Part 1. Overview Information

Key Dates

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

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

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

IMPORTANT: Per NOT-OD-24-086 updated application forms (FORMS-I) will be used for this opportunity. The updated forms are not yet available and will be posted 30 calendar days or more prior to the first application due date. Once posted, you will be able to access the forms using one of the following submission options:

1. NIH ASSIST
2. An institutional system-to-system (S2S) solution
3. Grants.gov Workspace

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

The goal of translational research is to transform basic science and clinical research discoveries into results that have direct clinical and health impact. Novel tools, methodologies, and other resources are essential to accelerate the translational process, particularly when they are of broad applicability to the scientific and clinical communities who work with pregnant persons, lactating persons, and children, including those with physical or intellectual disabilities.

Therapeutics discovery and development and precision medicine for fetal, neonatal, pediatric, pregnant, and lactating patients, including those with physical and intellectual disabilities, continue to lag behind research for adult and non-pregnant populations. Indeed, the unmet need for safe and effective therapies for these populations is so great that federal legislation has encouraged or mandated research supporting pediatric and obstetric drug development, such as the Best Pharmaceuticals for Children Act (BPCA) and most recently the 21^st Century Cures Act, which established the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC Task Force).

Pregnant and lactating persons undergo complex physiological changes affecting multiple organ systems, which may increase the risk of pregnancy-related conditions or complications and aggravate pre-existing conditions requiring pharmacotherapeutic intervention. Furthermore, time-dependent changes in drug metabolizing enzymes, transporters, and other components of the drug metabolism pathway can alter therapeutic absorption, distribution, metabolism, and excretion throughout the pregnancy and lactation periods and move toward pre-pregnancy baseline during the post-partum period. Therapeutics may also pass through the placenta to the developing fetus or through breastmilk to the neonate or infant. Pediatric ontogeny can affect pharmacokinetic (PK) processes at every developmental stage, from the developing fetus to adolescence. Finally, the impact of certain physical and intellectual disabilities on therapeutic pharmacokinetics is understudied and remains elusive throughout pediatric development to adulthood for many therapeutic classes.

The unique pharmacokinetic processes and drug pharmacodynamics (PD) properties for these populations could lead to altered therapeutic effectiveness and unexpected adverse events. Moreover, other factors such as inter-individual heterogeneity, pharmacogenomic and epigenetic characteristics, certain physical and intellectual disabilities, and environmental influences, among others, can influence drug effectiveness and safety in children, pregnant persons, and lactating persons, including those with intellectual and physical disabilities. Understanding the pharmacokinetic and pharmacodynamic properties of therapeutics as well as the role of other factors during the pregnancy, lactating, and post-partum periods, and throughout the spectrum of pediatric development is critical to optimally treat these populations as well as to prevent adverse effects.

Underrepresentation in clinical research due to ethical and safety concerns and fewer available studies, paired with the dynamic physiological changes unique to pregnant persons, lactating persons, children, and persons with physical or intellectual disabilities, suggest that new approaches are required to assess and predict therapeutic effectiveness and safety. New avenues for therapeutics research for the populations described above may include the development of pharmacometric models, dosing algorithms, or devices that use clinical, PK/PD, and/or biospecimens data to guide precision dosing. Novel in vitro or in silico model systems may be established to assess potential targets, therapeutic efficacy, and toxicities of therapeutic strategies for pregnant persons, lactating persons, fetuses, neonates, and children/adolescents as well as to predict the impact of drug exposure from the pregnant or lactating person to the fetus or breastmilk-fed neonate or infant. Real-world evidence and pharmacoepidemiologic data, along with machine learning, artificial intelligence, and bioinformatics could be used to develop novel tools, models, and other methodologies for precision medicine and drug safety prediction. Finally, new therapeutic modalities, including biologics such as genome editors, tissue constructs, or exosomes, may be necessary to treat conditions related to pregnancy or lactation or in treating severe neonatological conditions.

Objectives

The objectives of this notice of funding opportunity (NOFO) are to support translational and clinical research to (1) advance precision medicine in pregnant persons and lactating persons, and children/adolescents through the development of novel tools, models, and other technologies that could have a direct clinical or health impact; (2) enhance the understanding of the underlying mechanisms of drug action, including the role of pediatric ontogeny and the dynamic physiological changes that occur during pregnancy, lactation, or the post-partum period; and (3) discover and develop novel therapeutics or enhance the usage of existing drugs or drug repurposing for safer and more effective medications in pregnant, lactating, and postpartum persons, neonates, and children.

The overall goal is to improve safe and effective precision therapeutics for pregnant and lactating persons, fetuses, neonates, and children, including those with disabilities.

Scope

For the purpose of this NOFO, translational research in maternal and pediatric pharmacology and therapeutics encompasses tools, models, biomarkers, other technologies, and new and repurposed therapeutics that drive innovation for the safe and effective treatment of fetal, pediatric, obstetric, and lactating patients, including those with disabilities. Research on the physiological changes that impact drug distribution, effectiveness, and safety in these patients as well as the passage of drug from a from mother to fetus during pregnancy and to child during lactation, including the effects of those drugs on the fetus or child, are within scope of this announcement.

Examples of topics include, but are not limited to, the following:

• Development of a novel device using molecular or other biomarkers to predict drug effectiveness and fetal exposure in pregnant patients diagnosed with hyperemesis.
• Generation and use of machine-learning models to integrate multi-omics biosample data and patient data to guide precision prescribing in pregnant / lactating patients.
• Studies leveraging existing real-world data and bioinformatics to develop and validate in silico models to evaluate repurposed therapeutics to prevent preterm birth.
• Studies utilizing novel biological therapeutics (e.g. genome editors, exosomes, tissue constructs, etc.) to treat severe neonatological conditions impacting multi-organ systems, or studies that develop novel drug delivery systems to treat severe neonatological conditions in utero.
• Developing a precision dosing model that takes into account delayed gastric emptying, altered volume of distribution, and other physiologic changes due to a disabling condition.
• Validation and implementation of multi-drug class pharmacogene platforms for precision prescribing in pediatric patients in general pediatric practice.
• Development and use of microphysiological systems using iPSC-derived placental organoids to assess placental transfer and potential fetal disposition of drugs.
• Development of time-dependent physiologically based pharmacometric models incorporating changes in components of drug metabolism pathways to predict drug exposure changes during the pregnancy and post-partum periods to the pregnant/post-partum mother and fetus/breastfeeding child.
• Generation and validation of systems pharmacology models that evaluate the impact of pediatric ontogeny on drug absorption, distribution, metabolism, and excretion of biological therapeutics.
• Development of a decision-support tool designed to promote informed decision-making and communicate drug safety and risk information to parents/legally authorized representatives of children who are eligible for clinical trials, including those with disabilities.
• Development of machine learning or other tools to facilitate data extraction, harmonization, or interoperability for pediatric clinical trials; development of automated clinical data processing tools for adverse event or outcome assessment in pediatric clinical trials.
• Development of novel drug safety prediction methodologies for neonatal and pediatric patients using pharmacoepidemiologic data.
• Studies evaluating or facilitating the implementation of a label change initiated by the BPCA program into clinical practice.
• Development of pediatric pharmacodynamic measures where PD measures in pediatric populations are currently lacking, incorporating modeling that distinguishes age ranges or other variables.

Applications that are involved in inter- and multi-disciplinary collaborations and interactions are highly encouraged.

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

Applications developing tools, models, or other methodologies of broad applicability across pediatrics, obstetrics, and/or lactation are encouraged, particularly research that addresses the List of Recommendations from the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC) and/or the Best Pharmaceuticals for Children Act (BPCA) Framework to Enable Pediatric Drug Development.

Applications supported by the NICHD should align with maternal and/or pediatric therapeutics research priorities within the NICHD’s Division of Extramural Research, in particular, but not exclusive to, the research priorities of OPPTB. Applications should address research topics relevant to the NICHD 2020 Strategic Plan’s Theme Five on advancing safe and effective therapeutics for pregnant and lactating persons, children, and people with disabilities.

Scientific Interest of the National Institute of Allergy and Infectious Diseases (NIAID)

NIAID is interested in advancing discovery and development of treatment and prevention of infectious, immune-mediated and allergic diseases and precision medicine approaches for fetal, neonatal, pediatric, pregnant and lactating persons:

• Immune development in infants/children following antenatal exposure to drugs and therapeutics given to individuals during pregnancy
• Mechanisms by which current or novel therapeutics impact maternal immune function, and/or how transfer to the fetus or the infant during pregnancy or lactation affects immune system development and function in these children.
• Development of tools and strategies for predicting drug safety on immune function or development in pregnant women, lactating women, neonates, and children.
• Translational and clinical research that can accelerate access to next generation anti-HIV, anti-TB and antimalarial treatment and prevention including novel drug delivery approaches and long-acting dosage forms, for pediatric, pregnant and breastfeeding individuals including:
  • Foundational research into developmental physiologic parameters/processes influencing antiretroviral or anti-TB drug disposition, effective concentration at site of disease, or development/optimization of innovative approaches and tools such as microphysiological systems for early prediction of drug toxicity signals.
  • Methodological/statistical and other in silico approaches to refine models, improve model verification, predict exposure at tissue site of disease
  • Leveraging of artificial intelligence to integrate physiologically based PK models, PK/PD data, patient characteristics data and various other relevant data source to begin laying the foundation for a precision/personalized medicine-based adaptive dosing framework.

NIAID will not support clinical trials for this announcement.

Scientific Interests of the Office of Research on Women’s Health (ORWH)

The Office of Research on Women's Health (ORWH) is part of the Office of the Director of NIH and works in partnership with the 27 NIH Institutes and Centers to ensure that women's health research is part of the scientific framework at the NIH and throughout the scientific community.

The NIH-Wide Strategic Plan for Research on the Health of Women 2024-2028 identifies goals and objectives that aim to increase and improve research on the health of women across the life course. The health of an individual during pregnancy influences the health of the fetus, children, and family and impacts lifelong health. Research on safe and effective therapies for pregnant and lactating people is important to the ORWH mission and aligns with the NIH policies for the inclusion of women and minorities in clinical research (NIH Inclusion Policies | Office of Research on Women's Health). To enhance this research focus, ORWH worked in partnership as a member of the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC) to develop the PRGLAC Recommendations that were submitted within the Report to the HHS Secretary and Congress.

For the purposes of this funding opportunity, ORWH is interested in supporting applications in maternal therapeutics research for safer and more effective medications that would benefit pregnant and lactating persons.

Specific areas of interest include but are not limited to:

• The development of novel therapeutics, investigating the use of existing drugs or repurposing of drugs to produce safer and more effective medications for use during pregnancy and while lactating.
• Identifying the immediate, mid-, and long-term effects of drug actions on pregnancy-related clinical outcomes.
• Studies focused on the unique needs of pregnant and lactating persons from diverse and/or underserved populations not often recruited nor fully represented including those with chronic preexisting conditions.

Scientific Interests of the National Institute of Mental Health (NIMH)

There are currently no PD measures that have been established in pediatric psychiatric populations to date, yet PD measures are critical to advancing drug development in children to objectively establish dose-response effects before large efficacy trials are pursued. Therefore, the NIMH is specifically interested in clinical studies supporting the establishment of pharmacodynamic (PD) markers of psychopharmacologic drugs in pediatric populations. For instance, a study using an EEG measure that would change in proportion to an administered drug dose (a CNS PD marker of drug action) would be of interest. It is expected studies will include dose ranging PK/PD measures. Age-dependent effects would be of interest as well as the inclusion of comparator drugs. Using the EEG PD example, it is likely that the EEG measures reflecting drug action would be different in grade school children vs adults.

All other NIMH studies focused on testing investigational or repurposed drugs/compounds in pediatric psychiatric populations will need to submit their applications through the NIMH Clinical Trials NOFOs.

Please contact NIMH program staff prior to submitting your application.

Scientific Interests of the National Institute on Drug Abuse (NIDA)

There is a significant gap in our knowledge regarding the unique metabolic, pharmacokinetic, and pharmacodynamic processes in pregnant and lactating persons that determine the effects of substances that cause or that are used to treat substance use disorders. Also lacking is a comprehensive understanding of the transport of these substances and their metabolites through the placenta or through breastmilk and their impact on the fetus or breastmilk-fed infant. Therefore, NIDA is specifically interested in translational research that would expand our understanding of the metabolism, transport, distribution, and pharmacodynamics of substances that cause or that are used to treat substance use disorders, as well as in the discovery and development of novel, existing, or repurposed therapeutics for the treatment of substance use disorders in pregnant and lactating persons.

Specific areas of interest include but are not limited to:

• Foundational research into physiological and pharmacological parameters/processes in pregnant and lactating persons that influence the distribution, pharmacokinetics, and toxicology of drugs that cause or that are used for the treatment of substance use disorders.
• Research on structure and function of transporters in placenta involved in the transport of substances that cause substance use disorders and in the transport of medications for the treatment of substance use disorders.
• Research on mechanisms underlying the changes in placental function induced by substances that cause or that are used to treat substance use disorders that impact maternal, fetal and/or neonatal outcomes.
• The development of novel therapeutics, investigating the use of existing drugs, or repurposing of drugs to produce safer and more effective medications for treatment of substance use disorders during pregnancy and while lactating.

NIDA will not  support clinical trials for this announcement.

The following types of applications will not be considered responsive to this NOFO and will be withdrawn:

• Mechanistic research on normal biology, pathophysiology, or disease etiology/progression.
• Studies that do not address research projects in either maternal or pediatric pharmacology.
• Projects that focus on research for health-related outcomes outside of the interest of a sponsoring ICO, as described above.

Applicants are highly encouraged to reach out to the Scientific Contact(s) to discuss fit to the Institute and responsiveness to this NOFO prior to submission of an application.

Expectations and Requirements for Resource and Data Sharing for NICHD-Funded Research

NICHD expects that data, biospecimens, and results of NICHD-funded research will be shared with the larger research community and/or public in alignment with NIH policies. The NIH Policy for Data Management and Sharing (Policy) expects researchers to maximize the sharing of scientific data and data be accessible as soon as possible and no later than the time of an associated publication or the end of the award period, whichever comes first. NIH requires all applications submitted in response to this NOFO to include a Data Management and Sharing Plan (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.

For human data, 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. Information about DASH may be obtained at https://dash.nichd.nih.gov/. Studies sharing data in DASH are encouraged to share study-related biospecimens through DASH. For projects generating large-scale human genetic data, applicants should provide a Provisional or Institutional Certification specifying whether the individual-level data can be shared through an NIH approved repository, such as dbGaP and the Sequence Read Archive, in line with the NIH Genomic Data Sharing Policy.

If use of DASH is not feasible, NICHD expects awardees to share data and/or biospecimens through other equivalent broad-sharing data and/or biospecimen repositories. Researchers should submit information about the location and availability of data in other repositories to the DASH Catalog, if applicable.

For applications that aim to co-analyze already shared data with data that have not yet been shared with the broader research community, applicants must describe in their DMS Plans how such primary data will be shared with the broad research community.

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

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 NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 How to Apply- Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

Katie M. Vance, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6640
Email: Katie.Vance@nih.gov

Page Limitations

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

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy: The applicants must describe how the proposed research approach will initiate, continue, or advance maternal and pediatric pharmacology and/or precision therapeutics.

Additionally, the Research Strategy must include a labeled section, described below, detailing the project's proposed ‘Milestones and Timelines'. All applications that propose a clinical trial involving a drug or therapeutic must include a labeled component, described below, describing the proposed project’s ‘Initial Dose Selection Rationale’. Applications with clinical trials that do not propose to use a drug or therapeutic are not required to include the ‘Initial Dose Selection Rationale’ section. 

Milestones and Timelines

Without duplicating information in the PHS Human Subjects and Clinical Trial Information form, describe project performance milestone and timeline objectives, including:

• A clear description of all interim objectives to be achieved during the course of the project and how they relate to the overall goal of advancing maternal and pediatric pharmacology or precision therapeutics;
• A detailed schedule or timeline for the anticipated attainment of each milestone and the objective of advancing maternal and pediatric pharmacology or precision therapeutics;
• Plans for the future advancement of the concepts after a single funding period, including the translational potential for studies primarily using animal or computational studies.

Initial Dose Selection Rationale

All applicants proposing a clinical trial involving drug(s) or therapeutic(s) are required to include the rationale for the initial selection of the dose, or equivalent, for the drug(s) or therapeutic(s) proposed for study. The rationale is not meant to discourage innovative approaches or designs. This rationale should include, for each drug and therapeutic proposed, the following:

• A succinct description of the available information on dosing (or equivalent) for each drug and/or therapeutic in the proposed population;
• The approaches used to select the doses (or equivalent) for each drug and/or therapeutic proposed in the application (e.g., information from drug labels, pharmacometric modeling, existing real-world data);
• When applicable, an explanation of how dosing for each drug and/or therapeutic will be adjusted throughout the clinical trial.

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

Other Plan(s): 

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

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

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

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

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

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply-Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

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

See more tips for avoiding common errors.

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

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 a 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.

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

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

Post Submission Materials

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.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

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

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

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the 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.

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

• 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.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

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

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

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

2. Administrative and National Policy Requirements

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

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

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

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

Not Applicable

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

4. Reporting

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

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

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

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (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: support@grants.gov

Katie M. Vance, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6640
Email: Katie.Vance@nih.gov
 

Tania Lombo Rodriguez, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-7612
Email: Tania.Lombo@nih.gov

Subramaniam Ananthan, Ph.D.
National Institute on Drug Abuse (NIDA)
Phone: 301-435-2199
E-mail: sam.ananthan@nih.gov

Elena K Gorodetsky, M.D., Ph.D.
ORWH - Office of Research on Women's Health
Phone: (301) 594-9004
E-mail: egorod@mail.nih.gov

Margaret Grabb, Ph.D.
National Institute of Mental Health (NIMH)
Telephone:  301-443-7123
Email: mgrabb@mail.nih.gov

Mark Caprara, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-827-3076
Email: capraramg@mail.nih.gov 

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email:margaret.young@nih.gov

Ann Devine
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2988
Email: adevine@niaid.nih.gov

Pamela G Fleming
National Institute on Drug Abuse (NIDA)
Phone: 301-480-1159
E-mail: pfleming@mail.nih.gov

Tamara Kees
National Institute of Mental Health (NIMH)
Telephone: 301-443-8811
Email: tkees@mail.nih.gov

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.