Translational Research in Maternal and Pediatric Pharmacology and Therapeutics (R01 Clinical Trial Optional) is sponsored by National Institutes of Health (NIH). This grant supports translational research in maternal and pediatric pharmacology and therapeutics.

PAR-25-110: Translational Research in Maternal and Pediatric Pharmacology and Therapeutics (R01 Clinical Trial Optional) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) National Institute of Allergy and Infectious Diseases ( NIAID ) National Institute on Drug Abuse ( NIDA ) National Institute of Mental Health ( NIMH ) All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers.

The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Research on Women's Health ( ORWH ) Funding Opportunity Title Translational Research in Maternal and Pediatric Pharmacology and Therapeutics (R01 Clinical Trial Optional) R01 Research Project Grant Notices of Special Interest associated with this funding opportunity March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity Exploratory/Developmental Grants See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) 93. 865, 93.

855, 93. 279, 93. 242, 93.

313 Funding Opportunity Purpose The purpose of this notice of funding opportunity (NOFO) is to support translational and clinical research to (1) advance precision medicine in pregnant women, lactating women, and children 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 and lactation; 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 and lactating women, neonates, and children.

The overall goal is to improve safe and effective precision therapeutics for pregnant and lactating women, fetuses, neonates, and children, including those with disabilities. Open Date (Earliest Submission Date) The following table includes NIH standard due dates marked with an asterisk.

Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed 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.

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

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

Use the NIH ASSIST system to prepare, submit and track your application online. 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. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description 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 women, lactating women, 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 women 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 women, and lactating women, 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 women, lactating women, 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 women, lactating women, fetuses, neonates, and children/adolescents as well as to predict the impact of drug exposure from the pregnant or lactating woman 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.

The objectives of this notice of funding opportunity (NOFO) are to support translational and clinical research to (1) advance precision medicine in pregnant women and lactating women, 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 women, neonates, and children.

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

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 .

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 women: 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.

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 women.

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 women 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 women 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 women.

Specific areas of interest include but are not limited to: Foundational research into physiological and pharmacological parameters/processes in pregnant and lactating women 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 Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Optional: Accepting applications that either propose or do not propose clinical trial(s). Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Application budgets are not limited but need to reflect the actual needs of the proposed project. The scope of the proposed project should determine the project period. The maximum project period is 5 years.

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 Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

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

Eligible Individuals (Program Director/Principal Investigator) 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.

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

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

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.

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