study should be addressed and supported by the following:

• Describe how the study will test the proposed hypothesis.
• Describe the potential for the study results (positive or negative) to inform clinical care practices and/or national patient treatment guidelines.
• Describe the potential for the study results to inform US FDA device or medication indications and labeling if applicable.
• Provide evidence that equipoise, a genuine uncertainty that the intervention will be of benefit or not, exists in the medical and patient communities.
• Provide evidence that the intervention is ready for clinical development.

Investigators

• 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.
• Clearly describe the defined roles and responsibilities of the investigators and key personnel.

Innovation

• Describe the innovative aspects of the study (e.g. study design, intervention, assessment tools, etc.) and their potential to enhance the quality of the project and benefit the population served by the respective Network.

Approach

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.

• Clearly state the study objectives.
• Describe and provide the rationale for the study design, including study groups.
• Specify the primary and important secondary outcome measures that align with each objective and provide justification for the selection of the study outcomes.
• Describe how the primary and important secondary outcome variables will be collected, the duration of follow up and the criteria for measuring the outcomes.

• Provide a description of all assessments, including clinical, laboratory, physiological, behavioral, patient-centered, or other outcomes addressing the primary and secondary research questions. Use of patient reported outcomes as well as non-traditional data collection approaches (e.g. telephone, mobile devices or web-based systems) should be considered

• Describe the study population, including the sample size, pertinent sociodemographic information, required health status or disease condition, and geographic location.
• Explain why the study population is an appropriate group to address the study objectives. Do not duplicate information described in Section 2 (Study Population Characteristics) of the Study Record: PHS Human Subjects and Clinical Trials Information form.
• Describe the Network’s ability to enroll the target sample size.
• 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.
• Provide an approach for handling missing data in your statistical analysis plan.
• Provide a clear description of the use of Network resources to support the project.
• Discuss how the study investigators will be kept blinded to treatment group-specific data during the course of the clinical trial, if applicable.
• Discuss potential biases or challenges in the proposed study and how they will be minimized and/or addressed.

• Describe the plan for timely completion of the trial/study and the dissemination of important study findings. 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.

Environment

Network infrastructure must be used and the design must propose large scale biomedical clinical research projects that require multisite participation.

• Describe the organizational structure and procedures of the Network including, if applicable, how new sites will be integrated into the existing Network for the study.
• Provide reasonable estimates of the number of patients that each participating site is expected to enroll.

Multiple PD/PI Leadership Plan: Applicants are required to provide a detailed Multiple PD/PI Leadership Plan delineating specific roles and lines of communication. This plan must include a clear description for dispute resolution.

Letters of Support: Letters of support will be required from all participating Clinical Research Centers and should be signed by the Institutional Signing Official.

Resource Sharing Plan:

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

• 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 can submit information about the location and availability of biospecimens to the DASH catalog, if applicable.
• NICHD expect that tools, workflows, and/or pipelines created or used with support from this FOA will 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):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the SF424 (R&R) 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.

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 2 - Study Population Characteristics

2.7 Study Timeline

Describe objective, well-defined and measurable deliverables and milestones. Applications submitted in response to this FOA 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). Continued funding of the project will be dependent upon meeting proposed milestones, and it is expected that the study will be completed within the project period. Examples of milestones include, but are not limited to:

• Study activation
• Registering project on ClinicalTrials.gov, if applicable
• Enrollment of the first participant
• Enrollment of 25%, 50%, 75% and 100% of the projected study population
• Retention target for the study population
• Completion of data collection
• Completion of primary outcome data analyses
• Reporting of results in ClinicalTrials.gov, if applicable

3.5 Overall Structure of the Study Team

Include a description of the following:

• The Network Steering Committee as well as any relevant Network operational committees
• The oversight, responsibilities, communication with, and coordination of any sites proposed
• The role of any sub-contractors or providers of services, personnel, or facilities and their functional integration with the Network.

Section 4 - Protocol Synopsis

4.1.a. Detailed Description
Describe the protocol to be followed in each arm of the trial.

4.1.c Interventions
For clinical trials, provide the rationale for the selection of the intervention to be tested and a description of how and at what frequency the intervention will be administered. 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.

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 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.

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 fieldof 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 FOA 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 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 NICHD, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact the Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Applicants are required to follow the instructions for post-submission materials, as described 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.

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

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.

Overall Impact

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).

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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?

In addition, for applications involving clinical trials

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?

Specific to this FOA: Does the application describe the potential for the study results (positive or negative) to inform clinical care practices, national patient treatment guidelines and/or US FDA device or medication indications and labeling? Has evidence been provided that equipoise, a genuine uncertainty that the intervention will be of benefit or not, exists in the medical and patient communities? Has evidence been provided that the intervention is ready for clinical development?

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?

In addition, for applications involving clinical trials

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?

Specific to this FOA: Do the PD(s)/PI(s) have appropriate expertise in the content area of the proposed study? Does the multisite research team have the ability to implement the study, conduct collaborative clinical research and to perform the appropriate data analyses? Do the investigators and key personnel have clearly defined roles and responsibilities?

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?

In addition, for applications involving clinical trials

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?

Specific to this FOA: Does the application describe study innovations (e.g. study design, intervention, assessment tools, etc.) and their ability to enhance the quality of the project and benefit the population served by the respective Network?

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?

In addition, for applications involving clinical trials

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?

Specific to this FOA: Does the application present data supporting the Network’s ability to enroll the appropriate study population, including the targeted sample size, pertinent sociodemographic information, required health status or disease condition, and geographic location? Does the multisite research team have the ability to recruit and enroll patients and implement study procedures including 24 hours per day and seven days a week if necessary? Is there a clear description of the use of Network resources to support the project? For trials of drugs and biologics, does the application provide a compelling rationale 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 that the dose or proposed dose-ranging studies will modulate that mechanism of action? Does the project propose a timeline for the successful completion and timely dissemination of important project findings?

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?

In addition, for applications involving clinical trials

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?

Specific to this FOA: How well have the organizational structure and procedures of the Network been described including, if applicable, the rationale for new sites and their integration into the Network for this study? Have the sites provided adequate or reasonable estimates of the number of patients that they expect to be able to enroll?

Additional Review Criteria

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

Study Timeline

Specific to applications involving clinical trials

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

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

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

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

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 NICHD Scientific Review Branch, 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.

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. 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:

• 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.
• Compliance with resource sharing policies.

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 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.

Recipients 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 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

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, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, 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.

Should the applicant organization successfully compete for an award, 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 (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. 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 https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/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. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals 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 information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, 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, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. 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.
• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws 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 and 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.

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 primary responsibility for:

• 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;
• Retaining custody of and having primary rights to the data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies;
• 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 US FDA if an investigational agent or device is to be used;
• Making all final datasets available in the public domain (i.e. NICHD Data and Specimen Hub (DASH)), and making all study materials and procedure manuals prepared by the Network available in the public domain. Recipients are expected to publish and publicly disseminate results, data, and other products of the study, concordant with NICHD and NIH governance policies and protocols. 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 Officer, for changes in any of the key personnel identified in the Notice of Grant Award.

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

NICHD’s Office of Clinical Research staff, a Program Official, and a Grants Manager will be responsible for overall grant stewardship. A NICHD Project Scientist will provide scientific input to the Network.

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 of 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 may 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, 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 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

In addition to general grant stewardship, the NICHD Program Official 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 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 Network’s Data and Safety Monitoring Board (DSMB) in the manner delineated in the NICHD Data and Safety Monitoring Policy.

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: (a) failure to implement the study protocol; (b) a substantial shortfall in subject recruitment, follow-up, data reporting and dissemination, quality control, or other major breach of the protocol; (c) substantive changes in the agreed-upon protocol with which NIH does not concur; (d) reaching a major study objective substantially ahead of schedule with persuasive statistical evidence; (e) human subject safety or ethical issues that may dictate a premature termination; or (f) 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 timeframe, 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:

As appropriate to the funded study, the following collaborative responsibilities will be incorporated into the grant award:

• The PD(s)/PI(s) will work collaboratively with the respective NICHD Network 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 DCC and Clinical Research Center personnel will be active participants on study teams in conjunction with the trial PD(s)/PI(s), and a designated NICHD staff person will participate on study team teleconferences regularly to monitor progress with study development and implementation activities.

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. Members will be: a designee chosen by the PD(s)/PI(s), 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 DHHS regulation 45 CFR Part 16.

Dispute resolution for any disagreements among members of the investigative team including between the PIs of the multi-PI application should be addressed as part of the Multiple PD/PI Leadership Plan in the application.

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the 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.

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. NIH FOAs 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 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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: 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 Gorodetsky, M.D., Ph.D.
Office of Research on Women’s Health
Phone: 301-594-9004
Email: [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: 301-462-4552
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 45 CFR Part 75.