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

Background

The Human Placenta Project (HPP) is an initiative aimed at revolutionizing our understanding of the human placenta. By accelerating the development and application of innovative technologies, development of novel biomarkers which reflect placental status, and application of in-depth analysis of existing data and sample collections, researchers will be able to produce a new dynamic picture of placental structure and function in real time, one that assesses key developmental trajectories of placental formation and functional cues that are critical for successful human pregnancy. It is expected that the insights resulting from these approaches will ultimately lead to new ways to treat, cure, and even prevent placental dysfunction disorders such as preeclampsia, fetal growth restriction, spontaneous preterm birth, and stillbirth. Given the requirements for these approaches, it is likely that the methods developed will also be applicable to assessment of other internal organs, thus the impact may be far reaching.

There remains an urgent need for effective methods that allow safe real-time assessment of placenta development and function across gestation. The NICHD launched the HPP in 2014 to address this critical gap. NICHD has made nearly 40 awards and invested over $87M. There has been progress across multiple fronts, including MRI, Ultrasound, other novel imaging methods, extracellular vesicle analysis, and an array of omics approaches. However, making the jump from potential new approaches to clinical implementation requires additional clinical studies to provide confirmation and validation. In addition, by necessity the individual HPP awards represented primarily a single approach, and development of integrated approaches may provide the greatest clinical potential. It is noted that the HPP has stimulated research globally and there have been advances in centers around the world. This initiative would be open to all investigators, foreign or domestic.

This Funding Opportunity Announcement (FOA) invites grant applications that seek to advance or clinically validate emerging novel approaches for the development of safe, real-time, non-invasive (or minimally invasive) methods to assess the development and function of the human placenta across pregnancy This will facilitate the development of valuable clinical and research tools to enhance our understanding of placental biology and improve our clinical management of pregnancy.

Scope of Research to be Performed

This FOA is for the advancement of novel methods for assessing the placenta’s real time in vivo status with the ultimate goal of human use across pregnancy. Special consideration will be given to applications that develop methods that are applicable throughout pregnancy, preferably starting in early gestation during the period of trophoblast invasion and remodeling of the uterine spiral arteries, and which facilitate assignment of relative risk for pregancy complications.

The placenta is a dynamic organ which changes over the course of pregnancy. To be helpful, assessments need to yield results within a time frame that reflects the current structural/functional status. However, real-time is not meant to imply instantaneous results.

For this R21 mechanism, there is strong interest in novel high risk/high reward approaches.

Specific Requirements

All proposed research teams should include at least one obstetric clinician to provide insights into current or potential clinical functional or safety limitations of the chosen technology. They should have sufficient involvement to ensure that the proposed technology would be feasible in a clinical setting. It is strongly recommended that a biostatistician is included on any applications that propose clinical studies. The range of additional disciplines included may be either broad or relatively narrow (e.g., various subspecialties within a given field) as appropriate to the scientific goals of the application. The application should reflect the expertise of the proposed team. Strong academic-industrial partnerships are welcomed.

The rapid advancement of research in this area through data sharing is a priority for the HPP. Applicants are encouraged to share their data in real time to magnify the potential impact of their work through dissemination to the scientific community. NIH data sharing guidance is provided at this link: http://grants.nih.gov/policy/sharing.htm

General Technology Characteristics

This FOA promotes the advancement and/or further clinical validation of tools and technologies to enable real-time measurement of human placental processes that are currently relatively inaccessible during pregnancy and to assess changes in these processes as development progresses, including but not limited to:

• Anatomic and structural changes of the placenta across development.
• Villous cell structure and function.
• Blood flow, oxygenation, diffusion, and perfusion within the placenta.
• Maternal-fetal nutrient transfer across the placenta.
• Metabolic changes within the placenta including, but not limited to, oxygenation, oxidative stress, choline, lipids and lactate, and including measures of placental proteins and gene expression.
• Placental barrier (targeted, regional) permeability and function in the human placenta.
• Regulation of maternal and fetal immunologic function involved in placental processes.
• Circulating factors or other biomarkers that reflect placental status

There is high interest in applications focused on the development of biosensors and devices capable of multiplex analysis of molecules that reflect placental status from small samples of non-blood sources including saliva, breath, urine, or vaginal secretions.

This FOA encourages the use of multi-modal approaches to develop signatures of placenta status that allow for potential risk stratification in the clinical setting, including application of novel machine learning approaches or data analytics to development of risk assessment indices.

Solutions describing existing, well-established and/or currently supported approaches, especially commonly used strategies, are not of interest unless a compelling case is made that significant, quantifiable advance are proposed, and/or the methods and measures are used in unique combinations not previously tested together for the real-time assessment of human placental structure, development, and function.

This FOA is primarily intended to move nascent novel technologies forward. Applications that propose novel combinations of approaches are welcomed. Applications that propose completely new technologies for placenta assessment must provide a strong scientific premise and supportive preliminary data. Applicants are encouraged to contact Program Staff if they are uncertain about the suitability of their proposed studies.

For novel technologies proposed for measurement of circulating factors, any placental molecules utilized do not need to be predictive of abnormal placental function, but there should at least be potential for adding novel predictive biomarkers. Applications proposing discovery of biomarkers as a byproduct of technology development and testing are allowed. However, applications whose primary focus is on biomarker discovery will be given low priority. Investigators interested in focusing on placental biomarker discovery should consider other funding opportunities.

Projects that are considered low priority for this FOA include:

• Development of technologies that can only be applied in the third trimester of pregnancy or postpartum.
• Projects that only focus on data collection, data processing, data analysis, and computational modeling and simulation without direct application to placenta assessment or development of placenta risk indices.
• Basic research and studies of disease mechanisms that are not part of technology advancement or validation.
• Projects directed at understanding placental biology without the advancement or validation of novel technology to assess placental structure or function in real-time.
• Development of technology that has little potential for utility in late first trimester-early second trimester unless the conditions listed below are met.
• Development of projects whose primary focus is on the collection and analysis of imaging or omics data for biomarker identification or validation.
• Development of methods for isolation of placental vesicles or other circulating factors unless done in association with transformative assessment or implementation approaches with high clinical potential.
• Development of methodologies or technologies that are contraindicated for use in human pregnancy.
• Projects in non-mammalian systems that have little potential to be applied to human placenta assessment.

This funding opportunity is to facilitate advancement and validation of novel technology that may be used across pregnancy for assessment of placental structure and/or function. Achievement of this goal may require the use of multiple approaches and some may not be able to be utilized within the first trimester at this time. Projects which are directed at development of technologies with little potential for use in the first trimester will be accepted, provided:

• The reason(s) it cannot be used in the first trimester is detailed.
• The potential for use in the first trimester is addressed.
• The value of the technology to the goals of the Human Placenta Project is justified.

It is recognized that advancement of these novel technologies may require use of animal models. Studies carried out exclusively in animals may be proposed; however, the pathway for translation into humans and potential safety and technical issues associated with human application of the technology/tools must be clear.

Program Priorities

As the goal of this FOA is to support research-driven technology development to meet the objectives of the HPP, program priority will be given to applications that are exceptional in the following aspects: 1) potential for safe assessment of real time placental status in vivo during gestation, 2) the level of innovation, 3) the uniqueness within the portfolio of currently supported HPP projects, 4) the expected timeline for human applicability. Funds requested are expected to be used primarily to support technology development and validati.

Potential applicants are advised to consult with the Scientific/Research contact listed in Section VII for appropriateness of submission to this FOA

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal 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)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

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

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

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 full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with 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.

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.

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.

All proposed research teams should include at least one obstetric clinician to provide insights into current or potential clinical functional or safety limitations of the chosen technology. They should have sufficient involvement to ensure that the proposed technology would be feasible in a clinical setting. It is strongly recommended that a biostatistician is included on any applications that propose clinical studies. The range of additional disciplines included may be either broad or relatively narrow (e.g., various subspecialties within a given field) as appropriate to the scientific goals of the application. The application should reflect the expertise of the proposed team. Strong academic-industrial partnerships are welcomed.

R&R or Modular 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.

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

Research Strategy: The Research Strategy should be developed to address the topics below.

1) Background and Significance

• Define the technological problem/barrier to be addressed. Define the current state of technology as a benchmark against which the proposed new technology or improvements will be measured, with emphasis on the current resolution/timing/performance limits that would be improved.
• Outline the proposed technology/assay/device/treatment and its potential to improve placental assessment and risk stratification in real-time across pregnancy. Clearly state specific goals for the activities in the proposed project. A sound rationale should be provided as to why the approach proposed is the most appropriate and likely to generate an exceptionally high impact if successful.

2) Preliminary data – Preliminary data are not required, but the approach must be scientifically justified (e.g. based upon literature, theoretical underpinnings, or demonstrated use in another field of science).

• Summarize preliminary data documenting the technology's potential to achieve capabilities for improved real-time assessment of placenta structure/function beyond currently used technology.

3) Investigative Team

• Describe how the Investigative Team will be organized and managed. Address the coordination of efforts including: Engineering, assay/treatment development and oversight of practical and safety issues from a perspective of Obstetrics and Gynecology; development of research goals and objectives by personnel with expertise in placental structure and function across pregnancy in humans.
• For any proposed clinical studies, describe the involvement of a biostatistician.
• Any agreements establishing partnerships should delineate the roles of each partner to the agreement.

4) Approach

The approach section should outline as applicable:

• Plans to develop entirely new technology or modify existing technology to achieve transformational improvements in real-time placenta in vivo structure/function assessment across pregnancy.
• Plans to test functionality with clinical specimens, animal models or patients.
• Potential clinical utility (i.e., what clinical problem the assay/device/treatment addresses, how the assay/device/treatment will solve the clinical problem, its potential specificity, sensitivity, selectivity, and other key functional parameters).
• Discussion of any special challenges, limitations, or opportunities created by placental placement (anterior or posterior) or body habitus
• Discussion of any special challenges, limitations, or opportunities anticipated for persons with disability.
• The path for performing human validation studies, including plans to address regulatory and human subject issues, especially if developing and validating the technology in an animal model.
• Plans for any additional engineering or development that might be needed to optimize the technology for validation testing, for example by adding desirable attributes.
• Plans to validate the use of the technology in a pre-clinical or clinical model to demonstrate efficacy for real-time assessment of placental in vivo structural/functional status across pregnancy.
• A clear path for translation of animal validation study results to humans, including problems or obstacles anticipated with mitigation strategies clearly articulated.
• Plans to address technical, safety, or regulatory requirements and challenges for the translation of the technology into humans, including time, cost, accessibility, acceptance, etc.
• For any clinical study, the plan for ensuring inclusion of diverse (racial/ethnic) participants as well as those with disabilities
• Plans for sharing data, biospecimens, or model organisms developed

• Milestones and metrics of success.

The Research Strategy section should include specific performance specifications and milestones to be achieved. For any proposed technology, the application should outline:

• The expected time frame from applying the technology to return-of-results to the clinician.
• The potential for shortening the time frame.
• The expected utility of the proposed technology for determining placental structure and/or function status at the time that results are returned and potential clinical utility for risk stratification.
• Potential barriers to clinical translation should be discussed – cost, acceptability, time.

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

The following modifications also apply:

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

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, per NIH Policy, as amended.

For sharing human and non-human data, unless stipulated otherwise in each protocol’s approved Plan, investigators will be responsible for preparing and submitting protocol datasets to the NICHD Data and Specimen Hub (DASH https://dash.nichd.nih.gov/) and/or other NIH-approved repositories. For protocols that generate large-scale human genetic data, recruiting sites will have to 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). This will be done on a protocol-by-protocol basis.

For human studies, any recruiting site is responsible for ensuring that each study’s informed consent forms contain language allowing broad sharing and future use of study data and biospecimens in alignment with federal and local regulations and policies. Consent forms must notify participants that their data and, when relevant, imaging data and biospecimens (potentially for both maternal and child) may be shared with other Network investigators, the study sponsor(s), applicable federal agencies, and, when relevant, industry partners. In addition, de-identified data, imaging data, and remaining biospecimens from each study may be shared with researchers outside of the Network, including depositing them in NIH-approved public repositories. Recruiting sites may also be required to obtain approval(s) from appropriate regulatory authorities (e.g., IRB) for sharing that data, particularly for studies conducted under a waiver of consent.

For this FOA, applicants must indicate in their institution’s (and any satellite site’s) Letter of Support their agreement to comply with the Data and Specimen Sharing Plans.

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.

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.

Foreign Institutions

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

3. 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 components of participating organizations, NIH. Applications that are incomplete or non-compliant will not be reviewed.

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

Section V. Application Review Information

1. Criteria

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

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

For this particular announcement, note the following:
 

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

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?

Investigator(s)

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

Specific to this FOA:

Does the investigative team include expertise in clinical obstetrics and gynecology? If a clinical study is proposed, is there sufficient biostatistician support?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

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

Specific to this FOA:

Does the project offer potential for improved in-vivo placental assessment during gestation? For high risk studies, will the outcomes be significant if the feasibility can be demonstrated? Do the proposed studies address any special challenges, limitations, or opportunities created by placental placement (anterior or posterior) or body habitus? Do the proposed studies address any special challenges, limitations, or opportunities for persons with disability? Are potential barriers to clinical translation (cost, acceptability, time) adequately addressed? Have milestones and metrics of success been defined? If animal studies will be used for method/technology development and evaluation, is there a clear path described for translation into humans? Is there an adequate plan for sharing data, biospecimens or model organisms as applicable?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment, and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria

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

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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

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

Select Agent Research

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

Resource Sharing Plans

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 Center for Scientific Review, 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.

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

3. Anticipated Announcement and Award Dates

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.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that 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.

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.

Not Applicable

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.

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

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

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

David Weinberg, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6973
Email: [email protected]

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

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Margaret Young
Eunice Kennedy ShriverNational Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email:[email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.